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Cannabis foods

Cannabis foods

From Wikipedia, the free encyclopedia

A variety of space cakes from Amsterdam

Cannabis foods are foods prepared with cannabis in herbal or resin form to enjoy the psychoactive effects of the drug for those who prefer not to smoke it. Commonly it is cooked into a cake, cookie, brownie, or other baked product to be distributed socially. As with other illicit activities and drug culture in general there are many different names and slang terms for these recipes. Most are based on standard recipes for brownies, cakes or cookies. The addition of hash, cannabis, weed or the more euphemistic space, magic, adult, special prefixes gives some of the more common names like hash brownie, space cake etc.



[edit] Types of preparation

They are usually prepared by using oil or butter which has previously been used to extract the active ingredient from the cannabis. Sometimes, however, the ingredients are mixed in directly.

THC and other cannabinoids are hydrophobic oils. They are insoluble in water but soluble in alcohols, fats, and other oils. As cannabinoids are insoluble in water, THC in the presence of fats or oils simply accelerates the process of dissolution in the fats, from some hours at room temperature to minutes in the microwave.

[edit] Cannabutter

Making Cannabutter

Cannabutter is an oil/fat/butter based solution which has been infused with cannabinoids. This is achieved by heating the raw cannabis along with the oil or butter and allowing the cannabinoids (THC and others) to be extracted by the fat. The exact procedure for this varies greatly. The equipment necessary for the manufacture of cannabutter can be as simple as a sauce pan and spatula or as complicated as a double-boiler, or crock pot, and cheese cloth and funnel.

Another way to produce cannabutter is to boil a large pan of water and then add a block of butter and add cannabis trimmings (the leaves and stalks). The water stops the THC from being damaged by heat as the mixture will never reach over 100 C. After half an hour or so of boiling sieve the mixture to remove the leaves and cool the liquid in a fridge. When it has cooled you are left with a potent layer of cannabutter on top of dirty water.

The flavor and color of the oil or butter used are changed depending on the method used.

[edit] Leary biscuit

A Leary biscuit is a snack consisting of a cracker, cheese, and ground up marijuana bud. It is heated in a microwave oven and causes a cannabis "high" in the eater. The heating is said to activate the tetrahydrocannabinol (THC), the active ingredient in cannabis. In actuality, the heating simply increases the solubility of the THC in the fats and oils in the cheese.[citation needed] The plant material of cannabis is not easily digested, and so the THC is not readily absorbed into the bloodstream unless it is first dissolved in some kind of fat, oil, or alcohol. This is why cheese is used for the Leary biscuit - cheese has a high fat content, suitable for dissolving THC and making it more readily available for digestion.

[edit] Hash cookie

Hash cookies, also known as space cookies, hash cakes or space cakes are relatively common in regions with liberal drugs policies, including much of Europe (particularly the Netherlands). They are bakery products made using one of the forms of cannabis, including hashish.

Hash cookies are essentially the same as marijuana cookies, and are also seen in cake, ball, and brownie form. To make them, large amounts of hash (typically half a gram to as much as a gram a cookie) are baked into the product in careful steps, so that the user is able to achieve a high without actually smoking anything. Some users report that the high is not quite as intense as smoking, but instead it is felt throughout the body as a feeling of lightness, sometimes known as a "body high". The main benefits to preparing these cookies is that they can be used in many places where smoking is not convenient, as they can easily be brought to parties, cafes, and work. One is not usually able to tell the difference between regular baked goods and those containing drugs, but they tend to have a slight greenish tinge with marijuana, and they often emit a faint odor. Many resources for recipes, preparation, and dosage are available online, though they vary greatly in effectiveness and quality.

The writer Alice B. Toklas's inclusion of her friend Brion Gysin's recipe for "Haschich Fudge" in her 1954 literary memoir The Alice B. Toklas Cookbook caused a sensation at the time, and led to her name becoming associated with cannabis food with the use of the phrase "Alice B. Toklas brownies" for many years afterwards.

[edit] Drug effects

Eating such a food can result in a similar psychoactive effect or "high" as smoking marijuana, although it may be delayed or mitigated due to slower absorption of the tetrahydrocannabinol (THC) through the digestive tract. Some believe it imparts a smoother "high". However there are many accounts of stronger, longer lasting highs resulting from eating cannabis. Whereas the effects from smoking cannabis are usually felt within a few minutes, it can take up to two hours to get high from ingesting it.

Contrary to smoking, where one can feel the high coming gradually; the way the THC is digested can result in a significantly stronger high that can last for hours. Products containing cannabis are widely available in cannabis coffee shops in the Netherlands (and various European cities), where the consumption of marijuana is effectively legal.

[edit] In pop culture

  • The brownie was used in the 1968 film I Love You, Alice B. Toklas, in which a character portrayed by Peter Sellers becomes disillusioned with his mainstream life after falling in love with a free spirit, only to become just as disillusioned with the hippie subculture. Marijuana-spiked brownies are a key plot element.
  • In "Garage Sale" - the second season premiere of the FOX sitcom That '70s Show - Steven Hyde makes "special brownies" that end up being consumed by Red, Kitty, Midge and Bob.
  • In the movie Eurotrip, Scotty, played by Scott Mechlowicz, and Jenny, played by Michelle Trachtenberg eat some brownies in a Dutch bake shop that they assume are hash brownies and "suffer" the symptoms. They learn, however, that the brownies contain no cannabis, with the staff referring to the establishment as a "simple Dutch bakery", much to their embarrassment.
  • Ethan Embry's character in the film Empire Records consumes hash brownies while watching television.
  • In the movie Never Been Kissed, Josie eats a load of pot brownies.
  • In the movie How High, the Chancellor of Harvard University and his wife unknowingly consume large amounts of brownies mixed with marijuana, causing them to act silly at a Halloween costume party later that night.
  • In the movie "In a Noir York Minute", the character Jefferson, played by Regis Philbin, eats a hash brownie every night after work to "you know, just chill out a bit."
  • In the movie Can't Hardly Wait, the stoner character played by Eric Balfour is eating hash brownies with his friends when his female friend feels tricked and throws her hash brownie at Lauren Ambrose's hair, where it sticks. Eric Balfour's character runs over to the thrown hash brownie and licks it off her head, saying, "I don't wanna waste any."
  • In the movie Dick, Kirsten Dunst's character unknowingly makes hash brownies for President Nixon and his cabinet. (She believes the hash is "walnut leaves")
  • In the HBO series Oz, the character Stan Burkowsky makes marijuana brownies for the Homeboys in season six before being killed by the Italians.
  • In an episode of My Name Is Earl, Earl Hickey remembers about the time he switched Crabman's pot brownies with actual brownies. After dissatisfied customers found out they were eating real brownies (i.e. "I had to listen to a Phish sucked!"), they stoned him "biblically".
  • In the episode "High Holidays" of Frasier, Niles Crane plans to eat a cannabis brownie to experience the rite of teenage rebellion he had missed when he was a teenager. His father, a retired police officer, unwittingly eats the brownie.
  • In one episode of Greg the Bunny, Eugene Levy's character accidentally ingests marijuana brownies.
  • In an episode of Grounded for Life, "Henry's Working for the Drug Squad", Sean Finnerty eats cannabis brownie batter, still containing the seeds. He stumbles to his backyard and throws up. A marijuana plant grows in the puke.
  • Space Cake is the name of a metal/funk band from Surrey, England.
  • In an episode of Nip Tuck, a blond woman offers a chocolate-color cannabis brownie to Sean McNamara.
  • In the movie Next Friday, Roach gives Chico the dog a brownie with cannabis so Craig played by Ice Cube could break into The Jokers home.
  • In the novel, The Perks of Being a Wallflower the main character consumes a marijuana brownie accidentally while at a party.
  • In the 70s US television show Barney Miller the police detectives accidentally eat a marijuana brownie the girlfriend of Detective Stan 'Wojo' Wojciehowicz has given him.
  • In Deuce Bigalow: European Gigolo T.J. tricks Deuce into getting high on space cake while at a cafe in Amsterdam.
  • In an episode of Arrested Development (TV Series), following a comic misunderstanding with his nephew Michael, Oscar Bluth succeeds in getting his sister-in-law Lucille high on cannabis by "putting it in her brownie."
  • In the video game EarthBound, the player must buy and consume an item called "Magic Cake" in order to inhabit the body of Poo, the fourth and final party member.
  • In the movie 50 First Dates, Henry Roth makes numerous references to Marijuana and special brownies used by his friend Ula.
  • In Taxi, a pot brownie completely derails the life of a straightlaced Harvard student, turning him into the junkie cabbie Reverend Jim, played by Christopher Lloyd.
  • As part of his "Part Troll" tour, the stand-up comedian Bill Bailey encouraged the audience to suggest alternative foods that can be cooked using cannabis. On the DVD suggestions included lard, shepherd's pie and beef stroganoff.
  • In the FOX animated series Family Guy, when Stewie is hallucinating due to fever brought on by immunization shots and Meg asks what is wrong with him, Lois responds: "He's just having a little hallucination from the fever, just like when you were 2 and ate those adult brownies I was saving for the Doobie Brothers concert."
  • In season 4 of the TV series Desperate Housewives, Lynette's mother feeds her hash brownies so she can overcome her nausea caused by chemotherapy. This causes Lynette to hallucinate at Susan's charade night.

[edit] See also

Wikibooks' Cookbook has more about this subject:

Designer drug

Designer drug is a term used to describe psychoactive drugs which are created (or marketed, if they had already existed) to get around existing drug laws by modifying their molecular structures to varying degrees. [1]



[edit] History

The main term originated with law enforcement, but has gained widespread use. The term was originally coined in the 1980s to refer to various heroin-like synthetic substances, mostly based on the fentanyl molecule (such as α-methylfentanyl). The term gained widespread popularity when MDMA (ecstasy) experienced a popularity boom in the mid 1980s. In the United States, the Controlled Substances Act was amended by the Controlled Substance Analogue Enforcement of 1986, which attempted to ban designer drugs pre-emptively by making it illegal to manufacture, sell, or possess chemicals that were substantially similar in chemistry and pharmacology to Schedule I or Schedule II drugs. Other countries have dealt with the issue differently. In some, they simply ban new drugs as they become a concern, as do Germany, Canada, and the United Kingdom. Some countries, such as Australia and New Zealand, have gone the opposite direction and enacted sweeping bans based on chemical structure only, making chemicals illegal even before they are created—if a theoretical chemical fits a set of rules regarding substitutions and alterations of an already banned drug, it too is banned. The controlled substance analogue law in New South Wales, Australia, is so broad that it would cover millions of compounds that have never been made, simply on the basis that they bear a vague resemblance to one of the drugs on the illegal list. [2]

When the term was coined in the 1980s, a wide range of narcotics were being sold as heroin on the black market. Many were based on fentanyl or meperidine. One, MPPP, was found in some cases to contain an impurity called MPTP, which caused brain damage that could result in a syndrome identical to full-blown Parkinson's disease, from only a single dose. Other problems were highly potent fentanyl analogues, which were sold as China White, that caused many accidental overdoses. Because the government was powerless to prosecute people for these drugs until after they had been marketed successfully, laws were passed to give the DEA power to emergency schedule chemicals for a year, with an optional 6-month extension, while gathering evidence to justify permanent scheduling, as well as the analogue laws mentioned previously.

Emergency-scheduling power was used for the first time for MDMA. In this case, the DEA scheduled MDMA as a Schedule I drug and retained this classification after review, even though their own judge ruled that MDMA should be classified Schedule II on the basis of its demonstrated uses in medicine. The emergency scheduling power has subsequently been used for a variety of other drugs including 2C-B, AMT, and BZP. In 2004, a piperazine drug, TFMPP, became the first drug that had been emergency-scheduled to be denied permanent scheduling and revert to legal status.

In the late 1990s and early 2000s, there was a huge explosion in designer drugs being sold over the internet. The term and concept of "research chemicals" was coined by some marketers of designer drugs (particularly of psychedelic drugs in the tryptamine and phenethylamine family). The idea was that by selling the chemicals as for research rather than human consumption, the intent clause of the U.S. analogue drug laws would be avoided. This was later shown to be faulty logic when the DEA raided multiple suppliers, first JLF Primary Materials, and then multiple vendors several years later in Operation Web Tryp. This process was accelerated greatly when vendors began advertising via search engines like Google by linking their sites to searches on key words such as chemical names and terms like psychedelic or hallucinogen. Widespread discussion of consumptive use and the sources for the chemicals in public forums also drew the attention of the media and authorities.

Many substances that were sold as "research chemicals" in this period of time are hallucinogens and bear a chemical resemblance to well-known drugs, such as psilocybin and mescaline. As with other hallucinogens, these substances are often taken for the purposes of facilitating spiritual processes (see entheogen), mental reflection (see psychedelic) or recreation. Some research chemicals on the market were not psychoactive, but can be used as precursors in the synthesis of other potentially psychoactive substances, for example, 2C-H which could be used to make 2C-B and 2C-I among others. Extensive surveys of structural variations have been conducted by pharmaceutical corporations, universities and independent researchers over the last century, from which some of the presently available research chemicals derive. One particularly notable researcher is Dr. Alexander Shulgin, who presented syntheses and pharmacological explorations of hundreds of substances in the books TiHKAL and PiHKAL (co-authored with Ann Shulgin), and has served as an expert witness for the defense in several court cases against manufacturers of psychoactive drugs.

Most chemical suppliers sold research chemicals in bulk form as powder, not as pills, as selling in pill form would invalidate the claims that they were being sold for non-consumptive research. Active dosages vary widely from substance to substance, ranging from sub-microgram levels to hundreds of milligrams, but while it is critical for the end user to weigh doses with a precision scale, instead of guessing ("eyeballing"), many users did not do this and this led to many emergency room visits and several deaths, which were a prominent factor leading to the emergency scheduling of several substances and eventually Operation Web Tryp. When a chemical increases in popularity, it will often be sold in pill form to reach a wider market. Some of the most popular chemicals are also given street names (like "Foxy" or "Foxy Methoxy" for 5-Meo-DiPT). Once a chemical reaches this kind of popularity, it is usually just a matter of time before it is added to the list of scheduled (i.e. illegal) drugs.

[edit] Safety and law

Little if any research has been done on the toxicology or pharmacology of most of these drugs. Few, if any, human or animal studies have been done. Unlike better-known drugs like alcohol or marijuana, which have been used by millions of people worldwide, research chemicals are new and may only have been used by a few dozen people for a few months although some of the more popular drugs such as 2C-B and BZP have been used by tens of thousands of people. The safety of research chemicals is untested and due to the recent development of many of them, laws banning or restricting their use have not been developed yet. However, many of the chemicals fall under the various drug analogue legislations in different countries.

In 2004, the US Drug Enforcement Administration raided and shut down several internet based research chemical vendors in an operation called Web Tryp. With help from the authorities in India and China, two chemical manufacturers were also closed. Many other internet based vendors promptly stopped doing business, even though their products are still not scheduled.

[edit] Well-known designer drugs

Most research chemicals are structural analogues of tryptamines or phenethylamines, but there are also completely unrelated chemicals which are normally considered to be part of the group. It is impossible to determine psychoactivity or other pharmaceutical properties of these chemicals strictly from examining their structure, and many of the substances have common effects whilst structurally different and vice versa. Confusing nomenclature, similar names, and differing naming schemes can all lead to (and is anecdotally known to have led to) potentially hazardous mixups for end users.

  • Some of the early narcotic designer drugs:
  • Some prominent tryptamine-based substances:
    • 4-Acetoxy-DiPT, n, n-diisopropyl-4-acetoxytryptamine
    • 5-MeO-AMT, 5-methoxy-alpha-methyltryptamine
    • 5-MeO-DIPT, 5-methoxy-di-isopropyltryptamine (also known as "Foxy" or "Foxy Methoxy")
    • 5-MeO-DMT, 5-methoxy-dimethyltryptamine
    • AMT, α-methyltryptamine
    • AET, α-ethyltryptamine
    • DIPT, N,N-diisopropyl-tryptamine
    • DPT, N,N-dipropyltryptamine
  • Some prominent phenethylamine-based substances:
    • 2C-B, 4-bromo-2,5-dimethoxyphenethylamine (also known as "bromo-mescaline")
    • 2C-C, 2,5-dimethyoxy-4-chlorophenethylamine
    • 2C-I, 2,5-dimethoxy-4-iodophenethylamine
    • 2C-E, 2,5-dimethoxy-4-ethyl-phenethylamine
    • 2C-T-2, 2,5-dimethoxy-4-ethylthiophenethylamine
    • 2C-T-7, 2,5-dimethoxy-4-(n)-propylthiophenethylamine
    • 2C-T-21, 2,5-dimethoxy-4-(2-fluoroethylthio)phenethylamine
    • MDMA, 3,4-methylenedioxymethamphetamine
    • MDEA, 3,4-methylenedioxy-N-ethylamphetamine
    • DOB, 2,5-dimethoxy-4-bromoamphetamine
    • DOM, 2,5-dimethoxy-4-methylamphetamine
    • TMA-2, 2,4,5-Trimethoxyamphetamine
  • Some PCP analogues which have been sold as designer drugs:
    • TCP, 1-[1-(2-thienyl)-cyclohexyl]-piperidine or thienylcyclohexylpiperidine
    • PCE, (1-Phenylcyclohexyl)ethylamine
    • PCPy, 1-(1-phenylcyclohexyl)pyrrolidine
  • Some piperazine-based substances:
    • BZP, benzylpiperazine
    • TFMPP, 3-Trifluoromethylphenylpiperazine, has the unique distinction of being the only drug to be emergency scheduled into Schedule I and then allowed to become legal because the DEA was unable to justify permanent scheduling
    • mCPP, 1-(3-chlorophenyl)piperazine
    • pFPP, 1-(4-fluorophenyl)piperazine
  • Some designer steroids:
  • Some other designer drugs:
    • GBL, gamma-butyrolactone, both a precursor to and substitute for GHB
    • 1,4-Butanediol, another GHB analogue

[edit] References

  1. ^ Buchanan JF, Brown CR. Designer drugs. A problem in clinical toxicology. Medical Toxicology and Adverse Drug Experience. 1988 Jan-Dec;3(1):1-17.
  2. ^

[edit] See also

Extacy ( MDMA ) - Methylenedioxymethamphetamine

From Wikipedia, the free encyclopedia

Jump to: navigation, search
Systematic (IUPAC) name
CAS number 69610-10-2
ATC code  ?
PubChem 1615
Chemical data
Formula C11H15NO2 
Mol. mass 193.25 g/mol
SMILES search in eMolecules, PubChem
Pharmacokinetic data
Bioavailability  ?
Metabolism Hepatic, CYP extensively involved
Half life The half-life of MDMA is dose dependent, increasing with higher doses, but is around 6–10 hours at doses of 40–125 mg
Excretion Renal
Therapeutic considerations
Pregnancy cat.

C [2]

Legal status

Prohibited (S9)(AU) Schedule III(CA) Class A(UK) Schedule I(US)

Routes Sublingual salla

MDMA (3,4-methylenedioxy-N-methylamphetamine), most commonly known today by the street name ecstasy, (often abbreviated to E, X, or XTC) is a semisynthetic empathogen-entactogen of the phenethylamine family. It has greater stimulant effects and fewer visual effects than other common "trip" producing psychedelics. It is considered mainly a recreational drug, though is often used as an entheogen and as a tool to supplement various types of practices for transcendence, including in meditation, psychonautics, and psychedelic psychotherapy, whether self-administered or not. MDMA is illegal in most countries, and its possession, manufacture or sale may result in criminal prosecution.



[edit] History

MDMA is often rumored to have been first synthesized by the famous German chemist Fritz Haber in 1891; however, this is incorrect.[1]

The patent for MDMA—referred to as methylsafrylamin—which is not under dispute, was originally filed on December 24, 1912 by the German pharmaceutical company Merck, after being first synthesised for them by German chemist Anton Köllisch at Darmstadt earlier that year.[2][3] The patent was granted in 1914; Köllisch died in 1916 unaware of the impact his synthesis would have.

At the time, MDMA was not known to be a drug in its own right; rather, it was patented as an intermediate chemical used in the synthesis of a hydrastinine (a drug intended to control bleeding from wounds) analogs [citation needed]. During 1927, Max Oberlin used MDMA as a mimic for adrenaline as the compound has a similar chemical structure. At this time the first animal studies were performed to demonstrate the effects of MDMA on blood glucose levels and vascular tissue.[2]

This study was discontinued due to the high costs of the chemical synthesis. Interest was revived in the compound as a possible human stimulant by Wolfgang Fruhstorfer in 1959, although it is unclear if tests were actually performed on humans. The synthesis of the compound first appeared in 1960.[4]

The U.S. Army did, however, carry out lethal dose studies of MDMA and several other compounds on animals in the mid-1950s. It was given the name EA-1475, with the EA standing for either (accounts vary) "Experimental Agent" or "Edgewood Arsenal."[5] The results of these studies were not declassified until 1969.

Due to the wording of the existing Misuse of Drugs Act 1971, MDMA was automatically classified as a Class A drug in 1977 in the UK. MDMA was classified as a Schedule I controlled substance in the United States from May 31, 1985.[6] Before then, it was used both as an adjunct to psychotherapy and as a recreational drug.

MDMA began to be used therapeutically in the mid-1970s after the chemist Alexander Shulgin introduced it to psychotherapist Leo Zeff. As Zeff and others spread word about MDMA, it developed a reputation for enhancing communication, reducing psychological defenses, and increasing capacity for introspection. However, no formal measures of these putative effects were made and blinded or placebo-controlled trials were not conducted. A small number of therapists—including George Greer, Joseph Downing, and Philip Wolfson—used it in their practices until it was made illegal. There have even been accounts that the military also used this for interrogating enemy spies [citation needed].

MDMA appeared sporadically as a street drug in the late 1960s (when it was known as the "love drug"), but it rose to prominence in the early 1980s in certain trendy nightclubs in the Dallas area, then in gay dance clubs.[7] From there use spread to rave clubs, and then to mainstream society. The street name of "ecstasy" was coined in California in 1984. The drug was first proposed for scheduling by the DEA in July 1984.[4]

During the 1990s, along with the growing popularity of the rave subculture, MDMA use became increasingly widespread among young adults in universities and later in high schools. It rapidly became one of the four most widely used illegal drugs in the U.S., along with cocaine, heroin and cannabis.

In the late 1980s and early 1990s, ecstasy was widely used in the United Kingdom and other parts of Europe, becoming an integral element of rave culture and other psychedelic/dancefloor-influenced music scenes, such as Madchester and Acid House.

Despite government prosecution, today in the United States, MDMA is second only to Marijuana in the number of new users it will attract, making it one of the fastest-growing drugs in history. [3]

[edit] Effects

For more details on this topic, see Effects of MDMA on the human body.

[edit] Mode of Action

MDMA's effects are due primarily to the drug's higher affinity for SERT than serotonin itself. SERT is the part of the serotonergic neuron which removes serotonin from the synapse to be recycled for later use. Not only does MDMA inhibit the reuptake of serotonin, but it actually reverses the action of the transporter so that it actually begins pumping serotonin into the synapse from inside the cell [4]. This usually causes the serotonin storage vesicles to be emptied after only a few hours with a standard recreational dose.

In addition, MDMA has a partial affinity for blocking the reuptake of dopamine and a smaller affinity still for blocking that of norepinephrine as well as other neurotransmitters in smaller quantities. The former two neurotransmitters, amongst others which may also be released in small amounts, are responsible for increased energy and contribute to the "speedy" feeling of the drug experience, whereas serotonin contributes primarily to feelings of well-being, euphoria, and decreased hostility.

The empathic action of MDMA is yet to be understood well, but one theory is that oxytocin, a hormone and neurotransmitter crucial to social bonding, is released in large quantities when MDMA is taken.

[edit] Subjective effects

The primary effects of MDMA include an increased awareness of the senses, feelings of openness, euphoria, empathy, love, happiness, heightened self-awareness, feeling of mental clarity and an increased appreciation of music and movement. Tactile sensations are enhanced for some users, making physical contact with others more pleasurable.[8] Other side effects, such as jaw clenching and elevated pulse, are common. Some users report effects similar to those of softer stimulants such as caffeine, and a few report effects comparable to harder stimulants such as cocaine. Alexander Shulgin stated that the single best use of MDMA was to facilitate more direct communication between people involved in significant emotional relationships.[citation needed] Psychiatrist George Greer came to the same conclusion in his report on the first 29 subjects administered MDMA in his practice, with the MDMA having been synthesized in Shulgin's lab.[9]

[edit] Recreational use

Recreational uses:
  • euphoria
  • Sensory Enhancement (Auditory, visual, tactile)
  • Physical stimulation
  • Cognitive exploration
Other putative uses:
  • Not for use in combination with stimulants (amphetamines, large doses of caffeine, soda, energy drinks, etc).
  • Not for use in combination with diuretics (alcohol).
  • Not for use in individuals with high blood pressure, hypertension, or blood clotting disorders.
  • Not for use in individuals with Gilbert syndrome.
  • Not for use in individuals who have displayed allergies to amphetamine drugs.
  • Must never be used in combination with an unselective MAOI (Monoamine Oxidase Inhibitor), an MAO-A inhibitor or an MAO-B inhibitor being taken above selective dosages.
Side effects:
  • euphoria
  • Strong sense of empathy
  • Profound sense of well being
  • Ability to discuss any topic with out anxiety
  • Psychomotor activation
  • Feelings of insight
  • Short-term memory lapses
  • increased sweating
  • increased heart rate and blood pressure
  • increased body temperature
  • heightened tactile sensations
  • "chattiness"
  • restlessness
  • chattering teeth
  • muscle spasms

MDMA use has increased markedly since the late 1980s, and spread beyond its original subcultures to mainstream use, with prices generally falling, although there is still wide geographical variance, both regionally and between countries.

[edit] United Kingdom

In 1995 it reported that the street price per pill was, "about £15 each,"[10] although two years later this had shifted to a range of £8 to £15 each."[11] A 2001 Home Office study reported that the cost per pill to end-point consumer, "could be as little as £7.50, or as much as £10 to £15 when purchased in clubs."[12] In 2007 the Greater London Authority highlighted regional variations, reporting[13] that the average street price per pill in five selected cities was:

[edit] Supply

Worldwide, almost all MDMA is supplied via clandestine routes. The synthesis of MDMA is more complex than that of analogues such as methamphetamine, but still well within the grasp of a university-level chemistry student. Arguably the most difficult part of the synthesis is obtaining the necessary chemical precursors: some have few legitimate uses outside of clandestine drug production, and purchases of them are often illegal or heavily monitored by government agencies like the DEA.

[edit] Purity

Because of its illegality in most countries, the typical recreational user is unable to verify the purity of a substance sold as MDMA. However, DanceSafe, among other companies, provides home testing kits to verify the contents of MDMA pils, uses a lab to analyze MDMA pills for a fee, and and each provide the results home testing kits have provided on ecstasy pills in addition to the suspected contents when a test has not been performed.

A small percentage of MDMA pills have been found to be cut with various substances; typical substances include caffeine, methamphetamine and ephedrine, all of which have similar stimulant effects to MDMA. Recent surveys of seized Ecstasy pills indicate that purity levels are generally high, and that adulterants are rare.[14] In sharp contrast to this information, current (as of 11/16/07) stats indicate that on average over the past 11 years, only 37.4% of pills tested contained MDMA alone as an active ingredient. A staggering 44.2% of pills tested contained no MDMA at all, with the remaining 18.4% containing MDMA in addition to adulterants.[5] It may be reasonable to assume that the truth lies somewhere in the middle, that although most pills contain at least some MDMA, the majority are adulterated to some degree.

Although full and proper characterization of ecstasy pills requires advanced lab techniques such as high performance liquid chromatography-mass spectrometry (usually referred to as HPLC-MS), gas chromatography-mass spectrometry (usually referred to as GC-MS) and gas chromatography-infrared spectroscopy (usually referred to as GC-IRD), it is also possible to use a less accurate presumptive alkaloid test known as the Marquis reagent. Many organizations sell pill testing kits containing this reagent. DanceSafe is one such company, and it includes an extensive database of photographs of different pills, along with the results of a laboratory analysis of their contents.[15] is a non-profit site that tests the purity of street pills and compiles results.[16] also enables users to post reports on pills they have purchased, to share the experiences, pictures, and testing results; other users can then post what they think about the pill in question or even rate the report on the pill. Ecstacy take around 30 minutes to kick in, they give the user a feeling of complete happiness, as if this is the best time of their lives. However the "come-down" experienced in the days after can be character changing.

[edit] Ecstasy-pills

Ecstasy commonly appears in a tablet form, usually imprinted with a monogram.

Pills come in a variety of "brands", usually identified by the icons stamped on the pills. An example would be "Red Mercedes", which gets its name because of its red color and Mercedes-Benz logo imprinted on it. Most are named after famous persons or places such as "D&G's" (Dolce & Gabbana) and "Dom Vito's". However the brands do not consistently designate the actual active compound within the pill, as it is possible for "copycat" manufacturers to make their own pills which replicate the features of a well-known brand. Also known as Yellow Gators, Triple Stacks, Kabooms, and Xo's

[edit] MDMA powder/crystals

The pure form of MDMA hydrochloride.
Some users put the MDMA powder into capsules before consuming.

MDMA powder, usually the hydrochloride, is often simply called 'crystal' or 'molly', and 'mandy', and in the UK 'madman' (a play on words- MaDMAn), a mutation of 'madman' 'mandy', and 'MD'. This powder is produced in MDMA labs and provided to the pill-manufacturers to press the tablets at a different place. In many parts of the world the usage of plain MDMA powder instead of pills is popular. One of the reasons for this might be the control over dosage and purity. MDMA is very rarely cut, for its taste is so strong, distinctive and (many would argue) unpleasant that it would be very easy for a user to tell if it were impure. Dealers are more likely to simply sell an amount that is smaller than they claim. When pressed into pill tablets, MDMA powder is always mixed with pill binders because pure MDMA cannot be pressed. Powder or crystal MDMA can be snorted, which makes the effect begin and end quicker. Some users claim that snorting it results in a more intense effect. Snorting however is painful compared to drugs such as cocaine and ketamine, and many users prefer oral administration either by applying a 'dab' to the tongue and washing it down with water, or mixing it into a drink. Some people also 'bomb' pure MDMA, whereby a dose is wrapped in cigarette papers (e.g. Rizla) and then swallowed. This is the preferred method of ingestion for many users as the taste is quite unpleasant and can be exacerbated by the heightened sense of taste which can be a feature of MDMA use.

[edit] Use in psychotherapy

Some scientists have suggested that MDMA may facilitate self-examination with reduced fear, which may prove useful in some therapeutic settings. In 1980, psychiatrist George Greer synthesized MDMA in the lab of Alexander Shulgin, then administered it to about 80 of his clients over the next five years, until MDMA was scheduled in 1985. In a published summary of the effects,[17] subjects reported improvements in various, mild psychiatric disorders and other personal benefits, especially improved intimate communication with their significant others. In a subsequent publication on the treatment method, one patient with severe pain from terminal cancer reported definitive and lasting pain relief and improved quality of life.[18]

In 2001, the FDA granted permission for experimental administration of MDMA to patients suffering from post-traumatic stress disorder. This research is being sponsored by the Multidisciplinary Association for Psychedelic Studies (MAPS).[19] First of those studies was conducted by Jose Carlos Bouso, a Spanish therapist who used the MDMA with women that had been raped, but he only could finish the first part of the study for political reasons, awaiting to be completed. A parallel similar study is currently underway in Switzerland which should finish in 2008.[20] This research in patients builds on studies in which MDMA was given to healthy volunteers. The first of these healthy volunteer studies was conducted by Dr. Charles Grob, with other studies done by Dr. Franz Vollenweider in Switzerland, Drs. John Mendelson and Reese Jones at the University of California San Francisco, and Drs. Magi Faree and Rafael de la Torre in Spain.

It has been proposed that MDMA should be considered the prototypical member of a novel category of drug, called "empathogen" and/or "entactogen."[21][22]

[edit] Synthesis

Industrial scale methamphetamine/MDMA factory in Cikande, Indonesia

Safrole, a colorless or slightly yellow oil, extracted from the root-bark or the fruit of sassafras plants is the primary precursor for all manufacture of MDMA. There are numerous synthetic methods available in the literature to convert Safrole into MDMA via different intermediates. One common route is via the MDP2P (3,4-methylenedioxyphenyl-2-propanone, also known as piperonyl acetone) intermediate. This intermediate can be produced in at least two different ways. One method is to isomerize Safrole in the presence of a strong base to isosafrole and then oxidize isosafrole to MDP2P. Another, reportedly better method, is to make use of the Wacker process to oxidize safrole directly to the MDP2P (3,4-methylenedioxy phenyl-2-propanone) intermediate. This can be done with a palladium catalyst. Once the MDP2P intermediate has been produced it is then consumed via a reductive amination to form MDMA as the product.

According to DEA Microgram newsletters very little safrole is actually required to make MDMA. [23]"Ocotea cymbarum is an essential oil... that typically contains between 80 and 94 percent safrole," "a 500-milliliter bottle of Ocotea cymbarum sells for $20 to more than $100," "An MDMA producer with access to the proper chemicals can use a 500-milliliter quantity of Ocotea cymbarum to produce an estimated 1,300 to 2,800 tablets containing 120 milligrams of MDMA."

[edit] Legal issues

Use, supply and trafficking of ecstasy are currently illegal in most countries. In the United States, MDMA was legal and unregulated until May 31, 1985, at which time it was added to DEA Schedule I, for drugs deemed to have no medical uses and a high potential for abuse. During DEA hearings to criminalize MDMA, most experts recommended DEA Schedule III prescription status for the drug, due to its beneficial usage in psychotherapy. The judge overseeing the hearings, Francis Young, also made this recommendation. Nonetheless, the DEA classified it as Schedule I.[24]

That same year, the World Health Organization's Expert Committee on Drug Dependence recommended that MDMA be placed in Schedule I of the Convention on Psychotropic Substances. Unlike the Controlled Substances Act, the Convention has a provision (in Article 7(a)) that allows use of Schedule I drugs for "scientific and very limited medical purposes." The Committee's report stated:

The Expert Committee held extensive discussions concerning therapeutic usefulness of 3,4 Methylenedioxymethamphetamine. While the Expert Committee found the reports intriguing, it felt that the studies lacked the appropriate methodological design necessary to ascertain the reliability of the observations. There was, however, sufficient interest expressed to recommend that investigations be encouraged to follow up these preliminary findings. To that end, the Expert Committee urged countries to use the provisions of article 7 of the Convention on Psychotropic Substances to facilitate research on this interesting substance.

In the United Kingdom, MDMA is a Class A drug under the Misuse of Drugs Act 1971, making it illegal to sell, buy, or possess without a license. Penalties include a maximum of seven years and/or unlimited fine for possession; life and/or unlimited fine for production or trafficking. A mandatory seven year sentence is now the penalty for a third conviction for trafficking.

[edit] Health Concerns And Facts

There exists a significant risk for physical harm arising from excessive and irresponsible MDMA use. The chief executive of the UK Medical Research Council stated MDMA was "on the bottom of the scale of harm," and the Science & Technology Committee rated it of lower concern than for alcohol, tobacco, and cannabis, when examining the harmfulness of any given drug. The UK study placed great weight on the risk for acute physical harm, the propensity for physical and psychological dependency on the drug, and the negative familial and societal impacts of the drug. On these factors, the study places MDMA relatively low, which reflects its lower score in comparison to the risks of alcohol.[25][26]

[edit] Physical

The short-term health risks of taking MDMA include hypertension, dehydration and hyperthermia. In the raving subculture, use of MDMA can increase the risks of dehydration and hyperthermia, as the drug's stimulatory effects can mask the body's normal sense of exhaustion and thirst. The risk of hyperthermia may be increased by a high fat diet, and the mechanism the activation of uncoupling protein (UCP) in mitochondria. [6]

MDMA affects the regulation of the body's internal systems. Continuous dancing without sufficient breaks or drinks can lead to dangerous overheating and dehydration, and serves to significantly enhance the drug's neurotoxic action. Drinking too much water without adequate salt can cause hyponatremia or water intoxication, although this is less common than overheating.

Hypertension is a risk in some users due to the increase in heart rate and blood pressure. This risk increases as dose increases. [27]

[edit] Neurological Overview

To begin, it has been established that MDMA affects the brains of humans and lower primates differently, especially in terms of long-term changes. In both animals, MDMA causes a reduction in the concentration of serotonin transporters in the brain. Baboons who were given a neurotoxic dose of MDMA only showed partial regrowth of SERTs when scanned a year later.[7] In contrast, human studies differ in that those who had never used ecstasy were indistinguishable in PET brain scan studies from former ecstasy users. However, the same study also concluded that the reduction in memory performance due to MDMA use may be long-lasting.[8]

Although oxidative stress (see neurotoxicty theory below) may cause SERTs to degrade faster than they are able to be replaced, the serotonin axon itself seems to have been spared, which indicates that neurotoxicity may not be the means by which SERT count was reduced. It is possible that excess serotonin in the synapse due to MDMA, especially if uses occur within a short time, causes the serotonin cells to produce fewer SERTs, a phenomenon which has already been demonstrated with other serotonin-depleting drugs.[9] (See down-regulation theory below.)

For a detailed and comprehensive explanation of this topic, see's evaluation of studies. [10]

[edit] Receptor Down-Regulation Theory

One theory of SERT-depletion arising out of long-term MDMA use is receptor down-regulation which is one form of synaptic plasticity. When any neurotransmitter is present in excess for prolonged periods of time, the brain responds in an attempt to reestablish its own natural neuro-electrical balance. Weekly use of MDMA over a prolonged period may actually cause serotonin receptors to retreat into the dendrite of serotonin nerve cells [11], in addition to enticing serotonin cells lower its own SERT count. The change in synaptic serotonin concentration due to recreational MDMA use is at the extreme end of what is even possible in the brain and therefore, down-regulation could occur fairly easily with regular use.

This process causes the brain to become desensitized to the neurotransmitters present in the synapses and therefore also to the effects of MDMA itself. Therefore, in addition to a generally decreased quality of mood between doses, greater amounts of MDMA are required to achieve the same level of desired effects and thus more neurotoxic damage is produced via each use in a brain that may already be serotonergically exhausted. (This would be true in assuming that the neurotoxicity theory is concurrently viable, and would also require SERTs themselves to be destroyed by oxidative stress.) It is this cycle that is often believed to be the cause of long-term emotional problems among regular ecstasy users.

[edit] Neurotoxicity Theory

Under another theory, MDMA is considered neurotoxic. While the method of this toxicity has not been definitively established, the current leading theory is that the metabolism of MDMA-induced dopamine release leads to the lipid peroxidation of serotonergic neurons, reducing SERT count and possibly damaging or destroying the axon itself, and thus interfering with the integrity of the brain's serotonin network. [12] [13] Several studies have demonstrated that such changes in the brain are reversible after prolonged abstinence from the drug.[14] [15] In severe cases, however, the possibility for recovery of function may be much more limited. [16]

Neurotoxicity of serotonergic neurons would occur in selective areas of the human brain as serotonin cells are highly concentrated in certain areas such as the neocortex and hippocampus. Although some studies have demonstrated this, the rate at which this damage occurs is disputed. U.S. government-funded studies [28] performed by George Recaurte at John Hopkins University, which have demonstrated catastrophic brain damage occurring due to MDMA exposure, have been widely discredited by the scientific community.[17] [18] [19] The second study on the subject, which claimed that a single recreational dose of MDMA could cause Parkinson's Disease in later life, was actually retracted by Ricaurte himself after he admitted a fundamental error in his experiment. [20] For a comprehensive summary, see Neurotoxicity of MDMA controversy.

Antioxidants have been shown to prevent the neurotoxicity of MDMA in rats. In one study, intravenous administration of alpha lipoic acid completely blocked the neurotoxic effects of MDMA. No scientific experiment has been performed to date with human subjects, although some users report that taking various combinations of antioxidants before, during, and after using MDMA serves to moderate the subsequent mood-dip and improve recovery time. [21]

The administration of an SSRI in rats prior to the administration of MDMA has been shown to completely block neurotoxicity. This is likely due to the binding of such medications with SERT. However, administering an SSRI prior to administration of MDMA also completely or partially blocks the desired effects of the latter, something a large number of users prescribed an SSRI have reported. This effect is influenced by factors such as that medication's dose and half-life as well as the total duration of the treatment of the condition for which the medication was initially prescribed. As a compromise it has been shown that administration of an SSRI 3-4 hours after MDMA, at which time the primary effects will have tapered off significantly, markedly limits neurotoxicity overall despite some axonal damage having already occurred. [22] Once again, no such scientific experiment has been performed on human test subjects, and potential complications may still exist.[citation needed]

Many ecstasy users smoke cigarettes in combination with the former drug in order to enhance certain desired effects. Based on the pre-existing knowledge that dopamine plays the most significant role in MDMA neurotoxicity, smoking will aid neurotoxicity in that nicotine stimulates the release of dopamine in addition to certain ingredients in cigarettes other than nicotine inhibiting MAO (see nicotine), thereby preventing the breakdown of dopamine which has been shown to be toxic to serotonin cells by itself. [23] Additionally, because there is more dopamine that is ultimately broken down by Monoamine Oxidase, more damaging free radicals will be created overall. The same can be said when ecstasy is taken in conjunction with cocaine or any other kind of amphetamine and to a lesser degree even a regimen of any prescription dopamine reuptake inhibitor.

It should also be noted that the production and introduction into the active brain of serotonin is a much lengthier process than is that of dopamine. This is probably due to the fact that our brains have evolved to utilize the release of dopamine as the core of our psychological reward system which is essential in many instances throughout each day of our lives in giving inventive for us to meet our basic biological needs. Serotonin does not play this role. [24] Therefore, users who redose once the serotonergically-induced effects of MDMA have mostly diminished are likely not stimulating the release of serotonin at all as a single recreational dose of MDMA is likely to have depleted these rather limited reserves. Rather, only dopamine release is restimulated along with very minor stimulation of a few other neurotransmitters. The subsequent effects of redosing are therefore due almost entirely to the action of increased dopamine in the brain, and therefore, once again, neurotoxicity is significantly enhanced.

[edit] Psychological

MDMA use commonly results in a rebound period of poor mood or possibly depression commonly known as a "comedown", the length and severity of which depends on the user, the dose and the total duration of MDMA's activity in the body. Heavy or frequent use may precipitate lasting depression and anxiety in vulnerable users, particularly those prone to depression or other mental disorders as well as anyone in a state of crisis in their life. "Redosing" in an attempt to extend MDMA's desired effects has been shown to substantially increase neurotoxicity as well as the undesired physical side effects associated with MDMA use such as trisma and bruxia, which are caused by MDMA's partial dopaminergic affinity. The longer MDMA is active and being metabolized in the brain, the greater the neurotoxic damage and the greater the risk of short-term emotional problems. The more occasions MDMA is used, the greater the chances of long-term problems. [29]

Deficits of memory have been shown in long term MDMA users. [30] This may be due to long-term depletion of serotonin, one of the neurotransmitters involved in memory function. However, this is not conclusive proof of neurotoxicity and may be the result of neural plasticity.[31]

The preliminary results from an ongoing Dutch study indicate that the very moderate use of Ecstasy alleviates symptoms of depression by 28% and improved users' overall mental state. These users also appear to be free of neurological injury of any kind.[32]

[edit] Drug interactions

Individuals who have stopped taking any type of SSRI after prolonged medication may not be able to experience the desired effects of MDMA for as long as several months following discontinuation of the medication. This is due to the fact that SSRIs decrease the brain's sensitivity to the presence of serotonin as the brain seeks to reestablish a normal neuro-electrical balance.

Most people who die while under the influence of Ecstasy have also consumed significant quantities of at least one other drug. The risk of MDMA-induced death overall is very low. [25]

The use of MDMA can be dangerous when combined with other drugs (particularly monoamine oxidase inhibitors (MAOIs) and antiretroviral drugs, in particular Ritonavir). Combining MDMA with MAOIs can precipitate hypertensive crisis, as well as serotonin syndrome which can be fatal. [26] MAOI-B inhibitors such as deprenyl do not seem to carry these risks when taken at selective doses, and have been used to completely block neurotoxicity in rats. [27]

[edit] Purity

The MDMA content of tablets sold as Ecstasy varies widely between different brands of pills and fluctuates somewhat each year.[28] This is most likely due to changes in the criminal organizations manufacturing and cutting the drug; as one may be dismantled, another will rise to fill the gap in the market and will likely have somewhat different standards as to the constituents and purity of their final product(s). Pills often contain other active substances which commonly include amphetamine, methamphetamine, caffeine, and usually inactive filler material, all of which may be comparatively cheap and can help to boost profit overall. In some cases, tablets sold as Ecstasy do not even contain MDMA, chemicals in the Ecstasy Family, or even any kind of stimulant drug. Instead they sometimes contain drugs such as acetaminophen or ketamine. Some users will purchase pill testing kits in an attempt to better understand the make-up of a pill they have purchased. Organizations such as DanceSafe provide pill testing kits.[33]

As a rule, adulterated ecstasy pills which contain any substance that triggers dopamine release or inhibits its reuptake will increase neurotoxicity. Amphetamines and methamphetamine are the primary adulterant chemicals for which this is true.

[edit] PMA

There have been a number of deaths in which PMA, a potent and highly neurotoxic hallucinogenic amphetamine, has been sold as Ecstasy. PMA is unique in its ability to quickly elevate body temperature and heart rate at relatively low doses, especially in comparison to MDMA. Hence, a user who believes he is consuming 2 120mg pills of MDMA is actually consuming a dose of PMA that is potentially lethal, depending on the purity of the pill. Not only does PMA cause the release of serotonin, but also acts as an MAO-A inhibitor. When combined with an ecstasy-like substance, serotonin syndrome can result. However such cases are often over-publicized, actually quite rare, and do not represent a significant amount of pills being sold as ecstasy around the world.

The anti-drug literature on PMA (ex: [29]) is relatively limited, but much of it is scientifically unfounded. Some of the inaccuracies and discrepencies in the aforementioned example are addressed as follows:

To begin with, PMA is not an invention born out of "basement chemists" trying to evade the illegality of MDMA. In fact, while both PMA and MDMA are currently Schedule I in the U.S, PMA was scheduled more than 10 years before MDMA.[30] [31] Additionally, both drugs were rescued from obscurity by the same man, Alexander Shulgin, who at the time was synthesizing new psychoactive chemicals having been granted a license by the DEA to conduct autonomous research.

Since criminal organizations now control the production and content of pills sold as ecstasy, it is the profit motive of unregulated and predictably immoral clandestine drug manufacturers that when combined with drug prohibition has produced a renaissance of the presence of street PMA. Between the late 1970s and early 1990s, virtually no PMA-related deaths were reported worldwide. [32] It was not until safrole, one of the key ingredients in the original method of MDMA synthesis, was made more difficult to acquire that PMA began to be seen in batches of ecstasy pills in any notable quantity.

PMA is almost never sought after as a drug of choice, and this would not be practical to assume for several reasons. One reason is because it is so rare, another is that those who are aware of its existence are usually equally familiar with its unique hazards. The psychological effects of PMA as compared to MDMA are also quite different. PMA lacks the empathogenic qualities of MDMA, and depending on the analogue ingested, may only produce physical stimulation absent of any euphoria (see PMA).

[edit] Heredity

A small percentage of users may be highly sensitive to MDMA; this may make first-time use especially hazardous. This includes, but is not limited to, people with congenital heart defects. Some scientists have suggested that a small percentage of people lack the proper enzymes to break down the drug. One enzyme involved in MDMA's breakdown is CYP2D6, which is deficient or totally absent in 5–10% of the Caucasian population and those of African descent, and in 1–2% of Asians.[34] However, there is no clear evidence linking lack of this enzyme to problems in users, and the connection remains theoretical.

[edit] Poly Substance Use

Main article: Poly drug use

MDMA is known for being taken in conjunction with other recreational drugs. It is said to complement psychedelics such as LSD and hallucinogenic mushrooms. The two drugs are not taken simultaneously, but rather one is taken as the peak effects of the first are diminishing. A psychedelic such as LSD is usually the first drug taken but this is not always so. Because this practice has become more prevalent, most of the more common combinations have been given nicknames. Some examples include "candy flipping", MDMA combined with LSD[35], also known as trolling (tripping and rolling) , hippie flipping or flower flipping, which is MDMA combined with mushrooms,[citation needed] or triple flipping, which is MDMA with mushrooms and LSD.[citation needed]

Pills sold as 'ecstasy' very often contain amphetamine as well as MDMA. In the UK this is so common that pills containing amphetamine are not seen as adulterated, and it is taken for granted that ecstasy pills 'keep you going' for longer than crystal MDMA, due to the 'speed' content of many pills. Clubbers may also take speed during MDMA use to intensify the effects, or after MDMA use to stay awake and energised once tolerance and serotonin depletion has prevented them from gaining any more effect from MDMA. Using MDMA and amphetamine together makes both substances more neurotoxic than using them separately.

Clubbers in Europe are increasingly using ketamine during or after MDMA use. Using smaller amounts while on MDMA has little pronounced effect, as the stimulation from the MDMA balances out the depressant qualities of the ketamine. This may however increase the hallucinogenic effects of the MDMA. Clubbers more often use ketamine after the primary effects MDMA have worn off to make the comedown less dysphoric.

Many users use mentholated products while taking MDMA, as it is believed to heighten the drug's effects. Examples include menthol cigarettes, Vicks[36] lozenges, etc. This sometimes has deleterious results on the upper respiratory tract.[37]

Demerol - Pethidine (INN) or meperidine -

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Systematic (IUPAC) name
CAS number 57-42-1
ATC code N02AB02
PubChem 4058
DrugBank APRD00074
Chemical data
Formula C15H21NO2 
Mol. mass 247.33
Pharmacokinetic data
Bioavailability 50-60%
Protein binding 65-75%
Metabolism Liver
Half life 3-5 hours
Excretion Renal
Therapeutic considerations
Pregnancy cat.


Legal status

Controlled (S8)(AU) Class A(UK) Schedule II(US)

Routes oral, IV, IM

Pethidine (INN) or meperidine (USAN) (also referred to as: isonipecaine; lidol; pethanol; piridosal; Algil?; Alodan?; Centralgin?; Demerol?; Dispadol?; Dolantin?; Petidin? Dolargan? (in Poland);[1] Dolestine?; Dolosal?; Dolsin?; Mefedina?) is a fast-acting opioid analgesic drug. In the United States and Canada, it is more commonly known as meperidine or by its brand name Demerol.[2]

Pethidine is indicated for the treatment of moderate to severe pain, and is delivered as its hydrochloride salt in tablets, as a syrup, or by intramuscular or intravenous injection. For much of the 20th century, pethidine was the opioid of choice for many physicians; in 1983 60% of doctors prescribed it for acute pain and 22% for chronic severe pain.[3] Compared to morphine, pethidine was supposed to be safer and carry less risk of addiction, and to be superior in treating the pain associated with biliary spasm or renal colic due to its putative antispasmodic effects. In fact, pethidine is no more effective than morphine at treating biliary or renal pain, and its low potency, short duration of action, and unique toxicity (i.e. seizures, delirium, other neuropsychological effects) relative to other available opioid analgesics have seen it fall out of favor in recent years, for all but a very few, very specific indications.[4] Several countries, including Australia, have put severe limits on its use or curtailed it outright.[5] Nevertheless, some physicians continue to use it as a first-line strong opioid.



[edit] Pharmacodynamics/Mechanism of Action

Main article: Opioid

Pethidine's efficacy as an analgesic was discovered almost accidentally; it was synthesized in 1939 as an antimuscarinic agent.[6] Pethidine also has structual similarities to atropine and other tropane alkaloids and may have some of their effects and side effects.[2] Pethidine exerts its analgesic effects by the same mechanism as morphine, by acting as an agonist at the μ-opioid receptor. In addition to its strong opiodergic and anticholinergic effects, it has local anesthetic activity related to its interactions with sodium ion channels. Pethidine's apparent in vitro efficacy as an "antispasmodic" is due to its local anesthetic effects. It does not, contrary to popular belief, have antispasmodic effects in vivo.[7] Pethidine also has stimulant effects mediated by its inhibition of the dopamine transporter (DAT) and norepinephrine transporter (NAT). Because of its DAT inhibitory action, pethidine will substitute for cocaine in animals trained to discriminate cocaine from saline.[8] Several analogues of pethidine have been synthesized that are potent inhibitors of the reuptake of the monoamine neurotransmitters dopamine and norepinephrine via DAT and NAT.[9][10] It has also been associated with cases of serotonin syndrome, suggesting some interaction with serotonergic neurons, but the relationship has not been definitively demonstrated.[5][6][8][10] It is more lipid-soluble than morphine, resulting in a faster onset of action. Its duration of clinical effect is 120-150 minutes. Despite producing analgesia for 2-3 hours at most, pethidine is typically administered at 4-6 hour intervals, so that the patient spends at least an hour (and up to four hours) between doses without any analgesia, resulting in much unnecessary pain and suffering. In addition, pethidine has been shown to be less effective than morphine or hydromorphone at easing severe pain, or pain associated with movement or coughing.[6][8][10] Like other opioid drugs, pethidine has the potential to cause physical dependence or addiction. In fact, pethidine may be more addictive than other opioids because of its exceptionally rapid onset of action and associated "rush", and additional activity as a monoamine transporter inhibitor, which results in cocaine-like stimulant effects in addition to its typical opioid effects.[11] When compared with oxycodone, hydromorphone, and placebo, pethidine was consistently associated with more euphoria, difficulty concentrating, confusion, and impaired psychomotor and cognitive performance when administered to healthy volunteers.[12] The especially severe side effects unique to pethidine among opioids — serotonin syndrome, seizures, delirium, dysphoria, tremor — are primarily or entirely due to the action of its metabolite, norpethidine.[6][10]

[edit] Pharmacokinetics

Pethidine is quickly hydrolysed in the liver to pethidinic acid and is also demethylated to norpethidine, which has half the analgesic activity of pethidine but a longer elimination half-life (8-12 hours[13]); accumulating with regular administration, or in renal failure. Norpethidine is toxic and has convulsant and hallucinogenic effects. The toxic effects mediated by the metabolites cannot be countered with opioid receptor antagonists such as naloxone or naltrexone and are probably primarily due to norpethidine's anticholinergic activity probably due to its structural similarity to atropine though its pharmacology has not been thoroughly explored. The neurotoxicity of pethidine's metabolites is a unique feature of pethidine compared to other opioids. Pethidine's metabolites are further conjugated with glucuronic acid and excreted into the urine.

[edit] Interactions

Pethidine has serious interactions that can be dangerous with MAOIs (e.g. furazolidone, isocarboxazid, moclobemide, phenelzine, procarbazine, selegiline, tranylcypromine, and sibutramine). Such patients may suffer agitation, delirium, headache, convulsions, and/or hyperthermia. Fatal interactions have been reported. It is thought to be caused by an increase in cerebral serotonin concentrations. It is possible that Pethidine can also interact with a number of other medications, including muscle relaxants, some antidepressants, benzodiazepines, and alcohol.

Pethidine is also relatively contraindicated for use when a patient is suffering from liver, or kidney disease, has a history of seizures or epilepsy, has an enlarged prostate or urinary retention problems, or suffers from hyperthyroidism, asthma, or Addison's disease.

[edit] Adverse effects

Main article: Opioid

In addition to the adverse effects common to all opioids, such as constipation, dry mouth, lightheadedness, twitchiness, muscular twitches, and nausea, the repeated administration of pethidine can lead to neurotoxic effects.



MPPP - 1-methyl-4-phenyl-4-propionoxypiperidine, Desmethylprodine

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Systematic (IUPAC) name
(1-methyl-4-phenylpiperidin-4-yl) propanoate
CAS number 13147-09-6
ATC code  ?
PubChem 61583
Chemical data
Formula C15H21NO2 
Mol. mass 247.33 g/mol
Synonyms 4-propionyloxy-4-phenyl-N-methylpiperidine, MPPP, 3-desmethylprodine
Pharmacokinetic data
Bioavailability  ?
Metabolism  ?
Half life  ?
Excretion  ?
Therapeutic considerations
Pregnancy cat.


Legal status

Schedule I(US)

Routes  ?

MPPP (1-methyl-4-phenyl-4-propionoxypiperidine, Desmethylprodine) is an opioid analgesic drug. It is not used in clinical practice, but has been illegally manufactured for recreational drug use. It is an analog of meperidine (Demerol), but since it is not used in medicine, the DEA has labeled it a Schedule I drug in the United States. In fact, it is the reversed ester of meperidine and is listed as having 70% of the potency of morphine.

The drug was first illicitly synthesised by a graduate student called Barry Kidston. Kidston had apparently studied a 1947 paper by Albert Zeiring. By reversing the ester of the meperidine skeleton, a drug approaching the potency of morphine was produced. However, the intermediate tertiary alcohol is liable to dehydration in acidic conditions if the reaction temperature rises above -30°C, and since Kidston did not realise this and esterified the intermediate with propanoic anhydride at room temperature, MPTP was formed as a major impurity.[1]

1-methyl-4-phenyl-1,2,5,6-tetrahydropyridine (MPP+), a metabolite of MPTP, causes rapid onset of irreversible symptoms similar to Parkinson's Disease.[2][1] MPTP is metabolized to the neurotoxin MPP+ by the enzyme MAO-B, which is expressed in neurons. This selectively kills brain tissue in the area of the brain called the substantia nigra and causes Parkinsonian symptoms.[3]

[edit] References

  1. ^ Johannessen JN, Markey SP. Assessment of the opiate properties of two constituents of a toxic illicit drug mixture. Drug and Alcohol Dependence. 1984 Jul;13(4):367-74.
  2. ^ Davis GC, Williams AC, Markey SP, Ebert MH, Caine ED, Reichert CM, Kopin IJ. Chronic Parkinsonism secondary to intravenous injection of meperidine analogues. Psychiatry Research. 1979 Dec;1(3):249-54.
  3. ^ Schmidt N, Ferger B. Neurochemical findings in the MPTP model of Parkinson's Disease. Journal of Neural Transmission. (2001) 108: 1263–1282.


From Wikipedia, the free encyclopedia

Jump to: navigation, search
Systematic (IUPAC) name
CAS number 6740-88-1
ATC code N01AX03 N01AX14
PubChem 3821
DrugBank APRD00493
Chemical data
Formula C13H16ClNO 
Mol. mass 237.725 g/mol
Pharmacokinetic data
Bioavailability  ?
Metabolism  ?
Half life 2.5-3 hours.
Excretion renal (>90%)
Therapeutic considerations
Pregnancy cat.


Legal status

Schedule I(CA) Class C(UK) Schedule III(US)

Routes IV, IM, Insufflated, oral, topical

Ketamine is a dissociative anesthetic for use in human and veterinary medicine developed by Parke-Davis (1962). Its hydrochloride salt is sold as Ketanest, Ketaset, and Ketalar. Pharmacologically, ketamine is classified as an NMDA receptor antagonist,[1] and, like other drugs of this class such as tiletamine, and phencyclidine (PCP), induces a state referred to as "dissociative anesthesia."[2] As with other pharmaceuticals of this type, ketamine is used illicitly as a recreational drug.

Ketamine has a wide range of effects in humans, including analgesia, anesthesia, hallucinations, neurotoxicity [citation needed], arterial hypertension, and bronchodilation.[citation needed] It is primarily used for the induction and maintenance of general anesthesia, usually in combination with some sedative drug. Other uses include sedation in intensive care, analgesia (particularly in emergency medicine), and treatment of bronchospasm. It is also a popular anesthetic in veterinary medicine.

Ketamine is a chiral compound. Most pharmaceutical preparations of ketamine are racemic; however, some brands reportedly have (mostly undocumented) differences in enantiomeric proportions. The more active enantiomer, S-Ketamine, is also available for medical use under the brand name Ketanest S.[3]



[edit] History

Ketamine was first reported in 1962 as part of an effort to find a safer anaesthetic alternative to Phencyclidine (PCP), which was more likely to cause hallucinations, neurotoxicity and seizures. The drug was first given to American soldiers during the Vietnam War. It is still widely used in humans. There may be some evidence that Ketamine has the potential to cause emergence phenomena because of the drug's possible psychotomimetic effects.[citation needed] It is also used widely in veterinary medicine, or as a battlefield anaesthetic in developing nations.[4]

Ketamine's side effects eventually made it a popular psychedelic in 1965. The drug was used in psychiatric and other academic research through the 1970s, culminating in 1978 with the publishing of John Lilly's The Scientist and Marcia Moore and Howard Alltounian's Journeys into the Bright World, which documented the unusual phenomenology of ketamine intoxication.

The incidence of recreational ketamine use increased through the end of the century, especially in the context of raves and other parties. The increase in illicit use prompted ketamine's placement in Schedule III of the United States Controlled Substance Act in August 1999.[5] In the United Kingdom, it became outlawed and labelled a Class C drug on January 1, 2006.[6] In Canada ketamine is classified as a Schedule I narcotic.[7] In Hong Kong, as of year 2000, Ketamine is regulated under Schedule 1 of Hong Kong Chapter 134 Dangerous Drugs Ordinance. It can only be used legally by health professionals, for university research purposes, or with a physician's prescription.[8]

[edit] Medical use

10 ml bottles of Ketamine
Side effects:

Severe: Impairs all senses, especially:

  • Sight
  • Balance
  • Sense of time


  • Partial depressant



  • Relaxant



  • Partial depressant/stimulant

In medical settings, Ketamine is usually injected intravenously or intramuscularly,[9] but it is also effective when insufflated, smoked, or taken orally.[10]

Since it suppresses breathing much less than most other available anaesthetics,[11] ketamine is still used in human medicine as a first-choice anaesthetic for victims with unknown medical history (e.g. from traffic accidents), in podiatry and other minor surgery, and occasionally for the treatment of migraine. There is ongoing research in France, Russia, and the U.S. into the drug's usefulness in pain therapy, depression suppression, and for the treatment of alcoholism[12] and heroin addiction.[13]

In veterinary anesthesia, ketamine is often used for its anaesthetic and analgesic effects on cats, dogs, rabbits, rats, and other small animals. Veterinarians often use ketamine with sedative drugs to produce balanced anaesthesia and analgesia, and as a constant rate infusion to help prevent pain wind-up. Ketamine is used to manage pain among large animals, though it has less effect on bovines. It is the primary intravenous anaesthetic agent used in equine surgery, often in conjunction with detomidine and thiopental, or sometimes Glyceryl guaiacolate.

Ketamine may be used in small doses (0.1–0.5 mg/kg/h) as a local anesthetic, particularly for the treatment of pain associated with movement and neuropathic pain.[14] It has the added benefit of counter-acting spinal sensitization or wind-up phenomena experienced with chronic pain. At these doses, the psychotropic side effects are less apparent and well managed with benzodiazepines.[15] Ketamine is a co-analgesic, and so is most effective when used alongside a low-dose opioid; while it does have analgesic effects by itself, the higher doses required can cause disorienting side effects.[15] The combination of ketamine with an opioid is, however, particularly useful for pain caused by cancer.[16]

The effect of Ketamine on the respiratory and circulatory systems is different from that of other anaesthetics. When used at anaesthetic doses, it will usually stimulate rather than depress the circulatory system.[17] It is sometimes possible to perform ketamine anaesthesia without protective measures to the airways. Ketamine is also a potent analgesic and can be used in sub-anaesthetic doses to relieve acute pain; however, its psychotropic properties must be taken into account. Patients have reported vivid hallucinations, "going into other worlds" or "seeing God" while anesthetized, and these unwanted psychological side-effects have reduced the use of ketamine in human medicine. They can, however, usually be avoided by concomitant application of a sedative such as a benzodiazepine.[15]

Low-dose ketamine is recognized for its potential effectiveness in the treatment of complex regional pain syndrome (CRPS), according to a retrospective review published in the October 2004 issue of Pain Medicine.[18] Although low-dose ketamine therapy is established as a generally safe procedure, reported side effects in some patients have included hallucinations, dizziness, lightheadedness and nausea. Therefore nurses administering ketamine to patients with CRPS should only do so in a setting where a trained physician is available if needed to assess potential adverse effects on patients.[19]

[edit] Experimental antidepressant use

When treating patients suffering from complex regional pain syndrome (CRPS) with a low-dose (subanesthetic) ketamine infusion, it was observed that some patients made a significant recovery from associated depression. This recovery was not formally documented, as the primary concern was the treatment of the patient's pain. Needless to say, it was not possible to quantify to what degree depression recovery was secondary to the patient's recovery from CRPS. Based on this result, it was thought that a low-dose (subanesthetic) infusion of ketamine was worth a trial in patients who were suffering from treatment-resistant depression without other physical or psychiatric illness.

Correll et al. gave ketamine intravenously to patients commencing at 15–20 mg/h (0.1–0.2 mg/kg/h) and the dose increased until a maximum tolerated dose was achieved. This dose was assumed to be a therapeutic dose and was maintained for 5 days. Patients were able to eat, drink, watch television, or read. They could feel inebriated and/or unsteady when walking. If hallucinations occurred, the dose was to be reduced. The patient's normal medications were continued as it was feared that stopping them may result in a severe depressive episode. Before and following each treatment with ketamine, at patient clinic visits, the Beck Depression Inventory (BDI) and the Hamilton Depression Rating Score (HAMD-17) were obtained. Two of the patients were described with impressive improvement in depression being maintained for 12 months in patient A and recurrence at 2.5 months and 9 months in patient B.[20]

The National Institute of Health News reports that a study of 18 patients has found that ketamine significantly improved treatment-resistant major depression within hours of injection.[21] The improvement lasted up to one week after the single dose.[22] The patients in the study were previously treatment resistant, having tried an average of six other treatments that failed. NIMH director Dr. Thomas Insel said in the paper:

"To my knowledge, this is the first report of any medication or other treatment that results in such a pronounced, rapid, prolonged response with a single dose. These were very treatment-resistant patients."

The researchers apparently attribute the effect to ketamine being an NMDA receptor antagonist.[23] Those findings of Zarate et al corroborate earlier findings by Berman et al.[24] However Zarate et al do rise some concerns about their results due to a possible lack of blinding, because of the ebriating effects of low dose Ketamine infusion, and it is recommended that future studies shall include an active placebo.

The findings by Zarate et al. are confirmed by Liebrenz et al, who substantially helped a 55-year-old male subject with a treatment-resistant major depression and a co-occurring alcohol and benzodiazepine dependence by giving an intravenous infusion of 0.5 mg/kg ketamine over a period of 50 minutes and Goforth et al who helped a patient with severe, recurrent major depressive disorder that demonstrated marked improvement within 8 hours of receiving a preoperative dose of ketamine and 1 treatment of electroconvulsive therapy with bitemporal electrode placement.[25][26]

However, a new study in mice by Zarate et al. shows that blocking the NMDA receptor is an intermediate step. According to this study, blocking NMDA increases the activity of another receptor, AMPA, and this boost in AMPA activity is crucial for ketamine’s rapid antidepressant actions. NMDA and AMPA are receptors for the neurotransmitter glutamate. The glutamate system has been implicated in depression recently. This is a departure from previous thinking, which had focused on serotonin and norepinephrine. The glutamate system may represent a new avenue for treatment and research[27].

Krystal et al. retrospectively compared the seizure duration, ictal EEG, and cognitive side effects of ketamine and methohexital anesthesia with ECT in 36 patients.[28] Ketamine was well tolerated and prolonged seizure duration overall, but particularly in those who had a seizure duration shorter than 25 seconds with methohexital at the maximum available stimulus intensity. Ketamine also increased midictal EEG slow-wave amplitude. Thus, a switch to ketamine may be useful when it is difficult to elicit a robust seizure. Faster post-treatment reorientation with ketamine may suggest a lower level of associated cognitive side effects.

Kudoh et al. investigated whether ketamine is suitable for depressed patients who had undergone orthopedic surgery.[29] They studied 70 patients with major depression and 25 patients as the control (Group C). The depressed patients were divided randomly into two groups; patients in Group A, initial HAMD 12,7(n = 35) were induced with propofol, fentanyl, and ketamine and patients in Group B, initial HAMD 12,3 (n = 35) were induced with propofol and fentanyl. Depressed mood, suicidal tendencies, somatic anxiety, and hypochondriasis significantly decreased in Group A as compared with Group B. The group receiving ketamine also had significantly lower postoperative pain.

[edit] Treatment of addiction

The Russian doctor Evgeny Krupitsky (Clinical Director of Research for the Saint Petersburg Regional Center for Research in Addiction and Psychopharmacology) has gained encouraging results by using ketamine as part of a treatment for alcohol addiction which combines psychedelic and aversive techniques.[30][31] This method involved psychotherapy, controlled ketamine use and group therapy, and resulted in 60 of the 86 alcoholic males selected for the study remaining fully abstinent through one year of treatment. He has also treated heroin addicts and reached the conclusion that that one ketamine-assisted psychotherapy session was significantly more effective than active placebo in promoting abstinence from heroin during one year withhout any adverse reactions. In a recently published study 59 detoxified inpatients with heroin dependence received a ketamine-assisted psychotherapy (KPT) session prior to their discharge from an addiction treatment hospital, and were then randomized into two treatment groups. Participants in the first group received two addiction counseling sessions followed by two KPT sessions, (with a single im injection of 2 mg/kg Ketamine) with sessions scheduled on a monthly interval (multiple KPT group). Participants in the second group received two addiction counseling sessions on a monthly interval, but no additional ketamine therapy sessions (single KPT group). At one-year follow-up, survival analysis demonstrated a significantly higher rate of abstinence in the multiple KPT group. Thirteen out of 26 subjects (50%) in the multiple KPT group remained abstinent, compared to 6 out of 27 subjects (22.2%) in the single KPT group (p < 0.05). No differences between groups were found in depression, anxiety, craving for heroin, or their understanding of the meaning of their lives. It was concluded that three sessions of ketamine-assisted psychotherapy are more effective than a single session for the treatment of heroin addiction.[32][33]

In a 2007 chapter "Ketamine Psychedelic Psychotherapy" Krupitsky and Kolp summarize their work-to-date in Chapter 5 in Psychedelic Medicine: New Evidence for Hallucinogens as Treatments, [34]

Jovaisa et al from Lithuania demonstrated attenuation of opiate withdrawal symptoms with Ketamine. A total of 58 opiate-dependent patients were enrolled in a randomized, placebo-controlled, double-blind study. Patients underwent rapid opiate antagonist induction under general anesthesia. Prior to opiate antagonist induction patients were given either placebo (normal saline) or subanesthetic ketamine infusion of 0.5 mg/kg/h.Ketamine group presented better control of withdrawal symptoms, which lasted beyond ketamine infusion itself. Significant differences between Ketamine and Control groups were noted in anesthetic and early postanesthetic phases. There were no differences in effects on outcome after 4 months.[13]

[edit] Treatment of reflex sympathetic dystrophy

Ketamine is being used as a experimental and controversial treatment for Complex Regional Pain Syndrome (CRPS) also known as Reflex Sympathetic Dystrophy (RSD). CRPS/RSD is a severe chronic pain condition characterized by sensory, autonomic, motor and dystrophic signs and symptoms. The pain in CRPS is continuous, it worsens over time, and it is usually disproportionate to the severity and duration of the inciting event. The hypothesis is that ketamine manipulates NMDA receptors which might reboot aberrant brain activity.

There are two treatment modalities, the first consist of a low dose ketamine infusion of between 25-90 mg per day, over five days either in hospital or as an outpatient. This is called the awake technique. Open label, prospective, pain journal evaluation of a 10-day infusion of intravenous ketamine (awake technique) in the CRPS patient concluded that "A four-hour ketamine infusion escalated from 40-80 mg over a 10-day period can result in a significant reduction of pain with increased mobility and a tendency to decreased autonomic dysregulation".[35]

Case notes of 33 patients whose CRPS pain was treated by the inpatient administration of a continuous subanesthetic intravenous infusion of ketamine were reviewed at Mackay Base Hospital, Queensland, Australia. A total of 33 patients with diagnoses of CRPS who had undergone ketamine treatment at least once were identified. Due to relapse, 12 of 33 patients received a second course of therapy, and two of 33 patients received a third. There was complete pain relief in 25 (76%), partial relief in six (18%), and no relief in two (6%) patients. The degree of relief obtained following repeat therapy (N=12) appeared even better, as all 12 patients who received second courses of treatment experienced complete relief of their CRPS pain. The duration of relief was also impressive, as was the difference between the duration of relief obtained after the first and after the second courses of therapy. In this respect, following the first course of therapy, 54% of 33 individuals remained pain free for >/=3 months and 31% remained pain free for >/=6 months. After the second infusion, 58% of 12 patients experienced relief for >/=1 year, while almost 33% remained pain free for >3 years. The most frequent side effect observed in patients receiving this treatment was a feeling of inebriation. Hallucinations occurred in six patients. Less frequent side effects also included complaints of light-headedness, dizziness, and nausea. In four patients, an alteration in hepatic enzyme profile was noted; the infusion was terminated and the abnormality resolved thereafter. No long-term side-effects were noted.[36]

The second treatment modality consists of putting the patient into a medically-induced coma and given an extremely high dosage of ketamine; typically between 600-900 mg.[37] This version, currently not allowed in the United States, is most commonly done in Germany but some treatments are now also taking place in Monterrey, Mexico. According to Dr Schwartzman, 14 cases out of 41 patients in the coma induced ketamine experiments were completely cured. "We haven't cured the original injury," he says, "but we have cured the RSD or kept it in remission. The RSD pain is gone." "No one ever cured it before," he adds. "In 40 years, I have never seen anything like it. These are people who were disabled and in horrible pain. Most were completely incapacitated. They go back to work, back to school, and are doing everything they used to do. Most are on no medications at all. I have taken morphine pumps out of people. You turn off the pain and reset the whole system."[37] In Tuebingen, Germany Dr Kiefer treated a patient presented with a rapidly progressing contiguous spread of CRPS from a severe ligamentous wrist injury. Standard pharmacological and interventional therapy successively failed to halt the spread of CRPS from the wrist to the entire right arm. Her pain was unmanageable with all standard therapy. As a last treatment option, the patient was transferred to the intensive care unit and treated on a compassionate care basis with anesthetic doses of ketamine in gradually increasing (3-5 mg/kg/h) doses in conjunction with midazolam over a period of 5 days. On the second day, edema, and discoloration began to resolve and increased spontaneous movement was noted. On day 6, symptoms completely resolved and infusions were tapered. The patient emerged from anesthesia completely free of pain and associated CRPS signs and symptoms. The patient has maintained this complete remission from CRPS for 8 years now. The psychiatric side effects of ketamine were successfully managed with the concomitant use of midazolam and resolved within 1 month of treatment.[38]

[edit] Pharmacological model of schizophrenia

Ketamine and other NMDA antagonists such as PCP and MK-801 are considered to be the best available pharmacological models of schizophrenia to date. Unlike amphetamines, which influenced the synthesis of the "dopamine hypothesis of schizophrenia", ketamine can reliably produce the negative symptoms (social withdrawal, alogia), positive symptoms (hallucinations, delusions) and cognitive deficits of schizophrenia in healthy and schizophrenic humans, as well as in animal models of the illness. This has led to the development of the alternative "NMDA hypothesis of schizophrenia" which posits that the aetiology of schizophrenia results from NMDA receptor hypofunction, particularly in the prefrontal cortex. NMDA receptors in the prefrontal cortex modulate subcortical dopamine neurotransmission, whose hyperactivity is believed to produce the positive symptoms of schizophrenia. Disruption of the prefrontal cortex may also manifest the negative symptoms and cognitive deficits in schizophrenia. As disturbances in working memory, attention and executive functioning are consistently seen in schizophrenics and their healthy relatives, it is proposed that cognitive deficits in schizophrenia are the core of the disorder.

[edit] Neuropharmacology

Ketamine, like Phencyclidine, is primarily a non-competitive antagonist of the NMDA receptor,[1] which opens in response to binding of the neurotransmitter glutamate. This NMDA receptor mediates the analgesic (reduction of pain) effects of ketamine at low doses.[39] Evidence for this is reinforced by the fact that naloxone, an opioid antagonist, does not reverse the analgesia. Studies also seem to indicate that ketamine is 'use dependent' meaning it only initiates its blocking action once a glutamate binds to the NMDA receptor.[39]

At high, fully anesthetic level doses, ketamine has also been found to bind to opioid mu receptors and sigma receptors.[39] Thus, loss of consciousness that occurs at high doses may be partially due to binding at the opioid mu and sigma receptors.[39]

Ketamine is racemic, and its R and S stereoisomers have different binding affinities: (S)-Ketamine has about four times greater affinity for the PCP site of the NDMA receptor than does (R)-Ketamine (in guinea pig brain).[39] (S)-ketamine seems to induce drowsiness more strongly than the (R) enantiomer; it is probable that (R)-ketamine is the stronger sigma agonist and so this enantiomer is likely to be responsible for the lowering of the seizure threshold that can occur with ketamine.[39] Since (S)-ketamine has greater analgesic effects and less hallucinogenic side effects than (R)-ketamine, the pure (S) enantiomer is sometimes preferred to the racemic mix for use in medical procedures, especially when lower doses are used for minor surgical procedures where the patient remains conscious during the operation. [40]

The effects seem to take place mainly in the hippocampal formation and in the prefrontal cortex. This evidence, along with the NMDA receptor's connection with the memory formation process, explains ketamine's profound effects on memory and thought. These effects inhibit the filtering function of the brain and may mirror the sensory overload associated with schizophrenia and near death experiences.[citation needed]

The local anesthetic effects are likely from the blocking action of ketamine on sodium channels.[41] Its in vitro blocking potency of sodium channels in the resting state is similar to that of lidocaine[42]

Ketamine has a well-documented neuroprotective effect against ischemic brain-injury and glutamate induced brain injury.[43] One hypothesis of its working mechanism in case of chronic pain management and depression is that it works as an anti-dote to an overactivity and in glutamergic brain circuits.

[edit] Recreational use

[edit] Illicit sale

10 ml bottle of liquid Ketamine drying out into a powder

Ketamine sold illicitly comes from diverted legitimate supplies or theft, primarily from veterinary clinics. In the US near its border with Mexico, the drug is most commonly acquired in Mexico, where it can be bought over the counter in veterinary clinics, and smuggled across the border.

In 2006, Operation TKO[citation needed] was a probe conducted by the U.S. Drug Enforcement Agency (DEA). As a result of operation TKO, U.S. and Mexican authorities shut down the Mexico City company, Laboratorios Tokkyo, which was the biggest producer of ketamine in Mexico. According to the DEA, over 80% of ketamine seized in the U.S. is of Mexican origin.[citation needed] The World Health Organization (WHO) Expert Committee on Drug Dependence in its [44] thirty third report (2003) recommended research into its recreational use/misuse due to growing concerns about its rising popularity in Europe, Asia and North America.

[edit] Methods of use

Ketamine is sold in either powdered or liquid form. In powdered form, its appearance is similar to that of pharmaceutical grade cocaine and can be insufflated (referred to as a "bump of K"), injected, or placed in beverages. It is also possible to smoke the drug in a joint or pipe, usually mixed with marijuana and tobacco. The smoke has a distinctive bitter taste but the effects of the high hit much faster than when insufflated or ingested. Oral use usually requires more material, but results in a longer trip. However, when administered orally, ketamine is rapidly metabolised to norketamine, which possesses sedating effects; this route of administration is unlikely to produce a dissociative state characteristic of the k-hole. The liquid can be heated to drive off the solvent (usually saline), leaving powder. In therapeutic and psychedelic use, the liquid is typically injected intramuscularly. Intravenous injection is uncommon (recreationally), though possible. It is essentially identical in effect to intramuscular injection, but leads to a much quicker onset — usually within 10 to 15 seconds of dosing. Additionally, intravenous injection tends to lead to a more sudden and marked respiratory depression, especially if the solution is injected at too high of a potency (too fast). These factors make intravenous self-injection dangerous. Ketamine is also commonly combined with other drugs to enhance their effects. More recently in the UK it has been reportedly mixed with cocaine, crushed up 'Ecstasy' tablets - which usually contain one or more stimulant like caffeine and/or amphetamine - MDMA powder.

[edit] Psychological effects

Ketamine produces effects similar to PCP and DXM. Like other dissociative anesthetics in low- to upper-middle dosages, its hallucinogenic effects are only seen against a background lacking sensory stimulation, such as darkness. Unlike the other well known dissociatives PCP and DXM, ketamine is very short acting, its hallucinatory effects lasting fifteen minutes or less when insufflated or injected, the total experience lasting no more than one or two hours.

Like the other dissociative anaesthetics DXM and PCP, hallucinations caused by ketamine are fundamentally different from those caused by tryptamines and phenethylamines. At low doses, hallucinations are only seen when one is in a dark room with one's eyes closed, while at medium to high doses the effects are far more intense and obvious. These effects include changes in the perception of distances, relative scale, colour and durations/time, as well as a slowing of the visual system's ability to update what the user is seeing. There are reports of high-dosage users being able to see their surroundings in two sharp images, as if the brain is unable to merge the images each eye is sending. Speech often sounds unintelligible i.e. alogia, and auditory hallucinations may occur. At high doses sounds can be out of sync with the user's visual field.

Ketamine produces a dissociative state, characterised by a sense of detachment from one's physical body and the external world. At sufficiently high doses (e.g. 150 mg intramuscular), users may experience what is coined the "K-hole", a state of dissociation whose effects are thought to mimic the phenomenology of schizophrenia. This may include distortions in bodily awareness, such as the feeling that one's body is being tugged, or is gliding on silk, flying, or has grown very large or distended. Users often report feeling more skeletal or becoming more aware of their bones - the shape of their hands is also often of interest. Users may experience worlds or dimensions that are ineffable, all the while being completely unaware of their individual identities or the external world. Users may feel as though their perceptions are located so deep inside the mind that the real world seems distant (hence the use of a "hole" to describe the experience). Some users may not remember this part of the experience after regaining consciousness, in the same way that a person may forget a dream. Owing to the role of the NMDA receptor in long-term potentiation, this may be due to disturbances in memory formation. The "re-integration" process is slow, and the user gradually becomes aware of surroundings. At first, users may not remember their own names, or even know that they are human, or what that means. Movement is extremely difficult, and a user may not be aware that he or she has a body at all.

[edit] Long-term side effects

Main article: Olney's lesions

In 1989, psychiatry professor John Olney reported that ketamine caused reversible changes in two small areas of the rat brain. 40mg/kg resulted in fluid-filled bags ("vacuoles") appearing inside cells. The bags disappeared after several days, unless high doses of the far more toxic PCP or close relative MK801 were repeatedly given, in which case some cell death was seen. Roland Auer injected monkeys with MK801 and was unable to produce any vacuoles. I asked Auer in 1998 whether persons undergoing anesthesia with Ketalar were at risk of these changes. His reply was that he doubted that it was even a remote possibility because of fundamental differences in metabolism between the rat and human brain. Ketamine can block excito-toxicity (brain damage due to low oxygen, low sugar, epilepsy, trauma etc.) but it can also excite the brain at low doses by switching off the inhibitory system. Why isn't this damaging in monkeys and humans? The answer probably lies in the fact that ketamine binds to an increasingly wide range of different receptors as the dose level rises, and some of these receptors act to shut down the excitement. In humans, by the time a potentially toxic dose is reached, the "excitement window" has been passed and the drug is starting to activate other systems that switch cells off again, a result of ketamine's promiscuity that improves its safety relative to MK801. MK801 binds very specifically to N-P receptors. The other part of the explanation is that rats have rates of brain metabolism that are almost twice as high as those in humans to start with. It is because of this higher base rate of metabolism that ketamine causes over-excitement in rats at doses below those at which it activates shutdown systems.”[45][46][47]

Vutskits et al from Geneva showed that short-term exposure of cultures to ketamine at concentrations of > or =20 microg/ml leads to a significant cell loss of differentiated cells and that non-cell death-inducing concentrations of Ketamine (10 microg/ml) can still initiate long-term alterations of dendritic arbor in differentiated neurons, including dendritic retraction and branching point elimination. They also demonstrated that chronic (>24 h) administration of ketamine at concentrations as low as 0.01 microg/ml can interfere with the maintenance of dendritic arbor architecture. These results raise the possibility that chronic exposure to low, subanesthetic concentrations of ketamine, while not affecting cell survival, could still impair neuronal morphology and thus might lead to dysfunctions of neural networks.[48]

Ketamine effects on horses, which where applied by the US army in Arizona during the 1980's proved ketamine provided horses with the faculty to jump notably higher than when they were not under the influence of ketamine.

There is a long list of medicines that could counteract these potential toxic effects, including clonidine, anticholinergics, benzodiazepines and barbiturates.[46][47]

On 21 June 2007 Hong Kong Medical Journal has put up a report regarding the misuse of 'street K'. The report suggests that long term use may result in damage to the liver or urinary bladder, or even acute renal failure. However, the researchers suspect that the damage "may be due to other toxins that the 'street ketamine' has been contaminated with".[49]

In a study of 9 daily ketamine users, Shahani et al found "marked thickening of the bladder wall, a small capacity, and perivesicular stranding, consistent with severe inflammation. At cystoscopy, all patients had severe ulcerative cystitis. Biopsies in 4 patients revealed epithelial denudation and inflammation with a mild eosinophilic infiltrate. Cessation of ketamine use, with the addition of pentosan polysulfate, appeared to provide some symptomatic relief."[50]


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Systematic (IUPAC) name
methyl (1R,2R,3S,5S)-3- (benzoyloxy)-8-methyl-8-azabicyclo[3.2.1] octane-2-carboxylate
CAS number 50-36-2
ATC code N01BC01 R02AD03, S01HA01, S02DA02
PubChem 5760
DrugBank APRD00080
Chemical data
Formula C17H21NO4 
Mol. mass 303.353 g/mol
Physical data
Melt. point 195 °C (383 °F)
Solubility in water 1800 mg/mL (20 °C)
Pharmacokinetic data
Bioavailability Oral: 33%
Nasal: 19% (11%–26%)[1]
Metabolism Hepatic CYP3A4
Half life 1 hour
Excretion Renal (benzoylecgonine and ecgonine methyl ester)
Therapeutic considerations
Pregnancy cat.


Legal status

Controlled (S8)(AU) Schedule I(CA) Class A(UK) Schedule II(US)

Dependence Liability High
Routes Topical, Oral, Insufflation, IV, PO

Cocaine is a crystalline tropane alkaloid that is obtained from the leaves of the coca plant. The name comes from "coca" in addition to the alkaloid suffix -ine, forming cocaine. It is both a stimulant of the central nervous system and an appetite suppressant, giving rise to what has been described as a euphoric sense of happiness and increased energy. It is most often used recreationally for this effect. Because of the way it affects the mesolimbic reward pathway, cocaine is addictive. Nevertheless, cocaine is still used in medicine as a topical anesthetic, even in children, specifically in eye, nose and throat surgery.

Its possession, cultivation, and distribution are illegal for non-medicinal and non-government sanctioned purposes in virtually all parts of the world. Although its free commercialization is illegal and has been severely penalized in virtually all countries, its use worldwide remains widespread in many social, cultural, and personal settings.




Originally consumed without any processing, the chewing of coca leaves was popular among South American natives long before the arrival of the Spanish in the 16th century. The leaves were chewed in a manner consistent with modern use of coffee, chewed for a small burst of energy or stamina. The Spanish explorers noticed how the natives used the coca leaves and themselves partook in some cases, but the practice of chewing the raw leaves did not become especially popular among Europeans. Coca's turning point in Europe came in 1860 when Albert Niemann extracted pure cocaine powder from coca leaves. This refinement allowed the use of cocaine in many different medicinal products and beverages, most notably Coca-Cola and Vin Mariani. Freud began experimenting with cocaine around this time, consuming small quantities to combat depression, sharing his experience with other European physicians who also found cocaine to be an effective topical anesthetic. Freud became a fervent supporter of the use of cocaine as an anti-depressant, even publishing a manuscript detailing its virtues. Conan Doyle stood alone in the late 19th century depicting the destructive qualities of cocaine in his consulting detective, Sherlock Holmes.[2] As cocaine's popularity increased, health risks were noted and seized upon by American legislators, who made the substance all but illegal in 1916.



A pile of cocaine hydrochloride
A piece of compressed cocaine powder

Cocaine in its purest form is a white, pearly product. Cocaine appearing in powder form is a salt, typically cocaine hydrochloride (CAS 53-21-4). Street market cocaine is frequently adulterated or “cut” with various powdery fillers to increase its weight; the substances most commonly used in this process are baking soda; sugars, such as lactose, dextrose, inositol, and mannitol; and local anesthetics, such as lidocaine or benzocaine, which mimic or add to cocaine's numbing effect on mucous membranes. Cocaine may also be "cut" with other stimulants such as methamphetamine.[3] Adulterated cocaine is often a white, off-white or pinkish powder.

The color of “crack” cocaine depends upon several factors including the origin of the cocaine used, the method of preparation – with ammonia or baking soda – and the presence of impurities, but will generally range from white to a yellowish cream to a light brown. Its texture will also depend on the adulterants, origin and processing of the powdered cocaine, and the method of converting the base. It ranges from a crumbly texture, sometimes extremely oily, to a hard, almost crystalline nature.

Forms of cocaine

Cocaine sulfate

Cocaine sulfate is produced by macerating coca leaves along with water that has been acidulated with sulfuric acid, or an aromatic-based solvent, like kerosene or benzene. This is often accomplished by placing the ingredients into a vat and stomping on them, in a manner similar to the traditional method for crushing grapes. A more popular method in modern times is to form a makeshift "vat" by spreading a heavy nylon tarp on the floor of an enclosed area and shred the leaves with a gas-powered weed-eater. This method is fast, and not only shreds the leaves, but results in bruising and fragmenting of the remaining pieces, aiding the extraction process. After the maceration is completed, the water is evaporated to yield a pasty mass of impure cocaine sulfate. The sulfate salt itself is an intermediate step to producing cocaine hydrochloride.


Main article: Freebase (chemistry)

As the name implies, “freebase” is the base form of cocaine, as opposed to the salt form of cocaine hydrochloride. Whereas cocaine hydrochloride is extremely soluble in water, cocaine base is insoluble in water and is therefore not suitable for drinking, snorting or injecting. Whereas cocaine hydrochloride is not well-suited for smoking because the temperature at which it vaporizes is very high, and close to the temperature at which it burns; however, cocaine base vaporizes at a much lower temperature, which makes it suitable for inhalation.

Smoking freebase is preferred by many users[citation needed] because the cocaine is absorbed immediately into blood via the lungs, reaching the brain in about five seconds. The rush is much more intense than snorting the same amount of cocaine nasally, but the effects do not last as long. The peak of the freebase rush is over almost as soon as the user exhales the vapor, but the high typically lasts 5–10 minutes afterward. What makes freebasing particularly dangerous is that users typically do not wait that long for their next hit and will continue to smoke freebase until none is left. These effects are similar to those that can be achieved by injecting or “slamming” cocaine hydrochloride, but without the risks associated with intravenous drug use (though there are other serious risks associated with smoking freebase).

Freebase cocaine is produced by first dissolving cocaine hydrochloride in water. Once dissolved in water, cocaine hydrochloride (Coc HCl) dissociates into protonated cocaine ion (Coc-H+) and chloride ion (Cl ). Any solids that remain in the solution are not cocaine (they are part of the cut) and are removed by filtering. A base, typically ammonia (NH3), is added to the solution. The following net chemical reaction takes place:

Coc-H+Cl + NH3 → Coc + NH4Cl

As freebase cocaine (Coc) is insoluble in water, it precipitates and the solution becomes cloudy. To recover the freebase in the "traditional" manner, diethyl ether is added to the solution. Since freebase is highly soluble in ether, a vigorous shaking of the mixture results in the freebase being dissolved in the ether. As ether is practically insoluble in water, it can be siphoned off. The ether is then left to evaporate, leaving behind the nearly pure freebase.

Handling diethyl ether is dangerous because ether is extremely flammable, its vapors are heavier than air and can "creep" from an open bottle, and in the presence of oxygen it can form peroxides, which can spontaneously combust. Demonstrative of the dangers of the practice, comedian Richard Pryor used to perform a skit in which he poked fun at himself over a 1980 incident in which he caused an explosion and ignited himself attempting to smoke "freebase", presumably while still wet with ether (though his ex wife Jennifer Lee Pryor said that he poured high-proof rum over his body and torched himself in a drug psychosis).

Crack cocaine

Main article: Crack cocaine

Due to the dangers of using ether to produce pure freebase cocaine, cocaine producers began to omit the step of removing the freebase cocaine precipitate from the ammonia mixture. Typically, filtration processes are also omitted. The end result of this process is that the cut, in addition to the ammonium salt (NH4Cl), remains in the freebase cocaine after the mixture is evaporated. The “rock” that is thus formed also contains a small amount of water. Sodium bicarbonate (baking soda) is also preferred in preparing the freebase, for when commonly "cooked" the ratio is 50/50 to 40/60% cocaine/bicarbonate. This acts as a filler which extends the overall profitability of illicit sales. Crack cocaine may be reprocessed in small quantities with water (users refer to the resultant product as "cookback"). This removes the residual bicarbonate, and any adulterants or cuts that have been used in the previous handling of the cocaine and leaves a relatively pure, anhydrous cocaine base.

When the rock is heated, this water boils, making a crackling sound (hence the onomatopoetic “crack”). Baking soda is now most often used as a base rather than ammonia for reasons of lowered stench and toxicity; however, any weak base can be used to make crack cocaine. Strong bases, such as sodium hydroxide, tend to hydrolyze some of the cocaine into non-psychoactive ecgonine.


Coca leaves are typically mixed with an alkaline substance (such as lime) and chewed into a wad that is retained in the mouth between gum and cheek (much in the same as chewing tobacco is chewed) and sucked of its juices. The juices are absorbed slowly by the mucous membrane of the inner cheek and by the gastro-intestinal tract when swallowed. Alternatively, coca leaves can be infused in liquid and consumed like tea. Ingesting coca leaves generally is an inefficient means of administering cocaine. Advocates of the consumption of the coca leaf state that coca leaf consumption should not be criminalized as it is not actual cocaine, and consequently it is not properly the illicit drug. Because cocaine is hydrolyzed and rendered inactive in the acidic stomach, it is not readily absorbed when ingested alone. Only when mixed with a highly alkaline substance (such as lime) can it be absorbed into the bloodstream through the stomach. The efficiency of absorption of orally administered cocaine is limited by two additional factors. First, the drug is partly catabolized by the liver. Second, capillaries in the mouth and esophagus constrict after contact with the drug, reducing the surface area over which the drug can be absorbed. Nevertheless, cocaine metabolites can be detected in the urine of subjects that have sipped even one cup of coca leaf infusion. Therefore, this is an actual additional form of administration of cocaine, albeit an inefficient one.

Orally administered cocaine takes approximately 30 minutes to enter the bloodstream. Typically, only a third of an oral dose is absorbed, although absorption has been shown to reach 60% in controlled settings. Given the slow rate of absorption, maximum physiological and psychotropic effects are attained approximately 60 minutes after cocaine is administered by ingestion. While the onset of these effects is slow, the effects are sustained for approximately 60 minutes after their peak is attained.

Contrary to popular belief, both ingestion and insufflation result in approximately the same proportion of the drug being absorbed: 30 to 60%. Compared to ingestion, the faster absorption of insufflated cocaine results in quicker attainment of maximum drug effects. Snorting cocaine produces maximum physiological effects within 40 minutes and maximum psychotropic effects within 20 minutes, however, a more realistic activation period is closer to 5 to 10 minutes, which is similar to ingestion of cocaine. Physiological and psychotropic effects from nasally insufflated cocaine are sustained for approximately 40 - 60 minutes after the peak effects are attained.[4]

Mate de coca or coca-leaf infusion is also a traditional method of consumption and is often recommended in coca producing countries, like Peru and Bolivia, to ameliorate some symptoms of altitude sickness. This method of consumption has been practiced for many centuries by the native tribes of South America. One specific purpose of ancient coca leaf consumption was to increase energy and reduce fatigue in messengers who made multi-day quests to other settlements.

In 1986 an article in the Journal of the American Medical Association revealed that U.S. health food stores were selling dried coca leaves to be prepared as an infusion as “Health Inca Tea.”[5] While the packaging claimed it had been “decocainized,” no such process had actually taken place. The article stated that drinking two cups of the tea per day gave a mild stimulation, increased heart rate, and mood elevation, and the tea was essentially harmless. Despite this, the DEA seized several shipments in Hawaii, Chicago, Illinois, Georgia, and several locations on the East Coast of the United States, and the product was removed from the shelves. Nevertheless, today coca leaf teabags (named "mate de coca") illegally smuggled into the U.S. can be readily purchased online via Internet stores and even eBay.


Cocaine lines on a mirror

Insufflation (known colloquially as "snorting," "sniffing," or "blowing") is the most common method of ingestion of recreational powdered cocaine in the Western world. Cocaine is not inhaled using this method. The drug coats and is absorbed through the mucous membranes lining the sinuses. When insufflating cocaine, absorption through the nasal membranes is approximately 30-60%, with higher doses leading to increased absorption efficiency. Any material not directly absorbed through the mucous membranes is collected in mucus and swallowed (this "drip" is considered pleasant by some and unpleasant by others). In a study[6] of cocaine users, the average time taken to reach peak subjective effects was 14.6 minutes. Any damage to the inside of the nose is because cocaine highly constricts blood vessels – and therefore blood and oxygen/nutrient flow – to that area.

Prior to insufflation, cocaine powder must be divided into very fine particles. Cocaine of high purity breaks into fine dust very easily, except when it is moist (not well stored) and forms "chunks," which reduces the efficiency of nasal absorption.

Rolled up banknotes, hollowed-out pens, cut straws, pointed ends of keys, specialized spoons, and (clean) tampon applicators are often used to insufflate cocaine. Such devices are often called "tooters" by users. The cocaine typically is poured onto a flat, hard surface (such as a mirror) and divided into "bumps", "lines" or "rails", and then insufflated.[7] The amount of cocaine in a line varies widely from person to person and occasion to occasion (the purity of the cocaine is also a factor), but one line is generally considered to be a single dose and is typically 35 mg (a "bump") to 100 mg (a "rail").[citation needed] As tolerance builds rapidly in the short-term (hours), many lines are often snorted to produce greater effects.

A study by Bonkovsky and Mehta published in Am Acad Dermatol (2001 Feb;44(2):159-82) reported that, just like shared needles, the sharing of straws used to "snort" cocaine can spread blood diseases such as Hepatitis C.[8]


Drug injection provides the highest blood levels of drug in the shortest amount of time. Upon injection, cocaine reaches the brain in a matter of seconds, and the exhilarating rush that follows can be so intense that it induces some users to vomit uncontrollably which causes bleeding of the esophagus.[citation needed] In a study[6] of cocaine users, the average time taken to reach peak subjective effects was 3.1 minutes. The euphoria passes quickly. Aside from the toxic effects of cocaine, there is also danger of circulatory emboli from the insoluble substances that may be used to cut the drug. There is also a risk of serious infection associated with the use of contaminated needles.

An injected mixture of cocaine and heroin, known as “speedball” or “moonrock”, is a particularly popular and dangerous combination, as the converse effects of the drugs actually complement each other, but may also mask the symptoms of an overdose. It has been responsible for numerous deaths, particularly in and around Los Angeles, including celebrities such as John Belushi, Chris Farley (in Chicago), River Phoenix and Layne Staley (in Seattle).

Experimentally, cocaine injections can be delivered to animals such as fruit flies to study the mechanisms of cocaine addiction.[9]


See also: Crack cocaine above.

Smoking freebase or crack cocaine is most often accomplished using a pipe made from a small glass tube about one quarter-inch (about 6 mm) in diameter and on the average, four inches long. These are sometimes called "stems", "horns", "blasters" and "straight shooters," readily available in convenience stores or smoke shops. They will sometimes contain a small paper flower and are promoted as a romantic gift. Buyers usually ask for a "rose" or a "flower." An alternate method is to use a small length of a radio antenna or similar metal tube. To avoid burning the user's fingers and lips on the metal pipe, a small piece of paper or cardboard (such as a piece torn from a matchbook cover) is wrapped around one end of the pipe and held in place with either a rubber band or a piece of adhesive tape. A popular (usually pejorative) term for crack pipes is "glass dick." Tire pressure gauges have also been used by breaking off their tops and removing their numbered sticks. These can be purchased at most convenience stores or gas stations.

A small piece (approximately one inch) of clean heavy copper or occasionally stainless steel scouring pad—often called a "brillo" or "chore", from the scouring pads of the same name—is placed into one end of the tube and carefully packed down to approximately three-quarters of an inch. Prior to insertion, the "brillo" is burnt off to remove any oily coatings that may be present. It then serves as a reduction base and flow modulator in which the "rock" can be melted and boiled to vapor.

Another method is to use a deep socket, typically 12 mm, wrapped with electrical tape. Instead of Chore Boy, users typically employ high grade (very fine) speaker wire rolled into a ball as the filter medium. A Zippo lighter is often used because of its stronger flame,[citation needed] but the taste of naphtha is quite noticeable. However, the socket is practically indestructible and inconspicuous.

A less sophisticated but common method is to use a discarded soda can and puncture several small holes on the side of the can near its bottom. Tobacco ash is then placed in the divot created with the drug placed on top. The mouthpiece is the original opening of the can, creating a cost-effective alternative to a proper crack pipe.

To smoke the "rock," it is placed at the end of the pipe, closest to the filter. The other end is then placed in the user's mouth and a flame from a cigarette lighter or hand-held torch is held under the "rock." As the "rock" is heated, it melts and heats into vapor, which the user inhales as smoke.

The effects, felt almost immediately after smoking, are very intense and do not last long — usually five to fifteen minutes. In a study[6] performed on crack cocaine users, the average time taken for them to reach their peak subjective "high" was 1.4 minutes. Most (especially frequent) users crave more immediately after the peak. "Crack houses" depend on these cravings by providing a place for smoking crack to its users, and a ready supply of small bags for sale.

A heavily-used crack pipe tends to fracture at its end due to overheating from the flame used to heat the crack, typically because users attempt to inhale every last bit of the drug on the metal wool filter. The end is often broken further as users "push" the pipe. "Pushing" is a technique used to partially recover crack that hardens on the inside wall of the pipe as the pipe cools. This is accomplished by pushing the metal wool filter through the pipe from one end to the other in order to collect the build-up inside the pipe, which is a very pure and potent form of the base. The ends of the pipe can be broken by the object used to push the filter—frequently a small screwdriver or stiff piece of wire. Users will often remove the most jagged edges and continue using the pipe until it becomes so short that it burns their lips and fingers. To continue using the pipe, users will sometimes wrap a small piece of paper or cardboard around its one end and hold it in place with a rubber band or adhesive tape. Of course, not all crack cocaine users will allow it to get that short, and will instead opt for a new or different pipe. The telltale signs of a used crack pipe are a glass tube with burn marks at one or both ends and a clump of metal wool inside. The language referring to paraphernalia and practices of smoking cocaine vary across the United States, as do the packaging methods in the street level sale.

When smoked, cocaine is sometimes combined with other drugs, such as cannabis; often rolled into a joint or blunt. This combination is known as "primo","hype", "jay bomb", "shake and bake", a "turbo", a "yolabowla", "SnowCaps", "Canadian Health Care", "B-51er", a "cocoapuff", a "dirty", a "woo", or "geeking." Crack smokers who are being drug tested may also make their "primo" with cigarette tobacco instead of cannabis, since a crack smoker can test clean within two to three days of use, if only urine (and not hair) is being tested.

Powdered cocaine is sometimes smoked, but it is inefficient as the heat involved destroys much of the chemical. One way of smoking powder is to put a "bump" into the end of an unlit cigarette, smoking it in one go as the user lights the cigarette normally. This cigarette is then referred to as a "Jimmy". Alternatively, cocaine powder may be sprinkled onto the marijuana in a blunt or possibly a joint and then smoked. This is known as a "Chewy" or may also be referred to by one of the names mentioned above for crack-laced marijuana. When a marijuana bowl is laced with cocaine powder, it is often referred to as a "SnowCap" which is a reference to snow capped mountains."

Coca leaf infusions

Coca herbal infusion (also referred to as Coca tea) is used in coca-leaf producing countries much as any herbal medicinal infusion would elsewhere in the world. The free and legal commercialization of dried coca leaves under the form of filtration bags to be used as "coca tea" has been actively promoted by the governments of Peru and Bolivia for many years as a drink having medicinal powers. Visitors to the city of Cuzco in Peru, and La Paz in Bolivia are greeted with the offering of coca leaf infusions (prepared in tea pots with whole coca leaves) purportedly to help the newly-arrived traveler overcome the malaise of high altitude sickness. The effects of drinking coca tea are a mild stimulation and mood lift. It does not produce any significant numbing of the mouth nor does it give a rush like snorting cocaine. In order to prevent the demonization of this product, its promoters publicize the unproven concept that much of the effect of the ingestion of coca leaf infusion would come from the secondary alkaloids, as being not only quantitatively different from pure cocaine but also qualitatively different.

It has been promoted as an adjuvant for the treatment of cocaine dependence. In one controversial study, coca leaf infusion was used -in addition to counseling- to treat 23 addicted coca-paste smokers in Lima, Peru. Relapses fell from an average of four times per month before treatment with coca tea to one during the treatment. The duration of abstinence increased from an average of 32 days prior to treatment to 217 days during treatment. These results suggest that the administration of coca leaf infusion plus counseling would be an effective method for preventing relapse during treatment for cocaine addiction.[10] Importantly, these results also suggest strongly that the primary pharmacologically active metabolite in coca leaf infusions is actually cocaine and not the secondary alkaloids.

The cocaine metabolite benzoylecgonine can be detected in the urine of people a few hours after drinking one cup of coca leaf infusion.


Cocaine has been used medically and informally as an oral anesthetic. Many users rub the powder along the gum line, or onto a cigarette filter which is then smoked, which numbs the gums and teeth - hence the colloquial names of "numbies", "gummies" or "cocoa puffs" for this type of administration. This is mostly done with the small amounts of cocaine remaining on a surface after insufflation. Another oral method is to wrap up some cocaine in rolling paper and swallow it. This is sometimes called a "snow bomb."

Physical mechanisms

The pharmacodynamics of cocaine involve the complex relationships of neurotransmitters (inhibiting monoamine uptake in rats with ratios of about: Serotonin:Dopamine = 2:3, Serotonin:Norepinephrine = 2:5[11]) The most extensively studied effect of cocaine on the central nervous system is the blockage of the dopamine transporter protein. Dopamine transmitter released during neural signaling is normally recycled via the transporter; i.e., the transporter binds the transmitter and pumps it out of the synaptic cleft back into the pre-synaptic neuron, where it is taken up into storage vesicles. Cocaine binds tightly at the dopamine transporter forming a complex that blocks the transporter's function. The dopamine transporter can no longer perform its reuptake function, and thus dopamine accumulates in the extracellular space (synaptic cleft). This results in an enhanced and prolonged post-synaptic effect of dopaminergic signalling at dopamine receptors on the receiving neuron. Prolonged exposure to cocaine, as occurs with habitual use, leads to homeostatic dysregulation of normal (i.e. without cocaine) dopaminergic signaling via downregulation of dopamine receptors and enhanced signal transduction. The decreased dopaminergic signalling after chronic cocaine use may contribute to depressive mood disorders and sensitize this important brain reward circuit to the reinforcing effects of cocaine (e.g. enhanced dopaminergic signalling only when cocaine is self-administered). This sensitization contributes to the intractable nature of addiction and relapse.

Dopamine-rich brain regions such as the ventral tegmental area, nucleus accumbens, and prefrontal cortex are frequent targets of cocaine addiction research. Of particular interest is the pathway consisting of dopaminergic neurons originating in the ventral tegmental area that terminate in the nucleus accumbens. This projection may function as a "reward center", in that it seems to show activation is response to drugs of abuse like cocaine in addition to natural rewards like food or sex.[12] While the precise role of dopamine in the subjective experience of reward is highly controversial among neuroscientists, the release of dopamine in the nucleus accumbens is widely considered to be at least partially responsible for cocaine's rewarding effects. This hypothesis is largely based on laboratory data involving rats that are trained to self-administer cocaine. If dopamine antagonists are infused directly into the nucleus accumbens, well-trained rats self-administering cocaine will undergo extinction (i.e. initially increase responding only to stop completely) thereby indicating that cocaine is no longer reinforcing (i.e. rewarding) the drug-seeking behavior.

Cocaine also blocks sodium channels, thereby interfering with the propagation of action potentials; thus, like lignocaine and novocaine, it acts as a local anesthetic. Cocaine also causes vasoconstriction, thus reducing bleeding during minor surgical procedures. The locomotor enhancing properties of cocaine may be attributable to its enhancement of dopaminergic transmission from the substantia nigra. Recent research points to an important role of circadian mechanisms[13] and clock genes[14] in behavioral actions of cocaine.

Because nicotine increases the levels of dopamine in the brain, many cocaine users find that consumption of tobacco products during cocaine use enhances the euphoria. This, however, may have undesirable consequences, such as uncontrollable chain smoking during cocaine use (even users who do not normally smoke cigarettes have been known to chain smoke when using cocaine), in addition to the detrimental health effects and the additional strain on the cardiovascular system caused by tobacco.

In addition to irritability, mood disturbances, restlessness, paranoia, and auditory hallucinations, crack can cause several dangerous physical conditions. It can lead to disturbances in heart rhythm and heart attacks, as well as chest pains or even respiratory failure. In addition, strokes, seizures and headaches are common in heavy users.

Cocaine can often cause reduced food intake, many chronic users lose their appetite and can experience severe malnourishment and significant weight loss.

Metabolism and excretion

Cocaine is extensively metabolized, primarily in the liver, with only about 1% excreted unchanged in the urine. The metabolism is dominated by hydrolytic ester cleavage, so the eliminated metabolites consist mostly of benzoylecgonine, the major metabolite, and in lesser amounts ecgonine methyl ester and ecgonine.

If taken with alcohol, cocaine combines with the ethanol in the liver to form cocaethylene, which is both more euphorigenic and has higher cardiovascular toxicity than cocaine by itself[citation needed]. It is precisely this characteristic that has prompted heavily inebriated persons, since the early 20th century, to snort cocaine to relieve them of the depressive effects of alcohol abuse.

Depending on liver and kidney function, cocaine metabolites are detectable in urine. Benzoylecgonine can be detected in urine within four hours after cocaine intake and remains detectable in concentrations greater than 150 ng/ml typically for up to eight days after cocaine is used. Detection of accumulation of cocaine metabolites in hair is possible in regular users until the sections of hair grown during use are cut or fall out.

Effects and health issues


Data from The Lancet shows Cocaine to be the 2nd most dependent and 2nd most harmful of 20 drugs.

Cocaine is a potent central nervous system stimulant. Its effects can last from 20 minutes to several hours, depending upon the dosage of cocaine taken, purity, and method of administration.

The initial signs of stimulation are hyperactivity, restlessness, increased blood pressure, increased heart rate and euphoria. The euphoria is sometimes followed by feelings of discomfort and depression and a craving to experience the drug again. Sexual interest and pleasure can be amplified. Side effects can include twitching, paranoia, and impotence, which usually increases with frequent usage.

With excessive dosage the drug can produce itching, tachycardia, hallucinations, and paranoid delusions. Overdoses cause tachyarrhythmias and a marked elevation of blood pressure. These can be life-threatening, especially if the user has existing cardiac problems.

The LD50 of cocaine when administered to mice is 95.1 mg/kg.[15] Toxicity results in seizures, followed by respiratory and circulatory depression of medullar origin. This may lead to death from respiratory failure, stroke, cerebral hemorrhage, or heart-failure. Cocaine is also highly pyrogenic, because the stimulation and increased muscular activity cause greater heat production. Heat loss is inhibited by the intense vasoconstriction. Cocaine-induced hyperthermia may cause muscle cell destruction and myoglobinuria resulting in renal failure. Emergency treatment often consists of administering a benzodiazepine sedation agent, such as diazepam (Valium) to decrease the elevated heart rate and blood pressure. Physical cooling (ice, cold blankets, etc...) and acetaminophen may be used to treat hyperthermia, while specific treatments are then developed for any further complications.[16] However, there is no specific antidote for cocaine overdose.

In cases where a patient is unable or unwilling to seek medical attention, cocaine overdoses resulting in mild-moderate tachycardia (i.e.: a resting pulse less than 120 bpm), may be initially treated with 20 mg of orally administered diazepam or equivalent benzodiazepine (eg: 2mg lorazepam). Acetaminophen and physical cooling may likewise be used to reduce mild hyperthermia (<39 C). However, a history of high blood pressure or cardiac problems puts the patient at high risk of cardiac arrest or stroke, and requires immediate medical treatment. Similarly, if benzodiazepine sedation fails to reduce heart rate or body temperatures fails to lower, professional intervention is necessary. [17] [18] [19]

Cocaine's primary acute effect on brain chemistry is to raise the amount of dopamine and serotonin in the nucleus accumbens (the pleasure center in the brain); this effect ceases, due to metabolism of cocaine to inactive compounds and particularly due to the depletion of the transmitter resources (tachyphylaxis). This can be experienced acutely as feelings of depression, as a "crash" after the initial high. Further mechanisms occur in chronic cocaine use.

Studies have shown that cocaine usage during pregnancy triggers premature labor[20] and may lead to abruptio placentae.[21]

Cocaine can cause coronary artery spasms which lead to a myocardial infarction. This effect can happen randomly to any user. The coronary artery spasms can occur on the users first usage or any other usage after. The coronary spasms cause the ectopic ventricular foci of the heart to become hypoxic and the extreme irritability can trigger life-threatening ventricular arrhythmias.


Chronic cocaine intake causes brain cells to adapt functionally to strong imbalances of transmitter levels in order to compensate extremes. Thus, receptors disappear from the cell surface or reappear on it, resulting more or less in an "off" or "working mode" respectively, or they change their susceptibility for binding partners (ligands)—mechanisms called down-/upregulation. Chronic cocaine use leads to a DATS upregulation,[verification needed] further contributing to depressed mood states. Physical withdrawal is not dangerous, and is in fact restorative. The experience of insatiable hunger, aches, insomnia/oversleeping, lethargy, and persistent runny nose are often described as very unpleasant. Depression with suicidal ideation may develop in very heavy users. Finally, a loss of vesicular monoamine transporters, neurofilament proteins, and other morphological changes appear to indicate a long term damage of dopamine neurons.

All these effects contribute a rise in tolerance thus requiring a larger dosage to achieve the same effect. The lack of normal amounts of serotonin and dopamine in the brain is the cause of the dysphoria and depression felt after the initial high. The diagnostic criteria for cocaine withdrawal is characterized by a dysphoric mood, fatigue, unpleasant dreams, insomnia or hypersomnia, E.D., increased appetite, psychomotor retardation or agitation, and anxiety.

Cocaine abuse also has multiple physical health consequences. It is associated with a lifetime risk of heart attack that is seven times that of non-users. During the hour after cocaine is used, heart attack risk rises 24-fold.[22]

Side effects from chronic smoking of cocaine include hemoptysis, bronchospasm, pruritus, fever, diffuse alveolar infiltrates without effusions, pulmonary and systemic eosinophiliachest, pain, lung trauma, shortness of breath, sore throat, asthma, hoarse voice, dyspnea, and an aching, flu-like syndrome. A common but untrue belief is that the smoking of cocaine chemically breaks down tooth enamel and causes tooth decay. However, cocaine does often cause involuntary tooth grinding, known as bruxism, which can deteriorate tooth enamel and lead to gingivitis.[23]

Chronic intranasal usage can degrade the cartilage separating the nostrils (the septum nasi), leading eventually to its complete disappearance. Due to the absorption of the cocaine from cocaine hydrochloride, the remaining hydrochloride forms a dilute hydrochloric acid.[1]

Cocaine may also greatly increase this risk of developing rare autoimmune or connective tissue diseases such as lupus, Goodpasture's disease, vasculitis, glomerulonephritis, Stevens-Johnson syndrome and other diseases.[24][25][26][27] It can also cause a wide array of kidney diseases and renal failure.[28][29] While these conditions are normally found in chronic use they can also be caused by short term exposure in susceptible individuals.

Cocaine abuse doubles both the risks of hemorrhagic and ischemic strokes.[30]

Years after the abuse has ended, many ex-abusers report a noticeably reduced attention span.

Cocaine as a local anesthetic

Cocaine was historically useful as a topical anesthetic in eye and nasal surgery, although it is now predominantly used for nasal and lacrimal duct surgery. The major disadvantages of this use are cocaine's intense vasoconstrictor activity and potential for cardiovascular toxicity. Cocaine has since been largely replaced in Western medicine by synthetic local anaesthetics such as benzocaine, proparacaine, and tetracaine though it remains available for use if specified. If vasoconstriction is desired for a procedure (as it reduces bleeding), the anesthetic is combined with a vasoconstrictor such as phenylephrine or epinephrine. In Australia it is currently prescribed for use as a local anesthetic for conditions such as mouth and lung ulcers. Some ENT specialists occasionally use cocaine within the practice when performing procedures such as nasal cauterization. In this scenario dissolved cocaine is soaked into a ball of cotton wool, which is placed in the nostril for the 10-15 minutes immediately prior to the procedure, thus performing the dual role of both numbing the area to be cauterized and also vasoconstriction. Even when used this way, some of the used cocaine may be absorbed through oral or nasal mucosa and give systemic effects.

Prohibition currently

The production, distribution and sale of cocaine products is restricted (and illegal in most contexts) in most countries as regulated by the Single Convention on Narcotic Drugs, and the United Nations Convention Against Illicit Traffic in Narcotic Drugs and Psychotropic Substances. In the United States the manufacture, importation, possession, and distribution of cocaine is additionally regulated by the 1970 Controlled Substances Act.

Some countries, such as Peru and Bolivia permit the cultivation of coca leaf for traditional consumption by the local indigenous population, but nevertheless prohibit the production, sale and consumption of cocaine.

Some parts of Europe and Australia allow processed cocaine for medicinal uses only.

In certain countries in the Middle East and Asia, such as Singapore, Saudi Arabia and Indonesia, being in possession of cocaine can be punishable by death.[citation needed]


In 2004 , according to the United Nations, 589 metric tons of cocaine were seized globally by law enforcement authorities. Colombia seized 188 tons, the United States 166 tons, Europe 79 tons, Peru 14 tons, Bolivia 9 tons, and the rest of the world 133 tons. [1]

Illicit trade

Bricks of cocaine, a form in which it is commonly transported.

Because of the extensive processing it undergoes during preparation, cocaine is generally treated as a 'hard drug', with severe penalties for possession and trafficking. Demand remains high, and consequently black market cocaine is quite expensive. Unprocessed cocaine, such as coca leaves, are occasionally purchased and sold, but this is exceedingly rare as it is much easier and more profitable to conceal and smuggle it in powdered form. The scale of the market is immense: 770 tonnes times $100 per gram retail = up to $77 billion.


By 1999, Colombia had become the world's leading producer of cocaine. Three-quarters of the world's annual yield of cocaine was produced there, both from cocaine base imported from Peru (primarily the Huallaga Valley) and Bolivia, and from locally grown coca. There was a 28% increase from the amount of potentially harvestable coca plants which were grown in Colombia in 1998 . This, combined with crop reductions in Bolivia and Peru, made Colombia the nation with the largest area of coca under cultivation after the mid-1990s. Coca grown for traditional purposes by indigenous communities, a use which is still present and is permitted by Colombian laws, only makes up a small fragment of total coca production, most of which is used for the illegal drug trade. Attempts to eradicate coca fields through the use of defoliants have devastated part of the farming economy in some coca growing regions of Colombia, and strains appear to have been developed that are more resistant or immune to their use. Whether these strains are natural mutations or the product of human tampering is unclear. These strains have also shown to be more potent than those previously grown, increasing profits for the drug cartels responsible for the exporting of cocaine. The cultivation of coca has become an attractive, and in some cases even necessary, economic decision on the part of many growers due to the combination of several factors, including the persistence of worldwide demand, the lack of other employment alternatives, the lower profitability of alternative crops in official crop substitution programs, the eradication-related damages to non-drug farms, and the spread of new strains of the coca plant.

Estimated Andean Region Coca Cultivation and Potential Pure Cocaine Production, 2000–2004.[31]
2000 2001 2002 2003 2004
Net Cultivation (km²) 1875 2218 2007.5 1663 1662
Potential Pure Cocaine Production (tonnes) 770 925 830 680 645


Synthetic cocaine would be highly desirable to the illegal drug industry, as it would eliminate the high visibility and low reliability of offshore sources and international smuggling, replacing them with clandestine domestic laboratories, as are common for illicit methamphetamine. However, natural cocaine remains the lowest cost and highest quality supply of cocaine.

Actual full synthesis of cocaine is rarely done. Formation of inactive enantiomers and synthetic by-products limits the yield and purity.

Developing economical organic synthesis or recombinant DNA production of cocaine might cost $40 million[2], a tiny fraction of the tens of billions of dollars spent annually on cocaine. However, the legitimate pharmaceutical companies and genetic engineering companies are not inclined to explore cocaine mass-production. The multi-national cocaine industry remains predominantly low-tech.

Note, names like 'synthetic cocaine' and 'new cocaine' have been misapplied to phencyclidine (PCP) and various designer drugs such as fentanyl.

Trafficking and distribution

Organized criminal gangs operating on a large scale dominate the cocaine trade. Most cocaine is grown and processed in South America, particularly in Colombia, Bolivia, Peru, and smuggled into the United States and Europe, where it is sold at huge markups; usually in the US at $50-$75 for 1 gram (or a "fitty rock"), and $125-200 for 3.5 grams (1/8th of an ounce, or an "eight ball").

Cocaine shipments from South America transported through Mexico or Central America are generally moved over land or by air to staging sites in northern Mexico. The cocaine is then broken down into smaller loads for smuggling across the U.S.–Mexico border. The primary cocaine importation points in the United States are in Arizona, southern California, southern Florida, and Texas. Typically, land vehicles are driven across the U.S.-Mexico border. Sixty Five percent of cocaine enters the United States through Mexico, and the vast majority of the rest enters through Florida.[32]

Cocaine is also carried in small, concealed, kilogram quantities across the border by couriers known as “mules” (or “mulas”), who cross a border either legally, e.g. through a port or airport, or illegally through undesignated points along the border. The drugs may be strapped to the waist or legs or hidden in bags, or hidden in the body. If the mule gets through without being caught, the gangs will reap most of the profits. If he or she is caught however, gangs will sever all links and the mule will usually stand trial for trafficking by him/herself.

Cocaine traffickers from Colombia, and recently Mexico, have also established a labyrinth of smuggling routes throughout the Caribbean, the Bahama Island chain, and South Florida. They often hire traffickers from Mexico or the Dominican Republic to transport the drug. The traffickers use a variety of smuggling techniques to transfer their drug to U.S. markets. These include airdrops of 500–700 kg in the Bahama Islands or off the coast of Puerto Rico, mid-ocean boat-to-boat transfers of 500–2,000 kg, and the commercial shipment of tonnes of cocaine through the port of Miami.

Bulk cargo ships are also used to smuggle cocaine to staging sites in the western CaribbeanGulf of Mexico area. These vessels are typically 150–250-foot (50–80 m) coastal freighters that carry an average cocaine load of approximately 2.5 tonnes. Commercial fishing vessels are also used for smuggling operations. In areas with a high volume of recreational traffic, smugglers use the same types of vessels, such as go-fast boats, as those used by the local populations.


Cocaine is readily available in all major countries' metropolitan areas. According to the Summer 1998 Pulse Check, published by the U.S. Office of National Drug Control Policy, cocaine use had stabilized across the country, with a few increases reported in San Diego, Bridgeport, Miami, and Boston. In the West, cocaine usage was lower, which was thought to be because some users were switching to methamphetamine, which was cheaper and provides a longer-lasting high. Numbers of cocaine users are still very large, with a concentration among city-dwelling youth.

Cocaine is typically sold to users by the gram ($30-$120US) or eight ball (3.5 grams, or roughly 1/8th oz; hence the term "eight ball") ($100-$300) also can be sold in bill sizes such as $10 would be a dime bag purchasing a small amount (0.1 - 0.15 grams) most common amount would be $20 worth and would include .15-.3 grams this is very popular among youth because of it inexpensiveness and is easily concealed on one's body at any time. Quality and price can vary dramatically depending on demand and supply and in different countries.[33]

Wraps of cocaine. Wraps are used to distribute cocaine by street-level dealers.


World annual cocaine consumption currently stands at around 600 metric tons, with the United States consuming around 300 metric tons, 50% of the total, Europe about 150 metric tons, 25% of the total, and the rest of the world the remaining 150 metric tons or 25%. [3]

According to the United Nations Office on Drugs and Crime 2006 World Drug Report, the United States has the world's greatest rate of cocaine consumption by people aged 15 to 64, 2.8%. It is closely followed by Spain with 2.7%, and England & Wales with 2.4%. Most Western European countries have a consumption rate between 1% and 2%. [4]


According to a 2007 United Nations report, Spain is the country with the highest rate of cocaine usage (3.0% of adults in the previous year).[34] Other countries where the usage rate meets or exceeds 1.5% are the United States (2.8%), England and Wales (2.4%), Canada (2.3%), Italy (2.1%), Bolivia (1.9%), Chile (1.8%), and Scotland (1.5%).[34]

In the United States

General usage

Cocaine has become the second most popular illegal recreational drug in the U.S. (behind marijuana).[35] Cocaine is commonly used in middle to upper class communities. It is also popular amongst college students, not just to aid in studying, but also as a party drug. Its users span over different ages, races, and professions. In the 1970s and 80's, the drug became particularly popular in the disco culture as cocaine usage was very common and popular in many discos such as Studio 54.

The National Household Survey on Drug Abuse (NHSDA) reported in 1999 that cocaine was used by 3.7 million Americans, or 1.7% of the household population age 12 and older. Estimates of the current number of those who use cocaine regularly (at least once per month) vary, but 1.5 million is a widely accepted figure within the research community.

Although cocaine use had not significantly changed over the six years prior to 1999, the number of first-time users went up from 574,000 in 1991, to 934,000 in 1998 — an increase of 63%. While these numbers indicated that cocaine is still widely present in the United States, cocaine use was significantly less prevalent than it was during the early 1980s. Cocaine use peaked in 1982 when 10.4 million Americans (5.6% of the population) reportedly used the drug.[citation needed]

Usage among youth

The 1999 Monitoring the Future (MTF) survey found the proportion of American students reporting use of powdered cocaine rose during the 1990s. In 1991 , 2.3% of eighth-graders stated that they had used cocaine in their lifetime. This figure rose to 4.7% in 1999. For the older grades, increases began in 1992 and continued through the beginning of 1999. Between those years, lifetime use of cocaine went from 3.3% to 7.7% for tenth-graders and from 6.1% to 9.8% for high school seniors. Lifetime use of crack cocaine, according to MTF, also increased among eighth-, tenth-, and twelfth-graders, from an average of 2% in 1991 to 3.9% in 1999.

Perceived risk and disapproval of cocaine and crack use both decreased during the 1990s at all three grade levels. The 1999 NHSDA found the highest rate of monthly cocaine use was for those aged 18–25 at 1.7%, an increase from 1.2% in 1997. Rates declined between 1996 and 1998 for ages 26–34, while rates slightly increased for the 12–17 and 35+ age groups. Studies also show people are experimenting with cocaine at younger ages. NHSDA found a steady decline in the mean age of first use from 23.6 years in 1992 to 20.6 years in 1998.


Main article: Cocaine dependence

Cocaine dependence (or addiction) is physical and psychological dependency on the regular use of cocaine. It can result in physiological damage, lethargy, depression, or a potentially fatal overdose.


From Wikipedia, the free encyclopedia

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Systematic (IUPAC) name
3,4,5-trimethoxy-phenethylamine or 2-(3,4,5-trimethoxyphenyl) ethanamine
CAS number 54-04-6
ATC code  ?
PubChem  ?
Chemical data
Formula C11H17NO3 
Mol. mass 211.26 g/mol
SMILES search in eMolecules, PubChem
Physical data
Melt. point 183–186 °C (361–367 °F) (Sulfate dihydrate)
Pharmacokinetic data
Bioavailability  ?
Metabolism  ?
Half life  ?
Excretion  ?
Therapeutic considerations
Pregnancy cat.


Legal status

Prohibited (S9)(AU) Schedule III(CA) Class A(UK) Schedule I(US)

Routes Oral, Intravenous

Mescaline (3,4,5-trimethoxyphenethylamine) is a psychedelic alkaloid of the phenethylamine class. It is mainly used as; a recreational drug, an entheogen, and a tool in use to supplement various types of practices for transcendence, including in meditation, psychonautics, and illegal psychedelic psychotherapy, whether self administered or not.

It occurs naturally in the peyote cactus (Lophophora williamsii), the San Pedro cactus (Echinopsis pachanoi) and the Peruvian Torch cactus (Echinopsis peruviana), and in a number of other members of the Cactaceae. It is also found in small amounts in certain members of the Fabaceae (bean family), including Acacia berlandieri.[1] Mescaline was first isolated and identified in 1897 by the German Arthur Heffter and first synthesized in 1919 by Ernst Späth.



[edit] Usage and history

The use of peyote in Native American religious ceremonies has been noted since the earliest European contact, notably by the Huichols in Mexico, but other cacti such as the San Pedro have been used in different regions, from Peru to Ecuador.

[edit] Dosage and effects

In traditional peyote preparations, the top of the cactus is cut from the roots, and dried to make disk-shaped buttons. It is chewed to produce its effect or soaked in water for an intoxicating drink. However, the taste of the cactus is bitter, so users will often grind it into a powder and fill them in capsules to avoid having to taste it. The effective human dosage is 300–500 milligrams of pure mescaline, with the effects lasting for up to 12 hours. Hallucinations occur at 300–600 mg, which is the equivalent to approximately 20 mescal buttons. Users typically experience visual hallucinations and radically altered states of consciousness, often experienced as pleasurable and illuminating but occasionally is accompanied by feelings of anxiety or revulsion. Like most psychedelic hallucinogens, mescaline is not physically addictive. Mescaline-containing cacti can induce severe vomiting and nausea, which adds an important part to traditional Native-American or Shaman ceremonies as it is considered cleansing.

[edit] Mode of action

It is speculated that mescaline, along with LSD, psilocybin, 5-Meo-DMT and tryptamine bind to the 5-HT receptors, specifically the 5-HT2A receptor which is a G protein-coupled receptor. Binding to the receptor active site in the neuron causes the G protein to dissociate and become activated with GTP. This released G protein complex stimulates various physical and chemical changes within the cell. It can directly alter the membrane sensitivity to ion transport via conformational changes, stimulate the release of ions from cellular storage, and also stimulate transcription and editing of the primary transcript with the end result of increased ionic activity—all of these methods leading to a change in the neuronal potential. In certain neural cells, this stimulation is inhibitory in action (resulting in the changed perception of edges) while in others it is excitatory, resulting in the positive symptoms of the "hallucination" or "vision".

[edit] Pharmacokinetics

Although the ED50 is variable with dosage and individual, the LD50 has been measured in various animals and is reported as follows:

  • Crystals: 212 mg/kg i.p. (mice)
  • Crystals: 132 mg/kg i.p. (rats)
  • Crystals: 328 mg/kg i.p. (guinea pigs)

It is reported that mescaline is 1000-3000 times less potent than LSD, and 30 times less potent than psilocybin. About half the initial dosage is excreted after 6 hours, but some studies suggest that it is not metabolized at all before excretion.

Slow tolerance builds with repeated usage, and it is suggested that a cross tolerance can be developed with LSD.

[edit] Legal status

In the US it was made illegal in 1970 by the Comprehensive Drug Abuse Prevention and Control Act.[2] It was prohibited internationally by the 1971 Convention on Psychotropic Substances[3] and is categorized as a Schedule I hallucinogen by the CSA. Mescaline is only legal for certain natives (such as those involved in the Native American Church). Penalties for manufacture or sale can be as high as five years in jail and a fine of $15,000, with a penalty of up to one year and fine of $5000 for possession.

[edit] Chemistry

A common synthetic approach starts from 3,4,5-trimethoxybenzaldehyde. The chemical make-up is C11H17NO3 (PiHKAL entry). It is also synthesized from syringaldehyde, vanillin, and gallic acid. 3,4,5-trimethoxynitrostyrene can be reduced to mescaline using catalytic hydrogenation.

[edit] Effects and side effects

One or more of the following effects may or may not accompany any individual experience with mescaline.

In the science fiction movie The Matrix, Thomas Anderson (Neo) says to Choi, "Do you ever have that feeling where you're not sure if you're awake or still dreaming?" Choi replies, "Mmm. All the time. It's called mescaline. It's the only way to fly."

[edit] Analogs

Phenescaline, an analog of mescaline

Mescaline has a number of analogs, featuring the methoxy groups altered to include thio groups or to be extended. Examples include, but are not limited to, isomescaline, thiomescaline, escaline, thioescaline, proscaline, isoproscaline, buscaline, thiobuscaline, thioisomescaline, phenescaline, symbescaline, asymbescaline, thioasymbescaline, allylescaline, methallylescaline, metaescaline, and thiometaescaline.

The amphetamine homologue, TMA, 3,4,5-trimethoxyamphetamine, should be listed here as well.


Psilocybin (also known as psilocybine) is a psychedelic alkaloid of the tryptamine family, found in psilocybin mushrooms. It is considered mostly to be an entheogen and a tool in use to supplement various types of practices for transcendence including in meditation, psychonautics, and illicit psychedelic psychotherapy whether self administered or not. Though Psilocybin rarely attracts much attention from mainstream media, when it does, the focus tends to be on the recreational use to the exclusion of any other purpose. It is present in hundreds of species of fungi, including those of the genus Psilocybe, such as Psilocybe cubensis and Psilocybe semilanceata, but also reportedly isolated from a dozen or so other genera. Psilocybin mushrooms are commonly called "magic mushrooms" or more simply "shrooms". The intensity and duration of entheogenic and recreational use of psilocybin mushrooms vary depending on species of mushrooms, dosage, individual physiology, and set and setting.



[edit] Chemistry

Psilocybin is a prodrug that is converted into the pharmacologically active compound psilocin in the body by dephosphorylation.[1] This chemical reaction takes place under strongly acidic conditions or enzymatically by phosphatases in the body. Psilocybin is a zwitterionic alkaloid that is soluble in water, moderately soluble in methanol and ethanol, and insoluble in most organic solvents.

Albert Hofmann was the first to recognize the importance and chemical structure of the pure compounds psilocybin and psilocin. Hofmann was aided in this process by his willingness to ingest extracts isolated from Psilocybe. Hofmann's colleagues at the University of Delaware were also trying to isolate the active principle, but were unsuccessful.[2]

[edit] Biology

Psilocybin is a naturally-occurring compound found in high concentrations in some species of Psilocybe and Panaeolus (collectively called "psilocybin mushrooms" or "psilocybian mushrooms"), and at low levels in a large number of species of the Agaricales. The spores of these mushrooms are completely free of both psilocybin and psilocin. The total potency varies greatly between species and even between specimens of one species in the same batch. Younger, smaller mushrooms are relatively higher in alkaloids and have a milder taste than larger, mature mushrooms. Mature mycelium contains some amount of psilocybin, which can be extracted with an acidic solution, usually of citric acid or ascorbic acid (Vitamin C). Young mycelium (recently germinated from spores) does not contain appreciable amounts of alkaloids. Most species of hallucinogenic mushrooms also contain small amounts of the psilocybin analogs baeocystin and norbaeocystin. Many types of psilocybin mushrooms bruise blue when handled or damaged — this is due to the oxidization of active compounds though bruising is not a definitive method of determining a mushroom's potency.

[edit] Pharmacology

Psilocybin is rapidly dephosphorylated in the body to psilocin which then acts as a partial agonist at the 5-HT2A serotonin receptor in the brain where it mimics the effects of serotonin (5-HT). Psilocin is an 5-HT1A and 5-HT2A/2C agonist.

[edit] Medicine

Psilocybin has been studied as a treatment for several disorders. In 1961, Timothy Leary and Richard Alpert ran the Harvard Psilocybin Project, carrying out a number of experiments concerning the use of psilocybin in the treatment of personality disorders and other uses in psychological counseling.

In the United States, an FDA-approved study supported by Multidisciplinary Association for Psychedelic Studies (MAPS) began in 2001 to study the effects of psilocybin on patients with obsessive-compulsive disorder.[3] MAPS has also proposed studying psilocybin's potential application for the treatment of cluster headaches based on anecdotal evidence presented to them by a group of cluster headache sufferers.[4] In 2006, the MAPS study found psilocybin effective in relieving obsessive compulsive disorder symptoms, in some cases for more than a few days.[5]

In a current study of psilocybin, led by Charles Grob, 12 subjects are being administered with either the hallucinogen or a placebo in two separate sessions. Grob hopes to reduce the psychological distress that is associated with death by treating patients with psilocybin.[6][7][8]

[edit] Toxicity

The toxicity of psilocybin is relatively low; in rats, the oral LD50 is 280mg/kg — almost one and a half times that of caffeine. When administered intravenously in rabbits, Psilocybin's LD50 is approximately 12.5mg/kg. [9] Death from psilocybin intake alone is unknown at recreational or medicinal levels.

The psilocybin content of psychoactive mushrooms is quite varied and depends on species, growth and drying conditions, and mushroom size.

[edit] Effects

Psilocybin is absorbed through the lining of the mouth and stomach. Effects begin 10-40 minutes after ingestion of psilocybin-containing mushrooms if held in mouth for 20-60 minutes or if swallowed on an empty stomach, and last from 2-6 hours depending on dose, species, and individual metabolism.[10] Typical recreational dosage is from 10-50mg psilocybin, approximately 1-5g dried mushroom or 10-50g wet mushrooms.

The effects of psilocybin are often pleasant, even ecstatic, including a deep sense of connection to others, confusion, hilarity, and a general feeling of connection to nature and the universe. Bad trips may occur when psychedelic compounds are taken in a non-supportive or inadequate environment, by an inexperienced person, in an unexpectedly high dose (see: set and setting), or when the substance triggers difficult areas of one's psyche.

At low doses, hallucinatory effects occur, including walls that seem to breathe, a vivid enhancement of colors and the animation of organic shapes. At higher doses, experiences tend to be less social and more entheogenic, often catalyzing intense spiritual experiences. For example, in the Marsh Chapel Experiment, which was run by a graduate student at Harvard Divinity School under the supervision of Timothy Leary, almost all of the graduate degree divinity student volunteers who received psilocybin reported profound religious experiences. (A brief video about the Marsh Chapel experiment can be viewed here.)

In 2006, a group of researchers from Johns Hopkins School of Medicine led by Roland R Griffiths conducted an experiment assessing the degree of mystical experience and attitudinal effects of the psilocybin experience; this report was published in the journal Psychopharmacology. Thirty-six volunteers without prior experience with hallucinogens were given psilocybin and methylphenidate (Ritalin) in separate sessions, the methylphenidate sessions serving as a control and active placebo; the tests were double-blind, with neither the subject nor the administrator knowing which drug was being administered. The degree of mystical experience was measured using a questionnaire on mystical experience developed by Ralph W Hood; 61% of subjects reported a "complete mystical experience" after their psilocybin session, while only 13% reported such an outcome after their experience with methylphenidate. Two months after taking psilocybin, 79% of the participants reported moderately to greatly increased life satisfaction and sense of well-being. About 36% of participants also had a strong to extreme “experience of fear” or dysphoria (I.E. a “bad trip”) at some point during the psilocybin session (which was not reported by any subject during the methylphenidate session), with about one-third of these (13% of the total) reporting that this dysphoria dominated the entire session. These negative effects were reported to be easily managed by the researchers and did not have a lasting negative effect on the subject’s sense of well-being. [1] This research was widely covered in the major media outlets.[2].

A very small number of people are unusually sensitive to psilocybin's effects, where doses as little as 0.25 grams of dried Psilocybe cubensis mushrooms (normally a threshold dose of around 2 mg psilocybin) can result in effects usually associated with medium and high doses. Likewise, there are some people who require relatively high doses of psilocybin to gain low-dose effects. Individual brain chemistry and metabolism plays a large role in determining a person's response to psilocybin.

Psilocybin is metabolized mostly in the liver where it becomes psilocin. It is broken down by the enzyme monoamine oxidase. MAO inhibitors have been known to sustain the effects of psilocybin for longer periods of time; people who are taking an MAOI for a medical condition (or are seeking to potentiate the mushroom experience) should be careful.

Mental and physical tolerance to psilocybin builds and dissipates quickly. Taking psilocybin more than three or four times in a week (especially two days in a row) can result in diminished effects. Tolerance dissipates after a few days, so frequent users often keep doses spaced five to seven days apart to avoid the effect.

[edit] Adverse effects

Individuals that have relatives with schizophrenia should be very careful about consuming psilocybin or any hallucinogenic drug at all due to the risk of triggering a psychosis. [11]

In extremely rare cases the use of hallucinogens may trigger a malady called Hallucinogen persisting perception disorder. (HPPD).[12]

[edit] Social and legal aspects

Psilocybin and psilocin are listed as Schedule I drugs under the United Nations 1971 Convention on Psychotropic Substances.[3] Schedule I drugs are illicit drugs that are claimed to have no known therapeutic benefit. Parties to the treaty are required to restrict use of the drug to medical and scientific research under strictly controlled conditions. Most national drug laws have been amended to reflect this convention (for example, the US Psychotropic Substances Act, the UK Misuse of Drugs Act 1971, and the Canadian Controlled Drugs and Substances Act), with possession and use of psilocybin and psilocin being prohibited under almost all circumstances, and often carrying severe legal penalties.

Possession and use of psilocybin mushrooms, including the bluing species of Psilocybe, is therefore prohibited by extension. However, in many national, state, and provincial drug laws, there is a great deal of ambiguity about the legal status of psilocybin mushrooms and the spores of these mushrooms, as well as a strong element of selective enforcement in some places. For more details on the legal status of psilocybin mushrooms and Psilocybe spores, see: Psilocybe: Social and legal aspects.

Because of the ease of cultivating psilocybin mushrooms or gathering wild species, purified psilocybin is practically nonexistent on the illegal drug market.

Controlled Substances Act

The Controlled Substances Act (CSA) was enacted into law by the Congress of the United States as Title II of the Comprehensive Drug Abuse Prevention and Control Act of 1970.[1] The CSA is the legal basis by which the manufacture, importation, possession, and distribution of certain drugs are regulated by the federal government of the United States. The Act also served as the national implementing legislation for the Single Convention on Narcotic Drugs.

The legislation created five Schedules (classifications), with varying qualifications for a drug to be included in each. Two federal departments, the Department of Justice and the Department of Health and Human Services (which includes the Food and Drug Administration) determine which drugs are added or removed from the various schedules, though the statute passed by Congress created the initial listing. Classification decisions are required to be made on the criteria of potential for abuse, accepted medical use in the United States, and potential for dependence.

The Department of Justice is also the executive agency in charge of federal law enforcement. State governments also regulate certain drugs not controlled at the federal level.



[edit] Enforcement authority

Proceedings to add, delete, or change the schedule of a drug or other substance may be initiated by the Drug Enforcement Administration (DEA), the Department of Health and Human Services (HHS), or by petition from any interested party, including the manufacturer of a drug, a medical society or association, a pharmacy association, a public interest group concerned with drug abuse, a state or local government agency, or an individual citizen. When a petition is received by the DEA, the agency begins its own investigation of the drug.

The DEA also may begin an investigation of a drug at any time based upon information received from eryn laboratories, state and local law enforcement and regulatory agencies, or other sources of information.

Once the DEA has collected the necessary data, the DEA Administrator, by authority of the Attorney General, requests from HHS a scientific and medical evaluation and recommendation as to whether the drug or other substance should be controlled or removed from control. This request is sent to the Assistant Secretary of Health of HHS. Then, HHS solicits information from the Commissioner of the Food and Drug Administration and evaluations and recommendations from the National Institute on Drug Abuse and, on occasion, from the scientific and medical community at large. The Assistant Secretary, by authority of the Secretary, compiles the information and transmits back to the DEA a medical and scientific evaluation regarding the drug or other substance, a recommendation as to whether the drug should be controlled, and in what schedule it should be placed.

The medical and scientific evaluations are binding to the DEA with respect to scientific and medical matters. The recommendation on scheduling is binding only to the extent that if HHS recommends that the substance not be controlled, the DEA may not control the substance.

Once the DEA has received the scientific and medical evaluation from HHS, the DEA Administrator will evaluate all available data and make a final decision whether to propose that a drug or other substance be controlled and into which schedule it should be placed.

Under certain circumstances, the Government may temporarily schedule a drug without following the normal procedure. An example is when international treaties require control of a substance. In addition, 21 U.S.C. § 811(h) allows the Attorney General to temporarily place a substance in Schedule I "to avoid an imminent hazard to the public safety". Thirty days' notice is required before the order can be issued, and the scheduling expires after a year; however, the period may be extended six months if rulemaking proceedings to permanently schedule the drug are in progress. In any case, once these proceedings are complete, the temporary order is automatically vacated.

The CSA also creates a closed system of distribution for those authorized to handle controlled substances. The cornerstone of this system is the registration of all those authorized by the DEA to handle controlled substances. All individuals and firms that are registered are required to maintain complete and accurate inventories and records of all transactions involving controlled substances, as well as security for the storage of controlled substances.

[edit] History

Since its enactment in 1970, the Act has been amended several times:

[edit] International law

The Congressional findings in 21 U.S.C. § 801(7), 21 U.S.C. § 801(a)(2), and Template:21 state that a major purpose of the CSA is to "enable the United States to meet all of its obligations" under international treaties - specifically, the 1961 Single Convention on Narcotic Drugs and the 1971 Convention on Psychotropic Substances[1]. The CSA bears many resemblances to these Conventions. Both the CSA and the treaties set out a system for classifying controlled substances in several Schedules in accordance with the binding scientific and medical findings of a public health authority. Under 21 U.S.C. § 811 of the CSA, that authority is the Secretary of Health and Human Services (HHS). Under Article 3 of the Single Convention and Article 2 of the Convention on Psychotropic Substances, the World Health Organization is that authority.

A provision for automatic compliance with treaty obligations is found at 21 U.S.C. § 811(d), which also establishes mechanisms for amending international drug control regulations to correspond with HHS findings on scientific and medical issues. If control of a substance is mandated by the Single Convention, the Attorney General is required to "issue an order controlling such drug under the schedule he deems most appropriate to carry out such obligations," without regard to the normal scheduling procedure or the findings of the HHS Secretary. However, the Secretary has great influence over any drug scheduling proposal under the Single Convention, because 21 U.S.C. § 811(d)(2)(B) requires the Secretary the power to "evaluate the proposal and furnish a recommendation to the Secretary of State which shall be binding on the representative of the United States in discussions and negotiations relating to the proposal."

Similarly, if the United Nations Commission on Narcotic Drugs adds or transfers a substance to a Schedule established by the Convention on Psychotropic Substances, so that current U.S. regulations on the drug do not meet the treaty's requirements, the Secretary is required to issue a recommendation on how the substance should be scheduled under the CSA. If the Secretary agrees with the Commission's scheduling decision, he can recommend that the Attorney General initiate proceedings to reschedule the drug accordingly. If the HHS Secretary disagrees with the UN controls, however, the Attorney General must temporarily place the drug in Schedule IV or V (whichever meets the minimum requirements of the treaty) and exclude the substance from any regulations not mandated by the treaty, while the Secretary is required to request that the Secretary of State take action, through the Commission or the UN Economic and Social Council, to remove the drug from international control or transfer it to a different Schedule under the Convention. The temporary scheduling expires as soon as control is no longer needed to meet international treaty obligations.

This provision was invoked in 1984 to place Rohypnol (flunitrazepam) in Schedule IV. The drug did not then meet the Controlled Substances Act's criteria for scheduling; however, control was required by the Convention on Psychotropic Substances. In 1999, an FDA official explained to Congress[2]:

Rohypnol is not approved or available for medical use in the United States, but it is temporarily controlled in Schedule IV pursuant to a treaty obligation under the 1971 Convention on Psychotropic Substances. At the time flunitrazepam was placed temporarily in Schedule IV (November 5, 1984), there was no evidence of abuse or trafficking of the drug in the United States.

The Cato Institute's Handbook for Congress calls for repealing the CSA, an action that would likely bring the United States into conflict with international law[3]. The exception would be if the U.S. were to claim that the treaty obligations violate the United States Constitution. Many articles in these treaties - such as Article 35 and Article 36 of the Single Convention - are prefaced with phrases such as "Having due regard to their constitutional, legal and administrative systems, the Parties shall . . ." or "Subject to its constitutional limitations, each Party shall . . ." According to former United Nations Drug Control Programme Chief of Demand Reduction Cindy Fazey, "This has been used by the USA not to implement part of article 3 of the 1988 Convention, which prevents inciting others to use narcotic or psychotropic drugs, on the basis that this would be in contravention of their constitutional amendment guaranteeing freedom of speech"[4].

[edit] Drug schedules

The below lists include examples only. For a complete and up-to-date list of controlled substances, see [5]

The findings that the government must make in order to classify a drug in a certain schedule are specified at 21 U.S.C. § 812(b). The specific classification of any given drug is usually a source of controversy, as is the purpose and effectiveness of the entire regulatory scheme.

Tobacco, beer, wine, and spirits are explicitly exempt from the Controlled Substances Act. Some have argued that this is an important omission, since alcohol and tobacco are the two most widely abused drugs in the United States [6] [7], and have no accepted medical uses. Caffeine is also not on the list, although it is a psychoactive drug and it technically meets the requirements for schedule IV or V: it is often abused and it can lead to limited physical dependence.

The placement of some drugs is paradoxical: both morphine and fentanyl are on Schedule II, and heroin is on Schedule I. Fentanyl is approximately 80 times the potency of morphine, and heroin is somewhere between morphine and fentanyl. Clearly, morphine has been used by physicians for over 150 years. It is very addictive, but it is very effective for severe pain, so it is licensed for careful medical use. Heroin was introduced in the late 19th century and licensed the same way until it was completely banned in 1924. Fentanyl has been used for less than 50 years and has always been carefully restricted.

Dextromethorphan (DXM), a drug found in many OTC cough medications, is also explicitly exempt from scheduling under the original 1970 version of the CSA. However, the DEA has noted DXM to be abused recreationally as a dissociative anaesthetic similar to PCP or ketamine. DXM is therefore listed as a 'chemical of concern' and is being considered for possible evaluation for scheduling.

[edit] Schedule I drugs

Findings required:

(A) The drug or other substance has high potential for abuse.
(B) The drug or other substance has no currently accepted medical use in treatment in the United States.
(C) There is a lack of accepted safety for use of the drug or other substance under medical supervision.

No prescriptions may be written for Schedule I substances, and such substances are subject to production quotas by the DEA.

Under the DEA's interpretation of the CSA, a drug does not necessarily have to have the same abuse potential as heroin or cocaine to merit placement in Schedule I (in fact, cocaine is currently a Schedule II drug due to limited medical use):[2]

When it comes to a drug that is currently listed in schedule I, if it is undisputed that such drug has no currently accepted medical use in treatment in the United States and a lack of accepted safety for use under medical supervision, and it is further undisputed that the drug has at least some potential for abuse sufficient to warrant control under the CSA, the drug must remain in schedule I. In such circumstances, placement of the drug in schedules II through V would conflict with the CSA since such drug would not meet the criterion of "a currently accepted medical use in treatment in the United States." 21 USC 812(b).

Sentences for first-time, non-violent offenders convicted of trafficking in Schedule I drugs can easily turn into de facto life sentences when multiple sales are prosecuted in one proceeding.[3] Sentences for violent offenders are much higher.

Drugs on this schedule include

  • GHB (Gamma-hydroxybutyrate), which has been used as a general anaesthetic with minimal side-effects[citation needed] and controlled action but a limited safe dosage range. It was placed in Schedule I in March 2000 after widespread recreational use. Uniquely, this drug is also listed in Schedule III for limited uses, under the trademark Xyrem;
  • 12-Methoxyibogamine (Ibogaine), which has been used in opiate addiction treatment and psychotherapy.
  • Cannabis (includes tetrahydrocannibinols found in marijuana, hashish, and hashish oil). Controversy exists about its placement in Schedule I. Main article: Cannabis rescheduling in the United States.
  • Dimethyltryptamine (DMT), which is found in small quantities in the human brain but is pharmacologically active in larger quantities.
  • Heroin (Diacetylmorphine), which is used in much of Europe as a potent pain reliever in terminal cancer patients. (It is about twice as potent, by weight, as morphine.)
  • Other strong opiates and opioids used in many other countries, or even in the USA in previous decades for palliation of moderate to severe pain such as nicomorphine (Vilan), dextromoramide (Palfium), ketobemidone (Ketalgin), dihydromorphine (Paramorfan), piritramide (Dipidolor), diacetyldihydromorphine (Paralaudin), dipipanone (Wellconal), phenadoxone (Heptalgin) and many others.
  • Weak opioids used for relief of moderate pain, diarrhea, and coughing such as benzylmorphine (Peronine), nicocodeine (Tusscodin), thebacon, tilidine (Valoron), meptazinol (Meptid), propiram (Algeril), acetyldihydrocodeine and others.
  • MDMA (3,4-methylenedioxymethamphetamine,Ecstasy), which continues to be used medically, notably in the treatment of post-traumatic stress disorder (PTSD) (approved by the FDA for PTSD use in 2001). The medical community originally agreed upon placing it as a Schedule III substance, but the government denied this suggestion, despite two court rulings by the DEA's administrative law judge that placing MDMA in Schedule I was illegal. It was temporarily unscheduled after the first administrative hearing from December 22, 1987 - July 1, 1988.[4]
  • Psilocybin, the active ingredient in psychedelic mushrooms;
  • 5-MeO-DIPT (Foxy / Foxy Methoxy / 5-methoxy-n,n-diisopropyltryptamine)
  • Lysergic acid diethylamide (LSD / Acid), which has historically been used to treat alcoholism and other addictions, helped to stop cluster headaches, and has been shown to be useful in treating schizophrenia, bi-polar illness, childhood autism, and other psychological disorders;
  • Peyote, a cactus growing in nature primarily in northeastern Mexico, one of the few plants specifically scheduled, which has a narrow exception to its illegal status for religious use by members of the Native American Church;
  • Mescaline, the main psychoactive ingredients of the peyote, san pedro, and Peruvian torch cacti;
  • Methaqualone (Quaalude, Sopor, Mandrax), a sedative that was previously used for similar purposes as barbiturates, until it was rescheduled;
  • 2,5-dimethoxy-4-methylamphetamine (STP / DOM), a psychotropic hallucinogen that rose to prominence in 1967 in San Francisco when it appeared in pill form (known as "STP", in doses as high as four times the amounts previously considered "safe") on the black market;
  • Tetrahydrogestrinone (THG / "The Clear"), an anabolic progestegenic androgen first created by the BALCO athletic supplement company that was the drug of choice for athletes using steroids due to its "invisibility" in standard steroid screening tests until 2003, when Trevor Graham provided a sample to the U.S. Anti-Doping Agency; banned by the FDA for medical use and added to Schedule I in 2003;
  • 2C-T-7 (Blue Mystic / T7)
  • 2C-B (Nexus / Bees / Venus / Bromo Mescaline)
  • Cathinone (β-ketoamphetamine) is a monoamine alkaloid found in the shrub Catha edulis (Khat).
  • AMT (alpha-methyltryptamine)
  • Bufotenin (5-OH-DMT)[5]
  • Controlled Substance Analogs intended for human consumption (as defined by the Federal Analog Act)

[edit] Schedule II drugs

Findings required:

(A) The drug or other substance has a high potential for abuse.
(B) The drug or other substance has a currently accepted medical use in treatment in the United States or a currently accepted medical use with severe restrictions.
(C) Abuse of the drug or other substances may lead to severe psychological or physical dependence.

These drugs are only available by prescription, and distribution is carefully controlled and monitored by the DEA. Oral prescriptions are allowed, except that the prescription is limited to 30 days worth of doses, although exceptions are made for cancer patients, burn victims, etc. and oral prescriptions for schedule II drugs must be confirmed in writing within 3 days. No refills are allowed. Also, Schedule II drugs are subject to production quotas set by the DEA. Some of these drugs (notably Fentanyl) are never given to patients for home use, but are administered only by a physician. Fentanyl can be given to patients for home use in Duragesic transdermal therapeutic system patch form. The prescription must be hand delivered within 7 days to the pharmacy and the prescription is limited to 30 days worth of doses.

These drugs vary in potency: for example Fentanyl is about 80 times as potent as morphine. (Heroin is only twice as potent.)

Drugs on this schedule include

  • Methadone (used in treatment of heroin addiction as well as for treatment of extreme chronic pain)
  • Pure codeine and any drug for non-parenteral administration containing the equivalent of more than 90 mg of codeine per dosage unit.;
  • Pure hydrocodone and any drug for non-parenteral administration containing no other active ingredients or more than 15 mg per dosage unit.;
  • Amphetamines were originally placed on Schedule III, but were moved to Schedule II in 1971. Injectable methamphetamine has always been on Schedule II;

Many speculate that if scheduled Nicotine would be a Schedule II drug

[edit] Schedule III drugs

Findings required:

(A) The drug or other substance has a potential for abuse less than the drugs or other substances in schedules I and II.
(B) The drug or other substance has a currently accepted medical use in treatment in the United States.
(C) Abuse of the drug or other substance may lead to moderate or low physical dependence or high psychological dependence.

These drugs are available only by prescription, though control of wholesale distribution is somewhat less stringent than Schedule II drugs. Prescriptions for Schedule III drugs may be refilled up to five times within a six month period.

Drugs on this schedule include

  • Ketamine, a drug originally developed as a milder substitute for PCP (mainly to use as a human anesthetic) but has since become popular as a veterinary anesthetic;
  • Xyrem, a preparation of GHB used to treat narcolepsy. Xyrem is in Schedule III but with a restricted distribution system. All other forms of GHB are in Schedule I;
  • LSA, listed as a sedative but considered by most experts to be psychedelic. A pre-cursor to and chemical relative of LSD. LSA occurs naturally in Rivea corymbosa, morning glory seeds, and Hawaiian baby woodrose seeds. LSA is not biosynthesized by the ergot fungus Claviceps purpurea, but can be biosynthesized by other Claviceps species. LSA can be present as an artifact in extracts of ergot.

[edit] Schedule IV drugs

Findings required:

(A) The drug or other substance has a low potential for abuse relative to the drugs or other substances in schedule III.
(B) The drug or other substance has a currently accepted medical use in treatment in the United States.
(C) Abuse of the drug or other substance may lead to limited physical dependence or psychological dependence relative to the drugs or other substances in schedule III.

Control measures are similar to Schedule III. Prescriptions for Schedule IV drugs may be refilled up to five times within a six month period.

Drugs on this schedule include:

[edit] Schedule V drugs

Findings required:

(A) The drug or other substance has a low potential for abuse relative to the drugs or other substances in schedule IV.
(B) The drug or other substance has a currently accepted medical use in treatment in the United States.
(C) Abuse of the drug or other substance may lead to limited physical dependence or psychological dependence relative to the drugs or other substances in schedule IV.

Schedule V drugs are only available for a medical purpose.

Drugs on this schedule include:

  • Cough suppressants containing small amounts of codeine (e.g., promethazine+codeine);
  • Preparations containing small amounts of opium or diphenoxylate (used to treat diarrhea);
  • Pregabalin (Lyrica), an anticonvulsant and pain modulator.
  • Pyrovalerone
  • The centrally-acting anti-diarrhoeals diphenoxylate (Lomotil) and difenoxin (Motofen) when mixed with atropine to make it unpleasant for people to grind up, cook, and shoot up. Otherwise the drugs are in Schedule II.

[edit] Other provisions

The federal law has only five schedules, but some states have added a "Schedule VI" to cover certain substances which are not "drugs" in the conventional sense, but are nonetheless used, or abused, recreationally; these include toluene (found in many types of paint, especially spray paint) and similar inhalants such as amyl nitrite (or “poppers”), butyl nitrite, and nitrous oxide (found in many types of aerosol cans, though it is pharmacologically active, it is considered an inhalant). Many state and local governments enforce age limits on the sale of products containing these substances.

Pharmaceuticals that require a prescription to be dispensed often are not covered under the Controlled Substances Act. This category includes medicines which should only be taken under a doctor's care, or which may have harmful interactions with other substances, but which are not known to be addictive and which are not used recreationally. These medications are used to treat a wide variety of medical conditions and to manage chronic conditions.

Drugs requiring prescriptions are sometimes also known as legend drugs because legislation requires labels with the legend, "Caution! Federal law prohibits dispensing without a prescription."

The term controlled drugs is sometimes used for scheduled drugs because of the additional controls placed on them (beyond the need for a prescription).

[edit] Federal Regulation of Pseudoephedrine

Due to pseudoephedrine being widely used in the manufacture of methamphetamine (see also: pseudoephedrine, "Misuse and illicit use"), Congress passed the Methamphetamine Precursor Control Act which places restrictions on the sale of any medicine containing pseudoephedrine. That bill was then superseded by the Combat Methamphetamine Epidemic Act of 2005, which was passed as an amendment to the Patriot Act renewal and included wider and more comprehensive restrictions on the sale of pseudoephedrine containing products. This law requires[9] customer signature of a "log-book" and presentation of valid photo ID to purchase of pseudoephedrine (PSE) containing products from all retailers (see also [10].

The law restricts an individual to the retail sale of such products to no more than three packages or no more than nine grams in a single transaction (9 grams is equivalent to 300 standard 30 mg tablets of Sudafed nasal decongestant). A violation of this statute constitutes a misdemeanor. In states where OTC medications which contain pseudoephedrine are not regulated, many retailers, notably Target and Wal-Mart have restricted their purchase by requiring it to be sold behind the pharmacy or service counter and/or placing an age restriction on purchase. Additionally, pharmacies such as CVS and Walgreens also require photo ID and log-book signatures for sales of PSE containing products in compliance with Federal law.

Prior to this, the state of Oregon passed a law requiring a prescription for pharmacies to dispense any cold remedy containing pseudoephedrine. Likewise, the states of Alabama, Arizona, Georgia, Illinois, Indiana, Iowa, Kansas, Kentucky, Michigan, Minnesota, Missouri, South Carolina, New Mexico, New Jersey, North Carolina, Oklahoma, Pennsylvania, Tennessee, Texas, Virginia, Wisconsin and Wyoming restrict sales of pseudoephedrine-containing products to licensed pharmacies and require customers to show photo ID and sign a log book. California, Maryland, and Maine have also enacted degrees of controlled access to over the counter drugs that contain pseudoephedrine. This affects many preparations which were previously available over-the-counter without restriction, such as Actifed, their generic equivalents, etc. California Health & Safety Code sections 11100 and 11106 specify the new restrictions regarding over the counter (OTC) sale of ephedrine or pseudoephedrine containing products (PSE).

[edit] Constitutional disputes

Most of the Congressional findings and declarations in 21 U.S.C. § 801 are devoted to establishing the statute's constitutionality. Using similar language to Article I, Section 8 of the U.S. Constitution, the CSA cites the impact of intrastate drug offences on "interstate commerce" and the "general welfare" of the American people. However, David Boaz, executive director of the Cato Institute, claims that "The Tenth Amendment reserves to the states or the people all powers not granted to the federal government. At least the advocates of alcohol Prohibition had enough respect for the Constitution to seek a constitutional amendment to impose Prohibition, but Congress never asked the American people for the constitutional power to impose drug prohibition"[11].

In 2003, the United States Court of Appeals for the Ninth Circuit ruled the CSA illegal as it applied to the use of medical marijuana in the case Raich v. Ashcroft.[6] However, the case was appealed to the Supreme Court by the federal government, and in 2005, the Supreme Court ruled in favor of the federal government.[7]

[edit] Notes

  1. ^ Pub. L. No. 91-513, 84 Stat. 1236 (October 27, 1970), codified at 21 U.S.C. § 801 et. seq.
  2. ^ Government Printing Office
  3. ^ See United States v. Angelos, 433 F.3d 738 (10th Cir. 2006) (55 years for three sales of marijuana).
  4. ^ MAPS Legal History of MDMA
  5. ^ Drug Scheduling. DEA. Accessed on May 7, 2007.
  6. ^ 352 F.3d 1222 (9th Cir. 2003).
  7. ^ 545 U.S. 1 (2005).

[edit] See also

[edit] External links