Posts Tagged ‘ MDMA

The Mirrored Magic of MDMA

MDMA is one of the most popular illicit drugs in the world, and is unique relative to other stimulating drugs of abuse in that it possesses significant therapeutic potential and is less behaviorally reinforcing. Effects can be described as similar to both stimulants and classical psychedelics. This appears to be more than a simple qualitative description however, as the very geometry of the MDMA molecule seems to produce two distinct drugs.

It is easy to forget when looking at flat diagrams of molecules on paper, but these compounds exist in a three dimensional world. One of the consequences of this is the concept of chirality, or “handedness”. Both your left and right hand contain fingers, a palm, and a thumb which appear to be assembled in the same way – but they are not the same. We can put both of our palms downward – but our thumbs point in different directions. If we point our thumbs in the same direction, one palm faces up and the other down. No matter how hard we try, we cannot wave our hands around and make them line up together perfectly.

Something similar can happen to sufficiently complex molecules, and MDMA is one of these. There are two geometrically distinct enantiomers of MDMA.

R(-)-MDMA Rectus (Latin for right) rotates polarized light counterclockwise (-) in a pure sample
S(+)-MDMA Sinister (Latin for left) rotates polarized light clockwise (+) in a pure sample

Racemic MDMA is “normal” MDMA, a mixture of both.

In the late 1970s, Alexander Shulgin began to collect data about the subjective effects of these stereoisomers of MDMA. Various doses of R(-)-MDMA, S(+)-MDMA, and racemic MDMA were given to volunteers in doses from 40 to 200mg and the relative intensity of their reported experience rated zero to three on the Shulgin scale.

It soon became clear that a subjective difference in potency could be observed between the two stereoisomers. R(-)-MDMA was least potent, with only threshold effects observed between 100 and 200mg. Racemic MDMA caused full effects between 140 and 160mg, while S(+)-MDMA was most potent with full effects observed at 120mg. But was this difference in apparent potency the only distinction between the two?

Shulgin plotted the effects of racemic MDMA (red above) versus a simple average of the regressions he found earlier for R(-)-MDMA and S(+)-MDMA (black above). If the different stereoisomers differed only in apparent potency, these plots should be identical. Interestingly, they were not – with racemic MDMA quite literally reporting effects more than the sum of its parts. This was borne out by user reports as well. The S(+)-MDMA may have been more potent by weight at first glance, but alone it was more stimulating and lacked the indescribable “magic” of the full racemic MDMA experience.

Further investigation was undertaken by researchers including Kevin Murnane, who conducted experiments designed to further delineate the effects of each stereoisomer.


R(–)-MDMA

S(+)-MDMA
2C-T-7, a psychedelic phenethylamine, fully substituted for R(-)-MDMA in trained mice. DPT, a psychedelic tryptamine, acted as a partial substitute. S(+)-amphetamine substituted for S(+)-MDMA in trained mice. Cocaine acted as a partial substitute.
In rhesus monkeys, R(-)-MDMA significantly increased prolactin levels. S(+)-MDMA significantly increased both dopamine and serotonin levels.

In general, R(-)-MDMA appears to produce psychedelic effects and has a longer duration relative to the more stimulating effects of S(+)-MDMA. MDMA is an incredibly unique compound, where each stereoisomer has a distinct and centrally active mode of action. Unlike other compounds where one stereoisomer is more potent or responsible for the majority of effects, each stereoisomer of MDMA contributes to produce a full and complex experience.

Phenethylamines may be classified as stimulants (such as amphetamine where the S(+) entianomer is most active) or psychedelics (such as DOC where the R(-) entianomer is most active). MDMA appears to uniquely straddle this divide.

Shulgin, A.T. Personal Lab Notes (Book 2), page 238.

Murnane KS, Murai N, Howell LL, Fantegrossi WE. Discriminative stimulus effects of psychostimulants and hallucinogens in S(+)-3,4-methylenedioxymethamphetamine (MDMA) and R(-)-MDMA trained mice. J Pharmacol Exp Ther. 2009 Nov;331(2):717-23. Epub 2009 Aug 14.

Murnane KS, Fantegrossi WE, Godfrey JR, Banks ML, Howell LL. Endocrine and neurochemical effects of 3,4-methylenedioxymethamphetamine and its stereoisomers in rhesus monkeys. J Pharmacol Exp Ther. 2010 Aug;334(2):642-50. Epub 2010 May 13.

Rick Doblin Answers Anything

Dr. Rick Doblin of MAPS recently answered questions from the public, and I was lucky enough to be included.

Part 1 discusses his vision of a psychedelic future. Part 2 tackles “what can we do”, practical steps for the present.

2003 International Narcotics Control Strategy Report – The Netherlands

Summary

The Netherlands continues to be a significant transit point for drugs entering Europe (especially cocaine), an important producer and exporter of synthetic drugs (particularly Ecstasy and amphetamines), and an important consumer of most illicit drugs. U.S. law enforcement information indicates that the Netherlands still is by far the most significant source country for Ecstasy in the U.S. The current Dutch center-right coalition has made measurable progress in implementing the five-year strategy (2002-2006) against production, trade and consumption of synthetic drugs announced in May 2001. For example, there has been a significant increase in Dutch seizures of Ecstasy pills from 3.6 million in 2001 to six million in 2002 (last year for statistics). In July 2003, the National Criminal Investigation Department (Nationale Recherche) was set up with the key objective of enhancing the efficiency and effectiveness of criminal investigations and international joint efforts against narcotics trafficking. Operational cooperation between U.S. and Dutch law enforcement agencies is excellent, despite some differences in approach and tactics. Dutch popular attitudes toward soft drugs remain tolerant to the point of indifference. The Dutch government and public view domestic drug use as a public health issue first and a law enforcement issue second.

Cocaine Couriers

Despite fierce political opposition, the Dutch Parliament approved Justice Minister Donner’s plan to close down Schiphol airport to cocaine smuggling from the Caribbean on December 10, 2003. An estimated 20,000-40,000 kilos of cocaine, destined primarily for the European market, are smuggled annually through Schiphol (Dutch cocaine use is estimated at 4,000-8,000 kilos annually – in 2001 and 2002, more than 3,500 drug couriers were arrested and some 10,000 kilos of cocaine seized at the airport). Donner hopes to achieve 100% interdiction of the drugs coming into Schiphol on targeted high-risk flights from the Netherlands Antilles, Aruba and Suriname. He told the Second Chamber of Parliament on December 3, 2003, that, as a result of the 100% controls of passengers, luggage, freight and aircraft, the number of drug couriers is expected to rise significantly, fearing inadequate law enforcement capacity to handle the number of arrests. According to Donner, this justifies a temporary adjustment in prosecution policy – a certain category of drug couriers will not be prosecuted. He explained that criteria would be drawn up, which will not be made public in the interest of criminal procedures. However, couriers failing to meet these criteria will be prosecuted. (Unconfirmed reports suggested that only smugglers caught with 3 kilos or more are prosecuted.) Donner stated that summoning drug couriers in court at a later date would not be a solution, because this would also put a heavy burden on the Dutch judiciary. He did pledge the Chamber an early assessment of his proposals. Relevant data of drug couriers will be made available to airlines, which will be responsible for taking special measures against these persons, including an indefinite flight ban. Despite opposition within Donner’s own Christian-Democratic Party (CDA), the Second Chamber adopted his proposals on December 10, 2003.

The plan went into effect on December 11, and, during the first five days, 120 couriers were arrested on flights from the Netherlands Antilles, of whom 31 were released without a summons after drugs were recovered. The remaining 89 cases are being investigated or prosecuted. In addition, 104 potential passengers were turned away by the airlines and 375 passengers did not turn up. About 120 kilos of drugs were seized. During routine checks on flights from Suriname, 22 couriers were arrested, one of whom carried 14.5 kilos of cocaine.

Ecstasy Offensive

In July 2003, Justice Minister Donner published a progress report on the implementation of the five-year (2002- 2006) action plan against production, trade, and consumption of synthetic drugs. According to the report, six million Ecstasy pills were seized in 2002 compared to 3.6 million in 2001, and the number of dismantled Ecstasy laboratories rose to 43 in 2002 from 35 in 2001. The increase in Ecstasy seizures was attributed to intensified controls at Schiphol airport by the special team of Dutch customs and the military police (more than one million pills seized there in 2002), the introduction of five special police Ecstasy teams (total manpower: 90), and increased staffing at the Fiscal Intelligence and Investigation Service-Economic Control Service (FIOD-ECD). The progress report shows that the measures announced in the action plan are well underway. According to the 2002 annual report of the Unit Synthetic Drugs (USD), the five XTC teams conducted 36 investigations in 2002 and arrested some 76 suspects.

The chemical precursor PPK is the principal precursor used by Dutch Ecstasy laboratories. It comes mainly by sea from China through Rotterdam port. Due to human rights concerns, the Dutch government shares only limited information of an administrative nature with China. A Memorandum of Understanding formalizing this information- sharing arrangement was submitted to the Chinese in October 2003. No response has yet been received. The MOU states that China will keep the Netherlands informed regarding the progress and results of investigations that have been instigated on the basis of this administrative information. In addition to working directly with the Chinese, the Netherlands is an active participant in the INCB/PRISM project’s taskforce.

Cannabis

According to the fourth survey on coffeeshops in the Netherlands, published in October 2003, there were 782 officially tolerated coffeeshops at the end of 2002, which is a 3 percent drop over 2001, principally in the four major cities. About 73 percent of Dutch municipalities do not tolerate any shops at all, according to the study. In early 2004, Justice Minister Donner, whose CDA party has advocated closing of coffeeshops, is expected to publish a Cannabis Policy Paper, which should discourage cannabis use.

The 2002 National Drug Monitor shows that the number of recent (last-month) cannabis users in the Dutch population over the period 1997-2001 rose from some 326,000 to 408,000, or 3 percent of the Dutch population of 12 years and older (of a total population of 16 million). The largest increase is reported among young people aged 20-24, while use among the 12-15 year-old age group remained limited and hardly changed from 1997. Life-time prevalence (ever-use) of cannabis among the population of 12 years and older rose from 15.6 percent in 1997 to 17 percent in 2001. The average age of recent cannabis users is 28 years.

On November 27, 2003, the Netherlands agreed on an EU framework decision on harmonized sentencing of drug traffickers. Under the agreement, the maximum penalty for possessing a small quantity of cannabis will be raised from one month to one year imprisonment. The agreement, if ratified by Dutch parliament, would allow the Netherlands to maintain its coffeeshops.

Medicinal Cannabis

Since March 17, 2003, doctors are allowed to prescribe their patients medicinal cannabis. Two suitable government-controlled cannabis growers have been contracted, and, as of September 2003, the drug can be bought from pharmacies. The Health Ministry’s Bureau for Medicinal Cannabis controls quality and organizes the distribution. According to the Health Ministry, cannabis may have a favorable effect on seriously ill patients but the government recognizes the therapeutic effects of medicinal cannabis have not been proved and research continues.

Cultivation and Production

About 75 percent of the Dutch cannabis market is Dutch-grown marijuana (Nederwiet), although indoor cultivation of hemp is banned, even for agricultural purposes. Amsterdam University researchers estimate that the Netherlands has at least 100,000 illegal home growers of hashish and marijuana, with the number increasing. Together they produce more than 100,000 kilos of soft drugs and are the largest suppliers of coffeeshops, according to the study. The estimates are based on a significant rise in the number of lawsuits and police raids. Although the Dutch government has given top priority to the investigation and prosecution of large-scale commercial cultivation of Nederwiet, tolerated coffeeshops appear to create the demand for large-scale commercial cultivation.

The Netherlands remains one of the world’s largest producers of synthetic drugs. In 2002, the USD registered a total of 740 seizures of synthetic drugs around the world, of which 205 (some 30 percent) took place in the Netherlands. Of the remaining seizures registered in 35 other countries, some 70 percent could be related to Dutch criminal organizations. Of the 205 Dutch seizures, 141 involved synthetic drugs that were intended to be exported. The seizures of drugs around the world that could be related to the Netherlands involved some 24.6 million MDMA tablets and over 910 kilos of MDMA power. Of this total, the largest amount was seized in the Netherlands (6.1 million pills), Belgium (more than 5 million pills), followed by Germany (almost 3 million), the U.S. (2.5 million), France (2 million) and the UK (1.8 million). The USD reported lower amphetamine seizures in 2002 than in 2001, but the quantity of Dutch-related amphetamine seized in other countries went up. In 2002, the USD dismantled 43 production sites for synthetic drugs, of which 26 were situated in residential areas. Most production sites were MDMA laboratories. According to the USD, the production of synthetic drugs in residential areas is an alarming development. The FIOD-ECD, which is primarily responsible for intercepting chemical precursors, seized some 318 liters and 9,255 kilos of PMK and 1,228 liters of BMK in 2002.

Drug use among the general population of 12 years and older, 1997 and 2001 (life-time (ever) use and last-month use)

  Life-time use (%) Last-month use (%)
1997 2001 1997 2001
Cannabis 15.6 17.0 2.5 3.0
Cocaine 2.1 2.9 0.2 0.4
Amphetamine 1.9 2.6 0.1 0.2
Ecstasy 1.9 2.9 0.3 0.5
Hallucinogens 1.8 1.3 0.0 0.0
   of which LSD 1.2 1.0
Mushrooms 1.6 2.6 0.1 0.1
Heroin 0.3 0.4 0.0 0.1

Drug Seizures, source Europol

2001 2002
Heroin (kilos) 739 1,122
Cocaine (kilos) 8,389 7,968
Cannabis resin (kilos) 10,972 32,717
Herbal cannabis (kilos) 22,447 9,958
Ecstasy (tablets) 3,684,505 6,878,167
Amphetamine (kilos) 579 481
LSD (doses) 28,731 355

Cable Reference ID 04THEHAGUE4, 2004-01-02, Classification UNCLASSIFIED, Origin Embassy The Hague.

Psychedelics in the Public Consciousness

Google Ngram is a very interesting project which measures the frequency of the occurrence of words in a large body of books published over the last several hundred years. This can be considered somewhat as a measure of public awareness of a certain term, so let’s use it to see how various prominent psychedelic compounds (mescaline, LSD, psilocybin, and MDMA) have risen and fallen in the public consciousness from 1900 to 2000.

The first thing we see is that psychedelic compounds as a whole are a very new concept, entering popular usage only in the middle of the 20th century with knowledge becoming more widespread in the 1960s. The word LSD has an almost overwhelming frequency of use, reflecting the intimate association of the drug with the popular concept of the psychedelic experience. Switching this out for “lysergic acid diethylamide” should allow us to compare relative trends with other psychedelic compounds due to decreased frequency while still maintaining a sensible relation to the original term.

This normalizes the dataset somewhat.

Mescaline had been used for thousands of years until it was first isolated and identified in 1897. It slowly grew in the public consciousness until Aldous Huxley’s 1954 work The Doors of Perception thrust the compound into the mainstream.  
LSD (lysergic acid diethylamide) was first consumed by Albert Hofmann in 1943, initially introduced to the market as a psychiatic drug in 1947, and its potential became more clear with corporate and government experiments during the 1950s including the infamous Project MKULTRA. High potency and its positive character led to efficient distribution and widespread use in the 1960s.  
Psilocybin is another ancient compound with sacramental use spanning thousands of years. Vice President of J.P. Morgan and amateur mycologist R. Gordon Wasson travelled to a remote village of Mexico on a rumor that their religion included ingestion of mushrooms. In 1957, he published an article in Life magazine entitled Seeking the Magic Mushroom that did for psilocybin what Huxley did for mescaline.  
MDMA was first synthesized in 1912, but it languished in obscurity until the mid-1970s when Alexander Shulgin, then at University of California, heard from his students about unusual effects of the amphetamine derivative. In 1978 he and David Nichols published the first report on the drug’s psychotropic effect in humans and its use spread among the psychiatric community as an adjunct to therapy. MDMA used in a recreational context was first reported in gay nightclubs in the Dallas area in the early 1980s with usage peaking during the 1990s rave scene.  

Other trends become apparent when we separate our observations geographically. While the opportunity to do this is necessarily limited due to language restrictions, we can compare American English usage with British English usage quite easily from 1950 to 2000.

We can see that MDMA citations peaked in the mid 1990s in American English as the British rave scene made noise in North America, but the trend faded in the US while use continued to climb in British English.