In general this FAQ deliberately aims to have it's focus on MDMA risks and on gory technical details. The "sociological" aspects (not involving risks) will deliberately not be emphasized.
O //\ /\ NHCH3
/ \// \/ \ /
/ | || |
CH2 | || |
\ | || CH3
\ /\\ /
O \\/
MDMA
MDMA, 3,4-methylenedioxymethamphetamine, C11H15NO2.The melting point of MDMA depends on the hydration of the salt. Shulgin states: "It is apparent that with uncertain hydration, the melting point is not an acceptable criterion of identity or of purity."[ 1]. The various melting points are:
O //\ /\ NH2 O //\ /\ NHCH3 O //\ /\ NHCH2CH3
/ \// \/ \ / / \// \/ \ / / \// \/ \ /
/ | || | / | || | / | || |
CH2 | || | CH2 | || | CH2 | || |
\ | || CH3 \ | || CH3 \ | || CH3
\ /\\ / \ /\\ / \ /\\ /
O \\/ O \\/ O \\/
MDA MDMA MDE/MDEA
O //\ /\ NHCH3 O //\ /\ NHCH3 CH3O //\ /\ NH2
/ \// \/ \ / / \// \/ \ / \// \/ \/
/ | || | / | || | | ||
CH2 | || | CH2 | || | | ||
\ | || CH2CH3 \ | || CH3 | ||
\ /\\ / \ /\\ / /\\ /\
O \\/ O \\/ Br \\/ OCH3
|
OCH3
MBDB MMDA 2C-B
CH3O //\ /\ NH2 CH3O //\ /\ NH2 CH3O //\ /\ NH2
\// \/ \/ \// \/ \ / \// \/ \ /
| || | || | | || |
| || | || | | || |
| || | || CH3 | || CH3
/\\ / /\\ /\ /\\ /\
O \\/ CH3 \\/ OCH3 Br \\/ OCH3
CH3 |
OCH3
Mescaline DOM DOB
//\ /\ NH2 HO //\ /\ NH /\\ /\ NH2
// \/ \ / \// \/ \/ / \\_____/ \/
| || | | || || | ||
| || | | || || | ||
| || CH3 | || || | ||
\\ / /\\ / \ //\ /
\\/ HO \\/ \// \ /
N
Amphetamine Dopamine(DA) Serotonin(5-HT)
A by no means complete list of synonyms for the above includes:
Considering MDMA the prototype, then MDA tends to be more psychedelic with more of a tendency to induce visual hallucinations. MDA is also more 'speedy' with more jaw-clenching and other side-effects. MDA also takes about 1.5 times as long to hit and to come down off of as MDMA. MDE has a similar chronology to MDMA (perhaps shorter), but is somewhat more stoning than MDMA, but has equal or less side-effects as MDMA. MDE may be responsible for the "Heroin in Ecstasy" myths that abound. MBDB seems to be the closest in effects to MDMA, however it does not appear often on the illegal market (particularly outside of amsterdam). MMDA seems to be similar to MDA in that it produces stronger visual hallucinations than MDMA, however MMDA seems to be totally unknown on the illegal market.
The structures of Serotonin and Dopamine are included to provide a comparison to those endogenous neurotransmitters (neither of which would be active if ingested). With the exception of Serotonin all of the chemical structures above are of phenthylamines. It is not surprising that they tend to affect the Dopamine system in the brain fairly strongly. Amphetamine is the prototypical dopaminergic agent in this class. Methamphetamine, Ritalin (methylphenidate), Cylert (pemoline), 4-methylaminorex (U4-E-Uh), ephedrine and pseudophedrine are all CNS stimulants which are related to phenethylamine.
Many of the chemicals listed, however, tend to more strongly affect Serotonin than they do Dopamine which would not be immediately obvious from a comparison of their chemical structures. The substances Mescaline, DOM, and DOB are all "classical hallucinogens" with effects similar to d-LSD. DOM made an appearance on the illegal market in the 60's. DOB is the second most potent psychedelic seen on the illegal market (500 microgram active dose) and is sometimes substituted for d-LSD, although it has a substantially longer time of action than d-LSD. Mescaline is the active component of peyote. Very often d-LSD or DOB "microdot" tablets are sold as "Mescaline" (which is only active at levels above 200mg).
In between the MDMA-like "entactogens" and the DOB/DOM-like "classical psychedelics" is 2C-B. This compound is related to DOB by the removal of a single methyl group on the side chain (although one does not synthesize 2C-B in this fashion). It has effects somewhat similar to LSD but contains a certain "warmth" that LSD lacks. It does not produce hallucination as strong as LSD or psilocybin and it is not as euphoric as MDMA.
For further information, including synthesis instructions for many of these chemicals please see the hypertext version of Phenethylamines I Have Known and Loved ( http://www.hyperreal.com/drugs/pihkal)
MDMA breaks down barriers and gives one a general feeling of security allowing one in some cases a wider choice of options. However at the same time some barriers in the world are functional and entirely necessary. For example, sometimes it isn't good to suddenly tell people the truth the whole truth and nothing but the truth.
Of course bad choices for a given person can be good choices for another person. Suggesting that spontaneity and willingness to try new things should be suppressed while taking MDMA in some sense tends to defeat the purpose of taking MDMA. However, there is a line between MDMA-facilitated experimentation and recklessness.
A good suggestion is to think about your limits beforehand and then work to stick to those limits while you are on MDMA. Should you feel like reconsidering while you are on MDMA the best idea is to think it over again after you've come down and reassess your limits while you're not taking MDMA. Then try it when you're taking MDMA again. Take things gradually.
And most importantly don't drop X for the first time with someone who you think just wants to get you into bed and with whom you don't want to. This is probably the largest risk with MDMA (not the neurotoxicity or "heat stroke" or any other risk), and with a little bit of forethought it is entirely preventable. The first times you do MDMA do it around people you trust until you get the hang of it.
Proper Hydration
This has occured in at least two cases which recieved attention in the
mainstream media. One case was of Leah Betts in the UK[1],
and the other was of Anna Woods in Australia[2]. Both
cases generated a tremendous amount of media attention, with the usual
inaccuracies and the usual quotations from the parents of how "outraged"
they are at anyone who steps away from the Party Line of considering MDMA
to be only slightly more dangerous than tobacco[3].
The fact is that MDMA does cause SIADH (syndrome of inappropriate anti-diuretic hormone secretion), but this is only a problem if a person also concomitantly ingests several liters of water. Dr John Henry of Guy's Hospital, London states:
Some people may wish to label this death as a case of water intoxication in an attempt to exonerate the drug as a cause of death. However, although water intoxication was the mode of death the excess fluid ingestion would not have occurred if the drug had not been taken, and secondly the drug aggravates excessive water ingestion by causing SIADH.However, what Dr. Henry misses is that it was inaccurate information about MDMA which caused the excess fluid ingestion, not a direct chemical action of MDMA itself. I am not certain why this obvious fact seems to have escaped Dr. Henry. However, Dr. Henry makes medically sound recommendations on appropriate hydration:
The Department of Health in this country has included in its publicity the words 'water is an antidote to dancing, not an antidote to ecstasy.' People are recommended now to drink one pint of water or isotonic fluid per hour if they are dancing vigorously and not more than one cup of fluid per hour if they are not dancing vigorously. This modification of the original harm limitation message may help to avoid the two potentially fatal extremes of hyperthermic collapse (heatstroke) and hyponatraemia (water intoxication).1. http://www.cs.adelaide.edu.au/users/barrie/rave/Rave.letter4 http://www.ecstasy.org/dangers.html http://www.ecstasy.org/russell.html http://www.pcb.co.za/users/ravesafe/water.htm
2. http://www.hyperreal.com/drugs/mdma/water.intoxication.cases (this contains the coroner's report for Anna Wood).
3. Gibson-M., "The Ecstasy and the Agony," The Daily Telegraph, Sidney, Australia, May 24, 1996. http://www.ozemail.com.au/~coreweb/shine/art3.htm
One study of MDMA administered to primates most closely modelled human use and used doses of 2.5mg/kg given every 2 weeks for 4 months (2.5 mg/kg x 8) which found no evidence of neurotoxicity[2]. A single- dose study found a decrease in serotonin (5-HT) and it's major metabolite 5-hydroxyindoleacetic acid (5-HIAA) in rhesus monkeys at 5mg/kg but not 2.5mg/kg. Another study gave rhesus monkeys 2.5mg/kg twice daily for four days and found depletions of 5-HT and 5-HIAA, but without any evidence of neurotoxicity from [3H]paroxetine binding to the 5-HT reuptake transporter[3]. The finding that depletions of 5-HIAA could occur in the absense of 5-HT neurotoxicity creates problems in interpreting the results of CSF 5-HIAA reductions in human users, which remains the strongest evidence of putative MDMA neurotoxicity in humans[4].
Other results of human studies in MDMA users are at odds with the conclusion that MDMA is a human neurotoxin. McCann, et al. in the same study which analyzed CSF 5-HIAA, found that MDMA users tended to have better impulse control and lower hostility while lower serotonin levels are thought to be correlated with increased hostility. A study of sleep patterns of MDMA users found that MDMA users had normal sleep patterns, but with a statistically significant decrease in stage 2 sleep, leading to an overall improvement in sleep quality -- more importantly these results are not at all in accordance with studies on sleep patterns of humans given the 5-HT supressor para-chlorophenylalanine (PCPA) or with animals having lesioned 5-HT systems[5].
Prospective studies (giving users MDMA in a controlled environment with baseline testing and then checking for indications of neurotoxicity) rather than retrospective studies (after the fact with no baseline) are only just getting underway at the Harbor-UCLA medical center (other studies are starting in England, Switzerland and Germany[6]). Initial retrospective results of the UCLA study indicate that MDMA may increase cerebral blood flow [7]. This may be indicative of benficial rather than neurotoxic changes in the brain:
We are aware of a variety of neuro-psychiatric disorders associated with measurements of low blood flow, including Alzheimer's Disease, HIV Dementia, Major Depressive Disorders and Chronic Cocaine Abuse. However, there are no known clinical disorders or drugs which induce long-term elevations of rates of cerebral blood flow. -- Charles S. Grob.
There have been reports of adverse psychiatric effects in the literature particularly anxiety attacks, paranoia and depression. However, some cases present the onset of psychiatric symptoms after a single typical dose[8] which suggests a psychological rather than biological/neurotoxic mechanism. Also, some cases of paranoia reported appear to have occured after repeated daily abuse and probably represent a manifestation of amphetamine psychosis, possibly in part due to adulteration or substitution by amphetamines[9].
The diet drug d-fenfluramine (Redux) causes similar effects on the 5-HT system, and it has been suggested that the lack of adverse psychiatric effects to chronic ingestion of d-fenfluramine implies that MDMA is probably without adverse effects. However, it appears that the mechanism behind MDMA and d-fenfluramine neurotoxicity are not the same, and this may make extrapolation from one drug to the other problematic[10].
To summarize the clinical data, the available evidence tends to suggest that in human users a (probably reversable) decrease in 5-HT may occur (possibly via suppression of the enzyme tryptophan hydroxylase) but that 5-HT neurons remain functionally intact. However, neurotoxic levels in humans are probably "attainable" and the exact amount of MDMA required to elicit a neurotoxic response in humans is unknown.
The exact mechanism of MDMA neurotoxicity in animals is not presently known [11], but it seems to require dopamine activity, oxidation, and access to the 5-HT transporter. Increasing dopamine activity via ingestion of methamphetamine, l-tyrosine, phenylalanine or l-dopa would tend to increase MDMA neurotoxicity. This is a concern since phenylalanine is in diet soft drinks and products sweeted with aspartame(tm) and is also in many "smart drinks" sold at raves and of course methamphetamine is a concern since MDMA is often cut with crystal. On the other hand ascorbate (vitamin C) and l-cystine which are anti-oxidants have been shown to prevent MDMA induced neurotoxicity in animals, as has the administration of a SSRI antidepressant (Prozac, Zoloft, Paxil, Luvox, etc.). Studies indicate that taking either an anti-oxidant or a SSRI up to 5 hours after taking MDMA will prevent neurotoxicity in animals[12].
It may be sensible irregardless of if MDMA is neurotoxic in humans for users to take an antioxidant (e.g. 2-4 g vitamin C, orange juice) along with some 5-HT precursors (l-trytophan or 5-hydroxytryptophan (5-HTP), bananas, milk).
2. Ricarute, GA, personal communication on the findings of an unpublished study.
6. MAPS Newslatter Vol 6, No 3, Summer 1996. http://www.maps.org/news-letters/v06n3/
7. MAPS Newsletter Vol 5, No 4, Summer 1995. http://www.maps.org/news-letters/v05n4/05402mdm.html. Grob-C-S, Poland-R-E Chang-L, Ernst-T, "Psychobiologic effects of 3,4-methylenedioxymethamphetamine in humans: methodological considerations and preliminary observations," Behav. Brain Res., 1996 73(1-2), P 103-7.
The most common MDMA precursors are shown below.
O //\ /\ O //\ /\\ O //\ /\ O
/ \// \/ \ / \// \/ \\ / \// \/ \//
/ | || || / | || | / | || |
CH2 | || || CH2 | || | CH2 | || |
\ | || CH2 \ | || CH3 \ | || CH3
\ /\\ / \ /\\ / \ /\\ /
O \\/ O \\/ O \\/
safrole isosafrole MDP-2-P
The synthesis of MDMA usually starts with isosafrole which can be obtained
from sassafrass root bark extracts by purification and then isomerization
of safrole into isosafrole via heat + KOH. Isosafrole is then converted
into MDP-2-P (aka 3,4-methylenedioxyphenyl-2-propanone aka 3,4-methylenedioxyphenylacetone aka 3,4-methylenedioxybenzyl methyl ketone) There is a simple
method using hydrogen peroxide and formic acid which will accomplish this,
although with somewhat reduced yields [1]. A higher
yield method uses a palladium bromide catalyst [2].
The MDP-2-P is then converted to MDMA most easily via reductive amination with either NaBH3CN (sodium cyanoborohydride)[3] or aluminum amalgam [4]. The NaBH3CN synthesis may be slightly easier, but the Al Amalgam method does not use a potentially watched chemical like NaBH3CN.
A particularly simple and dirty way to synthesize MDMA is from safrole via the 2-bromopropane[5].
The Leukart reaction has been popularized in such books as Valentine
Michael Smith's, Psychedelic Chemistry, but produces low yields and
is more difficult than either the aluminum amalgam or NaBH3CN methods.
The method printed in Psychedelic Chemistry also contains 2 typos,
one of which is potentially dangerous, see [6].
For an overview of alternative routes see [7].
1. Shulgin and Shulgin, PiHKAL, #109.
http://www.hyperreal.org/drugs/pihkal/pihkal109.html. Fujisawa, T. and Deguchi, Y., "Concerning the Commercial Utilization of Safrole", J. Pharm. Soc. Japan, 74 975 (1954), CA 49:10958i (1955).
3. Shulgin and Shulgin, PiHKAL, #100, #105, #106, #109, #114 (substitute an equimolar amount of methylamine for the amine (e.g. ethylamine in #106) to obtain MDMA). http://www.hyperreal.org/drugs/pihkal/pihkal106.html. Braun, U., Shulgin, A.T. and Braun, G., "Centrally Active N- Substituted Analogs of 3,4-Methylenedioxyphenylisopropylamine (3,4-Methylenedioxyamphetamine)", J. Pharm. Sci. 69 192-195 (1980).
4. Shulgin and Shulgin, PiHKAL, #109. http://www.hyperreal.org/drugs/pihkal/pihkal109.html.
5. Fester, Secrets of Methamphetamine Manufacturing. http://www.hyperreal.org/drugs/mdma/mdma.synth. Anon: "Verfahren zur Darstellung von Alkyloxyaryl-, Dialkyloxyaryl- und Alkylendioxyarylaminopropanen bzw. deren am Stickstoff monoalkylierten Derivaten", German Patent, 274,350; Filed December 24, 1912, issued May 16, 1914, Assigned to E. Merck in Darmstadt. Biniecki, S. and Krajewski, E. "Preparation of DL-1-(3,4-Methylenedioxy)-2-(methylamino)propane and DL-1-(3,4-dimethoxyphenyl)- 2-(methylamino)propane," Acta Polon. Pharm. 17 421-425 (1960), CA 55:14350e (1961).