From: honig@calliope.ICS.UCI.EDU ("David A. Honig")

     Subject: Compleat Info on X XTC MDMA MDA etc.

     Last Update: 19 Jun 91 23:38:30 GMT

     

     

     ..............................

     

     MDMA ;(extacy) (XTC); metheylenedimethoxymethamphetamine. Is an analog

     of MDA (methylenedimethoxyamphetamine). MDA Was first synthesized in

     1917 by Parke-Davis company as an appetite suppressant drug. The drug,

     in addition to suppressing appetite, produced what is now termed as an

     "entacto-effect" in the test subjects. Because of the adverse side

     effects, Parke-Davis did not market the drug and let the patent expire.

     The drug resurfaced in the 1960's along with the advent of many other

     psychoactive substance. Known negative side effects are around a 40%

     reduction of serotonergic synapses in the rat brain with a 5mg/kg dosage

     (no data is available for neurotoxicity in humans). Cerebral spinal

     fluid of admitted users has been shown to have a marked decrease in 5-HT

     levels. More on the pharmacology later....

     

     

     ..............................

     

     

     I can't find the strand, but this is intended to correct/clarify some

     recent discussions of DOM (AKA STP).

     

     When DOM (2,5-dimethoxy-4-methylphenylisopropylamine) first hit the

     streets of San Francisco in the late sixties, it was distributed in

     tablets of 10 or 20 mg. Threshold effects begin at 1 mg (you get

     muscle tremors, facial flushing, and minor sensory amplification)

     and the more you do, the longer and more intense the trip. Obviously,

     if people took two or three tablets, they'd be in for a long trip.

     So, the stories of DOM trips lasting for days are just the result

     of people not knowing the ED. It is really a nice psychedlic at

     5 mgs or so, no worse than LSD.

     

     As for the stories of antipsychotics not helping or worsening a DOM trip,

     such stories are nonsense from a pharmacological standpoint. There is

     nothing really unusual about DOM as a psychedelic, if anything it is a

     cleaner 5-HT2 agonist than LSD. This rumor was studied using 50-200 m

     g chlorpromazine to counteract large DOM doses. While the effects of DOM w

     eren't completely reversed, the chlorpromazine did calm the people down.

     

     Check out Snyder et al (1968) in Amer. J. Psychiat. 125: 357-364 and

     Hollister et al (1969) in Psychopharmacologia 14: 62-73 for studies on

     humans with low and high doses respectively.

     

     ..............................

     

     Subject: Re: Aminization of Nutmeg or Calamus

     

     mcbeeb@jacobs.CS.ORST.EDU (Brian Mcbee) writes:

     

     >So, if I had a batch of nutmeg or calamus, and I soaked it in an aqueous

     >solution of ammonia... Hmm. Anyone have a recipe for making quick and

     >dirty psychedelics from natural precursors? Something that doesn't involve

     >expensive lab equipment or dangerous chemicals?

     

     Try refluxing an Et2O extract of either in NH2CH3 with 200 mesh Al and

     HgCl2 for a few hours. Try this and you will see God in short order.

     

     Quick and dirty aminations are hard enough to do in your bath tub

     with pure reagents.

     

     ..............................

     

     alt.drugs by the one and only Tyrone Slothrop. Please edit

     

      Asarone can be easily extracted from Acorus calamus roots by steam

     distillation. This is a really nice process because it doesn't require

     the use of any smelly, flammable and poisonous solvents. I've used it

     to extract safrole from sasafrass roots. This will get rid of most of

     the ``gunk'', but of course you will have a mix of aromatic oils.

     

      Shulgin (1978) states: ``It is used as a medicine by the indians of

     northern Canada (Hoffer and Osmond, 1967) where it is known by the name

     of rat-root, and is claimed to have intoxicating properties similar to

     those of LSD. The conversion of asarone to TMA-2 is easily realized...''

     

      However, asarone is not the ``precursor to all the MDA analogs''.

     It is the precursor to TMA-2. This is discussed in chapter 5 of

     Strafford (1983). TMA-2 is 2,4,5-trimethoxyphenylisopropylamine.

     Shulgin (1976) describes the effects as follows:

     

      The first indications of intoxication usually noted are signs of physical

      disturbance such as nausea, paraesthesia, and a modest reflexive mydriasis.

      The central sensory changes appear in the second hour and are character-

      ized by some exaggeration of visual input (especially in the appreciation of

      colors and contrasts of lighting) and of empathy with irrational objects in

      one's environment. These preludes lead to a plateau, form three to about

      six hours following administration, which is an impressive altered state of

      consciousness virtually free of the distortions and portentousness so com-

      mon with LSD. The experience dissipates gradually, and is usually com-

      pleted in 8-10 hours. A sharp dose-response curve exists for TMA-2 in that

      several additional toxic symptoms have been reported at 25-30 mg levels.

      There can be a pervasive mausea throughout the entire experimental

      period, accompanied by actual vomiting, apparent fainting, and brief but

      repeated periods of amnesia. Peripheral vision can be lost (this, apparently,

      of hysterical origin) and the accompanying fear of being irrepaprably severed

      from reality has led to situations that have proved difficult to manage.

     

      Here was a world of simplicity and certainty no acidhead, no revolutionary

      anarchist would ever find, a world based on the one and zero of life and

      death. Minimal, beautiful. The patterns of lives and deaths....

     

      ...it would all be done with keys on alphanumeric keyboards that stood

      for weightless, invisible chains of electronic presence or absence. If

      patterns of ones and zeros were ``like'' patterns of human lives and

      deaths, if everything about an individual could be represented in a

      computer record by a long string of ones and zeros, then what kind of

      creature would be represented by a long string of lives and deaths? It

      would have to be up one level at least -- an angel, a minor god,

      something in a UFO. It would take eight human lives and deaths just to

      form one character in this being's name -- its complete dossier might

      take up a considerable piece of the history of the world. We are digits

      in God's computer... And the only thing we're good for, to be dead or

      to be living, is the only thing He sees. What we cry, what we contend

      for, in our world of toil and blood, it all lies beneath the notice of

      the hacker we call God. -- Pynchon (1990)

     

      - Tyrone Slothrop - from his scattering

     

     Hoffer, A., and H. Osmond. 1967. The Hallucinogens, pp. 55-56. Academic

     Press, New York.

     

     Pynchon, Thomas. 1990. Vineland. Little, Brown and Co. Pp. 385.

     

     Shulgin, A. T. 1976. Profiles of psychedelic drugs. 2. TMA-2.

     J. Psychedelic Drugs 8: 169.

     

     _____. 1978. Psychotomimetic drugs: structure-activity relationships.

     In: Handbook of Psychopharmacology, Vol. 11: Stimulants. Iversen, Iversen

     and Snyder (eds.). Plenum Press, New York. Pp. 243-333.

     

     Strafford, Peter. 1983. Psychedelics Encyclopedia. Houghton Mifflin.

     Pp. 420.

     

     -------end forwarded message--------

     ----------------begin forwarded message------------------

     

     Subject: Re: Legal and better highs

     

     >MDE - "Eve" An intellectual buzz, no emotional effects

     >2-CB - (CBR) MDMA analog, visuals(sometimes frightening)

     > Ultimate in telepathic communications

     >

     >2CT2 - Laboratory exotic - dark earthy visuals, like shrooms

     >DIPT - Obscure compound - said only to effect perception of music

     >DOET - "visual, pretty & pyschedlic, low dosages remove writing

     > blocks

     

     CBr a MDMA analog? CBr is 2,5-Dimethoxy-4-Bromophenethylamine. The

     "sometimes frightening" part probably comes from taking more than the

     full dose, and the literature suggests that with larger dosages come

     disproportionately larger responses, unlike some other psychedelics

     we all know and love. I've had very enlightening experiences with CBr,

     and they grew better in quantum leap fashion.

     

     + wonderful and gently insightful (semi-wilderness, daytime, friends).

     + profoundly sexual with glimpses of bird-animal forms (indoors, nightime,

      lover) minor telepathic imagery.

     + sexual and shamanic, native american imagery (indoors, day-night, alone).

     + profound native american imagery (indoors, night, after cannabis, friend)

      actually slept a bit (too much cannabis) and awoke to the most wonderful

      visuals (friend in other room - ditto).

     + full-blown spirit animals all night long (desert, night, friend, good THC

      1/2 way thru trip) - mountain lion (very playful) and eagle most prominent

      two deer (incredibly loving), a wolf (very brief), fantastic living plant

      spirits, entities in mountain, mucho native american imagery, et. al.

      very telepathic with friend. brief teleportation/desert-zoom experience.

      understood the ancients' fascination with constellations. imparted with

      sudden knowledge in extreme detail - confirmed later by ex-lover, scared

      ex-lover shitless.

     

     My last experience with CBr changed my life in many profound ways (for the

     better). With THC and a little concentration I can get back to some of those

     places. With no THC and a lot of concentration I can get back to some of

     those places. Remember.

     

     I believe CBr is recognized as an enthogen and an entactogen, and

     unfortunately it's now Schedule 1. :-( Put this one on the top of

     the list of drugs to be legalized.

     

     DO NOT TAKE ANY DRUG YOU DO NOT UNDERSTAND. KNOW THE SOURCE.

     

     

     >A friend of mine needs some information on a chemical called _SAPHROL_...

     

     Safrole is 4-allyl-1,2-methylenedioxybenzene. Sassafras oil is about 75%

     safrole. It has quite a pleasant and characteristic odor.

     

     >The way he spoke about it makes me think that it is an illegal substance

     >used in making some illicit substance.

     

     The methylenedioxybenzene nucleus is found in MDA and MDMA. Amination at

     the appropriate carbon of the olefinic side chain yields the former,

     methylamination, the latter. I think this reaction is non-trivial due

     to conjugation of the double bond with the aromatic ring; the syntheses

     I have seen start with the ketone.

     

     

     In article eesnyder@boulder.Colorado.EDU (Eric E. Snyder) writes:

     (regarding safrole)

     >methylamination, the latter. I think this reaction is non-trivial due

     >to conjugation of the double bond with the aromatic ring; the syntheses

      ^^^^^^^^^^^ ^^ ^^^ ^^^^^^ ^^^^

     >I have seen start with the ketone.

     

     That's isosafrole. The reaction isn't too difficult. One tries for

     an anti-Markownikov addition in the presence of peroxide or other

     source of free radicals. For the purposes mentioned, safrole undergoes

     the appropriate addition very conveniently. Both safrole and isosafrole

     do have a pleasant odor and have been used in flavorings, but perhaps

     they can't be used anymore due to a possible cancer risk? Although I

     think some "natural" root beers can contain some amount of "natural"

     safrole, but none can be added. Regulations, regulations...

     --

     David J. Heisterberg djh@osc.edu We are NOT all

     The Ohio Supercomputer Center djh@ohstpy.bitnet Keynesians now.

     Columbus, Ohio 43212 ohstpy::djh

     

     

     

     >Just for the record, mescaline is 3,4,5-trimethoxyphenylethylamine. It does not

     >contain an indole ring, it is one of the hallucinogenic amphetamines, as is MDMA.

     

     ...just for the record, mescaline is *not* a so-called psychedelic amphetamine.

     Amphetamine, aka phenylisopropylamine, has an alpha methyl group, and thus

     possesses a chiral center. Phenylethylamines are achiral. This is important

     because the alpha methyl group makes phenylisopropylamines poor substrates for

     MAO. In contrast, phenylethylamines are excellent substrates for MAO. As a

     result, mescaline is not a potent psychedelic (ED ca. 300 mg). However,

     3,4,5-TMA, the phenylisopropylamine analog of mescaline is active at around

     20 mg.

     

     

     eesnyder@boulder.Colorado.EDU (Eric E. Snyder) writes:

     

     >...just for the record, mescaline is *not* a so-called psychedelic amphetamine.

     >Amphetamine, aka phenylisopropylamine, has an alpha methyl group, and thus

     >possesses a chiral center. Phenylethylamines are achiral. This is important

     >because the alpha methyl group makes phenylisopropylamines poor substrates for

     >MAO. In contrast, phenylethylamines are excellent substrates for MAO. As a

     >result, mescaline is not a potent psychedelic (ED ca. 300 mg). However,

     >3,4,5-TMA, the phenylisopropylamine analog of mescaline is active at around

     >20 mg.

     

     Yeah, but does it get you off?

     

     ..............................

     

     This is some information I recieved by email regarding a "new form"

     of methamphetamine which has been reportedly appearing in Hawaii....

     

     Here are some passages from an article titled "A Chemical and

     Pharmacological Review of U4Euh/Intellex" by the "New Age Chemist"

     in volume 4 of Psychedelic Monographs & Essays

     (available from Rosetta, PO Pox 4611, Berkeley, CA 94704 ).

     

     "Chemical names: 4-methyl aminorex, 4-methyl-5-phenyl-2-amino-oxazoline,

     4,5-dihydro-4-methyl-5-phenyl-oxazolamine.

     

     (note: oxazoline appears to be the ring formed by

      -O-C(NH2)=N-CH(CH3)-CH-

      1 2 3 4 5

     

     "Common names: U4Euh, Euphoria, Intellex, Ice, Verbosamine

     

     "History: 4-methyl aminorex was first synthesized and its anorexigenic

     and stimulant properties discovered by the research group of George Poos

     at McNeil labs in Ft. Washington, PA, in the early 60's. (see J. Med. Chem,

     6:266, 1963). ... Attention was primarily directed at the anorexegenic

     properties and the central effects were regarded as unwanted side effects.

     

     "When a high production lab was discovered in Gainesville, Florida in

     1986, the DEA investigated and the material has subsequently been

     consigned to Schedule I under the emergency scheduling provision of the

     Controlled Substance Act for a one year period beginning Oct. 15, 1987.

     

     (i don't know what the final disposition of the drug was but it's not

     hard to guess...)

     

     "Chemistry: 4-methyl aminorex is prepared through an addition and

     spontaneous cyclizing reaction involving PPA.

     

     (another paper in the the same volume says it is synthesized from PPA

     and cyanogen bromide)

     

     The simplicity of the synthesis, the ready availability of precursors,

     high yields, and the interesting central effects suggest that this

     material will be around for a long time to come.

     

     "Pharmacological profile: ... Quantitatively, the experience is similar

     to a long-lasting MDMA intoxication superimposed with methamphetamine,

     with the added benefits of easy verbalization, free association, integration,

     and elaboration of previous insights, making it a useful tool for

     lecturers... Nothing is know about the pharmacokinetics or pharmacodynamics

     of 4-methyl aminorex. The central effects (sympathomimetic) are believed

     to be the result of increased release of catecholamines, and mimicking the

     effects of these transmitters at receptor sites in the brainstem.

     

     

     Subject: Ice, 4-methylaminorex (was Re: Mad About MDA...)

     Message-ID: <1854@ursa-major.SPDCC.COM>

     Date: 26 Feb 90 18:43:05 GMT

     References: <11478@nigel.udel.EDU> <1990Feb23.043735.3160@spectre.ccsf.caltech.edu> <357@tau-ceti.isc-br.com>

     Reply-To: dyer@ursa-major.spdcc.COM (Steve Dyer)

     Distribution: alt

     Organization: S.P. Dyer Computer Consulting, Cambridge MA

     Lines: 17

     

     Aminorex was withdrawn from the European market in the late 60's

     after women who were given this drug as an appetite suppressant

     developed chronic pulmonary hypertension, leading in most cases

     to death and significant impairment in the rest. It was never

     marketed in the U.S.

     

     Since the mechanism of this deleterious effect is not known,

     and knowing how similar 4-methyl aminorex is chemically and

     pharmacologically to aminorex (it's related to aminorex in the

     same way as methamphetamine is related to amphetamine or

     phendimetrazine is to phenmetrazine), it seems imprudent

     to recommend its recreational use.

     

     ..............................

     

     In article <2160@sunset.MATH.UCLA.EDU> trainor@MATH.UCLA.EDU (Douglas J. Trainor) writes:

     >Anyone got a list of common MAO inhibitors (i.e. food stuffs) that

     >should not be consumed with MDMA? E.g., red wine, chicken liver,

     >non-pasturized yogurt, ...

     

     You've got it backwards. You're thinking of tyramine (a sympathomimetic

     amine found in aged foods formed from the breakdown of tyrosine).

     People taking MAO inhibitors avoid such foods because tyramine is

     ordinarily quickly destroyed by MAO. In the presense of a MAO inhibitor,

     tyramine is absorbed from the gut and produces symptoms of excessive

     adrenergic activity: headache, raised blood pressure, etc. Severe cases

     can cause a stroke.

     

     I don't think there's any evidence that MDMA is a MAO inhibitor.

     

     Yogurt probably isn't a big deal, though it's sometimes included on the list

     of foods to avoid. Most cheeses other than cottage cheese are verboten.

     Dried meats and sausages are out. Vegemite has loads of the stuff. Figures.

     

     ..............................

     

     >No, those will do... "spinal drains" and "cheese toxins"... Cheese, I mean,

     >sheesh.

     

     Now that I've recovered from my sarcasm attack, let me tell you what I see

     the risks are.

     

     A real concern of mine is that you can't be sure with street drugs that what

     you're taking is MDMA or not, how pure it is, or how much you're taking.

     I suppose it depends on how trustworthy your source is.

     

     Now, onto the drug itself. MDMA isn't much of a monoamine oxidase inhibitor,

     so the bit about cheese is bogus. You'll hear other crap about not taking

     any dairy products, but other rumor mongers will say that you need calcium

     to keep you from grinding your teeth. All ridiculous. I'd eat whatever

     you wanted in moderation (i.e., like always). Given a high enough dose of

     MDMA, you're likely to demonstrate some teeth grinding; it's a simple

     menifestation of the drug's dopaminergic actions and it comes with the

     territory. Calcium isn't going to help.

     

     MDMA has been shown to be toxic to serotonergic neurons in rats and primates

     at doses only slightly higher than the typical recreational dose in humans

     (on a mg/kg basis.) This should be tempered by the observation that there

     have been no observable long-term behavioral effects in people who have

     taken MDMA, but it is unfashionable to decapitate humans and examine their

     brains' serotonergic neurons directly. Additionally, many drugs (meth-

     amphetamine, fenfluramine) have similar effects in animal models, but they

     are still used without any ill effects. I think the jury is still out, myself.

     

     --

     Steve Dyer

     

     ..............................

     

     

     

     

     >

     >MDMA has been shown to be toxic to serotonergic neurons in rats and primates

     >at doses only slightly higher than the typical recreational dose in humans

     >(on a mg/kg basis.) This should be tempered by the observation that there

     >have been no observable long-term behavioral effects in people who have

     >taken MDMA, but it is unfashionable to decapitate humans and examine their

     >brains' serotonergic neurons directly. Additionally, many drugs (meth-

     >amphetamine, fenfluramine) have similar effects in animal models, but they

     >are still used without any ill effects. I think the jury is still out, myself.

     >Steve Dyer

     >dyer@ursa-major.spdcc.com aka {ima,harvard,rayssd,linus,m2c}!spdcc!dyer

     >dyer@arktouros.mit.edu

     >

      I agree with that conclusion, but would also like to point to

     a couple of related facts. First, people will show symptoms of

     Parkinson's disease only after about 80 % of their dopaminergic

     neurons are destroyed. Second, patients will notice a loss of memory

     only after tests show their short term memory has been impaired by 85%

     Which means that half your serotonergic receptors could be destroyed

     and you would probably not notice any difference. The brain is a

     wonderful organ with a lot of redundancy built in it! The problem is

     that you might feel this loss of receptors later in life as some of

     your brain cells die due to normal aging and there are not enough

     "backup" receptors. Of course, no data exist on MDMA users who have been

     using it for 50 years. Since MDMA has been shown to be toxic to some

     animals, no research is likely to be done on humans for ethical

     reasons. I have used MDMA (when it was legal) and enjoyed it, but now

     I would be scared to do it even assuming it was still legal. This is of

     course a personal opinion. Has there been some more recent info on

     this serotonergic receptor stuff in the litterature?

     

      Pierre St-Hilaire

      MIT Media Laboratory

     

     

     Subject: Re: long term dangers of MDMA

     

     

     In article <90341.021142MASSOUD@auvm.auvm.edu> MASSOUD@auvm.auvm.edu (NADIM MASSOUD) writes:

     >Hi, could any knowledgeble person tell me about the possible dangers

     >of occasional MDMA use? I have read lots of articles on the subject,

     >but no study offered convincing evidence as to the negative effects

     >on humans.... All answers are greatly appreciated.. Thanks..

     

     Well, that's because there ISN'T evidence of any observable deleterious

     behavioral or neuropsychological effects in humans, but what is observed

     in animal models (histological and neurochemical) probably should be

     interpreted conservatively. Matt F. mentions that there are some upcoming

     studies of HIAA levels in spinal fluid in MDMA users, a test which may be

     a marker for evidence of neurotoxicity. On the other hand, Ricaurte's other

     human studies have not been without criticism. We'll have to see.

     

     I have no reason to beat the drum for MDMA, but the thing that makes me

     somewhat suspicious and uneasy about the facileness of these studies

     purporting to point to MDMA's neurotoxicity (and thus support the conclusion

     that the drug should be banned), is that drugs which are far more neurotoxic

     in the same models are used quite routinely without harm. Fenfluramine, a

     serotonergic appetite suppressant is three times more potent than MDMA in

     producing the same experimental lesions in animals. It has been marketed

     and sold for more than 25 years, and millions of doses have been administered

     to people, usually chronically, without any particular side effects which

     would point to a lasting neurological lesion. In fact, one of its two isomers,

     d-fenfluramine, is in the middle of clinical trials for FDA approval as an

     appetite suppressant which lacks some of the side-effects of the racemic drug.

     Methamphetamine also appears to be neurotoxic in the same models, but even

     though it is a very abusable drug, no one would say that it produces obvious

     neurological deficits when used in the treatment of narcolepsy or attention-

     deficit disorder.

     

     The lack of evidence of side effects in people who have used MDMA,

     even in those who have used it more than a few times, taken together

     with the evidence of the safe use of other drugs which would otherwise

     be thought to be dangerous according to this model, suggests that

     the neurotoxicity of MDMA in humans might very well have been exaggerated.

     Now, you have to balance that rather cool assessment with the question

     "Well, just what IS going on?" (especially if the studies in humans become

     better refined.) Maybe there is a lot of redundancy in the areas where

     MDMA (and other drugs) ostensibly exert their serotonergic neurotoxicity,

     such that any deficit remains subclinical. What might it take to unmask

     that damage in the future? Who knows?

     

     It depends on how conservative you want to be.

     

     --

     Steve Dyer

     dyer@ursa-major.spdcc.com aka {ima,harvard,rayssd,linus,m2c}!spdcc!dyer

     dyer@arktouros.mit.edu, dyer@hstbme.mit.edu

     

     

     Subject: Re: MDMA/Ecstasy

     Summary: MDMA, MDA are neurotoxic to serotonergic neurons

     

     

     In article <26C35239.2952@ics.uci.edu> honig@ics.uci.edu (David Honig) writes:

     

     >I don't believe the neurotoxicity reports are relevent to human use; I know

     >of people who've taken several times the usual dose with no adverse effects

     >other than tiredness afterwards, and slight visuals during.

     

     >David A. Honig

     

     Yes, and I have a few friends who shoot MPTP and they haven't had any problems

     either.

     

     While I generally find your opinions to be thoughtful and well-informed, I

     have a difficult time understanding your reasoning here, David. Are you

     saying that, since you and people you know have noticed no obvious behavioral

     (or introspective) correlates to MDMA's neurotoxicty, that neurotoxicity is

     irrelevant? If so, this seems to be a very premature judgement to me. After

     all, although we don't generally see any effects of dopamine depletion in

     humans until they've lost 80 or more percent (at which point they develop

     parkinson's syndrome), it isn't really advisable to shoot MPTP. Why weaken

     the reliability of your system unless there are significant benefits to the

     medication (as may be true in MDMA's use in psychotherapy)? Furthermore,

     it may be that our tests just aren't sensitive enough to detect the behavioral

     changes associated with the damage. There's been some recent success in

     detecting damage to the dopaminergic system using reactions. While I don't

     think this has yet been replicated in humans, researchers (Spirduso et all,

     I think) have found that rats with dopamine losses of approx. 45% and more

     have slightly impaired reaction times. Basically, it seems to me that

     uncontrolled, anecdotal data shouldn't be relied on.

     

     I realize that the serotonergic system is very different from the dopamine

     one and that NO behavioral changes have been found for MDMA-induced seroton-

     ergic depletion, still judging the neurotoxicity as "irrelevant" seems to

     me to be very premature.

     

     It seems to me that the benefits would have to be better than a good trip in

     order to out weight the cost. Neurotoxic effects of MDMA have

     been found at 3-4 times the effective dose (IP injected) in rats and monkeys

     are even more susceptable. Admittedly, the "effective dose" is probably

     on the high end (since one can't ask a rat if it feels good, but must give

     enough to alter its behavior measurably), but even if we couldn't pick up

     the neurotoxicity until 6-8 times the ED, that's still wouldn't be a very

     safe window (given the variables and unknown doses involved and the likely-

     hood of better tests revealing neurotoxicity at lower doses).

     

     For those interested in reading primary sources on this subject, I recommend

     the work by George Ricaurte, who's done a great deal of MDMA research

     (including studies involving oral doses in squirrel monkeys). G. Battaglia's

     also active in this field. I recall a paper in Pharmacol-Biochem-Behav.

     (journal) in the Feb. 88 issue on the parameters of the neurotoxicity. In

     any case, one would want to look up the latest articles by these two and read

     the abstracts, intros, and discussions. People interested in the importance

     of serotonin (5-hydroxytryptamine, 5-HT) should find the target article in

     Behavioral and Brain Sciences (BBS, an excellent, readable journal with

     important articles and extensive peer reviews). Serotonin is believed to

     be related to aggression, sexual behavior, and sleep, to name a few things.

     Oh, and it's also important in the activity of hallucinogens.

     

     --Matt Funkchick.

      den0@quads.uchicago.edu

     

     

     

     Subject: Nutmeg & Psychedelic Amphetamines

     

     In article <3894@ursa-major.SPDCC.COM>

     dyer@ursa-major.spdcc.COM (Steve Dyer) writes:

     >Huh? I believe that nutmeg contains several methoxy- and methylenedioxy-

     >phenyl alkenes (essentially the deaminated forms of the psychedelic

     >amphetamines.) I know of no evidence that they are biotransformed

     >into the corresponding amphetamines.

     

     As you may remember, we discussed this exact point some time ago. What

     follows is a posting I made on the subject in October 1988. After posting

     I tried 2 tablespoons of McCormick's (sp?) new from the store. I was

     more moist and aromatic than I remembered, so maybe freshness makes a

     difference. It left me slightly speedy and trippy. I've never taken

     psychedelic amphetamines, but what I experienced was inline with what

     I would have expect them.

     

     

     Newsgroups: alt.drugs

     Subject: Nutmeg

     Date: 11 Oct 88 19:46:42 GMT

     

     In article <451@husc6.harvard.edu> gallaghe@husc8.UUCP

     (Paul Gallagher) writes (a nice article):

     >Another household substance with psychedelic properties is nutmeg, which

     >contains small amounts of the methoxylated amphetamine, myristicin.

     

     In article <7388@bloom-beacon.MIT.EDU> dyer@arktouros.MIT.EDU

     (Steve Dyer) writes:

     >Myristicin is not a methoxylated amphetamine. It is in fact

     >non-nitrogenous and only resembles the methoxylated amphetamines in their

     >phenyl rings.

     

     In article <1722@laidbak.UUCP> rayd@laidbak.UUCP (Ray Dueland) writes:

     >The constituents of nutmeg don't contain psychedelic amphetamines, but

     >do contain good MDMA, MDA, and DMA precursors. I'm not familiar with

     

     

     I got curious enough about nutmeg to do some reading. Nutmeg contains

     a variety of allylbenzenes (double bond between beta and gamma carbons),

     all very similar to psychedelic amphetamines. I tried drawing the

     compounds, but they're difficult in ASCII. The compounds all have the

     allylbenzene in common, the differ in their substitutions at the 3,4,5

     positions of the benzene ring. The compounds and their concentrations

     from (1):

     

     compound substitutions concentration

     -------- ------------- -------------

     myristicin 3-methoxy, 4,5-methylenedioxy 4.0%

     safrole 3,4-methylenedioxy 0.6%

     eugenol 3-methoxy, 4-hydroxyl 0.2%

     elemicin 3,4,5-trimethoxy *

     methyleugenol 3,4-dimethoxy *

     ----

     *-mentioned in (4) and stated as being previously included with

     the myristicin portion incorrectly.

     

     Weil's (1) paper gives a broad history of nutmeg use as food and as

     narcotic, and gives a summary of research into the pharmacological

     effects of nutmeg. Some of the more interesting work cited is that by

     Alexander Sulgin (3,4). Unfortunately some of the cited work is from an

     unpublished paper, and the library didn't have the journal another

     article was in (3) so I only saw excerpts.

     

     The descriptions of the experience mentioned by Weil are consistent

     with pyschedelic amphetamine experiences, although the initial phase

     of an excitment and distorted perception is often followed by

     narcosis, the effects sometimes reported as lasting days. There are a

     wide variety of other toxic effects reported (infrequently, death) with

     enough frequency to make it clear why this is not a widely abused

     substance.

     

     The psychedelic component is examined by Shulgin who concludes that

     the hallucinogenic action is mainly from the myristicin and related

     components. He notes that only know mechanism of metabolism of any of

     the compounds is the detoxification of safrole to piperonylic acid.

     This reaction show the capacity to oxidize an olefinic side chain.

     He uses this fact to speculate on a possible pharmacologic mechanism

     (quoted from Weil):

     

      "Shulte suggests that, if this degradative process is `applicable to

      myristicin, or especially to elemicin, a theoretical intermediate, a

      vinyl alcohol, could undergo transamination producing the known

      psychotomimetic drug, 3,4,5-trimethoxy amphetamine (TMA). The recent

      description of the new, synthetic hallucinogen -

      3-methoxy-4,5-methylenedioxy amphetamine (MMDA)-which might be

      derived by an analogous process from myristicin, itself, is even more

      suggestive of a psychotropic function for this component of nutmeg.'"

     

     References

     ----------

     1. Weil, Andrew (1965). Nutmeg as a Narcotic. 19(3), 194-217.

     

     2. Truitt, Edward and others (1961). The Pharmacology of Myristicin; A

     Contribution to the Psychoparmacology of Nutmeg. 2(4), 205.

     

     3. Shulgin, Alexander T. (1963). Concerning the pharmacology of nutmeg.

     Mind 299-303.

     

     4. Shulgin, Alexander T. (1964). Composition of the myristicin fraction

     from oil of nutmeg. Nature, 197:4865, p.379.

     

     --

     Ray Dueland

     raydu@ico.isc.com

     ...uunet!ico!raydu

     

     

     Subject: Shulgin

     

     More on Shulgin from Email sent to me -

     

     --

     

     I sent away to shulgin for his book on the controlled substances act.

     He sent me back a letter which included the following:

     

     "I am presently struggling through my book on the entire phenylethylamine

     area, and with the smiles of the almighty, it will be done soon. This is

     a novel, PIHKAL, that embodies all I have uncovered in my research over the

     last forty years, some published but mostly unpublished. It will have the

     world's longest footnote, with the recipes and dosages and duration and

     descriptions of experiences and related comments on all the phenylethylamines

     I have ever made or looked at. Some 250 of them. (!) ... And, as I had

     said, all published as fiction. PIHKAL is the acronym for "Phenylethylamines

     I Have Known and Loved"

     

     The book should be done by the end of the year.

     

     

     

      DRUG QUIZ

      (answers follow posting)

     

     (1) What is the present Schedule, within the CSA, for each of the

      following drugs:

      (a) the hallucinogen Tiletamine?

      (b) the stimulant U-4-E-uh (Methylaminorex)?

      (c) the narcotic Benzylfentanyl?

     (2) Was MDMA (Ecstasy) a Scheduled drug on March 1, 1988?

     (3) What material is listed as #8254 in the DEA computer?

     (4) What drug is Scheduled but has yet to be synthesized?

     

     

      THE CONTROLLED SUBSTANCES ACT

     

     This is a 383 page manual containing all details of the Federal Drug

     Law, including names, schedules, definitions, DEA code numbers,

     structures, regulatory authority, history, drug formulae, plant

     sources, synonyms, CAS registries, chemical names, and more.

     

     $34.95, plus $4.00 s/h ____ Bill me ____ Check enclosed

     

     SHIP TO: ORDER FROM:

      Name ___________________ Alexander T. Shulgin

      Address ___________________ 1483 Shulgin Road

      City, Zip ___________________ Lafayette, CA 94549

     

     

     

     Answers:

      (1) a: not scheduled

      b: Schedule I

      c: not scheduled

      (2) No.

      (3) Tapioca starch

      (4) MMDA-4

     

     

     ..............................

     

     Just in case you were having trouble getting the Shulgin bibliography

     to come out right, I have received the following.

     

     --------begin forwarded message---------------

     

     Mr. Berryhill:

     

     In article <10567@nigel.udel.EDU> you give a bibliography of

     Dr. Alexander T. Shulgin's work:

     

     >. . . I have the references in troff format. For those not

     >familiar with this format, I include a list of the format commands.

     

     Now, I consider myself a neutral in the so-called "War" on drugs,

     because I have strong feelings on both sides of the issue, but

     out of sheer hacker curiosity, I tried yesterday to troff your

     bibliography. Here are a few suggestions, based on what works

     at my site and what doesn't:

     

     

     

     

     Tyrone Slothrop wishes to add the following remarks to the recent

     posting of the re-formatted bibliography of Shulgin's publications...

     

     ------begin forwarded message-------------

     

      I haven't read alt.drugs in ages. But looking in today I am glad to see

     that my efforts to make the Shulgin bibliography available were not wasted.

     Some persons have even endeavored to make the troff formatting nicer. Thank

     you. I noticed that somehow, some pieces of the file have gotten lost.

     There was a deletion of a second author in one 1976 reference. These were

     present in the original, so I am making it available again. The guess by

     Rich Thomson (5739) and others on this reference was not correct.

     

      While I am glad that the bibliography is being passed around, I am

     disappointed that the Pynchon quote was stripped off. I add these quotes

     for their literary merit, to turn people on to Pynchon, to raise the

     collective conscious level, and your indulgence is a small price I ask in

     exchange for the information I provide.

     

      - Tyrone Slothrop -- from his scattering

     

     Subject: The End of Psychedelic Exploration - from Slothrop

     Homage To: Shulgin's Psychedelic Publications

     

     Alexander Shulgin is the worlds foremost developer and explorer of

     psychedelic drugs. He has been, and remains, a prolific writer. His

     publications provide a great introduction to the diverse world of

     psychedelics, and provide and inspiration for psychedelic exploration.

     However, Shulgin has informed me that the publishing of any

     human data on new compounds had to stop abruptly with the enactment

     of the Analogue Drug Bill in 1986. This particular bit of obscenity

     makes the generation, or even the attempted generation, of any altered

     state of consciousness a felonious act. The continuing publication of

     experimental results in the medical and scientific literature is now

     totally impossible. For this reason I think it is worthwhile to

     provide a complete list of his psychedelic publications. They are

     well referenced, and can lead to much other psychedelic literature.

     

     Shulgin crossed the diamond with the pearl and gave birth to all forms of

     light: "It is early morning now. Slothrop's breath is white on the air.

     He is just up from a dream. Part I of a poem, with woodcuts accompanying

     the text - a woman is attending a dog show which is also, in some way, a

     stud service. She has brought her Pekingese, a female with a sickeningly

     cute name, Mimsy or Goo-Goo or something, here to be serviced. She is

     passing the time in a garden setting, with some other middle-class ladies

     like herself, when from some enclosure nearby she hears the sound of

     her bitch, coming. The sound goes on and on for much longer than

     seems appropriate, and she suddenly realizes that the sound is her own

     voice, this interminable cry of dog-pleasure. The others, politely, are

     pretending not to notice. She feels shame, but is helpless, driven now by

     a need to go out and find other animal species to fuck. She sucks the

     penis of a multicolored mongrel who has tried to mount her in the

     street. Out in a barren field near a barbed-wire fence, winter fires across

     the clouds, a tall horse compels her to kneel, passively, and kiss his

     hooves. Cats and minks, hyenas and rabbits, fuck her inside automo-

     biles, lost at night in the forests, out beside a waterhole in the desert.

     

     "As Part II begins, she has discovered she's pregnant. Her husband, a

     dumb, easygoing screen door salesman, makes an agreement with her:

     her own promise is never stated, but in return, nine months from now,

     he will take her where she wants to go. So it is that close to the end of

     her term he is out on the river, and American river, in a rowboat, hauling

     on the oars, carrying her on a journey. The key color in this section is

     violet.

     

     "Part III finds her at the bottom of the river. She has drowned. But all

     forms of life fill her womb. 'Using her as mermaid' (line 7), they trans-

     port her down through these green river-depths. 'It was down, and out

     again./ Old Squalidozzi, ploughman of the deep,/ At the end of his

     day's sowing/ Sees her verdigris belly among the weeds' (lines 10-13),

     and brings her back up. He is a classically-bearded Neptune figure with

     an old serene face. From out of her body streams a flood now of dif-

     ferent creatures, octopuses, reindeer, kangaroos, 'Who can say all the

     life/ That left her womb that day?' Squalidozzi can only catch a

     glimpse of the amazing spill as he bears her back toward the surface.

     Above, it is a mild and sunlit green lake or pond, grassy at the banks,

     shaded by willows. Insects whine and hover. The key color now is

     green. 'And there as it broke to sun/ Her corpse found sleep in the

     water/ And in the summer depths/ The creatures took their way/ Each

     to its proper love/ In the height of afternoon/ As the peaceful river

     went....'" Pynchon (1973, p. 446-447)

     

     For reprints of Shulgin's publications, write to:

     

     Alexander T. Shulgin

     1483 Shulgin Road

     Lafayette, CA 94549

     

     Be merciful. He is out of many of the older papers, and probably doesn't

     have reprints of the longer review articles. Don't request reprints of

     articles that you can get at the library. After each article I have

     included a number. These are the numbers that Shulgin uses to reference

     his papers. If you include these it will make it easier for him to

     locate them. I have the references in troff format. For those not

     familiar with this format, I include a list of the format commands.

     

     \fI start italics

     \fG start greek

     \fR end italics or greek

     \u shift up half line, begin superscript or end subscript

     \d shift down half line, begin subscript or end superscript

     \s+2 increase point size by two

     \s-2 decrease point size by two

     \*' accent on preceding letter

     \*: umlaut on preceding letter

     

     .XP

     Pynchon, Thomas. 1973. Gravity's Rainbow. The Viking Press, N.Y. Pp. 760.

     .XP

     Shulgin, A. T., S. Bunnell, and T. Sargent. 1961. The psychotomimetic

     properties of 3,4,5-trimethoxyamphetamine. Nature 189: 10011-1012. 12

     .XP

     _____. 1963. Psychotomimetic agents related to mescaline. Experientia

     19: 127. 19

     .XP

     _____. 1963. Composition of the myristicin fraction from oil of nutmeg.

     Nature 197: 379. 20

     .XP

     _____. 1963. Concerning the pharmacology of nutmeg. Mind 1: 299-302. 23

     .XP

     _____. 1964. 3-methoxy-4,5-methylenedioxy amphetamine, a new

     psychotomimetic agent. Nature 201: 1120-1121. 29

     .XP

     _____. 1964. Psychotomimetic amphetamines: methoxy 3,4-dialkoxyamphetamines

     Experientia 20: 366. 30

     .XP

     _____, and H. O. Kerlinger. 1964. Isolation of methoxyeugenol and trans-

     isoelemicin from oil of nutmeg. Naturwissenschaften 15: 360-361. 31

     .XP

     _____. 1965. Synthesis of the trimethoxyphenylpropenes. Can. J. Chem.

     43: 3437-3440. 43

     .XP

     _____. 1966. Possible implication of myristicin as a psychotropic substance

     Nature 210: 380-384. 45

     .XP

     _____. 1966. The six trimethoxyphenylisopropylamines

     (trimethoxyamphetamines). J. Med. Chem. 9: 445-446. 46

     .XP

     _____, T. Sargent, and C. Naranjo. 1966. Role of 3,4-dimethoxyphenethylamin

     in schizophrenia. Nature 212: 1606-1607. 48

     .XP

     _____, T. Sargent, and C. Naranjo. 1967. The chemistry and psychopharmacolo

     of nutmeg and of several related phenylisopropylamines. \fIIn\fR D. H.

     Efron (ed.): Ethnopharmacologic search for psychoactive drugs. U. S. Dept.

     of H. E. W., Public Health Service Publication No. 1645. Pp. 202-214.

     Discussion: ibid. pp. 223-229. 49

     .XP

     _____, and T. Sargent. 1967. Psychotropic phenylisopropylamines derived

     from apiole and dillapiole. Nature 215: 1494-1495. 50

     .XP

     Sargent, T. W., D. M. Israelstam, A. T. Shulgin, S. A. Landaw, and N. N.

     Finley. 1967. A note concerning the fate of the 4-methoxyl group in

     3,4-dimethoxyphenethylamine (DMPEA). Biochem. Biophys. Res. Commun.

     29: 126-130. 52

     .XP

     Naranjo, C., A. T. Shulgin, and T. Sargent. 1967. Evaluation of

     3,4-methylenedioxyamphetamine (MDA) as an adjunct to psychotherapy.

     Med. Pharmacol. Exp. 17: 359-364. 53

     .XP

     Shulgin, A. T. 1968. The ethyl homologs of 2,4,5-trimethoxyphenylisopropyl-

     amine. J. Med. Chem. 11: 186-187. 54

     .XP

     _____, T. Sargent, and C. Naranjo. 1969. Structure activity relationships

     of one-ring psychotomimetics. Nature 221: 537-541. 57

     .XP

     _____. 1969. Recent developments in cannabis chemistry. J. Psyched. Drugs

     2: 15-29. 58

     .XP

     _____. 1969. Psychotomimetic agents related to the catecholamines.

     J. Psyched. Drugs 2(2): 12-26. 59

     .XP

     _____. 1970. Chemistry and structure-activity relationships of the

     psychotomimetics. \fIIn\fR: D. H. Efron (ed.). Psychotomimetic Drugs.

     Raven Press, New York. Pp. 21-41. 60

     .XP

     _____. 1970. The mode of action of psychotomimetic drugs; some qualitative

     properties of the psychotomimetics. Neur. Res. Prog. Bull. 8: 72-78. 61

     .XP

     _____. 1970. 4-alkyl-dialkoxy-\fGa\fR-methyl-phenethylamines and their

     pharmacologically-acceptable salts. U. S. Patent 3,547,999, issued Dec. 15,

     1970. 63

     .XP

     _____, T. Sargent, and C. Naranjo. 1971. 4-bromo-2,5-dimethoxyphenyliso-

     propylamine, a new centrally active amphetamine analog. Pharmacology

     5: 103-107. 64

     .XP

     _____. 1971. Chemistry and sources. \fIIn\fR: S. S. Epstein (ed).

     Drugs of abuse: their genetic and other chronic nonpsychiatric hazards.

     The MIT Press, Cambridge, Mass. Pp 3-26. 65

     .XP

     _____. 1971. Preliminary studies of the synthesis of nitrogen analogs

     of \fGD\fR\u\s-21\s+2\d-THC. Acta Pharm. Suec. 8: 680-681. 66

     .XP

     _____. 1972. Hallucinogens, CNS stimulants, and cannabis. \fIIn\fR:

     S. J. Mule/*' and H. Brill (eds.): Chemical and biological aspects of

     drug dependence. CRC Press, Cleveland, Ohio. Pp. 163-175. 67

     .XP

     _____. 1973. Stereospecific requirements for hallucinogenesis.

     J. Pharm. Pharmac. 25: 271-272. 68

     .XP

     _____. 1973. Mescaline: the chemistry and pharmacology of its analogs.

     Lloydia 36: 46-58. 69

     .XP

     _____. 1973. The narcotic pepper - the chemistry and pharmacology of

     \fIPiper methysticum\fR and related species. Bull. Narc. 25: 59-74.

     Le poivre stupe\*'fiant - chemie et pharmacologie du \fIPiper methysticum\fR

     et des espe\*'ces apparente\*'es. Bull. Stupe\*'fiants 25: 61-77. 70

     .XP

     _____, T. Sargent, and C. Naranjo. 1973. Animal pharmacology and human

     psychopharmacology of 3-methoxy-4,5-methylenedioxyphenylisopropylamine

     (MMDA). Pharmacology 10: 12-18. 71

     .XP

     _____. Drugs of abuse in the future. Drug abuse in America Vol. 1.

     pp. 209-236. U.S.G.P.O. 5266-00004. Reprinted: Clin. Tox. 8: 405-456. 72

     .XP

     Kalbhen, D. A., T. Sargent, A. T. Shulgin, G. Braun, H. Stauffer, N. Kusubov,

     and M. L. Nohr. 1974. Human pharmacodynamics of the psychodysleptic

     4-bromo-2,5-dimethoxyphenylisopropylamine labelled with \u82\dBr.

     IRCS (Int. Res. Comm. Sys.) 2: 1091. 73

     .XP

     Sargent, T., D. A. Kalbhen, A. T. Shulgin, H. Stauffer, and N. Kusubov. 1975

     A potential new brain-scanning agent: 4-\u77\dBr-2,5-dimethoxyphenyliso-

     propylamine (4-Br-DPIA). J. Nucl. Med. 16: 243-245. 74

     .XP

     Shulgin, A. T., and M. F. Carter. 1975. Centrally active phenethylamines.

     Psychopharm. Commun. 1: 93-98. 75

     .XP

     Sargent, T., D. A. Kalbhen, A. T. Shulgin, G. Braun, H. Stauffer, and

     N. Kusubov. 1975. \fIIn vivo\fR human pharmacodynamics of the

     psychodysleptic 4-Br-2,5-dimethoxyphenylisopropylamine labelled with

     \u82\dBr or \u77\dBr. Neuropharmacology 14: 165-174. 76

     .XP

     _____. 1975. The chemical catalysis of altered states of consciousness.

     Altered states of consciousness, current views and research problems.

     The drug abuse council, Washington, D. C. Pp. 123-134. 77

     .XP

     _____. 1975. Drug use and anti-drug legislation. The PharmChem

     Newsletter 4 (#8). 79

     .XP

     _____, and D. C. Dyer. 1975. Psychotomimetic phenylisopropylamines. 5.

     4-alkyl-2,5-dimethoxyphenylisopropylamines. J. Med. Chem. 18: 1201-1204. 80

     .XP

     _____, and C. Helisten. 1975. Differentiation of PCP, TCP, and a

     contaminating precursor PCC, by thin layer chromatography. Microgram 8:

     171-172. 81

     .XP

     Helisten, C., and A. T. Shulgin. The detection of 1-piperidinodydlohexane-

     carbonitrile contamination in illicit preparations of 1-(1-phenylcyclohexyl)

     piperidine and 1-(1-(2-thienyl)cyclohexyl)piperidine. J. Chrom. 117:

     232-235. 82

     .XP

     Shulgin, A. T. 1976. Psychotomimetic agents. \fIIn\fR: M. Gordon (ed.)

     Psychopharmacological agents, Vol. 4. Academic Press, New York.

     Pp. 59-146. 83

     .XP

     _____. 1976. Abuse of the term "amphetamines". Clin. Tox. 9: 351-352. 84

     .XP

     _____. 1976. Profiles of psychedelic drugs. 1. DMT. J. Psychedelic

     Drugs 8: 167-168. 85

     .XP

     _____. 1976. Profiles of psychedelic drugs. 2. TMA-2. J. Psychedelic

     Drugs 8: 169. 86

     .XP

     _____, and D. E. MacLean. 1976. Illicit synthesis of phencyclidine (PCP)

     and several of its analogs. Clin. Tox. 9: 553-560. 87

     .XP

     Nichols, D. E., and A. T. Shulgin. 1976. Sulfur analogs of psychotomimetic

     amines. J. Pharm. Sci. 65: 1554-1556. 89

     .XP

     Sargent, T., A. T. Shulgin, and N. Kusubov. 1976. Quantitative

     measurement of demethylation of \u14\dC-methoxyl labeled DMPEA and TMA-2

     in rats. Psychopharm. Commun. 2: 199-206. 90

     .XP

     Standridge, R. T., H. G. Howell, J. A. Gylys, R. A. Partyka, and A. T.

     Shulgin. 1976. Phenylalkylamines with potential psychotherapeutic utility.

     1. 2-amino-1-(2,5,-dimethoxy-4-methylphenyl)butane. J. Med. Chem.

     19: 1400-1404. 91

     .XP

     _____. 1976. Profiles of psychedelic drugs. 3. MMDA. J. Psychedelic

     Drugs 8: 331. 92

     .XP

     _____. 1977. Profiles of psychedelic drugs. 4. Harmaline. J. Psychedelic

     Drugs 9: 79-80. 93

     .XP

     _____. 1977. Profiles of psychedelic drugs. 5. STP. J. Psychedelic Drugs

     9: 171-172. 94

     .XP

     Nichols, D. E., A. T. Shulgin, and D. C. Dyer. 1977. Directional lipophilic

     character in a series of psychotomimetic phenethylamine derivatives. Life

     Sciences 21: 569-576. 95

     .XP

     Jacob, P. III, G. Anderson III, C. K. Meshul, A. T. Shulgin, and N.

     Castagnoli Jr. 1977. Mononethylthio analogues of 1-(2,4,5-trimethoxyphenyl)

     2-aminopropane. J. Med. Chem. 20: 1235-1239. 96

     .XP

     White, T. J., D. Goodman, A. T. Shulgin, N. Castagnoli Jr., R. Lee, and

     N. L. Petrakis. 1977. Mutagenic activity of some centrally active aromatic

     amines in \fISalmonella typhimurium\fR. Mutation Research 56: 199-202. 97

     .XP

     Braun, U., A. T. Shulgin, G. Braun, and T. Sargent III. 1977. Synthesis

     and body distribution of several iodine-131 labeled centrally acting

     drugs. J. Med. Chem. 20: 1543-1546. 98

     .XP

     Sargent, T. III, T. F. Budinger, G. Braun, A. T. Shulgin, and U. Braun.

     1978. An iodated catecholamine congener for brain imaging and metabolic

     studies. J. Nucl. Med. 19: 71-76. 99

     .XP

     Shulgin, A. T. 1978. Psychotomimetic drugs: structure-activity

     relationships. \fIIn\fR: L. L. Iversen, S. D. Iversen, and S. H. Snyder

     (eds.), Handbook of psychopharmacology, Vol. 11. Plenum Press, New

     York. Pp. 243-333.

     .XP

     Sargent, T. III, G. Braun, U. Braun, T. F. Budinger, and A. T. Shulgin.

     1978. Brain and retina uptake of a radio-iodine labeled psychotomimetic

     in dog and monkey. Commun. Psychopharm. 2: 1-10. 101

     .XP

     Braun, G., A. T. Shulgin, and T. Sargent III. 1978. Synthesis of

     \u123\dI-labelled 4-iodo-2,5-dimethoxyphenylisopropylamine. J. Labelled

     Comp. and Radiopharm. 14: 767-773. 102

     .XP

     Murdock, J. E., J. R. Patty, and A. T. Shulgin. 1978. A novel illicit

     amphetamine laboratory. Microgram 11: 98-101. 103

     .XP

     Anderson, G. M. III, G. Braun, U. Braun, D. E. Nichols, and A. T. Shulgin.

     1978. Absolute configuration and psychotomimetic activity. \fIIn\fR:

     G. Barnett, M. Trsic, and R. Willette (eds.), QuaSAR Research Monograph 22.

     N.I.D.A. Washington, D.C. Pp. 8-15. 104

     .XP

     Braun, U., G. Braun, P. Jacob III, D. E. Nichols, and A. T. Shulgin.

     Mescaline analogs: substitutions at the 4-position. \fIIn\fR:

     G. Barnett, M. Trsic, and R. Willette (eds.), QuaSAR Research Monograph 22.

     N.I.D.A. Washington, D.C. Pp. 27-37. 105

     .XP

     Partyka, R. A., R. T. Standridge, H. G. Howell, and A. T. Shulgin. 1978.

     2-amino-1-(2,5-dimethoxyphenyl)butanes. U.S. Patent 4,105,695, issued

     Aug. 8, 1978. 106

     .XP

     Shulgin, A. T., and D. E. Nichols. 1978. Characterization of three new

     psychotomimetics. \fIIn\fR: R. C. Stillman and R. E. Willette (eds.),

     The psychopharmacology of hallucinogens. Pergamon Press, New York.

     Pp. 74-83. 107

     .XP

     Glennon, R. A., L. B. Kier, and A. T. Shulgin. 1979. Molecular

     connectivity analysis of hallucinogenic mescaline analogs. J. Pharm.

     Sci. 68: 906-907. 108

     .XP

     Shulgin, A. T. 1979. Chemistry of phenethylamines related to mescaline.

     J. Psychedelic Drugs 11: 41-52. 109

     .XP

     _____. 1979. Profiles of psychedelic drugs. 6. \fGa\fR,O-DMS.

     J. Psychedelic Drugs 11: 247. 110

     .XP

     _____. 1979. Profiles of psychedelic drugs. 7. Mescaline. J.

     Psychedelic Drugs 11: 355. 111

     .XP

     Standridge, R. T., H. G. Howell, H. A. Tilson, J. H. Chamberlain, H. M.

     Holava, J. A. Gylys, R. A. Partyka, and A. T. Shulgin. 1980.

     Phenylalkylamines with potential psychotherapeutic utility. 2. Nuclear

     substituted 2-amino-1-phenylbutanes. J. Med. Chem. 23: 154-162. 112

     .XP

     Braun, U., A. T. Shulgin, and G. Braun. 1980. Centrally active

     N-substituted analogs of 3,4-methylenedioxyphenylisopropylamine

     (3,4-methylenedioxyamphetamine). J. Pharm. Sci. 69: 192-195. 113

     .XP

     Kantor, R. E., S. D. Dudlettes, and A. T. Shulgin. 1980. 5-methoxy-

     \fGa\fR-methyltryptamine (\fGa\fR,O-dimethylserotonine) a hallucinogenic

     homolog of serotonin. Biol. Psychiat. 15: 349-352. 114

     .XP

     Shulgin, A. T. 1980. Profiles of psychedelic drugs. 8. psilocybin.

     J. Psychedelic Drugs 12: 79. 115

     .XP

     Braun, U., A. T. Shulgin, and G. Braun. 1980. Pru\*:fung auf

     Aktivita\*:t und Analgesia von N-substituierten Analogen des Amphetamin-

     Derivates 3,4-Methylendioxyphenylisopropylamin. Arzneim. Forsch.

     30: 825-830. 116

     .XP

     Shulgin, A. T. 1980. Profiles of psychedelic drugs. 9. LSD.

     J. Psychedelic Drugs 12: 173-174. 117

     .XP

     _____. 1981. Hallucinogens. \fIIn\fR: M. E. Wolff (ed.), Burger's

     medicinal chemistry. Wiley & Co. Pp. 1109-1137.

     .XP

     _____. 1981. Profiles of psychedelic drugs. 10. DOB. J. Psychoactive

     Drugs 13: 99. 119

     .XP

     _____, and M. F. Carter. 1981. N,N-diisopropyltryptamine (DIPT) and

     5-methoxy-N,N-diisopropyltryptamine (5-MeO-DIPT). Two orally active

     tryptamine analogs with CNS activity. Commun. Psychopharmacol.

     4: 363-369. 120

     .XP

     Jacob, P., and A. T. Shulgin. 1981. Sulfur analogues of psychotomimetic

     agents. Monothio analogues of mescaline and isomescaline. J. Med. Chem.

     24: 1348. 121

     .XP

     Domelsmith, L. N., T. A. Eaton, K. N. Houk, G. M. Anderson, R. A. Glennon,

     A. T. Shulgin, N. Castagnoli, and P. A. Kollman. 1981. Photoelectron

     spectra of psychotropic drugs. 6. Relationships between physical

     properties and pharmacological actions of amphetamine analogues.

     J. Med. Chem. 24: 1414. 122

     .XP

     Shulgin, A. T. 1981. Chemistry of psychotomimetics. \fIIn\fR:

     F. Hoffmeister and G. Stille (eds.), Handbook of experimental pharmacology,

     Vol. 55/III. Springer-Verlag, Berlin Heidelberg. Pp. 3-29.

     .XP

     _____. 1981. Profiles of psychedelic drugs. 11. Bufotenine.

     J. Psychoactive Drugs 13: 389. 124

     .XP

     _____, and P. Jacob. 1982. Potential misrepresentation of 3,4-methylene-

     dioxyamphetamine (MDA). A toxicological warning. J. Anal. Tox. 6: 71. 127

     .XP

     _____, and P. Jacob. 1982. 1-(3,4-methylenedioxyphenyl)-3-aminobutane:

     a potential toxicological problem. J. Toxicol. - Clin. Toxicol. 19: 109. 12

     .XP

     Jacob, P., and A. T. Shulgin. 1983. Sulfur analogues of psychotomimetic

     agents. 2. Analogues of (2,5-dimethoxy-4-methylphenyl)- and (2,5-

     dimethoxy-4-ethylphenyl)-isopropylamine. J. Med. Chem. 26: 746. 130

     .XP

     Shulgin, A. T. 1983. Twenty years on an ever-changing quest. \fIIn\fR:

     L. Grinspoon and J. B. Bakalar (eds.), Psychedelic Reflections. Human

     Sciences Press, New York. 131

     .XP

     Sargent, T., A. T. Shulgin, and C. A. Mathis. 1982. New iodinated

     amphetamines by rapid synthesis for use as brain blood flow indicators.

     J. Lab. Cmpds. and Radiopharm. 19: 1307. 132

     .XP

     Jacob, P., and A. T. Shulgin. 1984. Sulfur analogues of psychotomimetic

     agents. 3. The ethyl homologues of mescaline and their monothio analogues.

     J. Med. Chem. 27: 881-888. 133

     .XP

     Sargent, T., A. T. Shulgin, and C. A. Mathis. 1984. Radiohalogen-labeled

     imaging agents. 3. Compounds for measurement of brain blood flow by

     emission tomography. J. Med. Chem. 27: 1071-1077. 135

     .XP

     Repke, D. B., D. B. Grotjahn, and A. T. Shulgin. 1985. Psychotomimetic

     N-methyl-N-isopropyltryptamines. Effects of variation of aromatic

     oxygen substituents. J. Med. Chem. 28: 892. 136

     .XP

     Shulgin, A. T. 1985. What is MDMA? PharmChem Newsletter 14: 3

     (May-June, #3). 137

     .XP

     Lemaire, D., P. Jacob, and A. T. Shulgin. 1985. Ring substituted

     beta-methoxyphenethylamines: a new class of psychotomimetic agents active

     in man. J. Pharm. Pharmacol. 37: 575. 138

     .XP

     Mathis, C. A., T. Sargent, and A. T. Shulgin. 1985. Iodine-122 labeled

     amphetamine derivatives with potential for PET brain blood-flow studies.

     J. Nucl. Med. 26: 1295. 139

     .XP

     _____, _____, and _____. 1986. Synthesis of 122-I and 125-I-labeled-

     \fImeta\fR-dimethoxy-N,N-dimethyliodophenylisopropylamines. J. Labelled

     Comp. Radiopharm. 23: 115. 140

     .XP

     Shulgin, A. T., L. A. Shulgin, and P. Jacob. 1986. A protocol for the

     evaluation of new psychoactive drugs. Methods and Findings in

     Experimental and Clinical Pharmacology 8: 313. 141

     .XP

     Nichols, D. E., A. J. Hoffman, R. A. Oberlender, P. Jacob, and A. T.

     Shulgin. 1986. Derivatives of 1-(1,3-benzodioxol-5-yl)-2-butanamine:

     representatives of a novel therapeutic class. J. Med. Chem. 29: 2009. 143

     .XP

     Mathis, C. A., A. T. Shulgin, Y. Yano, and T. Sargent. 1986. \u18\dF-

     labelled N,N-dimethylamphetamine analogues for brain imaging studies.

     Appl. Radiat. Isot. 37: 865. 144

     .XP

     Shulgin, A. T. 1986. The background and chemistry of MDMA. J. Psychoactive

     Drugs 18: 291-304. 145

     .XP

     Sargent, T. W., A. T. Shulgin, and C. A. Mathis. 1987. Rapid brain

     scanning pharmaceutical. U. S. Patent 4,647,446. 146

     .XP

     McKenna, D. J., C. A. Mathis, A. T. Shulgin, T. Sargent, and J. M. Saavedra.

     1987. Autoradiographic localization of binding sites for \u125\dI-DOI,

     a new psychotomimetic radioligand, in the rat brain. Eur. J. Pharmacol.

     137: 289-290. 147

     .XP

     Shulgin, A. T. 1987. The 'social-chemistry' of pharmacological discovery.

     Social Pharmacology 1: 279-290. 148

     .XP

     _____. 1987. Reference information on MDMA. Analog 9: #4 (page 10). 149

     .XP

     _____. 1988. DIPT: the distortion of music. Reality Hackers #6 (Winter

     1988) p. 27. 152.

     .XP

     _____. 1988. THE CONTROLLED SUBSTANCES ACT: A resource manual of the

     current status of the federal drug laws. 383 pp., published in Lafayette,

     California 94549 April 1988. 154

     .XP

     _____. In press. History of MDMA. \fIIn\fR: S. Peroutka (ed.), MDMA:

     "Ecstasy" and human neurotoxin? Kluwer Academic Publishers, Norwell, MA,

     02061.

     

     

     ------end forwarded message----------

     --

     Subject: mdma neurotoxocity

     

     

     Yesterday, I posted info on MDMA, working from memory. Today, I brought

     the June '91 High Times article on the Bridge Conference, held at

     Stanford (!) February 2-3. Here are some excerpts from the article

     regarding MDMA:

     

      ... Bruce Eisner eloquently characterized MDMA ("ecstasy") as a

      substance which reveals "the inner nature of human beings, that

      we all have a core of love and beauty that we can tap into".

      The question on everyone else's minds seemed to be whether

      this miraculous chemical also causes brain damage in humans.

     

      In several presentations, audience questions about this issue

      were addressed by Debby Harlow and Jerome Beck, authors of a

      sociological study of MDMA funded by the National Institute

      on Drug Abuse; Dennis McKenna, who has been associated with

      some of the major MDMA neurotoxicity researchers; and David

      Nichols, whose 20 years of research on the effects of psychedelics

      on rats at the Pharmacology Department of Purdue University has

      also been funded by the NIDA. They did their best to dispel

      several myths about MDMA toxicity, and to set the record straight

      on what is known about MDMA neurotoxicity in humans.

     

      The first myth put to rest was that MDMA causes Parkinson's

      disease or a Parkinson's-like syndrome. This rumor was

      apparently caused by confusion of MDMA with MPTP, an impurity

      present in a designer analog of heroin, long-term use of which

      has caused at least one case of this kind of effect. The second

      misapprehension concerned the fact that MDMA causes some sort of

      drainage of spinal fluid. This misconception somehow resulted

      from a misunderstanding of research into the effects of MDMA on

      levels of the neurotransmitter serotonin, which are accessed

      through spinal taps. It's the spinal taps that drain the fluid,

      NOT the MDMA.

     

      Research into possible MDMA-caused damage to serotonin neurons

      has spawned a great deal of anxiety and misinterpretation. (Some

      of the problem results from the fact that MDMA research has been

      frequently confused with MDA research). Huge, repeated doses of

      MDMA administered to rats DO cause selective damage to serotonin-

      receptor sites. (Mice are apparently less sensitive). A similar

      effect has been observed in primates at dosages above, but

      approximating, human levels. Recovery from this damage seems to

      occur in about four months, followed mysteriously by a reappearance

      of deterioration.

     

      David Nichols offered the most detailed and cogent explanation of

      what happens in this process. The temporary decrease in serotonin

      levels following an MDMA trip, which initiates a massive release

      of serotonin, causes the absorption into serotonin neurons of

      another neurotransmitter, dopamine, in place of serotonin.

      Dopamine does not belong in these serotonin-receptor sites, and

      it is likely that a toxic metabolite created by the enzyme-induced

      breakdown of dopamine causes the observed damage. This

      deterioration is "axodentritic", which means that it occurs in the

      terminals of the nerve cell, not in its main body.

     

      A number of other relevant facts were noted. Nichols pointed out

      that for over 20 years, large doses of fenfluoramine -- an FDA-

      approved, MDMA-related chemical prescribed as an appetite

      suppressant -- have been taken by one and a half to two million

      people in the US. This drug is twice as toxic as MDMA and is

      ingested on a daily basis. However, no aberrations have been

      observed.

     

      Furthermore, Harlow remarked that there are no "behavioral

      correlates" to MDMA neurotoxicity in any mammals, including

      humans. This means that no cognitive, emotional, or physiological

      dysfunctions have been observed to occur as a result of this

      nerve damage. Harlow asked how, without such correlates, "can

      we know that this is a negative thing ? What the neurotoxicity

      researchers are calling brain DAMAGE is really brain CHANGE".

      Dennis McKenna agreed: "There is no rational reason to assume

      that this is negative, given the well-known plasticity of the

      brain".

     

      One psychopharmacologist, who has asked not to be quoted by name,

      takes this issue even further. "Who knows ? Maybe the trimming

      back of serotonin receptors has the effect of pruning the psyche!"

     

      For those still concerned about brain damage from MDMA, Nichols

      referred to a study involving MDMA and the popular antidepressant

      Prozac. The latter drug blocks the "reuptake" or reabsorption of

      serotonin into serotonin nerve cells, and has been shown to

      counteract as well the absorption of the culprit neurotransmitter

      dopamine into these same cells after administration of MDMA in

      rats. The conclusion is that a single therapeutic dose of Prozac

      taken three hours after MDMA would block any possible neuro-

      toxicity in humans, and one dose three-to-six-hours after MDMA

      should significantly decrease such damage.

     

      In spite of all the controversy, there is still no positive

      indication that the animal studies have any bearing on humans.

      Nichols flatly summed up the situation: "There is no evidence

      of MDMA neurotoxicity in humans".

     

     

     In article <1083@tau-ceti.isc-br.com> geraldb@tau-ceti.isc-br.com (Gerald

     Bryan (Denver)) writes:

     

     >Here's what I've read about MDMA's effects:

     >

     > o In the average person, given the right set and setting, there are no

     > long lasting psychological effects that would generally be considered

     > deleterious.

     >

     > o One of the arguments used by the DEA to schedule MDMA was that tests

     > done with MDA (note, not the same as MDMA) on rats showed some damage

     > at nerve cell receptor sites.

     

     > o After being scheduled, similar tests were done with MDMA, also showing

     > similar "neurotoxocity", though not as bad as that with MDA.

     

     > o Further tests revealed that the nerve cell receptor site damage goes

     > away after a period of abstinence (I believe the period of time was

     > 1 month). Also, the amounts of MDMA needed to produce the neurotoxicity

     > were significantly higher than human dosages (I think based on body

     > weight).

     

     You get the quote unquote neurotoxic effect in squirrel monkeys at about

     2-3 times the human ED orally (based on body weight).

     

     > o There is at least one commonly prescribed drug, called something like

     > Fleurotin (help me on this one, netters), that fails the neurotoxicity

     > test worse than MDMA, yet no one seems concerned about it when

     > prescribing the drug.

     

     Fenfluramine. Used for weight loss.One difference between MDMA and Fenfluramine

     is that MDMA is used recreationally. The comparison is a good one given

     that Fenfluramine has been prescribed for many years with no noticable

     problems. My inclination would be to hold off on it for a few years. It's

     good for weight loss but there are other drugs.

     

     Given MDMA's very probable efficacy in therapy (as Lester Grinspoon has

     argued), there is no way that it should be Schedule I. At worst, it

     should be categorized with its cousins, amp and MA, in Schedule II where

     researchers can get to it more easily.

     

     As has been previously posted here (by, I think, Tim Basher) there is a

     good chance that the neurotoxic effects of MDMA can be prevented, without

     effecting its psychactive effects. The neurotoxic effects of MDMA happen

     AFTER the psychoactive ones. A 5-HT reuptake blocker administered at

     this point can prevent the 5-HT neurotoxicty. I've all but seen it done

     in real time with microdialysis (with fenfluramine and fluoxetine) in

     rats.

     

     > o The neuro-toxicity has never been observed in humans (but, I've

     > always wondered, how would they know ?)

     

     5-HIAA levels in the spinal fluid have been found to be lowered in human users,

     suggesting that the neurotoxicity exists as well.

     

     > o There is some disagreement about what the perceived (and temporary)

     > neuro-toxicity means, if anything. It's more than just a

     > disagreement -- I don't think anyone has ventured to guess what it

     > implies. Not saying that I agree with this, but I once heard

     > Andrew Weil venture that the supposed neurotoxicity might even be

     > beneficial brain pruning, much like that that occurs normally

     > in infants.

     

     The only successful experiments I've seen were with dopamine neurotoxicity

     from MA. This was a poster at Neuroscience which found that DA loss of

     about 50% was correlated with the number of times a rat slipped when

     walking across a thin beam. Weil's 'beneficial brain pruning' seems

     intuitively implausible to me, but that's just my inclination.

     

     > o According to Dr. David Nichols (within the last several months),

     > MDMA has not been proven to cause any damage (he may have qualified

     > this with the word "permanent" -- see the HT article mentioned below).

     > Dr. David Nichols, by the way, is probably the number 2 psychedelic

     > chemist in the world today, right after Alexander Shulgin.

     

     Dr. Nichols is correct. And Gerald is correct that Nichols knows what he's

     talking about.

     

     >Sources: "Ecstasy: The MDMA Story" by Bruce Eisner.

     > This month's High Times coverage of the psychedelics conference

     > held in Santa Cruz, San Francisco, or some place like that.

     >--

     >gerald Bryan | "I don't like myself sober," confided Alan Watts to a

     > | friend of mine, "so I spend much of my time drunk."

     > | -- Robert S. deRopp

     

     

     

     From: Chemical & Engineering News. September 9, 1985.

     

      "3,4-methylenedioxymethamphetamine (MDMA)....

     

      H H To a number of psychiatrists scattered across

      \ / the country, MDMA is a useful therapeutic tool.

      C Those psychiatrists have been using MDMA quietly

      / \ since the mid-1970's in counseling sessions as

      O O an adjunct to psychotherapy. They report that,

      \ / when used under controlled conditions, MDMA has

      ----- few negative side effects and can act to ease

      // \\ psychic trauma and break down barriers to

      '< >` communication.

      \ /

      ===== The National Institute on Drug Abuse (NIDA)

      \ maintains that MDMA is a 'nationwide problem

      / as well as a serious health threat.' According

      H C--< to a NIDA publication, MDMA users experience problems

      3 \ similar to those associated with use of amphetamines

      NHCH and cocaine. The publication cites specifically

      3 'psychological difficulties, including confusion,

      depression, sleep problems, drug craving, severe

      anxiety, and paranoia - during and sometimes weeks

      after taking MDMA.'

     

      MDMA was first synthesized and patented by E. Merck & Co., Germany,

      in 1914 as an appetite suppressant. The compound was never marketed,

      however, and the patent on it has long since expired.

     

      It is currently accepted CHEMICAL ABSTRACTS designation is

      N, alpha-dimethyl-1,3-benzodioxole-5-ethanamine. On the street,

      it is sold as MDMA, MDM, Adam, Ecstasy, or XTC.

     

      Chemically, MDMA is related both to methamphetamine and

      3,4-methylenedioxyamphetamine (MDA). According to a number of

      research workers, however, it bears little pharmacological relationsh\

     ip

      to those drugs. 'It stands out as unique in its constellation of

      properties,' says one.

     

      Unlike MDA, MDMA appears to have almost no hallucinogenic properties.

      Nor is its effects primarily that of a stimulant such as

      methamphetamine. Instead, MDMA seems to break down barriers to

      communication between people, ease psychic trauma, and allow

      individuals access to repressed psychological information.

     

      George Greer, a psychiatrist in private practice in Santa Fe, N.M.,

      ...concluded that 'the single best use of MDMA is to facilitate

      more direct communication between people involved in a significant

      emotional relationship....'

     

      The psychiatrists who have used MDMA in therapy also believe that

      it has relatively low abuse potential because its beneficial or

      pleasant side effects diminish rapidly with regular use.

     

      ...DEA proposed in July, 1984 that MDMA be classified as a Schedule I

      controlled substance.

     

      ...DEA's Frank Sapienza...defends DEA's action on the grounds that

      research conducted at the University of Chicago demonstrated that

      MDA is selectively neurotoxic to seratonergic neurons in the brain.

      Although MDMA's mechanism of action remains unknown, research has

      shown that its action involves seratonergic neurons. By extrapolatio\

     n,

      MDMA also might be neurotoxic to such neurons.

     

      Such a classification, however, creates a catch-22 situation for

      the proponents of MDMA as a useful therapeutic drug. The laws

      applying to Schedule I controlled substances make it quite difficult

      to obtain approval to conduct clinical trials of a drug. Because

      it is impossible to obtain patent protection on MDMA, it is unlikely

      that a pharmaceutical firm will undertake the costly effort to

      obtain FDA approval for its use. "

     

     *** END QUOTE

     

     If anyone is interested I would be willing to find out if there has been

     any further research on MDMA and report any results of the research.

     

     

     

     

     A few people have written to me, asking for more information on the

     possible neurotoxic effects of MDMA. So off I went, once more, to the

     library in search of...

     

     "The Journal of Phamacology and Experimental Therapeutics", 1987, 240(1), 1-7.

     _Neurotoxicity of the Psychedelic Amphetamine, Methylenedioxymethamphetamine_

      by Christopher Joseph Schmidt

     

      (Ed. note - All emphasis mine)

      "The neurochemical effects of the unique psychedelic agent,

      methylenedioxymethamphetamine (MDMA), inidicate it may be a

      seratonergic neurotoxin related to agents such as p-chloro-

      amphetamine (PCA)."

     

      "The results clearly demonstrate that MDMA has two distinct

      influences on the serotonergic system of the rat brain, both

      of which are manifested by a significant decrease in the

      concentration of 5-HT (serotonin). Whereas the first effect

      of MDMA appears to produce a REVERSIBLE depletion of 5-HT,

      the second is due to a NEUROTOXIC effect of the drug on

      serotonergic neurons or nerve terminals."

     

      "As demonstrated by the results of the experiments...these

      two effects can be separated temporally into an early and a

      later phase."

     

      "This early phase of depletion was REVERSIBLE because cortical

      serotonin concentrations had recovered to control levels by

      24 hours."

     

      "The depletion observed at 3 hr is due almost completely

      to the acute effect of the drug inasmuch as it is reversed

      completely by 24 hr...."

     

      "However, transmitter concentrations were reduced significantly

      1 week later, indicating a second phase of depletion. The

      latter phase of depletion was associated with a decrease in

      synaptosomal serotonin uptake due to a loss in the number of

      uptake sites with no change in the affinity of the carrier

      for serotonin."

     

      "The similarities between the neurochemical effects of

      MDMA and those reported for PCA led us to suggest that

      the long-term depletions of 5-HT produced by MDMA and PCA

      occurred though similar mechanisms, i.e., a selective

      degeneration of seratonergic neurons or nerve terminals."

     

      "... The results from the uptake studies here present (the

      confirming) biochemical evidence of TERMINAL DAMAGE."

     

     Okay, folks. That is the bottom line. Ecstasy does have a neurotoxic effect.

     I will quote some more on the author's views on what this means to humans.

     

      "Although it is difficult to extrapolate from animal studies

      to the human situation, some comment about the risk to human

      MDMA users seems appropriate ...."

     

      "It is first important to point out that the parenteral doses

      used in this study are approximately 4 to 8 times the human

      oral dose. There is also evidence to suggest that drugs such

      as MDMA and MDA may be subject to significant first pass

      metabolism .... This would mean that the does used in this

      study may be even further from those to which a user taking

      the drug p.o. is normally exposed. However, all effects

      described in this study were produced with a SINGLE ADMINISTRATION

      of MDMA; consequently, the possible cumulative effects of

      multiple MDMA exposures remain to be evaluated. Finally ...

      the possibility that humans might ... be more sensitive

      to MDMA-induced neurotoxicity must not be overlooked."

     

     Well that's the bad news. The good news is ...

     

      "Coadministration of the selective seratonin uptake inhibitor,

      fluoxetine, completely blocked the reduction in cortical

      serotonin concentrations 1 week after MDMA. Administration

      of fluoxetine at various times after MDMA revealed that the

      long-term effects of the drug developed independently of the

      acute depletion of serotonin."

     

      "...(The) inhibition of the uptake system by 3 hr postMDMA can

      still completely protect the serotonergic neurons from the later

      effects of MDMA."

     

     But the good news gets worse ...

     

      "At 6 hr after MDMA the irreversible effects of the drug have

      progress to the extent that the administration of the fluoxetine

      at this point blocks only an approximate 50% of