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From: lamontg@u.washington.edu (Lamont Granquist) Newsgroups: alt.drugs Subject: New info on MDMA neurotoxicity Date: 1 Apr 1994 21:57:24 GMT Message-ID: <2ni5c4$nq1@news.u.washington.edu> this is from my e-mail (fwd w/permission)... From rickmaps@aol.com Fri Apr 1 13:54:00 1994 >Date: Fri, 01 Apr 94 00:21:22 EST >From: rickmaps@aol.com >To: lamontg@u.washington.edu >Subject: Re: MDMA References > >Lamont, > >You already have virtually all the essential information. The Ricaurte >primate study is unpublished, so its not surprising that you didn't find >anything written about it. Here is the section of the IND application Sasha >referred to: > >Ricaurte (personal communication,1992) and associates at Johns Hopkins >University recently completed the data analysis portion of a primate study >which for the first time has identified a no-effect level for MDMA >neurotoxicity. The study involved six primates, three controls and three >experimental animals who received an oral administration of 2.5 mg/kg of MDMA >once every two weeks for four months (8x). Eight brain regions were examined >for 5-HT and 5-HIAA content. There were no significant differences between >experimental and control animals in any of the brain regions studied. Since a >previous study by Ricaurte (1988a) has shown that a single oral dose of 5.0 >mg/kg causes neurotoxicity only in the thalamus and hypothalamus, this >study demonstrates that the primate no-effect level lies somewhere between >2.5 and 5.0 mg /kg. > >Here is something else from that application: > >H >uman study of response of MDMA users to DMT > > Strassman (personal communication,1992) recently completed an FDA-approved >human study in which the physiological and psychological responses of ele >ven subjects to various i.v. doses of DMT were studied. Physiological >measures included x-endorphin, ACTH, prolactin, corticol, growth hormone, >baseline and maximum rise temperature and pupil diameter responses. >Psychological measures included the Profile of Mood States (POMS) and the >Hallucinogenic Rat >ing Scale (HRS) developed specifically for this experiment. > > Subjects were divided in >to two groups, "MDMA Positive" and "MDMA Negative". The "MDMA Positive" >group included six subjects who had taken MDMA five or more times. Not >including one of those had taken MDMA 75 >-100 times, the average exposure for the "MDMA Positive" group was about >10x. The "MD >MA Negative" group included the remaining five subjects had taken MDMA never >or only once, with an >average exposure of less than 1x. > > Analysis of the physiological measurements revealed no > significant differences between the groups in x-endorphin, ACTH, prolactin, >corticol, growth hormone, baseline and maximum rise temperature responses, >across all four doses of DMT and placebo. The standard analytic tool was >ANOVA with repeated measures. The only significant difference between the " >MDMA Positive" and "MDMA Negative" groups was that the maximum change in >pupil diameter relative to baseline was less in the positives than the >negatives, across all doses of drug/placebo. > Dr. Strassman noted "If one believes that 5-HT2 receptors in the eye >mediate the effect of DMT >on pupil size, then this is oppostive what one would expect; i.e. if >"denervation hypersensitivity" > occurred, one would expect more robust pupil dilation. The pupil data was >the least complete (people were reluctant to open their eyes during the >period of DMT intoxication), thus ANOVA without repea >ted measurements was used as a less than ideal tool." > > Analysis of the psychological data showed no significant differences in the >POMS given both before and after the injections of DMT. Rega >rding the HRS, no differences were noted in responses for any of the 6 >factors between the "MDMA P >ositive" and "MDMA Negative" groups across all doses of DMT/placebo; neither >were there any interaction effects. > > >The most important paper you have missed is by O'Callaghan, in NIDA >Monograph # 136, Assessing Neurotoxicity of Drugs of Abuse. Its available for >free from the National Clearinghouse for Alcohol and Drug Information (301) >468-2600, or 800 729-6686. The paper discusses data that suggests that >lowered serotonin levels do not always reflect neurotoxicity. > >Also, have you seen Charlie Grob's paper in Journal of Nervous and Mental >Disease, Vol. 180, No. 6, June, 1992, p. 345-356 ? > >I'd be curious to learn of your estimation of the neurotoxic risk of MDMA. > >Also, in case you are interested you are invited to join MAPS. The address >is 1801 Tippah Avenue, Charlotte, NC 28205, and general memberships are $30 >or more. The latest newsletter is at the printers and will be send out to >members in the next few weeks. Since earlier today, MAPS can accept credit >card orders. > >Rick Doblin > >