Anderson et al. (1978). Absolute configuration and psychotomimetic activity.
Anderson, G. M., Braun, G., Braun, U., Nichols, D. E. & Shulgin, A. T. (1978). Absolute
configuration and psychotomimetic activity. NIDA Research Monograph, 22, 8-15.
http://www.maps.org/publications/1978_anderson_1.pdf
Purpose: Pharmacological, psychological; Comparison of effects of the R and S isomers of MDMA, and argument for placing MDMA in a classification separate from the classic hallucinogens on the basis of the profile of these isomers.
Design: Non-experimental uncontrolled within-subjects design, wherein all volunteers received at least one dose of each form of MDMA; racemate, R-MDMA and S-MDMA, at doses including those of 40-200 mg. (Also performed comparative studies on rabbits wherein hyperthermic response to racemate and each isomer of MDMA was compared with response to the phenethylamine classic hallucinogen, DOM).
Subjects: Unspecified number (perhaps 6 (6 x 5)?) of human volunteers, probably including the authors, gender and ages of volunteers not provided. Information on subject recruitment not provided. Criteria for Inclusion – Prior experience with psychedelic drugs. (An unspecified number of rabbits were used in studies of drug-induced hyperthermia).
Measures: An author-constructed five-point rating scale for overall drug effects, with rating dependent upon degree and intensity / intrusiveness (described as “disruptiveness”) of subjective drug effects, and open-ended narratives wherein volunteers described drug effects. (Rectal hyperthermia in rabbits)
Analyses: No formal analyses were performed. Comparative drug effects of racemic MDMA, R-MDMA and S-MDMA are presented in descriptive form.
Results: Volunteers reported that racemic MDMA was active at 5 mg – 150 mg. S-MDMA was reported to be effective at doses of 80 mg – 120 mg. The effective doses for R-MDMA were far higher, and even 200 mg. R-MDMA did not produce the full intoxication obtained with racemic MDMA. Most of the emotional and sensory effects reported with the racemate are present with S-MDMA, but volunteers reported that they preferred the racemate to S-MDMA alone. The physiological effects of the racemate were also present with S-MDMA, including dilated pupils (mydriasis) and jaw clenching. R-MDMA did not produce these physiological effects. However, 2 / 6 or 2 / 35 reported “color enhancement” with RMDMA but not with S-MDMA. (These volunteers reported experiencing color enhancement with racemic MDMA). The authors conclude that the effects found with each isomer, alone or summed, did not account for the effects of racemic MDMA. (In rabbits, S-MDMA produced greater elevation in body temperature (rectal hyperthermia) than either R-MDMA or racemic MDMA).
Overall Effects: S-MDMA was far more active than the R-enantiomer and moderately more active than the racemate. S-MDMA had a lower effective dose than the R-enantiomer and it seemed to produce most or all of the effects associated with racemic MDMA, including psychological effects and side effects. R-MDMA was found to have a much higher effective dose range, and it did not produce an intoxication comparable to racemic MDMA even after 200 mg R-MDMA. With the possible exception of altered perception of color, S-MDMA appeared to possess most of the effects of the racemate. Nevertheless, volunteers preferred the effects of the racemate to either R-MDMA or S-MDMA, and the authors conclude that racemic MDMA produces effects that are not simply the sum of the effects produced by each enantiomer alone. The authors argue that because the R-enantiomers of hallucinogens are typically more potent than S-enantiomers and MDMA was more active as the S-enantiomer, MDMA should not be classed as a hallucinogen. (As with humans, studies with rabbits indicated that the S-enantiomer of MDMA was more active than the R-enantiomer, when hyperthermia is used as a test of activity).
Adverse Effects: See above; an unspecified number of volunteers reported sweating and jaw clenching with racemic MDMA and with S-MDMA.
