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The Psychotomimetic Properties of 3,4,5-Trimethoxyamphetamine

Alexander T. Shulgin, S. Bunnell, T. SargentIII
Nature 189, 1011-1012 (1961)

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dl-3,4,5-Trimethoxyamphetamine (dl-TMA), first prepared as a homologue of mescaline in 19471, has remained to a large measure unexplored. A single paper has described its effects in human subjects2, demonstrating that the drug allows stroboscope-induced hallucinations at the levels employed, namely, 0.8-2.0 mg/kg, orally. In the present work, dl-3,4,5-trimethoxyamphetamine was synthesized by the general method of Ramirez and Burger3 and was chemically identical to that previously described1. Pharmacological similarity was demonstrated by the administration of between 1.6 and 2.0 mg/kg as the hydrochloride, to three adult male subjects. The responses were found to be parallel in intensity and duration to those described earlier2, although the vivid hallucinations reported were not observed.

It has been found, however, that with an increased dosage of the drug, the psychotropic response changed in a most dramatic manner. Dosages of 2.8-3.5 mg/kg were given to five adult male subjects, all of whom had had previous experience with either mescaline or lysergic acid diethylamide.

The physical changes observed were similar for all subjects employed. In each case, after about half an hour, there ensued a period of autonomic distress, characterized by sweating, tremor, and chills as well as nausea and dizziness. This phase lasted no more than an hour. The slight but definite systolic blood pressure increase of about 10 mm. mercury returned to normal at the end of this phase. The concurrent diastolic increase was barely perceptible (ca. 2 mm. mercury). During the remainder of each experiment (approximately another 6-8 hr., which includes the period of extreme mental derangement described below) very few overt physical signs of drug effect were evident. Pupillary dilatation and slight motor incoordination were noted. Pulse increase was negligible.

The psychic changes observed, however, were extreme and showed considerable individual variability. The initial effects, at about 2 hr. from the ingestion of the drug, were mescaline-like, involving intensification of visual experience, including amplification and distortion of colour, texture, form, and spatial relationships. These effects were distinctly less than those expected from a pharmacologically equivalent dose (2x) of mescaline. Auditory and tactile sensations were also intensified, and both paraesthesia and synaesthesia were noted on occasion. None of the subjects displayed the enhanced capacity for empathy characteristic of mescaline.

The emotional responses elicited during the period of maximum dl-3,4,5-trimethoxyamphetamine intoxication (3-5 hr. from the start of the experiment) were striking in their intensity. Anger, hostility, and megalomaniac euphoria dominated the subject's thoughts and conversation. Actual acts of hostility were not observed, but it was felt that, in at least two subjects, provocation would have precipitated homicidal violence. All subjects reported imagery, either patterned or scenic, with eyes closed. Recollection of past experiences did not seem to be enhanced, and intellectual performance appeared to be somewhat impaired. Once the plateau of intoxication had passed, return to normal was rapid. The subjects experienced no clouding of consciousness, and subsequent recall of events was excellent.

Due to unexpectedly anti-social character of the response to larger doses of the drug (a response unobserved in more than 40 mescaline subjects), a warning concerning adequate supervision during experimentation with this new drug seems desirable.

Investigations employing the optical isomers, as well as structural homologues, of dl-3,4,5-trimethoxy- amphetamine are in progress.


  1. Hey, P., Quart. J. Pharm. Pharmacol., 20, 129 (1947)
  2. Peretz, D. I., Smythies, J. R., and Gibson, W. C., J. Mental Sci., 101, 317 (1955)
  3. Ramirez, F. A., and Burger, A., J. Amer. Chem. Soc., 72, 2782 (1950)