We completed our DMT tolerance study, in which volunteers received either 0.3 mg/kg IV DMT (0.4 mg/kg being our maximum dose), every 30 minutes, 4 times; or else 4 similarly spaced injections of sterile saline placebo. We were interested in assessing whether and how tolerance developed to closely spaced doses of DMT, as field reports were quire variable with respect to this issue. In addition, whether naturally occurring DMT elicits tolerance to its own effects has bearing on what the role of DMT might be in human psychophysiology; that is, if is is involved in naturally occurring "psychedelic" states, tolerance development would suggest that these states would have to be relatively short-lived before reduced effects from tolerance was seen. This is obviously contrary to what is seen clinically.
We have analyzed the data, and have written up and published our results. Biologically, the heart rate effects were reduced over time (i.e. demonstrated "tolerance"), but the primary change was from the first to the second dose, and looked more like volunteers getting used to the experimental set-up, than true tolerance. Blood pressure responses did not vary throughout the morning. However, blood levels of ACTH (adrenal gland stimulating hormone) and prolactin (responsible for lactation and sexual characteristics) both showed gradually decreasing peak effects, and strongly suggested tolerance development. Temperature data was uninterpretable, because of the slowly responding nature of this variable. Elevated temperature in response to DMT does not start manifesting for 15-20 minutes after injection, and does not start falling for at least an hour. Thus, temperature slowly climbed all morning, with a plateau occurring between the end of the third and the fourth sessions. I believe this plateau was not tolerance development, but rather the body compensating for increased core temperature by sweating, which occurred in most of our volunteers by morning’s end. Hallucinogen Rating Scale (HRS) data showed no tolerance developing, except for a trend (rather than truly significant finding) towards a lowering of "Volition" scores, wherein the feelings of "loss of control", "inability to move if asked to", "unable to remind oneself of being in a research ward", and the like are tapped. Other factors: "Somatic", and "Emotional" effects stayed relatively level throughout the sessions.
We have completed our pindolol study, which was intended to block one of the serotonin receptors believed important in mediating DMT’s effects, the serotonin-1A subtype. We have analyzed HRS, blood pressure, and heart rate data, and will soon begin analyzing temperature, ACTH and prolcatin responses. Interestingly, pindolol, discovered by Hofmann at Sandoz, is a lysergaminde derivative, like LSD. It is a small world. Three of the six HRS factors’ responses to DMT were enhanced by pindolol, while another two showed strong trends toward enhanced responses. One was unaffected. Blood pressure responses diminished. Thus, it appears, at least for subjective effects, that the 5-HT-1A receptor has a "buffering" effect on DMT, and when this buffering is blocked, psychological and blood pressure responses are more robust. We have begun magnetic resonance spectroscopy (MRS) studies of DMT’s effects, having studied three volunteers at fully psychedelic doses, but have failed to see much in the visual cortex, where we assumed most activity would reside. However, these negative results are being used to help justify upgrading our scanning center’s hardware and software to allow a newer, more sophisticated method of scanning.
We are hoping to begin our psilocybin dose-response study in the spring, which will be similar in nature to the first DMT study, in which 12 volunteers receive several doeses of psilocybin orally, and biological and psychological responses are characterized. I am interested in hearing from MAPS readers about their experience with synthetic psilocybin concerning dose range. The literature is quite mixed, saying as little as 6 mg or as much as 90 mg is necessary for a "hallucinogenic" effect. I need to get an idea how much pure synthetic psilocybin has what sorts of effects.
One fourth year medical student from the University of Chicage spent a 6 week elective with us in November, 1992, and another was here for a month in March, 1993 from Brooklyn, Both are interested in psychotherapeutic applications of psychedelics, and one is considering coming here to train is psychiatry. Certainly, additional investigators at the University of New Mexico will aid in the expansion of this work from the purely psychopharmacological, to the "pharmaco-therapeutic".
For more information, see Dr. Strasman’s recent scientific articles, Dose-Response Study of N,N-Dimethyltryptamine in Humans, Neuroendocrine, Autonomic, and Cardiovascular Effects, and Subjective Effects and Preliminary Results of A New Rating Scale, in Archives of General Psychiatry, Vol. 51, Feb. 1994, 85-97, and 98-108.