Cross tolerance between LSD and psilocybin
In two experiments, using a cross-over design, the development of “direct” tolerance to LSD and psilocybin was measured after 10 (Experiment I) or 9 (Experiment II) volunteers had taken LSD in doses increasing to 1.5 meg/kg over the course of 6–7 days (Experiment I) or 13 days (Experiment II). On another occasion, the same patients received psilocybin in doses increasing to 150 mcg/kg over the course of 6–7 days (Experiment I) or 210 mcg/kg over the course of 13 days (Experiment II).
The development of “cross” tolerance to psilocybin in patients “directly” tolerant to LSD was measured by “challenging” the patients, after they had received LSD chronically, with 150 mcg/kg (Experiment I) or 210 mcg/kg (Experiment II) of psilocybin. “Cross” tolerance to LSD was evaluated by “challenging” the patients, after they had received psilocybin chronically, with 1.5 meg/kg of LSD.
A high degree of “direct” tolerance to LSD developed in both experiments, as manifested by statistically significant reductions in six of the seven parameters of response. Patients “directly” tolerant to LSD were also “cross” tolerant to psilocybin on five (Experiment I) or four (Experiment II) parameters.
Definite “direct” tolerance also developed after chronic administration of psilocybin in both experiments, but statistically significant reductions occurred in fewer parameters of response (four in Experiment I and three in Experiment II) than was the case with LSD. Patients chronically treated with psilocybin were also “cross” tolerant to LSD on four (Experiment I) or three (Experiment II) measurements. The degree of “direct” tolerance to psilocybin was less than the degree of “direct” tolerance to LSD.
The development of “cross” tolerance between LSD and psilocybin reinforces the idea that these two drugs cause psychic disturbances by acting on some common mechanism, or on mechanisms acting through a common final pathway.
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- Balestrieri, A.: Studies on cross tolerance with LSD-25, UML-491 and JB-366. Psychopharmacologia 1, 257–259 (1960).Google Scholar
- Cerletti, A.: Étude pharmacologique de la psilocybine. Section 5, Chapter VII in R. Heim and R. G. Wasson, Les champignons hallucinogènes du Mexique. Paris: Editions du Muséum d'Histoire Naturelle 1958.Google Scholar
- Delay, J., P. Pichot, T. Lemperière, P. J. Nicolas-Charles, et A. M. Quétin: Étude psycho-physiologique et clinique de la psilocybine. Section 5, Chapter VII in R. Heim and R. G. Wasson, Les champignons hallucinogènes du Mexique. Paris: Editions du Muséum d'Histoire Naturelle 1958.Google Scholar
- Edwards, A. L.: Statistical analysis for students in psychology and education. New York. Rhinehart & Co. 1946.Google Scholar
- Hofman, A. R., R. Heim, A. Brack and H. Kobel: Psilocybin, ein psychotroper Wirkstoff an dem Mexikanischen Rauschpilz. Psilocybe Mexicana Heim. Experientia (Basel) 14, 107 (1958a).Google Scholar
- — and P. Troxler: Konstitutionsaufklärung und Synthese von Psilocybin. Experientia (Basel) 14, 397 (1958b).Google Scholar
- Isbell, H.: Comparison of the reactions induced by psilocybin and LSD-25 in man. Psychopharmacologia 1, 29–38 (1959).Google Scholar
- Isbell, H., R. E. Belleville, H. F. Fraser, A. Wikler and C. R. Logan: Studies on lysergic acid diethylamide (LSD-25). I. Effects in former morphine addicts and development of tolerance during chronic intoxication. Arch. Neurol. Psychiat. (Chicago) 76, 468–478 (1956).Google Scholar
- — and E. J. Miner: Studies on lysergic acid diethylamide (LSD-25). III. Attempts to attenuate the LSD-reaction in man by pretreatment with neurohumoral blocking agents. Arch. Neurol. Psychiat. (Chicago) 81, 20–27 (1959).Google Scholar
- Wasson, V. P., and R. G. Wasson: Mushrooms, Russia and history. New York: Pantheon Books 1957.Google Scholar
- Wilcoxon, F.: Some rapid approximate statistical procedures. New York: American Cyanamid Company 1949.Google Scholar
- Winter, C. A., and L. Flataker: Studies on heptazone (6-morpholino-4,4-diphenyl-3 heptanone hydrochloride) in comparison with other analgesic agents. J. Pharmacol. exp. Ther. 98, 305–317 (1950).Google Scholar