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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Isbell, H., Wolbach, A.B., Wikler, A. et al. Cross tolerance between LSD and psilocybin. Psychopharmacologia 2, 147–159 (1961). https://doi.org/10.1007/BF00407974
- Common Mechanism
- Chronic Administration
- Common Final Pathway
- Final Pathway