Discussion
psychedelic drug
The present study directly compared the acute effects of mescaline, LSD, and psilocybin within the same healthy participants. Contemporary research has mostly focused on investigating a single psychedelic substance. Comparisons of serotonergic psychedelics are lacking, except for one recently published study that directly compared LSD and psilocybin [We hypothesized that mescaline, LSD, and psilocybin would induce comparable subjective effects due to their shared 5-HTSubjective effects of equivalent doses of the three substances (500 mg mescaline, 100 µg LSD, and 20 mg psilocybin) were similar across various acute effect rating scales. Interestingly, on the AMRS, the condition that caused the highest level of “inactivity” was the low 300 mg mescaline dose. In summary, subjective effects of mescaline, LSD, and psilocybin at equivalent doses were comparable.The three substances differed in their pharmacokinetics and associated durations of action. As previously reported [The present study was the first to accurately determine the pharmacokinetics of mescaline in humans in a large study using validated analytical methods. The half-life of mescaline was previously reported to be 6 h [Autonomic effects of mescaline were comparable to those of LSD and psilocybin [In the present study, blinding across substances was largely sustained during the peak/plateau phase and to a lesser degree even after the study. The condition with the highest probability of being correctly identified was placebo. However, no condition was identified correctly in 100% of the cases, not even placebo at the end-of-study visit. The high 500 mg mescaline dose was never mistaken for psilocybin during the session at t = 3 h and was never mistaken for placebo after the study. LSD and psilocybin were never mistaken for placebo at either t = 3 h or after the study. Placebo was mistaken for 500 mg mescaline by one participant at t = 3 h and was mistaken by another participant for 300 mg mescaline after the study. At t = 3 h, the high mescaline dose was most commonly mistaken for LSD and the low mescaline dose was most commonly mistaken for either LSD or placebo. LSD was most commonly mistaken for either psilocybin or the mescaline 300 mg dose and psilocybin was most commonly mistaken for LSD. This pattern persisted, though at lower numbers, after the study despite the clear differences in effect durations. These findings indicate that any differences in alterations of consciousness that are induced by mescaline, LSD, and psilocybin are dose-dependent rather than substance-dependent and that their distinct pharmacological profiles [In the present study, both 500 mg mescaline and LSD, but not psilocybin, enhanced circulating oxytocin. Therefore, the present study was the first to document elevated plasma oxytocin levels in response to mescaline as it was previously shown for LSD [The strengths of the present study include its evaluation and use of equivalent doses of three classic psychedelics in a within-subjects design, compared with placebo and in a double-blind laboratory setting. A large study sample was used, with equal numbers of male and female participants. Plasma substance concentrations of all compounds were determined at short intervals up to 24 h. All substances were analyzed with validated analytical methods. As for its limitations; we failed to achieve instant dose equivalence, leading to a subsequent increase in the mescaline dose from 300 to 500 mg. The study thus tested two doses of mescaline against LSD and psilocybin. The comparison of the low and high mescaline doses was between-subjects and their allocation was neither random nor blinded. The study used a highly controlled hospital setting and included only healthy participants, most of whom were experienced psychedelic drug users. Therefore, patients who undergo psychedelic therapy may respond differently to mescaline, LSD, or psilocybin. Lastly, our psychometric instruments may not have been sufficiently sensitive to capture the complex phenomenology of these substances. Subtle qualitative subjective effect differences between mescaline, LSD, and psilocybin may not necessarily be excluded.