Abstract
Growing interest has been seen in using lysergic acid diethylamide (LSD) and psilocybin in psychiatric research and therapy. However, no modern studies have evaluated differences in subjective and autonomic effects of LSD and psilocybin or their similarities and dose equivalence. We used a double-blind, randomized, placebo-controlled, crossover design in 28 healthy subjects (14 women, 14 men) who underwent five 25 h sessions and received placebo, LSD (100 and 200 µg), and psilocybin (15 and 30 mg). Test days were separated by at least 10 days. Outcome measures included self-rating scales for subjective effects, autonomic effects, adverse effects, effect durations, plasma levels of brain-derived neurotrophic factor (BDNF), prolactin, cortisol, and oxytocin, and pharmacokinetics. The doses of 100 and 200 µg LSD and 30 mg psilocybin produced comparable subjective effects. The 15 mg psilocybin dose produced clearly weaker subjective effects compared with both doses of LSD and 30 mg psilocybin. The 200 µg dose of LSD induced higher ratings of ego-dissolution, impairments in control and cognition, and anxiety than the 100 µg dose. The 200 µg dose of LSD increased only ratings of ineffability significantly more than 30 mg psilocybin. LSD at both doses had clearly longer effect durations than psilocybin. Psilocybin increased blood pressure more than LSD, whereas LSD increased heart rate more than psilocybin. However, both LSD and psilocybin showed comparable cardiostimulant properties, assessed by the rate-pressure product. Both LSD and psilocybin had dose-proportional pharmacokinetics and first-order elimination. Both doses of LSD and the high dose of psilocybin produced qualitatively and quantitatively very similar subjective effects, indicating that alterations of mind that are induced by LSD and psilocybin do not differ beyond the effect duration. Any differences between LSD and psilocybin are dose-dependent rather than substance-dependent. However, LSD and psilocybin differentially increased heart rate and blood pressure. These results may assist with dose finding for future psychedelic research.Trial registration: ClinicalTrials.gov identifier: NCT03604744
Highlights
IntroductionLysergic acid diethylamide (LSD) and psilocybin are both classic serotonergic psychedelics that are used recreationally [1] and have recently become promising candidates for the treatment of various psychiatric disorders (e.g., anxiety disorders and major depressive disorder) and neurologic disorders (e.g., cluster headache and migraine) [2,3,4,5,6]
Lysergic acid diethylamide (LSD) and psilocybin are both classic serotonergic psychedelics that are used recreationally [1] and have recently become promising candidates for the treatment of various psychiatric disorders and neurologic disorders [2,3,4,5,6]
The subjects were never alone during the acute effect phase, and the investigator was in a room next to the subject for up to 24 h
Summary
Lysergic acid diethylamide (LSD) and psilocybin are both classic serotonergic psychedelics that are used recreationally [1] and have recently become promising candidates for the treatment of various psychiatric disorders (e.g., anxiety disorders and major depressive disorder) and neurologic disorders (e.g., cluster headache and migraine) [2,3,4,5,6]. Both substances induce complex alterations of mind via stimulation of the serotonin 5hydroxytryptamine-2A (5-HT2A) receptor [7,8,9]. Differences between the two substances with regard to their acute effects, similarities, and doseequivalence remain unclear
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
