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Direct comparison of the acute effects of lysergic acid diethylamide and psilocybin in a double-blind placebo-controlled study in healthy subjects

Summary

This study directly compared two popular psychedelic drugs, LSD and psilocybin (magic mushrooms), in 28 healthy volunteers. Researchers found that these substances produce very similar mental effects when given at equivalent doses, with the main difference being that LSD lasts longer. The study establishes that about 20 milligrams of psilocybin is roughly equivalent to 100 micrograms of LSD. These findings could help guide dosing for future psychiatric treatments using these psychedelics.

Background

Growing interest has emerged in using lysergic acid diethylamide (LSD) and psilocybin in psychiatric research and therapy. However, no modern studies have directly compared the subjective and autonomic effects of these two classic serotonergic psychedelics or established their dose equivalence.

Objective

To directly compare the acute subjective, autonomic, and endocrine effects of LSD and psilocybin at two doses each within the same healthy subjects using a double-blind, placebo-controlled crossover design.

Results

The 100 and 200 µg LSD doses and 30 mg psilocybin produced comparable subjective effects, while 15 mg psilocybin produced significantly weaker effects. LSD had longer effect durations than psilocybin. Psilocybin increased blood pressure more than LSD, whereas LSD increased heart rate more than psilocybin. Both substances showed similar cardiostimulant properties and dose-proportional pharmacokinetics.

Conclusion

Alterations of consciousness induced by LSD and psilocybin do not differ qualitatively beyond effect duration, with differences being dose-dependent rather than substance-dependent. The dose equivalence of LSD to psilocybin is approximately 1:200, with 20 mg psilocybin equivalent to 100 µg LSD. These findings may assist with dose finding for future psychedelic research.
  • Published in:Neuropsychopharmacology,
  • Study Type:Clinical Trial,
  • Source: PMID: 35217796, DOI: 10.1038/s41386-022-01297-2
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