Potential safety, benefits, and influence of the placebo effect in microdosing psychedelic drugs: A systematic review

This systematic review (2020) of (mostly) observational studies on microdosing psychedelics (LSD & psilocybin) finds that it is experienced both positively and negatively by participants (n=3,619).

Abstract

“Microdosing psychedelic drugs-that is, taking sub-behavioral doses of lysergic acid diethylamide (LSD) or psilocybin-is a growing practice in Western societies. Taken mainly for creative or mood-enhancing purposes, thousands of users are increasingly being exposed to (micro)doses of psychedelic drugs. In this systematic review, we searched the available evidence from human studies, focusing our results in terms of three main axes: efficacy, safety, and the influence of the placebo effect in microdosing practices. While the available evidence has some strengths (e.g. large sample sizes, robust methodologies) there are also remarkable limitations (e.g. gender bias, heterogeneity of dosing schedules and drugs used). Highly contradictory results have been found, showing both the benefits and detriments of microdosing in terms of mood, creative processes, and energy, among other regards. This review provides a general overview of the methods and approaches used, which could be useful for improving future studies.”

Authors: Genís Ona & José C. Bouso

Notes

This review included 17 studies, of which 10 were observational, three qualitative, and (only) 4 randomized, double-blind, placebo-controlled clinical trials. The latter are linked below:

• Bershad et al (2019) – effects at increased dosages, n=20, 6.5-26µg LSD
• Bershad et al (2020) – mostly fMRI measures, n=20, 13µg LSD
• Family et al (2020) – no negative effects on elderly population, n=48, 5-20µg LSD
• Yanakieva et al (2019) – same participants as one above

The review focused on 1) efficacy/benefits, 2) safety, and 3) placebo effects.

1. Survey studies and the qualitative interviews found positive effects on mood, focus, and creativity. Bershad et al (2019) found increases in experiences of unity and bliss.
2. The legality of drugs was the biggest safety worry (e.g. getting arrested, unknown purity), followed by physiological discomfort, impaired focus and anxiety. The clinical studies found small effects on anxiety (at 26 µg), an increase in blood pressure (at 13 µg), and more frequent headaches.
3. Placebo effects are described in the article with regards to the clinical studies, but it (fully?) misses the expectancy effect which is (probably) a big part of the effects in the observational studies.