The effects of classical psychedelics on mood and depression Original paper

Psychedelics — especially “classical psychedelics”, such as LSD and psilocybin — have regained popularity as a potential treatment for mood disorders, such as anxiety and depression. Is this popularity warranted?

The 12 randomized controlled trials in this meta-analysis assessed the effects of LSD, psilocybin, and ayahuasca on mood and depression in people with or without depression, treatment-resistant depression, or life-threatening illnesses.

• In seven trials, the control was a placebo.
• In two trials, the control was niacin (which makes the skin flush and tingle).
• In one trial, the control was methylphenidate (a stimulant commonly used for ADHD)
• In one trial, the control was an LSD dose ten times smaller than the intervention.
• In one trial, the control was a psilocybin dose ten times smaller than the intervention.

LSD and psilocybin were similarly effective at alleviating negative mood in healthy individuals and people with mood disorders.

LSD, psilocybin, and ayahuasca alleviated depression acutely (3 hours to 1 day) and on the medium term (2 to 15 days). Psilocybin also alleviated depression on the long term (16 to 60 days). All of the studies on depression were conducted in people with mood disorders. In all cases, the effect was medium to large.

The psychedelics were generally well tolerated, but were sometimes associated with anxiety, crying, headache, mild nausea, and vomiting, and with small increases in heart rate, blood pressure, and pupil size.

There was no evidence of publication bias.

Because taking psychedelics produces an obvious and fairly unique experience, it can be difficult to decide what to give people in the control group. The 12 trials included in this meta-analysis took varied approaches, each with its benefits and drawbacks.

For instance, since LSD can be quite stimulating, methylphenidate and niacin (which makes your body tingle) are decent controls — but they don’t produce visual or emotional effects comparable to LSD’s.

If, in the future, researchers gain the ability to design new psychedelics that vary slightly in their pharmacokinetics and pharmacodynamics, they’ll be able to run better controlled studies.