Psilocybin with psychotherapy and loss of pleasure in treatment-resistant depression

The question

Does psilocybin given alongside psychotherapy reduce anhedonia — the loss of pleasure or interest in things once enjoyed — in people whose depression has not responded to standard treatments?

What they did

This was a secondary analysis of a randomized, waitlist-controlled trial. Thirty people with treatment-resistant depression, diagnosed with either major depressive disorder or bipolar II disorder, received at least one 25 mg oral dose of psilocybin together with psychotherapy. Anhedonia was measured with the Snaith-Hamilton Pleasure Scale, and overall depression with the Montgomery-Asberg Depression Rating Scale.

What they found

Anhedonia scores fell significantly two weeks after treatment, the study’s main time point (F(8, 143.48) = 3.43, p = 0.001, n = 29). The authors report that improvements they considered clinically meaningful were still present at three months and six months. An exploratory analysis looked at whether the change in anhedonia was explained by change in overall depression severity; the abstract does not report the result of that analysis.

The fine print

Only 30 people took part, and the comparison group was a waitlist rather than a placebo, so expectation effects cannot be ruled out. Participants and therapists knew who received psilocybin. This was a secondary analysis, meaning anhedonia was not the original trial’s main question, and the abstract gives no data on side effects. This summary is based on the abstract alone.

What it means

In a small, unblinded trial, psilocybin with psychotherapy was followed by reduced loss of pleasure in people with hard-to-treat depression, but larger placebo-controlled trials are needed before drawing firm conclusions.

Evidence grade: Low. This is a small secondary analysis of a waitlist-controlled trial with no placebo and no blinding, so the findings are preliminary.

This summary is based on the study’s published abstract.