Depression affects an estimated 300 million people around the world and is the leading cause of disability. Therapeutics for depression are widely available. However, they have limited efficacy and can have serious adverse effects that are associated with low patient adherence. The naturally occurring serotonergic hallucinogen psilocybin found in several species of mushrooms has been discussed as a potential treatment for depression. Now, a team of researchers from the University of Oxford and the Northern Ireland Methodology Hub at Queen’s University sought to determine the efficacy of psilocybin as an antidepressant compared with placebo or non-psychoactive drugs. The researchers say their findings are encouraging but further research is needed to clarify the factors that maximize psilocybin’s treatment potential for symptoms of depression.

The findings are published in BMJ Today in an article titled, “Efficacy of psilocybin for treating symptoms of depression: systematic review and meta-analysis.”

The researchers examined databases looking for randomized controlled trials that compared psilocybin as a treatment for symptoms of depression with controls, such as placebo, niacin (vitamin B), or micro doses of psychedelics.

They found seven relevant trials for analysis involving 436 participants with depression (52% female; 90% white). Changes in depression scores were measured using a statistical method called Hedges’ g. A Hedges’ g of 0.2 indicates a small effect, 0.5 a moderate effect, and 0.8 or more a large effect.

The change in depression scores was significantly greater after treatment with psilocybin than with a comparator treatment, with an overall Hedge’s g of 1.64 indicating a large effect size favoring psilocybin.

Further analyses to account for trial differences indicated that having secondary depression (related to an underlying disease) rather than primary depression, being assessed with a self-reported scale rather than a clinician assessed scale, older age, and previous use of psychedelics, were correlated with greater improvements.

The study authors acknowledge that high levels of variation (heterogeneity) between trials resulted in a low certainty of evidence to support a strong antidepressant effect of psilocybin, and generalisability of findings were limited by the lack of participant diversity.

Furthermore, in clinical trials, patients receive psilocybin in a calm living room with soothing music, supervised by a psychotherapist, which is unlikely to be achievable in a healthcare system.

As such, the authors concluded that, although this review’s findings are encouraging for psilocybin’s potential as an effective antidepressant, issues such as cost, lack of regulatory guidelines, and legal safeguards associated with psilocybin treatment need to be dealt with before it can be established in clinical practice.

Furthermore, there is still ongoing debate on whether psychedelics can express antidepressant activity on their own rather than by assisting specific forms of psychotherapy.

The researchers concluded that these promising findings “support a prudent approach in both scholarly and public settings, because more and better evidence is needed before any clinical recommendation can be made about therapeutic use of psilocybin.”

For similar GEN stories related to psilocybin and psychedelics for depression treatment read “Psychedelics Coming into the Modern Age of Medicine,” “Clinical Study Shows Hallucinogenic Magic Mushroom Compound Psilocybin Relieves Depression,” and “No Hallucination: The Launch of Psychedelic Medicine.”

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