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Psilocybin Compared to Antidepressant in Breakthrough Trial

By Ruairi J Mackenzie

Published: Apr 15, 2021   
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A new trial has directly compared the antidepressant effects of the compound psilocybin with a classical selective serotonin reuptake inhibitor (SSRI) antidepressant, showing the two are matched in their mood-altering potential.

The results were published today in the New England Journal of Medicine by researchers from Imperial College London’s Centre for Psychedelic Research. The study team compared two regimens, one a six-week course with the classical antidepressant, escitalopram, and the other two sessions of psychedelic therapy using psilocybin, which is the active compound in magic mushrooms.

The study involved 59 people and is one the most rigorous trials yet conducted of the therapeutic potential of a psychedelic compound.

The study’s results suggested that psilocybin and escitalopram were evenly matched in their antidepressant potential. While the psychedelic compound’s treatment effect trended towards being faster and more pronounced than that of the SSRI, no significant differences between the groups were found, which the researchers say is evidence that a follow up study with more participants is required.

Study lead Dr Robin Carhart-Harris, head of the Centre for Psychedelic Research at Imperial, said that “these results comparing 2 doses of psilocybin therapy with 43 daily doses of one of the best performing SSRI antidepressants help contextualize psilocybin’s promise as a potential mental health treatment. Remission rates were twice as high in the psilocybin group than the escitalopram group.”

The 2 groups of volunteers were initially given either a 25 mg or a 1 mg dose of psilocybin, with the latter being so small as to not have any biological effect. This was to ensure that both groups thought they had received the psilocybin treatment. After a therapy session, both groups were given unmarked pills to take over a six-week period – placebo pills for the psilocybin group and escitalopram for the comparison group.

The team urged caution in their discussion, pointing out that the small number of participants and their cohort’s lack of sexual or ethnic diversity meant that results could not be widely extrapolated. Importantly, they also emphasized the controlled environment in which their volunteers consumed the psychedelic – patients with depression should not attempt to self-medicate with psilocybin.

Carhart-Harris encouraged researchers and the public to look into their data, concluding that “these latest findings build on our previous research testing psilocybin therapy for treatment resistant depression, and offer the most compelling evidence yet to support efforts towards licensing psilocybin therapy as a regulated mental health intervention.”


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