A single does psilocybin help with depression?, the mind-altering component of magic mushrooms, improved depression in treatment-resistant patients, a new study suggests. In the largest-ever randomized clinical trial of this hallucinogen, psilocybin significantly reduced symptoms in people with major depressive disorder (MDD) who had failed to respond to two previous antidepressants and psychotherapies. The findings were published Wednesday in the New England Journal of Medicine. The researchers gave the participants 25 milligrams of the synthetic drug COMP360, in combination with a sedative and psychological support. The scientists found that the drug had an immediate and sustained effect, which lasted at least one month.
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The researchers measured the change in the participants’ Montgomery-Asberg Depression Rating Scale scores — the standard measurement of depression — from baseline to one week after treatment. They also compared their results to a control group that received the same therapy, but did not receive a psilocybin dose. The results suggest that a single, moderate dose of psilocybin reduces MDD symptoms more than placebo and that the drug does so in an open-label setting. However, the researchers note that larger trials with longer follow-up periods are needed to confirm the results.
Scientists have known for some time that psychedelic drugs increase neuroplasticity, the brain’s ability to strengthen connections between neurons. In a 2022 study, for example, Nutt and his team found that psilocybin reduced depression in some patients more than SSRIs did, even though the latter increased neuroplasticity.
The researchers in the new study also found that the intensity of the psilocybin experience did not predict how well it worked to treat depression. They speculate that psilocybin might disrupt negative cycles of rumination that are typical in depression, rather than directly acting on monoamine neurotransmitters. The results are encouraging, but it’s too early to say if psilocybin could be used as a standalone antidepressant. The results from the study may help guide future trials, however.