A small study suggests that the key ingredient in hallucinogenic mushrooms, psilocybin, can quickly and dramatically relieve depression in the right therapeutic context.
A month after receiving two doses of the psychedelic drug, 13 people had major falls in depressive symptoms, according to researchers Nov. 4 at JAMA Psychiatry.
Because the study was small and lacked diversity of participants, it is unclear whether the positive results would extend to wider populations. Still, “the current results are clear,” says Jay Olson, a psychology researcher at Harvard University who did not participate in the study. "At least for some people, psilocybin can reduce depression better than several common treatment options."
Existing antidepressant drugs do not work well for an estimated 30 to 50 percent of people who try them; when they work, the effects can take weeks to start. Psilocybin, a compound that can profoundly alter consciousness and perceptions of reality, could be a powerful alternative, says co-author Roland Griffiths, a neuropsychopharmacologist at the Johns Hopkins School of Medicine.
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In the new study, patients with moderate or severe depression received two doses of psilocybin tablets spaced about a week and a half apart. Participants also received therapy and support from researchers before, during, and after taking psilocybin.
A comparison group of 11 people waited eight weeks, and also received both doses of psilocybin and supportive therapy. This delay allowed researchers to look for improvements in symptoms that were not drug-related.
Clinicians used a common depression rating scale consisting of 17 items to measure participants ’symptoms. Scores can range from 0 to 52, with higher numbers indicating more severe depression. Before receiving psilocybin, participants who took the drug without delay scored an average of 22.9 points, indicating the end of moderate depression. Four weeks after the second dose, mean scores dropped to 8.5. A score of 7 or lower does not indicate depression. The scores of the comparison group were around 23 while those people were waiting their turn to get the drug.
Overall, 13 of 24 people, including those who received psilocybin immediately and those who did so later, met the definition of remission four weeks after their respective treatments. Griffiths says the drops in depressive symptoms are substantial compared to those found by some standard antidepressant tests.
As with clinical studies in general, positive effects may arise simply from participants ’expectations, not from the drug itself. But such effects are unlikely to explain the magnitude of the observed drop, Olson says.
New findings on the antidepressant effects of psilocybin fit with previous ones: a dose of the drug relieves depression and anxiety in a small group of cancer patients, effects that in some cases lasted for years, some of the same researchers reported in January (SN: 28 / 01/20). Another study, published in Lancet Psychiatry in 2016, found that signs of depression fell in 12 people three months after two doses of psilocybin and psychological support.
Overall, the approach is promising, Griffiths says, but questions still remain. “We still need to collect more security data and we need to know the conditions for optimal administration,” he says.
Other questions refer to who might benefit from the drug and who might not, and a diverse study population could help address this. In the new study, however, almost all participants were white; there was only one Asian participant and one African American participant. “We really need to think more about who we include in these studies,” says psychologist Monnica Williams of the University of Ottawa, who was not involved in the research.
Increasing participation rates among people of color requires additional effort, especially in the context of racial health disparities. A history of negative health care experiences can shape a psychedelic treatment experience, which is sensitive to configuration, Williams says. “A person of color can have many reasons to feel very guarded and anxious in that situation, which will make it harder for that approach to be effective,” he says.
Of 282 people who participated in psychedelic studies between 1993 and 2017, the vast majority (82 percent) were white, Williams and colleagues reported in a review article published in 2018 in BMC Psychiatry. “We’re in the 21st century now,” she says. "There's no longer a reason for that."