A study found that high doses of psilocybin led to a significant reduction in depressive symptoms, with effects observed from the first treatment and sustained over several weeks. The 2024 trial, published in the American Journal of Psychiatry, investigated the effects of psilocybin for severe, treatment-resistant depression.
"Psilocybin, when administered with psychological support, may offer a rapid and durable antidepressant effect for individuals who have not responded to conventional therapies," the authors conclude.
This was a 12-week, open-label trial conducted at Sheppard Pratt Hospital. Participants were 18–65 years of age, in a major depressive episode with documented insufficient benefit from at least five treatments during the current episode. A single dose of synthetic psilocybin (25 mg) was administered. Psychotropic medications were discontinued at least 2 weeks prior to dosing through at least 3 weeks post-dosing. Therapists met with patients for three sessions during pretreatment, during the 8-hour dosing day, and for three integration sessions posttreatment. The primary outcome measure was change in Montgomery-Åsberg Depression Rating scale (MADRS) at 3 weeks posttreatment. Secondary measures including MADRS scores up to 12 weeks posttreatment, and subject-rated scales capturing depression and level of function were completed at baseline and all subsequent visits.
Twelve participants (six male, six female; mean age=40.6 years [SD=9.6]) with severe TRD were followed over the study period. Depressive symptoms were significantly decreased at week 3 (MADRS least-squares mean change=−15.8, 95% CI=−25.4 to −6.3) and Week 12 (MADRS least-squares mean change=−17.2, 95% CI=−25.2 to −9.1). In exploratory analyses, the Oceanic Boundlessness (OB) dimension of the psychedelic experience correlated with post-dosing antidepressant responses. Patients with comorbid PTSD (N=5) showed significantly less antidepressant effect of psilocybin.
Psilocybin is a naturally occurring psychedelic compound found in shrooms, occasionally referred to as "magic mushrooms." Shrooms grow in various regions worldwide, particularly in humid, tropical, and subtropical environments. Once ingested, psilocybin is converted in the body to psilocin, a substance that interacs with serotonin receptors in the brain. Traditionally used as an entheogen or a recreational drug, psilocybin is now being studied for its potential to treat conditions such as depression, anxiety, and addiction.
"As an initial foray into psilocybin treatment for patients with MDD (major depressive disorder) that is difficult-to-treat, this study provided an early indication of safety, tolerability, and promising potential efficacy. An unexplored question concerns the durability of the antidepressant effect beyond 12 weeks and whether durability can be extended with additional dosing," wrote the authors.
Additional dosing is indeed indicated.
Single-Dose Psilocybin for Depression With Severe Treatment Resistance: An Open-Label Trial [psychiatryonline.org]
Previously:
• Mycologist answers the internet's questions about mushrooms
• Psychedelic mushrooms decriminalized in Colorado
• Police raid Oakland's psychedelic mushroom church
• Research into magic mushrooms pondered by Arizona legislators
• A fungi farmer shares his perspective on psilocybin mushrooms
• Tripping on magic mushrooms to treat anorexia nervosa
