Researchers at Dartmouth have identified a neural receptor that promotes the therapeutic benefits of psilocybin—a psychedelic compound from certain “magic” mushrooms—without producing hallucinogenic effects. The findings, reported in Molecular Psychiatry, may support development of non-hallucinogenic psilocybin-like medications that are safer and more cost-efficient.
Psilocybin has been shown in trials to provide long-term treatment for depression and anxiety, with some evidence suggesting a single dose can relieve symptoms for 6 to 12 months. However, the compound’s hallucinogenic effects limit its use, as it can trigger psychosis in people with schizophrenia spectrum disorders or family histories of psychosis. Additionally, testing and administering psilocybin-derived drugs requires caretakers to safely guide users through the hallucinogenic experience, significantly increasing treatment costs.
Researchers used a mouse model to study psilocybin’s antidepressant and anti-anxiety effects and found that the compound’s beneficial behavioral effects are routed through serotonin receptor 1B in addition to the receptor 2A, which is responsible for hallucinations. While psilocybin binds to nearly all serotonin receptors, previous research narrowly focused on blocking receptor 2A. The serotonin system is similar across species including mice and humans, with the 1B receptor already serving as a target for many anti-migraine medications.
In the United States, psilocybin remains a Schedule I controlled substance at the federal level, though it has received FDA “Breakthrough Therapy” designation for treating major depressive disorder and treatment-resistant depression. Some states have decriminalized possession and others have proposed or passed laws regulating its clinical use. The new findings could help overcome the obstacles to medical psilocybin use and support development of therapeutic drugs with better safety profiles and efficiency.
This article is an AI-assisted summary. All facts and figures are drawn from the original report: https://home.dartmouth.edu/news/2026/01/study-finds-non-hallucinogenic-psilocybin-neural-receptor