Psilocybin

Psilocybin, a psychoactive compound from over 200 mushroom species, has a long history in Indigenous sacred rituals. It binds to serotonin receptors, activating the serotonergic system to promote neuroplasticity, which helps individuals derive meaning from psychedelic experiences. Evidence suggests benefits for major depressive disorder, anxiety disorders, existential suffering, and substance use disorders. Dosing ranges from low psycholytic to high psychoactive levels. While physiological harm to humans appears low, further research is needed on cardiac and neurological safety in diverse and vulnerable groups. Legal access is expanding through decriminalization, legalization, and right-to-try approaches, varying by region.

Study at a glance

Abstract

Abstract Psilocybin, a naturally occurring psychoactive compound found in more than 200 mushroom species, has an enduring history of use in sacred rituals of Indigenous healers worldwide. With selective serotonin receptor binding, activation of the serotonergic neurological system enables psilocybin to potentiate neuroplasticity, enabling individuals to engage in meaning-making from psychedelic experiences. There is growing evidence of benefit in major depressive disorder, anxiety disorders, existential suffering/demoralization, and promise in substance use disorders. Dosing ranges from lower “psycholytic” doses to higher “psychoactive” doses. Although there is low evidence of physiological harm to humans, further studies are needed to explore cardiac and neurological safety in diverse and vulnerable populations. Legal access is expanding through decriminalization, legalization, and “right-to-try” approaches, depending on the country and region. Future directions include expanded research; equitable access for vulnerable populations; reciprocity for Indigenous populations; and ensuring palliative patients, caregivers, and health care providers benefit from ethical and transparent research and clinical practice.