The science of psychedelic medicine.

Classic psychedelics, acting at the serotonin 5-HT2A receptor, alter brain function and consciousness. Research converges on two complementary processes: acute neural desynchronization, which destabilizes entrenched network patterns, and subacute neuroplasticity, which opens a window for psychological and behavioral change. Evidence of therapeutic response across neuropsychiatric indications is reviewed, integrating mechanistic findings. Challenges include discrepancies between preclinical evidence that non-hallucinogenic psychedelic analogs engage putative therapeutic mechanisms and clinical evidence linking subjective experience to therapeutic response, risks of enhanced neuroplasticity, and questions about trial design, scalability, and regulatory approval. The growth of psychedelic science may compel a rethinking of the relationship between subjective experience and biological change in psychiatry.

Study at a glance

Abstract

Classic psychedelics typically act at the serotonin 5-HT2A receptor to profoundly alter brain function and consciousness. Research on these compounds has accelerated. Major strides have been made in understanding their unique mechanisms of action and clinical potential. This Review outlines the state of psychedelic science, spanning cellular mechanisms, systems neuroscience and clinical investigation. We show that preclinical and human research findings converge on two complementary processes: acute neural desynchronization, which destabilizes entrenched network patterns, and subacute neuroplasticity, which opens a window for psychological and behavioral change. We review evidence of therapeutic response across neuropsychiatric indications and consider how this integrates with mechanistic findings. We also explore challenges and opportunities, including discrepancies between preclinical evidence that non-hallucinogenic psychedelic analogs engage putative therapeutic mechanisms, and clinical evidence linking the subjective experience to therapeutic response; the risks inherent to enhanced neuroplasticity; and questions surrounding trial design, scalability and regulatory approval. The growth of psychedelic science and medicine may compel a fundamental rethinking of the relationship between subjective experience and biological change in psychiatry.