• Daniel F Kelly, Keith Heinzerling, Akanksha Sharma, Shanthi Gowrinathan, Karina Sergi, and Regin Jay Mallari.
• Treatment & Research in Psychedelics Program, Pacific Neuroscience Institute, Santa Monica, California, USA.
• Neurosurgery. 2023 Apr 1; 92 (4): 680694680-694.

AbstractAfter a decades-long pause, psychedelics are again being intensely investigated for treating a wide range of neuropsychiatric ailments including depression, anxiety, addiction, post-traumatic stress disorder, anorexia, and chronic pain syndromes. The classic serotonergic psychedelics psilocybin and lysergic acid diethylamide and nonclassic psychedelics 3,4-methylenedioxymethamphetamine and ketamine are increasingly appreciated as neuroplastogens given their potential to fundamentally alter mood and behavior well beyond the time window of measurable exposure. Imaging studies with psychedelics are also helping advance our understanding of neural networks and connectomics. This resurgence in psychedelic science and psychedelic-assisted therapy has potential significance for the fields of neurosurgery and neuro-oncology and their diverse and challenging patients, many of whom continue to have mental health issues and poor quality of life despite receiving state-of-the-art care. In this study, we review recent and ongoing clinical trials, the set and setting model of psychedelic-assisted therapy, potential risks and adverse events, proposed mechanisms of action, and provide a perspective on how the safe and evidence-based use of psychedelics could potentially benefit many patients, including those with brain tumors, pain syndromes, ruminative disorders, stroke, SAH, TBI, and movement disorders. By leveraging psychedelics' neuroplastic potential to rehabilitate the mind and brain, novel treatments may be possible for many of these patient populations, in some instances working synergistically with current treatments and in some using subpsychedelic doses that do not require mind-altering effects for efficacy. This review aims to encourage broader multidisciplinary collaboration across the neurosciences to explore and help realize the transdiagnostic healing potential of psychedelics.Copyright © 2022 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the Congress of Neurological Surgeons.

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