PSYCHEDELIC PRESENTATION
Transcript: Psychedelics in Psychiatry: A Paradigm Shift by TYLER COWDRY ARNP, COE OBJECTIVES OBJECTIVES Understand what psychedelics are and which compounds are being focused on for mental health Develop an understanding of the research, pharmacodynmics, considerations regarding these compounds Discover what psychedelic-assisted therapy is and why preperation and integration is pivotal for efficacy Know the current laws and emerging legislation governering the use of psychedelics OVERVIEW CATALYSTS, NOT CURES • Psychedelics are substances that modulate perception, cognition, and affect, often inducing profound shifts in consciousness • Unlike traditional psychotropics, psychedelics do not simply dampen symptoms but appear to facilitate emotional processing, neuroplasticity, and reconnection to the self — potentially addressing the root causes of psychiatric distress rather than managing surface-level symptoms • Psychedelics induce a transient disintegration of the Default Mode Network resulting in increased cognitive flexibility, enhanced emotional processing, disruption of maladaptive belief systems, and access to unconscious content Psychedelics do not work in isolation — they catalyze psychotherapeutic processes producing non-ordinary states allowing patients to access repressed emotional material, experience profound shifts in self-concept and connection PSILOCYBIN (classic) & MDMA (empathogen) COMP0UNDS PSILOCYBIN PSILOCYBIN (CLASSIC) • 5HT hallucinogenic (LSD, DMT) HISTORY Single-Dose Psilocybin Treatment for Major Depressive Disorder A Randomized Clinical Trial (JAMA, 2023) Efficacy and safety of psilocybin-assisted treatment for major depressive disorder: Prospective 12-month follow-up (Journal of Psychopharmacology, 2022) Mayan and Aztec cultures of Mesoamerica. Teonanácatl ("god" + "fungus") Catholic church suppressed its use after the Spanish exploration Siberian cultures and Santa Claus María Sabina and R. Gordon Wasson Albert Hofman and Sandoz pharmaceuticals 1966 US passed laws prohibiting the production, trade or ingestion of hallucinogenic drugs. 1970 Federal Comprehensive Drug Abuse Prevention and Control Act making psilocybin illegal for research purposes and Schedule I status. PHARMACOLOGY Psilocybin vs. Psilocin Psilocin similar to 5HT with affinity to 1A, 2A, (and 2C) 5HT-2A agonism is responsible for the psychedelic experience, left of right? 5HT-1A turns off the inhibitory interneurons mediated by cortical pyramidal cells = thickened dendritic spines. Pyramidal neurons = “projection neurons” Accelerates activation of AMPA/NMDA receptors = increase in BDNF Induces transient disintegration of the Default Mode Network (DMN) — implicated in self-referential thought, rumination, and rigid cognitive patterns. Dampening of the DMN: increased cognitive flexibility enhanced emotional processing disruption of maladaptive belief systems access to unconscious content increased connection RESEARCH RESEARCH CONT. Therapeutic Effect of Psilocybin in Addiction: A Systematic Review (Frontiers in Psychiatry 2023) Acute Effects of Psilocybin After Escitalopram or Placebo Pretreatment in a Randomized, Double-Blind, Placebo-Controlled, Crossover Study in Healthy Subjects (Clinical Pharmacology & Therapeutics, 2021) Psilocybin Based Therapy for Cancer Related Distress, a Systematic Review and Meta Analysis (BAHI Camile, 2018) ONGOING RESEARCH OCD - Yale University & Brown University trials underway Anorexia Nervosa - University of California, San Francisco (UCSF), Johns Hopkins University, COMPASS Pathways: A phase 2 clinical trial is underway OUD - University of Wisconsin–Madison Clinical Trials, Johns Hopkins University Study, Imperial College London Trial MEASURE 109 PROPOSITION 122 Oregon's Psilocybin Services Act Natural Medicine Health Act WASHINGTON LEGISLATION Drug-drug Interactions Between Psychiatric Medications and MDMA or Psilocybin: A Systematic Review (Psychopharmacology (Berl) 2022) Drug-drug Interactions Between Psychiatric Medications and MDMA or Psilocybin: A Systematic Review (Psychopharmacology Berl, 2023) • 2022 Legislation: The Washington State Legislature directed the Health Care Authority (HCA) to establish a work group. • 2023 Legislation: In May 2023, Governor Jay Inslee signed Senate Bill 5263 into law, mandating University of Washington School of Medicine to facilitate study for clinicians effected by the COVID pandemic • 2024 Ballot Measure: SB 5201, led by Sen. Jesse Salomon which would allow adults 21+ to access certain “psychedelic substances” in a regulated context • Local Decriminalization Efforts: Olympia, Tacoma, Port Townsend OREGON COLORADO Trial of Psilocybin versus Escitalopram for Depression. (New England Journal of Medicine 2021) PSILOCYBIN SESSION Duration: 4-6 hours (depending factors: d2d, food intake, metabolization) Peak effect: 1.5 – 2 hours, Anxiety period at 45 minutes Dose: 25-50 mg of psilocin (this is typically 2.5-5 g) of dried mushrooms (this is variable and depends