Chronic Stress
August 12, 2020
Alan K. Davis, Lynnette A. Averill, Nathan D. Sepeda et al.
83 citations
Among U.S. Special Operations Forces Veterans who completed a psychedelic treatment program with ibogaine and 5-methoxy-N,N-dimethyltryptamine in Mexico between 2017 and 2019, retrospective reports showed very large reductions in suicidal ideation, cognitive impairment, PTSD symptoms, depression, and anxiety from 30 days before to 30 days after treatment, along with a large increase in psychological flexibility. Increased psychological flexibility was strongly linked to reduced cognitive impairment and mental health symptoms. Most participants rated the experience among the top five most personally meaningful, spiritually significant, and psychologically insightful experiences of their lives. The findings are preliminary due to the retrospective, self-report, non-randomized design.
Neuropharmacology
August 13, 2022
Ingrid Donato, Veronica Magar, Sean J. Belouin et al.
49 citations
Psychedelic and entactogen medicines like psilocybin and MDMA, when combined with psychosocial support, show potential for safe, rapid, and durable clinical improvements. Both have received Breakthrough Therapy designation from the US FDA and may gain full approval, with similar regulatory steps in other countries. Regulatory changes are also increasing access to legal or decriminalized psychedelic use outside medical settings. This review covers historical use, current evidence, and policy considerations around standards of practice, consumer protection, community engagement, equitable access, and data standards. It suggests a public-private partnership involving diverse stakeholders to co-create best practices and public policies supporting responsible, ethical use.
Journal of Psychedelic Studies
November 19, 2021
Pratheek Mangini, Lynnette A. Averill, Alan K. Davis
18 citations
Among 27 Special Operations Forces Veterans who reported risky drinking before a psychedelic clinical program in Mexico, retrospective reports showed very large reductions in alcohol use and post-traumatic stress symptoms from before to after treatment, with 85% reducing drinking to non-risky levels (33% abstinent, 52% non-risky drinking). Psychological flexibility increased substantially and was strongly associated with both reductions. The authors call for rigorous longitudinal studies to determine whether psychedelic-assisted therapy holds promise for this population.
Frontiers in Psychiatry
November 23, 2023
Anya Ragnhildstveit, Ryan Khan, Paul Seli et al.
17 citations
A single dose of vaporized bufotoxin from the Sonoran Desert Toad, containing an estimated 10-15 mg of 5-MeO-DMT, produced clinically significant improvements in chronic, treatment-resistant PTSD in a 23-year-old female. Next-day effects included marked reductions in hopelessness and suicide risk, with improvements sustained at 1-, 3-, 6-, and 12-month follow-ups. The subject reported a complete mystical experience, which may underlie the therapeutic activity. No serious adverse events occurred, but acute nausea, overwhelming subjective effects, and late-onset night terrors were reported. Results suggest 5-MeO-DMT is generally tolerable and effective for PTSD, though the findings are non-generalizable and rely on methods not clinically accepted.
Frontiers in Psychiatry
February 9, 2023
Anya Ragnhildstveit, Miriam Kaiyo, Matthew Brian Snyder et al.
10 citations
A 28-year-old woman with complex dissociative posttraumatic stress disorder (D-PTSD) underwent ten sessions of cannabis-assisted psychotherapy (CAP) over five months, combined with cognitive behavioral therapy. After treatment, her pathological dissociation score, measured by the Multidimensional Inventory of Dissociation, dropped by 98.5%, and she no longer met criteria for D-PTSD. She also experienced reduced cognitive distractibility, less emotional suffering, and improved psychosocial functioning. The patient has maintained these gains for over two years. The authors suggest CAP, which produced subjective effects similar to psychedelics like psilocybin and ketamine, warrants further research as a potential treatment for D-PTSD.
European journal of psychotraumatology
August 29, 2023
Lihong Jiang, Amanda J. F. Tamman, Christopher L. Averill et al.
8 citations
Early trauma is linked to stronger glutamatergic synaptic strength in people with PTSD, measured via a novel in vivo marker called energy per cycle (EPC). In a sample of 34 adults (16 with PTSD, 18 healthy controls), higher early trauma correlated with higher EPC only in the PTSD group. Greater synaptic strength was associated with reduced behavioral inhibition, and EPC mediated stronger links between reward responsiveness and early trauma. These findings suggest that trauma-induced changes in synaptic plasticity may underlie psychiatric risk and point to potential targets for treatments like ketamine and psilocybin.
Psychiatric Annals
February 1, 2020
Lynnette A. Averill, Christopher L. Averill, Chadi G. Abdallah
6 citations
Ketamine's discovery as a rapid antidepressant has transformed drug development and understanding of chronic stress pathology. This review covers the history of NMDA receptor modulators leading to ketamine's psychiatric use, its rapid antidepressant and antisuicidal effects, a model of synaptic loss and dysconnectivity underlying chronic stress pathology, clinically relevant biomarkers and mechanisms, and how ketamine may both reverse chronic stress pathology and serve as a research tool. The authors discuss outstanding questions and the ongoing debate between optimism and concern about ketamine's widespread use.
medRxiv Preprint Server
April 10, 2020
Chadi G. Abdallah, Kyung-Heup Ahn, Lynnette A. Averill et al.
1 citation
preprint
A robust and reproducible brain connectivity fingerprint (CFP) was identified during ketamine infusion in healthy participants, characterized by reduced connectivity within primary cortices and the executive network, but increased connectivity between the executive network and the rest of the brain. This same CFP measured one week after treatment in major depressive disorder patients predicted response to eight weeks of sertraline, but not placebo. The findings suggest a brain network biomarker that links ketamine's acute effects to the mechanisms of conventional antidepressants.
Expert Opinion on Drug Discovery
July 4, 2026
Christopher D. Verrico, Lynnette A. Averill, Cameron J Moore et al.
Ibogaine, a natural alkaloid, shows potential for treating substance use disorders, trauma, mood disorders, and suicidality, but clinical use is limited by safety concerns and regulatory barriers. Researchers are pursuing two main strategies: developing ibogaine-like compounds that keep broad effects while reducing risks, and creating selective 'bespoke' analogs targeting specific conditions like opioid use disorder, traumatic brain injury, or PTSD. The authors emphasize that the field should avoid oversimplified views that derivatives are uniformly better or interchangeable, and call for greater conceptual clarity and mechanistic humility as ibogaine-based therapies move toward regulated medical use.