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      Psychedelic Therapies at the Crossroads of Trauma and Substance Use: Historical Perspectives and Future Directions, Taking a Lead From New Mexico

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          Abstract

          Post-traumatic stress disorder (PTSD), a common condition with potentially devastating individual, family, and societal consequences, is highly associated with substance use disorders (SUDs). The association between PTSD and SUD is complex and may involve adverse childhood experiences (ACEs), historical and multi-generational traumas, and social determinants of health as well as cultural and spiritual contexts. Current psychosocial and pharmacological treatments for PTSD are only modestly effective, and there is a need for more research on therapeutic interventions for co-occurring PTSD and SUD, including whether to provide integrated or sequential treatments. There is a current resurgence of interest in psychedelics as potential treatment augmentation for PTSD and SUDs with an appreciation of the risks in this target population. This paper reviews the historical perspective of psychedelic research and practices, as well as the intersection of historical trauma, ACEs, PTSD, and SUDs through the lens of New Mexico. New Mexico is a state with high populations of Indigenous and Hispanic peoples as well as high rates of trauma, PTSD, and SUDs. Researchers in New Mexico have been leaders in psychedelic research. Future directions for psychedelic researchers to consider are discussed, including the importance of community-based participatory approaches that are more inclusive and respectful of Indigenous and other minority communities.

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          The effect of multiple adverse childhood experiences on health: a systematic review and meta-analysis

          A growing body of research identifies the harmful effects that adverse childhood experiences (ACEs; occurring during childhood or adolescence; eg, child maltreatment or exposure to domestic violence) have on health throughout life. Studies have quantified such effects for individual ACEs. However, ACEs frequently co-occur and no synthesis of findings from studies measuring the effect of multiple ACE types has been done.
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            Psilocybin-assisted treatment for alcohol dependence: a proof-of-concept study.

            Several lines of evidence suggest that classic (5HT2A agonist) hallucinogens have clinically relevant effects in alcohol and drug addiction. Although recent studies have investigated the effects of psilocybin in various populations, there have been no studies on the efficacy of psilocybin for alcohol dependence. We conducted a single-group proof-of-concept study to quantify acute effects of psilocybin in alcohol-dependent participants and to provide preliminary outcome and safety data. Ten volunteers with DSM-IV alcohol dependence received orally administered psilocybin in one or two supervised sessions in addition to Motivational Enhancement Therapy and therapy sessions devoted to preparation for and debriefing from the psilocybin sessions. Participants' responses to psilocybin were qualitatively similar to those described in other populations. Abstinence did not increase significantly in the first 4 weeks of treatment (when participants had not yet received psilocybin), but increased significantly following psilocybin administration (p < 0.05). Gains were largely maintained at follow-up to 36 weeks. The intensity of effects in the first psilocybin session (at week 4) strongly predicted change in drinking during weeks 5-8 (r = 0.76 to r = 0.89) and also predicted decreases in craving and increases in abstinence self-efficacy during week 5. There were no significant treatment-related adverse events. These preliminary findings provide a strong rationale for controlled trials with larger samples to investigate efficacy and mechanisms.
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              Pilot study of the 5-HT2AR agonist psilocybin in the treatment of tobacco addiction.

              Despite suggestive early findings on the therapeutic use of hallucinogens in the treatment of substance use disorders, rigorous follow-up has not been conducted. To determine the safety and feasibility of psilocybin as an adjunct to tobacco smoking cessation treatment we conducted an open-label pilot study administering moderate (20 mg/70 kg) and high (30 mg/70 kg) doses of psilocybin within a structured 15-week smoking cessation treatment protocol. Participants were 15 psychiatrically healthy nicotine-dependent smokers (10 males; mean age of 51 years), with a mean of six previous lifetime quit attempts, and smoking a mean of 19 cigarettes per day for a mean of 31 years at intake. Biomarkers assessing smoking status, and self-report measures of smoking behavior demonstrated that 12 of 15 participants (80%) showed seven-day point prevalence abstinence at 6-month follow-up. The observed smoking cessation rate substantially exceeds rates commonly reported for other behavioral and/or pharmacological therapies (typically <35%). Although the open-label design does not allow for definitive conclusions regarding the efficacy of psilocybin, these findings suggest psilocybin may be a potentially efficacious adjunct to current smoking cessation treatment models. The present study illustrates a framework for future research on the efficacy and mechanisms of hallucinogen-facilitated treatment of addiction.
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                Author and article information

                Contributors
                Journal
                Front Pharmacol
                Front Pharmacol
                Front. Pharmacol.
                Frontiers in Pharmacology
                Frontiers Media S.A.
                1663-9812
                27 June 2022
                2022
                : 13
                : 905753
                Affiliations
                [1] 1 Department of Psychiatry and Behavioral Sciences , University of New Mexico , Albuquerque, NM, United States
                [2] 2 Department of Family and Community Medicine , University of New Mexico , Albuquerque, NM, United States
                [3] 3 College of Nursing , University of New Mexico , Albuquerque, NM, United States
                [4] 4 College of Population Health , University of New Mexico , Albuquerque, NM, United States
                [5] 5 Center for Native American Health , University of New Mexico , Albuquerque, NM, United States
                [6] 6 American Indian Health Research and Education , University of New Mexico , Albuquerque, NM, United States
                [7] 7 Executive Vice President , University of New Mexico Health Sciences Center , Albuquerque, NM, United States
                Author notes

                Edited by: Candace R. Lewis, Arizona State University, United States

                Reviewed by: Brian Barnett, Cleveland Clinic, United States

                Anna Forsyth, The University of Auckland, New Zealand

                *Correspondence: Snehal R. Bhatt, sbhatt@ 123456salud.unm.edu

                This article was submitted to Neuropharmacology, a section of the journal Frontiers in Pharmacology

                Article
                905753
                10.3389/fphar.2022.905753
                9273054
                35833023
                f65c4832-c7c7-4936-804f-38b032888a58
                Copyright © 2022 Bhatt, Armstrong, Parker, Maviglia, Kass, Leeman, Romo and Ziedonis.

                This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

                History
                : 27 March 2022
                : 02 June 2022
                Categories
                Pharmacology
                Review

                Pharmacology & Pharmaceutical medicine
                ptsd,psychedelics,adverse childhood experiences,social determinants of health,ai/an health,substance use

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