Expert Opinion on Drug Discovery
July 4, 2026
Christopher D. Verrico, Lynnette A. Averill, Cameron J Moore et al.
INTRODUCTION: Ibogaine is a naturally occurring indole alkaloid with suggested therapeutic potential across substance use disorders, trauma-related conditions, mood disorders, and suicidality. However, its clinical translation has been hindered by safety concerns, regulatory barriers, and uncertainty regarding its complex pharmacology. Recent interest has surged in developing ibogaine analogs...
FOCUS The Journal of Lifelong Learning in Psychiatry
July 1, 2026
Lynnette A. Averill, Logan Neitzke-Spruill
Psychedelic-assisted therapies (PATs) are emerging as novel combination treatments for selected stress- and trauma-related psychiatric conditions, particularly in cases where existing pharmacologic and psychotherapeutic approaches have provided limited benefit. Although current mechanistic models emphasize neuroplasticity, large-scale network changes, and modulation of neurotransmitter systems,...
iScience
January 16, 2026
Amir Valizadeh, John D Roache, Xinyu Zhang et al.
2 citations
Post-traumatic stress disorder (PTSD) exhibits extensive clinical and biological variability, making treatment challenging. The Consortium to Alleviate PTSD (CAP)-ketamine trial, the largest randomized study of ketamine for PTSD, found no overall benefit of ketamine over placebo, underscoring the necessity to identify responsive subgroups. Using pre-treatment blood DNA methylation profiles and...
JAMA Netw Open
January 2, 2026
Amy L. Mcguire, Logan Neitzke-Spruill, Jill O. Robinson et al.
4 citations
Importance: The availability of psychedelic retreats has grown to meet the demand for access to these substances. Despite centuries of use among Indigenous communities, psychedelics can pose serious risks for some users. Objective: To determine safety precautions that retreat organizations that offer psychedelic substances currently use. Design, Setting, and Participants: This qualitative study...
The American journal of bioethics : AJOB
2025
Logan Neitzke-Spruill, Caroline Beit, Lynnette A. Averill et al.
19 citations
In August 2024, The U.S. Food and Drug Administration rejected Lykos Therapeutics, Inc.'s new drug application for midomafetamine with psychological intervention (MDMA-AT) to treat post-traumatic stress disorder (PTSD). Among the many issues raised during review was concern about a highly publicized case of alleged sexual misconduct by an unlicensed therapist during a Phase 2 study of MDMA and...
Brazilian Journal of Psychiatry
2025
David S. Mathai, Jill O. Robinson, Kevin Wagner et al.
1 citation
OBJECTIVE: Despite growing research on the potential mental health benefits of psychedelics, there has been limited study of these drugs in populations with obsessive-compulsive disorder (OCD) and with Hispanic and Latin American (H/L) ancestry. METHODS: Demographic and clinical assessments were conducted as part of the Latin American Trans-ancestry Initiative for OCD genomics (LATINO) Study in...
Military psychology : the official journal of the Division of Military Psychology, American Psychological Association
2024
Stacey B. Armstrong, Yitong Xin, Nathan D. Sepeda et al.
19 citations
This study evaluated prospective associations of ibogaine and 5-MeO-DMT treatment for risky alcohol use and post-traumatic stress disorder (PTSD) symptoms among United States (US) Special Operations Forces Veterans (SOFV). Data were collected during standard clinical operations at pre-treatment and 1-month (1 m), 3-months (3 m), and 6-months (6 m) post-treatment in an ibogaine and 5-MeO-DMT...
Perspectives in biology and medicine
2024
Logan Neitzke-Spruill, Neşe Devenot, Dominic Sisti et al.
7 citations
ABSTRACT:Psychedelics have again become a subject of widespread interest, owing to the reinvigoration of research into their traditional uses, possible medical applications, and social implications. As evidence for psychedelics' clinical potential mounts, the field has increasingly focused on searching for mechanisms to explain the effects of psychedelics and therapeutic efficacy of...
Frontiers in Psychiatry
November 23, 2023
Anya Ragnhildstveit, Ryan Khan, Paul Seli et al.
17 citations
Psychedelic therapy is, arguably, the next frontier in psychiatry. It offers a radical alternative to longstanding, mainstays of treatment, while exciting a paradigm shift in translational science and drug discovery. There is particular interest in 5-methoxy- N,N -dimethyltryptamine (5-MeO-DMT)—a serotonergic psychedelic—as a novel, fast-acting therapeutic. Yet, few studies have directly...
The American Journal of Drug and Alcohol Abuse
September 3, 2023
Alan Kooi Davis, Yitong Xin, Nathan D. Sepeda et al.
29 citations
Background: Research in psychedelic medicine has focused primarily on civilian populations. Further study is needed to understand whether these treatments are effective for Veteran populations.Objectives: Here, we examine the effectiveness of psychedelic-assisted therapy among trauma-exposed Special Operations Forces Veterans (SOFV) seeking treatment for cognitive and mental health problems in...
European Journal of Psychotraumatology
August 29, 2023
Lihong Jiang, Amanda J. F. Tamman, Christopher L. Averill et al.
8 citations
Background: Early trauma predicts poor psychological and physical health. Glutamatergic synaptic processes offer one avenue for understanding this relationship, given glutamate's abundance and involvement in reward and stress sensitivity, emotion, and learning. Trauma-induced glutamatergic excitotoxicity may alter neuroplasticity and approach/avoidance tendencies, increasing risk for...
Neuropsychopharmacology
April 19, 2023
N. Murphy, Amanda J. F. Tamman, Marijn Lijffijt et al.
18 citations
Ketamine is an effective intervention for treatment-resistant depression (TRD), including late-in-life (LL-TRD). The proposed mechanism of antidepressant effects of ketamine is a glutamatergic surge, which can be measured by electroencephalogram (EEG) gamma oscillations. Yet, non-linear EEG biomarkers of ketamine effects such as neural complexity are needed to capture broader systemic effects,...
Frontiers in Psychiatry
February 9, 2023
Anya Ragnhildstveit, Miriam Kaiyo, Matthew Brian Snyder et al.
10 citations
Background A dissociative subtype of posttraumatic stress disorder, known as “D-PTSD”, has been included in the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition. In addition to meeting criteria for PTSD, patients endorse prominent dissociative symptoms, namely depersonalization and derealization, or detachment from one's self and surroundings. At present, this population is...
Journal of Psychedelic Studies
January 16, 2023
Madeline Brendle, Anya Ragnhildstveit, Matthew Slayton et al.
7 citations
Ketamine and esketamine have garnered interest in both psychiatric research and clinical practice for treatment-resistant depression (TRD). In this review, we examined registered trials investigating the therapeutic use of ketamine or esketamine for TRD, with the aim of characterizing emerging trends and knowledge gaps.The ClinicalTrials.gov electronic registry and results database was queried...
Therapeutic Advances in Psychopharmacology
2023
Anya Ragnhildstveit, Jeremy Roscoe, Lisa C. Bass et al.
49 citations
Posttraumatic stress disorder (PTSD) is a devastating condition, for which there are few pharmacological agents, often with a delayed onset of action and poor efficacy. Trauma-focused psychotherapies are further limited by few trained providers and low patient engagement. This frequently results in disease chronicity as well as psychiatric and medical comorbidity, with considerable negative...
Neuropharmacology
August 13, 2022
Ingrid Donato, Veronica Magar, Sean J Belouin et al.
49 citations
There is mounting evidence suggesting psychedelic and entactogen medicines (namely psilocybin and 3,4-methylenedioxymethamphetamine [MDMA]), in conjunction with proper psychosocial support, hold the potential to provide safe, rapid acting, and robust clinical improvements with durable effects. In the US, both psilocybin and MDMA have been granted Breakthrough Therapy designations by the US Food...
Expert Opinion on Investigational Drugs
February 1, 2022
Lynnette A. Averill, Chadi G. Abdallah
The unfortunate reality of the mental health crisis plaguing much of the world, in tandem with and exacerbated by the COVID-19 pandemic [1–3], highlights the limited effective pharmacologic treatments in our toolbox for posttraumatic stress disorder (PTSD). There are only two FDA-approved medications indicated for PTSD, both selective serotonin reuptake inhibitors (SSRIs). Though these...
Journal of Affective Disorders
2022
L. Averill, C. Averill, R. Gueorguieva et al.
Suicide is a public health crisis with limited treatment options. Ketamine has demonstrated rapid and robust improvements in suicidal ideation (SI). The parent study for the secondary pilot analyses presented here was a double-blind, cross-over trial that found pretreatment with the mechanistic target of rapamycin complex 1 (mTORC1) prolonged the antidepressant effects of ketamine. Here we...
Journal of Psychedelic Studies
November 19, 2021
Pratheek Mangini, Lynnette A. Averill, Alan K. Davis
18 citations
Abstract Background & aims Special Operations Forces Veterans (SOFV) have unique treatment needs stemming from multiple repeated forms of combat exposure resulting in a complex sequela of problems including alcohol misuse and post-traumatic stress symptoms. Current approved pharmacologic treatments for alcohol misuse and PTSD are lacking in adherence and efficacy, warranting novel treatment...
Chronic Stress
August 12, 2020
Alan K. Davis, Lynnette A. Averill, Nathan D. Sepeda et al.
83 citations
Background U.S. Special Operations Forces Veterans are at increased risk for a variety of mental health problems and cognitive impairment associated with military service. Current treatments are lacking in effectiveness and adherence. Therefore, this study examined psychedelic treatment with ibogaine and 5-methoxy-N,N-dimethyltryptamine for trauma-related psychological and cognitive impairment...
medRxiv Preprint Server
April 10, 2020
Chadi G. Abdallah, Kyung-Heup Ahn, Lynnette A. Averill et al.
1 citation
preprint
Over the past decade, various N-Methyl-D-Aspartate modulators have failed in clinical trials, underscoring the challenges of developing novel rapid-acting antidepressants based solely on the receptor or regional targets of ketamine. Thus, identifying the effect of ketamine on the brain circuitry and networks is becoming increasingly critical. In this longitudinal functional magnetic resonance...
Neuropsychopharmacology
February 24, 2020
Chadi G. Abdallah, Lynnette A. Averill, Ralitza Gueorguieva et al.
181 citations
Twenty-four hours after administration, ketamine exerts rapid and robust antidepressant effects that are thought to be mediated by activation of the mechanistic target of rapamycin complex 1 (mTORC1). To test this hypothesis, depressed patients were pretreated with rapamycin, an mTORC1 inhibitor, prior to receiving ketamine. Twenty patients suffering a major depressive episode were randomized...
Psychiatric Annals
February 1, 2020
Lynnette A. Averill, Christopher L. Averill, Chadi G. Abdallah
6 citations
The serendipitous discovery of ketamine's robust antidepressant effects has served as a major catalyst to usher in new era of drug development and a paradigm shift in our understanding of the neurobiology of chronic stress pathology (CSP). This review provides a selective synthesis of (1) the historical foundations of N-methyl-D-aspartate receptor modulators and the path to discovering...
Annals of the New York Academy of Sciences
February 27, 2015
Chadi G. Abdallah, Lynnette A. Averill, John H. Krystal
117 citations
The discovery of ketamine's rapid and robust antidepressant effects opened a window into a new generation of antidepressants. Multiple controlled trials and open-label studies have demonstrated these effects across a variety of patient populations known to often achieve little to no response from traditional antidepressants. Ketamine has been generally well tolerated across patient groups, with...