American Journal of Psychiatry
June 3, 2026
D. D'Souza, J. Cortes-Briones, Justin Raj et al.
OBJECTIVE Cannabis use is a known risk factor for psychosis, but it remains unclear whether cannabis-associated psychosis (CAP) differs meaningfully from non-cannabis-associated psychosis (NCAP) in clinical presentation, biology, or illness course. The objective of this study was to characterize the presentation and course of first-episode psychosis with and without cannabis exposure. METHODS...
American Journal of Psychiatry
September 10, 2025
Gerard Sanacora, Muhammad Ahmed, Brianne Brown et al.
24 citations
OBJECTIVE The objective of this study was to comprehensively examine the real-world safety of esketamine using 58 months of postapproval data in the United States. METHODS U.S. safety data from patient monitoring forms submitted to the esketamine Risk Evaluation and Mitigation Strategy (REMS) program and reports submitted to the Janssen U.S. Global Medical Safety (US-GMS) database were...
American Journal of Psychiatry
September 10, 2025
Songze Li, Kristina T. Kumpf, Julian Urrutia et al.
13 citations
This review examines ketamine's neurotoxic potential across preclinical and clinical studies. The authors synthesized data from preclinical models, then integrated findings from human clinical trials of esketamine and observational studies in recreational users. Animal studies have found that repeated or high-dose subanesthetic ketamine administration results in consistent excitotoxic neuronal...
American Journal of Psychiatry
July 1, 2025
Y. Hurd
The convergence of early initiation, increasing product potency, and widespread availability has reshaped the contemporary cannabis landscape, heightening concerns about its impact on adolescent mental health. Translational research combining longitudinal human neuroimaging and animal models provides compelling evidence that cannabis use-particularly with high-tetrahydrocannabinol (THC)...
American Journal of Psychiatry
May 7, 2025
Matthew B. Wall, Lysia Demetriou, Bruna Giribaldi et al.
16 citations
Despite large improvements in depressive symptoms in the psilocybin group, psilocybin therapy had only a minor effect on brain responsiveness to emotional stimuli. These results are consistent with prior findings that the antidepressant action of SSRIs is often accompanied by a reduction in emotional responsiveness, but this effect may not occur in psychedelic therapy.
American Journal of Psychiatry
2025
Scott T Aaronson, Andrew van der Vaart, Tammy Miller et al.
31 citations
This open-label study suggests efficacy and safety of psilocybin in severe TRD and supports further study of psychedelics in this population, including consideration of PTSD interaction effects.
American Journal of Psychiatry
2025
Namik Kirlic, Molly Lennard-Jones, Merve Atli et al.
27 citations
The psychedelic experience can be challenging. There is a need for a structured framework for providing psychological support to individuals with mental health conditions receiving investigational psilocybin treatment. The primary benefit of such a framework is to support a safe and meaningful psilocybin experience. It also enables future research on the facets of psychological support and/or...
American Journal of Psychiatry
2025
Johannes G. Ramaekers, Johannes T. Reckweg, Natasha L. Mason
25 citations
Unlike classical antidepressants, psychedelics such as psilocybin have been shown to induce a rapid antidepressant response. In the wake of this development, interest has emerged in ultra-fast, short-acting psychedelics such as 5-methoxy-N,N-dimethyltryptamine (5-MeO-DMT) and N,N-dimethyltryptamine (DMT) with the expectation that these can produce rapid antidepressant effects following an...
American Journal of Psychiatry
2025
Noam Goldway, Snehal Bhatt, Stephen Ross et al.
23 citations
PAT elicited durable shifts in personality, suggesting normalization of abnormal personality trait expression in AUD. Further study is needed to clarify whether PAT exerts its beneficial effects by reducing impulsiveness or whether impulsive individuals inherently respond better to PAT.
American Journal of Psychiatry
2025
Adrienne Grzenda, Gregory A. Fonzo, Aaron Wolfgang et al.
14 citations
The evidence is currently insufficient to recommend psilocybin with PST as a psychiatric treatment. Additional rigorously designed clinical trials are needed to definitively establish efficacy in larger and more diverse samples, address dosing considerations, improve blinding, and provide information on mechanisms of action and moderators of clinical response. Head-to-head comparisons with...
American Journal of Psychiatry
October 9, 2024
Caesar G. Imperio, Frances R. Levin, Diana Martínez
9 citations
Substance use disorder (SUD) is common in psychiatric patients and has a negative impact on health and well-being. However, SUD often goes untreated, and there is a need for psychiatrists, of all specialties, to address this pervasive clinical problem. In this review, the authors' goal is to provide a resource that describes treatments for SUD, using neuroscience as a framework. They discuss...
American Journal of Psychiatry
January 10, 2024
Eric L. Garland, Y. Nakamura, Craig J. Bryan et al.
OBJECTIVE. Evaluate the efficacy of Mindfulness-Oriented Recovery Enhancement (MORE) for past and current military personnel prescribed long-term opioid therapy (LTOT) for chronic pain. METHODS. In a clinical trial, 230 past and current U.S. military personnel prescribed LTOT were randomized (1:1) to MORE or supportive psychotherapy (in-person and then online via Zoom after onset of COVID-19)....
American Journal of Psychiatry
July 28, 2022
Joseph Wielgosz, Tammi R. A. Kral, David M Perlman et al.
21 citations
OBJECTIVE: Mindfulness-based interventions are widely used to target pain, yet their neural mechanisms of action are insufficiently understood. The authors studied neural and subjective pain response in a randomized active-control trial of mindfulness-based stress reduction (MBSR) alongside long-term meditation practitioners. METHODS: Healthy participants (N=115) underwent functional...
American Journal of Psychiatry
May 18, 2022
Herriot Tabuteau, A. Jones, Ashley Anderson et al.
OBJECTIVE Altered glutamatergic neurotransmission is implicated in the pathogenesis of major depressive disorder. AXS-05 (dextromethorphan-bupropion) is an oral NMDA receptor antagonist and sigma-1 receptor agonist, which utilizes inhibition of CYP2D6 to increase its bioavailability. This phase 2 trial assessed the efficacy and safety of dextromethorphan-bupropion in the treatment of major...
American Journal of Psychiatry
January 11, 2022
Meryem Grabski, Amy Mcandrew, Will Lawn et al.
169 citations
OBJECTIVE: Early evidence suggests that ketamine may be an effective treatment to sustain abstinence from alcohol. The authors investigated the safety and efficacy of ketamine compared with placebo in increasing abstinence in patients with alcohol use disorder. An additional aim was to pilot ketamine combined with mindfulness-based relapse prevention therapy compared with ketamine and alcohol...
American Journal of Psychiatry
March 17, 2021
Roger S McIntyre, Joshua D. Rosenblat, Charles B. Nemeroff et al.
694 citations
Replicated international studies have underscored the human and societal costs associated with major depressive disorder. Despite the proven efficacy of monoamine-based antidepressants in major depression, the majority of treated individuals fail to achieve full syndromal and functional recovery with the index and subsequent pharmacological treatments. Ketamine and esketamine represent...
American Journal of Psychiatry
March 3, 2021
J. Dwyer, Angeli Landeros‐Weisenberger, Jessica A. Johnson et al.
163 citations
OBJECTIVE Adolescent depression is prevalent and is associated with significant morbidity and mortality. Although intravenous ketamine has shown efficacy in adult treatment-resistant depression, its efficacy in pediatric populations is unknown. The authors conducted an active-placebo-controlled study of ketamine's safety and efficacy in adolescents. METHODS In this proof-of-concept randomized,...
American Journal of Psychiatry
January 5, 2021
Adriana Feder, Sara Costi, Sarah B. Rutter et al.
239 citations
OBJECTIVE Posttraumatic stress disorder (PTSD) is a chronic and disabling disorder, for which available pharmacotherapies have limited efficacy. The authors' previous proof-of-concept randomized controlled trial of single-dose intravenous ketamine infusion in individuals with PTSD showed significant and rapid PTSD symptom reduction 24 hours postinfusion. The present study is the first...
American Journal of Psychiatry
December 2, 2019
Elias Dakwar, Frances R. Levin, C. Hart et al.
179 citations
OBJECTIVE Pharmacotherapy and behavioral treatments for alcohol use disorder are limited in their effectiveness, and new treatments with innovative mechanisms would be valuable. In this pilot study, the authors tested whether a single subanesthetic infusion of ketamine administered to adults with alcohol dependence and engaged in motivational enhancement therapy affects drinking outcomes....
American Journal of Psychiatry
June 24, 2019
Elias Dakwar, E. Nunes, C. Hart et al.
179 citations
OBJECTIVE Research has suggested that subanesthetic doses of ketamine may work to improve cocaine-related vulnerabilities and facilitate efforts at behavioral modification. The purpose of this trial was to test whether a single ketamine infusion improved treatment outcomes in cocaine-dependent adults engaged in mindfulness-based relapse prevention. METHODS Fifty-five cocaine-dependent...
American Journal of Psychiatry
May 21, 2019
Vanina Popova, Ella Daly, Madhukar H. Trivedi et al.
879 citations
OBJECTIVE: About one-third of patients with depression fail to achieve remission despite treatment with multiple antidepressants. This study compared the efficacy and safety of switching patients with treatment-resistant depression from an ineffective antidepressant to flexibly dosed esketamine nasal spray plus a newly initiated antidepressant or to a newly initiated antidepressant (active...
American Journal of Psychiatry
March 29, 2019
J. Phillips, S. Norris, J. Talbot et al.
416 citations
OBJECTIVE Subanesthetic ketamine doses have been shown to have rapid yet transient antidepressant effects in patients with treatment-resistant depression, which may be prolonged by repeated administration. The purpose of this study was to evaluate the antidepressant effects of a single ketamine infusion, a series of repeated ketamine infusions, and prolongation of response with maintenance...
American Journal of Psychiatry
January 4, 2019
Satoshi Deyama, Eunyoung Bang, Eric S. Wohleb et al.
100 citations
OBJECTIVE: -methyl-d-aspartate receptor antagonist ketamine produces rapid and sustained antidepressant actions even in patients with treatment-resistant depression. Vascular endothelial growth factor (VEGF) has been implicated in the effects of conventional monoamine-based antidepressants, but the role of VEGF in the rapid antidepressant actions of ketamine remains unclear. The authors...
American Journal of Psychiatry
August 29, 2018
Nolan Williams, Boris D. Heifets, Christine Blasey et al.
510 citations
OBJECTIVE: In addition to N-methyl-d-aspartate receptor antagonism, ketamine produces opioid system activation. The objective of this study was to determine whether opioid receptor antagonism prior to administration of intravenous ketamine attenuates its acute antidepressant or dissociative effects. METHOD: In a proposed double-blind crossover study of 30 adults with treatment-resistant...
American Journal of Psychiatry
April 16, 2018
Carla M. Canuso, Jaskaran Singh, Maggie Fedgchin et al.
666 citations
OBJECTIVE: The authors compared the efficacy of standard-of-care treatment plus intranasal esketamine or placebo for rapid reduction of symptoms of major depression, including suicidality, among individuals at imminent suicide risk. METHOD: In a double-blind, multicenter, proof-of-concept study, 68 participants were randomly assigned to receive esketamine (84 mg) or placebo twice weekly for 4...