Ketamine rapidly reduces suicidal ideation in major depressive disorder (MDD), but its effects are transient. Preclinical and clinical studies suggest that ketamine's antidepressant and antisuicidal effects may be partly mediated by mu-opioid receptor (MOR) modulation. The authors investigated the efficacy and safety of low-dose sublingual buprenorphine, a partial MOR agonist, as a follow-on...
Igor D Bandeira, MD, PhD, Luke A Jelen, MD, PhD, Jason M Tucciarone, MD, PhD, Boris D Heifets, MD, PhD, Carolyn I Rodriguez, MD, PhD, Alan F Schatzberg, MD
Rapidly acting therapeutics like 3,4-methylenedioxymethamphetamine (MDMA) are promising treatments for disorders such as posttraumatic stress disorder (PTSD). However, understanding who benefits most and the underlying neural mechanisms remains a critical gap. Stratifying individuals by neural circuit profiles could help differentiate neural, behavioral, and affective responses to MDMA,...
MDMA (i.e., 3,4-methylenedixoymethamphetamine), commonly known as "Ecstasy" or "Molly," has been used since the 1970s both in recreational and therapeutic settings. The Food and Drug Administration (FDA) designated MDMA-Assisted Therapy (MDMA-AT) as a Breakthrough Therapy for posttraumatic stress disorder (PTSD) in 2017, and the FDA is requiring an additional phase 3 trial after rejecting the...
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...
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...
Posttraumatic stress disorder (PTSD) is a highly prevalent psychiatric disorder that can become chronic and debilitating when left untreated. The most commonly recommended first-line treatments for PTSD among adults are individual trauma-focused psychotherapies. Other evidence-based treatments include specific antidepressant medications and non-trauma-focused psychotherapies. Despite the...
Ketamine commonly and rapidly induces dissociative and other altered states of consciousness (ASCs) in humans. However, the neural mechanisms that contribute to these experiences remain unknown. We used functional neuroimaging to engage key regions of the brain’s affective circuits during acute ketamine-induced ASCs within a randomized, multi-modal, placebo-controlled design examining placebo,...
The United States is in the midst of rapidly changing laws regarding cannabis. The increasing availability of cannabis for recreational and medical use requires that mental health clinicians be knowledgeable about evidence to be considered when counseling both patients and colleagues. In this review, the authors outline the evidence from randomized double-blind placebo-controlled trials for...
Ketamine is a non-competitive antagonist of the N-methyl-D-aspartate (NMDA) glutamate receptor that is both a drug of abuse and an FDA-approved anesthetic used off-label for treatment-resistant depression. Despite its growing clinical use for depression and pain, the relationships between the acute dissociative and affective effects of ketamine that contribute to its abuse liability and...
Objective: The authors provide an evidenced-based summary of the literature on the clinical application of psychedelic drugs in psychiatric disorders. Methods: Searches of PubMed and PsycINFO via Ovid were conducted for articles in English, in peer-reviewed journals, reporting on “psilocybin,” “lysergic acid diethylamide,” “LSD,” “ayahuasca,” “3,4-methylenedioxymethamphetamine,” and “MDMA,” in...
Obsessive-Compulsive Disorder (OCD), characterized by intrusive thoughts (obsessions) and repetitive behaviors (compulsions), is associated with dysfunction in fronto-striatal circuits. There are currently no fastacting pharmacological treatments for OCD. However, recent clinical studies demonstrated that an intravenous infusion of ketamine rapidly reduces OCD symptoms. To probe mechanisms...
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...
Psychoactive drugs profoundly alter consciousness, but the neural mechanisms by which they do so remain poorly understood. Global workspace theory may provide a framework for investigating these mechanisms. The global workspace, a candidate neural substrate of consciousness, is a set of brain regions that integrate and disseminate information to the rest of the brain. According to a recent...