The neural basis of psychedelic action

Nature Neuroscience, Journal Year: 2022, Volume and Issue: 25(11), P. 1407 - 1419

Published: Oct. 24, 2022

Language: Английский

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Psychedelics reopen the social reward learning critical period

Nature, Journal Year: 2023, Volume and Issue: 618(7966), P. 790 - 798

Published: June 14, 2023

Abstract Psychedelics are a broad class of drugs defined by their ability to induce an altered state consciousness 1,2 . These have been used for millennia in both spiritual and medicinal contexts, number recent clinical successes spurred renewed interest developing psychedelic therapies 3–9 Nevertheless, unifying mechanism that can account these shared phenomenological therapeutic properties remains unknown. Here we demonstrate mice the reopen social reward learning critical period is property across drugs. Notably, time course reopening proportional duration acute subjective effects reported humans. Furthermore, reinstate adulthood paralleled metaplastic restoration oxytocin-mediated long-term depression nucleus accumbens. Finally, identification differentially expressed genes ‘open state’ versus ‘closed provides evidence reorganization extracellular matrix common downstream underlying drug-mediated reopening. Together results important implications implementation psychedelics practice, as well design novel compounds treatment neuropsychiatric disease.

Language: Английский

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Signaling snapshots of a serotonin receptor activated by the prototypical psychedelic LSD

Neuron, Journal Year: 2022, Volume and Issue: 110(19), P. 3154 - 3167.e7

Published: Sept. 9, 2022

Language: Английский

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Treatment of Posttraumatic Stress Disorder: A State-of-the-art Review

Current Neuropharmacology, Journal Year: 2023, Volume and Issue: 22(4), P. 557 - 635

Published: May 3, 2023

Abstract: This narrative state-of-the-art review paper describes the progress in understanding and treatment of Posttraumatic Stress Disorder (PTSD). Over last four decades, scientific landscape has matured, with many interdisciplinary contributions to its diagnosis, etiology, epidemiology. Advances genetics, neurobiology, stress pathophysiology, brain imaging have made it apparent that chronic PTSD is a systemic disorder high allostatic load. The current state includes wide variety pharmacological psychotherapeutic approaches, which are evidence-based. However, myriad challenges inherent disorder, such as individual barriers good outcome, comorbidity, emotional dysregulation, suicidality, dissociation, substance use, trauma-related guilt shame, often render response suboptimal. These discussed drivers for emerging novel including early interventions Golden Hours, interventions, medication augmentation use psychedelics, well targeting nervous system. All this aims improve symptom relief clinical outcomes. Finally, phase orientation recognized tool strategize position step progression pathophysiology. Revisions guidelines systems care will be needed incorporate innovative treatments evidence emerges they become mainstream. generation well-positioned address devastating disabling impact traumatic events through holistic, cutting-edge efforts research.

Language: Английский

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Therapeutic effect of psilocybin in addiction: A systematic review

Frontiers in Psychiatry, Journal Year: 2023, Volume and Issue: 14

Published: Feb. 9, 2023

Background Psychedelic-assisted therapy [e.g., with lysergic acid diethylamide (LSD)] has shown promising results as treatment for substance use disorders (SUDs). Previous systematic reviews assessing the efficacy of psilocybin in SUDs only included clinical trials conducted last 25 years, but they may have missed that were before 1980s, given much research been done psychedelics mid-20th century. In this review, we specifically assessed patients a SUD or non-substance-related disorder no publication date restrictions our search strategy. Methods A literature was performed according to Preferred Reporting Items Systematic and Meta-Analysis (PRISMA) guidelines from earliest published manuscript up September 2, 2022, seven electronic databases, including evaluating psilocybin. Results total four studies (six articles, which two articles long-term follow-up same trial) review. Psilocybin-assisted administered n = 151 dose ranging 6 40 mg. Three focused on alcohol disorder, one study tobacco disorder. pilot ( 10), percentage heavy drinking days decreased significantly between baseline weeks 5–12 (mean difference 26.0, 95% CI 8.7–43.2, p 0.008). another single-arm 31), 32% (10/31) became completely abstinent duration years). double-blind, placebo-controlled randomized controlled trial (RCT, 95), during 32-week double-blind period lower compared placebo 13.9, 3.0–24.7, 0.01). 15), 7-day point prevalence smoking abstinence at 26 80% (12/15), 52 67% (10/15). Conclusion Only RCT three small identified combined some form psychotherapy All indicated beneficial effect psilocybin-assisted symptoms. Larger RCTs need evaluate whether is effective SUD.

Language: Английский

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A complex systems perspective on psychedelic brain action

Trends in Cognitive Sciences, Journal Year: 2023, Volume and Issue: 27(5), P. 433 - 445

Published: Feb. 3, 2023

Language: Английский

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Are “mystical experiences” essential for antidepressant actions of ketamine and the classic psychedelics?

European Archives of Psychiatry and Clinical Neuroscience, Journal Year: 2024, Volume and Issue: unknown

Published: Feb. 27, 2024

The growing interest in the rapid and sustained antidepressant effects of dissociative anesthetic ketamine classic psychedelics, such as psilocybin, is remarkable. However, both psychedelics are known to induce acute mystical experiences; can cause symptoms out-of-body experience, while typically bring about hallucinogenic experiences, like a profound sense unity with universe or nature. role these experiences enhancing outcomes for patients depression currently an area ongoing investigation debate. Clinical studies have shown that following administration (S)-ketamine (esketamine) not directly linked their properties. In contrast, potential (R)-ketamine (arketamine), thought lack side effects, has yet be conclusively proven large-scale clinical trials. Moreover, although activation serotonin 5-HT

Language: Английский

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MDMA and MDMA-Assisted Therapy

American Journal of Psychiatry, Journal Year: 2025, Volume and Issue: 182(1), P. 79 - 103

Published: Jan. 1, 2025

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 Drug Administration (FDA) designated MDMA-Assisted Therapy (MDMA-AT) a Breakthrough for posttraumatic stress disorder (PTSD) 2017, FDA is requiring an additional phase 3 trial after rejecting initial New Application 2024. Unlike other psychedelics, uniquely induces prosocial subjective effects of heightened trust self-compassion while maintaining ego functioning well cognitive perceptual lucidity. While use nonmedical settings may still cause harm, especially due to adulterants when without proper precautions, conclusions that can be drawn from studies are limited by many confounds. This limits extent which evidence related extrapolated use. A considerable body preliminary suggests MDMA-AT delivered controlled clinical setting safe efficacious treatment PTSD. After course involving three administrations supported psychotherapy, 67%-71% individuals with PTSD no longer meet diagnostic criteria versus 32%-48% placebo-assisted therapy, endure at long-term follow-up. review primarily aims distinguish nonclinical using pharmaceutical-grade further describes putative neurobiological mechanisms underlying its effects, MDMA-AT, considerations level public health policy, future research directions.

Language: Английский

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Psilocybin: From Psychiatric Pariah to Perceived Panacea

American Journal of Psychiatry, Journal Year: 2025, Volume and Issue: 182(1), P. 54 - 78

Published: Jan. 1, 2025

The authors critically examine the evidence base for psilocybin administered with psychological support/therapy (PST) in treatment of psychiatric disorders and offer practical recommendations to guide future research endeavors.

Language: Английский

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Emerging paradigms for target discovery of traditional medicines: A genome-wide pan-GPCR perspective

The Innovation, Journal Year: 2025, Volume and Issue: 6(3), P. 100774 - 100774

Published: Jan. 18, 2025

Traditional medicines serve not only as an integral part of medical treatments prescribed by healthcare providers but also a fundamental reservoir for novel molecular scaffolds. However, gaps remain in our understanding the mechanisms underlying their activity. A superfamily membrane proteins, G protein-coupled receptors (GPCRs), have been demonstrated to be potential targets several compounds isolated from traditional medicines. Given that GPCRs approximately one-third all marketed drugs, they may compelling repurposing Despite this potential, research investigating activity or ligands across GPCRome, library human GPCRs, is scarce. Drawing on functional and structural knowledge presently available, review contemplates prospective trends GPCR drug discovery, proposes innovative strategies medicines, highlights ligand screening approaches identifying drug-like molecules. To discover bioactive molecules either directly bind indirectly modify function, genome-wide pan-GPCR discovery platform was designed identification components targets, evaluation pharmacological profiles. This aims aid exploration all-sided relations between GPCRome using advanced high-throughput techniques. We present various used many, including ourselves, illuminate previously unexplored aspects GPCRs.

Language: Английский

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