Biological Psychiatry - The Consciousness Library

Cannabis Use and Age-Related Acceleration of Psychosis Onset: A Meta-Analysis.

Biological Psychiatry August 1, 2026 Carl M. Stevens, Hannah Pincham, M. Large

BACKGROUND Increases in cannabis use, potency, and legal liberalization have raised concerns about psychiatric consequences. Previous studies suggest an association between cannabis use and earlier age at onset (AAO) of psychosis, but an updated meta-analysis is needed. METHODS MEDLINE, Embase, and PsycInfo were searched from inception to April 2025. Peer-reviewed cohort and case-control...

DOI: 10.1016/j.biopsych.2026.06.025 Full text

Cannabidiol Mitigates Ketamine-Induced Hyperlocomotion Via Allosteric Potentiation of Ventral Tegmental Glycine Receptor α1 Signaling.

Biological Psychiatry March 16, 2026 Xianglian Wang, Jing Xia, Heyi Luo et al.

Ketamine produces rapid antidepressant and antidepressant-like effects in both humans and animal models. However, its therapeutic benefits are tempered by psychoactive side effects, such as hyperlocomotion associated with enhanced dopaminergic activity in the ventral tegmental area (VTA). We tested the therapeutic effect of cannabidiol (CBD) on locomotor activity after systemic (30 mg/kg) or...

DOI: 10.1016/j.biopsych.2026.03.992 Full text Cannabidiol Ketamine Antidepressant Glycine receptor +2

MDMA and psilocybin regulate oligodendrocyte-lineage cell numbers and anxiety-like behaviors in a rat model of fear.

Biological Psychiatry February 3, 2026 Mehmet Bostancıklıoğlu, Davut Sinan Kaplan, Ramazan Bal et al.

Psilocybin and 3,4-methylenedioxymethamphetamine (MDMA) produce rapid, enduring therapeutic effects in post-traumatic stress disorder (PTSD); however, the underlying cellular mechanisms remain incompletely understood. This study investigated whether adult myelin plasticity contributes to the therapeutic actions of psilocybin and MDMA in a rat model of contextual fear conditioning. Adult male...

DOI: 10.1016/j.biopsych.2026.01.016 Full text MDMA Psilocybin Fear-related behaviors Myelination +2

Psychedelics and the Extracellular Matrix: Rewiring Neuroplasticity and Metaplasticity for Next-Generation Psychiatric Therapies

Biological Psychiatry February 1, 2026 Jin Zhang, Cong Lin, Xinyou Lv et al. 1 citation

Classic psychedelics, such as psilocybin, lysergic acid diethylamide (LSD), and N,N-dimethyltryptamine (DMT), have emerged as potent modulators of neuroplasticity and metaplasticity in the adult brain, offering novel therapeutic strategies for neuropsychiatric disorders. Recent findings reveal that beyond their transient psychotropic effects, these compounds activate serotonin 5-HT2A receptors...

DOI: 10.1016/j.biopsych.2026.02.011 Neuroplasticity Synaptic plasticity Perineuronal net Regulator +6

Cannabis Perturbs Dynamic Brain States

Biological Psychiatry October 21, 2025 Katharina S Lege, Pablo Mallaroni, Sepehr Mortaheb et al. 1 citation

Background The impact of acute cannabis exposure on brain function and cognitive performance varies among individuals. Acute effects of cannabis on behavior may be absent or benign in chronic users, while occasional users experience significant impairment in day-to-day operations. It is hypothesized that repeated cannabis use induces neuroadaptations leading to tolerance and desensitization,...

DOI: 10.1016/j.biopsych.2025.10.015 Effects of cannabis Relevance law Cognition Neuroimaging +5

Mu Opioid Receptor Activation is Required for NMDA Receptor Antagonist Effects on Stress-induced Maladaptive Behavior.

Biological Psychiatry July 7, 2025 Cory B Langreck, Briana K Chen, Victor M Luna et al. 9 citations

Contradictory evidence has emerged regarding the role of the mu opioid receptor (MOR) in the antidepressant actions of (R,S)-ketamine. Here, we used the long-acting MOR-selective antagonist methocinnamox (MCAM) to determine the contribution of MOR to the actions of (R,S)-ketamine and the more selective N-methyl-D-aspartate receptor (NMDAR) antagonist fluoroethylnormemantine (FENM) against...

DOI: 10.1016/j.biopsych.2025.07.004 Full text Ketamine Fear Nmdar antagonists nmdar Similar compounds +10

Heightened anxiety with distinct prefrontal substrates is differentially sensitive to the anxiolytics, citalopram and ketamine: Prefrontal substrates and anxiolytic sensitivity.

Biological Psychiatry June 25, 2025 Kevin G Mulvihill, Gemma J Cockcroft, Angela C Roberts 2 citations

Individual variability in pharmacological treatment efficacy remains a persistent obstacle to ameliorating clinical anxiety. This may originate, in part, from the different neural aetiologies underlying pathological anxiety. To provide novel insights into patient heterogeneity in anxiolytic responsiveness we compare the efficacy of distinct anxiolytic drugs, a Selective Serotonin Re-uptake...

DOI: 10.1016/j.biopsych.2025.06.013 Full text Ketamine Prefrontal cortex Orbitofrontal cortex Threat reactivity 6 +20

Network localization of functional brain changes associated with ketamine's therapeutic effects in depression.

Biological Psychiatry June 13, 2025 Shaoqiang Han, Ya Tian, Huiting Yang et al. 1 citation

Although numerous studies have attempted to identify the functional pathways underlying the rapid antidepressant effects of ketamine, their findings remain inconsistent, limiting our understanding of the neural mechanisms involved. This study aims to delineate a specific brain circuit by integrating diverse functional findings related to ketamine's efficacy in depression. We conducted a...

DOI: 10.1016/j.biopsych.2025.06.006 Full text Ketamine: ketamine Therapeutic effects Unique power Depression: depression +8

Social Homeostasis and Psychoactive Drugs: What Can We Learn From Opioid and Amphetamine Drug Challenge Studies in Humans?

Biological Psychiatry May 15, 2025 Anya K. Bershad, Harriet de Wit 3 citations

Social disequilibrium, or disrupted social homeostasis, underlies many behavioral disorders, including problematic drug use. One way to study the relationship between drug use and social homeostasis is to determine whether single doses of psychoactive drugs relieve some of the discomfort of social isolation and promote social connection. In this narrative review, we discuss challenges and...

DOI: 10.1016/j.biopsych.2024.09.006 Full text Loneliness Opioids Social homeostasis Social stress +2

Ketamine evokes acute behavioral effects via μ-opioid receptor expressing neurons of the central amygdala.

Biological Psychiatry May 5, 2025 Matthew B Pomrenze, Sam Vaillancourt, Pierre Llorach et al. 11 citations

Ketamine has anesthetic, analgesic, and antidepressant properties which may involve multiple neuromodulatory systems. In humans, the opioid receptor (OR) antagonist naltrexone blocks the antidepressant effect of ketamine. This mechanism may differentiate ketamine from other NMDA receptor antagonists. Animal models that reflect OR-dependent behavioral effects of ketamine may shed light on the...

DOI: 10.1016/j.biopsych.2025.04.020 Full text Antidepressant Central amygdala Mu opioid receptor Naltrexone +5

Prophylactic (R,S)-Ketamine and (2S,6S)-Hydroxynorketamine Decrease Fear Expression by Differentially Modulating Fear Neural Ensembles.

Biological Psychiatry May 1, 2025 Alessia Mastrodonato, Michelle Jin, Noelle Kee et al. 5 citations

We previously reported that a single injection of (R,S)-ketamine or its metabolite (2S,6S)-hydroxynorketamine (HNK) prior to stress attenuated learned fear. However, whether these drugs attenuate learned fear through divergent or convergent effects on neural activity remains to be determined. 129S6/SvEv male mice were injected with saline, (R,S)-ketamine, or (2S,6S)-HNK 1 week before a 3-shock...

DOI: 10.1016/j.biopsych.2024.09.024 Full text Depression Contextual fear conditioning Metabolite Neural network +5

The Impact of Intravenous Ketamine on Attentional Bias: Probing Mechanisms of Rapid-Acting Antidepressant Effects in Two Clinical Studies.

Biological Psychiatry April 15, 2025 Mary L Woody, Rebecca Rohac, Iya Cooper et al. 1 citation

Ketamine is known for its rapid antidepressant effect, but its impact on affective information processing (including attentional bias [AB], a putative cognitive mechanism of depression) remains largely unexplored. We leveraged a novel measurement of AB and sought to 1) establish adequate test-retest reliability and validity among participants with depression prior to ketamine treatment and 2)...

DOI: 10.1016/j.biopsych.2024.10.024 Full text Depression Attentional bias Intravenous ketamine Psychedelics +2

Prophylactic Ketamine: Current Knowledge and Future Directions.

Biological Psychiatry March 28, 2025 Astrid M Cardona-Acosta, Lyonna F Parise, Carlos A. Bolaños-Guzmán et al. 2 citations

The prevalence of stress-induced disorders, including depression, anxiety, posttraumatic stress disorder, and postpartum depression, has been increasing, while current treatment approaches are limited. As a result, researchers are exploring alternative treatments that include ketamine as a prophylactic against these disorders. This review provides an overview of the current knowledge on the use...

DOI: 10.1016/j.biopsych.2025.03.015 Full text Neuroprotective drugs Prophylactic treatment Stress resilience Stress-induced psychiatric disorders +5

Ketamine and Hydroxynorketamine as Novel Pharmacotherapies for the Treatment of Opioid Use Disorders.

Biological Psychiatry March 15, 2025 Anna Onisiforou, Andria Michael, Markos Apostolakis et al. 14 citations

Opioid use disorder (OUD) has reached epidemic proportions, with many countries facing high levels of opioid use and related fatalities. Although currently prescribed medications for OUD are considered lifesaving, they inadequately address negative affect and cognitive impairment, resulting in high relapse rates to nonmedical opioid use even years after drug cessation (protracted abstinence)....

DOI: 10.1016/j.biopsych.2024.09.008 Full text Hydroxynorketamine Opioid crisis Opioid use disorders Relapse +4

Current Evidence for the Role of Rapid-Acting Antidepressants in Bipolar Depression: A Perspective and Plan for Action

Biological Psychiatry March 8, 2025 Jonathan Repple, Maximilian Bayas, Chiara Möser et al. 8 citations

After decades of limited progress in depression treatment, recent advancements have sparked renewed interest in developing novel antidepressants, particularly rapid-acting antidepressants (RAADs). Despite these promising developments, there remains a significant gap in research on bipolar depression. While several antipsychotics have been investigated for their efficacy in bipolar depression...

DOI: 10.1016/j.biopsych.2025.02.903 Mdd #bipolardisorder manic depression Bipolar affective disorder #ketamine ketamine therapy +5

Treatment Approaches for Posttraumatic Stress Disorder Derived From Basic Research on Fear Extinction.

Biological Psychiatry February 15, 2025 Jessica L Maples-Keller, Laura E Watkins, Natalie Hellman et al. 12 citations

This brief review article will describe treatment approaches for posttraumatic stress disorder (PTSD) based on findings from basic research. The focus of this review will be fear conditioning and extinction models, which provide a translational model of PTSD that can help translate basic research in nonhuman animals through well-controlled trials confirming the efficacy of treatment approaches...

DOI: 10.1016/j.biopsych.2024.07.010 Full text Combination treatment Exposure therapy Fear extinction Translational +5

Fluoxetine and Ketamine Enhance Extinction Memory and Brain Plasticity by Triggering the p75 Neurotrophin Receptor Proteolytic Pathway.

Biological Psychiatry February 1, 2025 Cassiano Ricardo Alves Faria Diniz, Ana Paula Crestani, Plinio Cabrera Casarotto et al. 15 citations

Diverse antidepressants were recently described to bind to TrkB (tyrosine kinase B) and drive a positive allosteric modulation of endogenous BDNF (brain-derived neurotrophic factor). Although neurotrophins such as BDNF can bind to p75NTR (p75 neurotrophin receptor), their precursors are the high-affinity p75NTR ligands. While part of an unrelated receptor family capable of inducing completely...

DOI: 10.1016/j.biopsych.2024.06.021 Full text Ketamine Neuroplasticity Binding Extinction memory +12

Mindfulness Meditation and Placebo Modulate Distinct Multivariate Neural Signatures to Reduce Pain.

Biological Psychiatry 2025 Gabriel Riegner, Jon G Dean, Tor D Wager et al.

Rather than a passive reflection of nociception, pain is shaped by the interplay between one's experiences, current cognitive-affective states, and expectations. The placebo response, a paradoxical yet reliable phenomenon, is postulated to reduce pain by engaging mechanisms shared with active therapies. It has been assumed that mindfulness meditation, practiced by sustaining nonjudgmental...

DOI: 10.1016/j.biopsych.2024.08.023 Full text Meditation Mindfulness Mvpa Pain +2

Psilocybin Desynchronizes Brain Networks

Biological Psychiatry April 29, 2024 Joshua S. Siegel, Subha Subramanian, Nico U.f. Dosenbach et al. 14 citations

1 Summary The relationship between the acute effects of psychedelics and their persisting neurobiological and psychological effects is poorly understood. Here, we tracked brain changes with longitudinal precision functional mapping in healthy adults before, during, and for up to 3 weeks after oral psilocybin and methylphenidate (17 MRI visits per participant) and again 6+ months later....

DOI: 10.1016/j.biopsych.2024.02.132 Full text Psilocybin Hallucinogen Pharmacology

Neural Mechanisms of Resting-State Networks and the Amygdala Underlying the Cognitive and Emotional Effects of Psilocybin

Biological Psychiatry January 5, 2024 Devon Stoliker, Leonardo Novelli, Adeel Razi et al. 42 citations

Our findings suggest that temporary amygdala signal attenuation is associated with mechanistic changes to resting-state network connectivity. These changes are significant for altered cognition and perception and suggest targets for research investigating the efficacy of psychedelic therapy for internalizing psychiatric disorders. More broadly, our study suggests the value of quantifying the...

DOI: 10.1016/j.biopsych.2024.01.002 Psilocybin Amygdala Cognition Resting State FMRI +3

Attenuation of Anxiety-Potentiated Startle After Treatment With Escitalopram or Mindfulness Meditation in Anxiety Disorders.

Biological Psychiatry 2024 Elizabeth A Hoge, Caroline H Armstrong, Mihriye Mete et al. 10 citations

Biological markers for anxiety disorders may further understanding of disorder pathophysiology and suggest potential targeted treatments. The fear-potentiated startle (FPS) (a measure of startle to predictable threat) and anxiety-potentiated startle (APS) (startle to unpredictable threat) laboratory paradigm has been used to detect physiological differences in individuals with anxiety disorders...

DOI: 10.1016/j.biopsych.2023.06.003 Full text Anxiety-potentiated startle Escitalopram Fear-potentiated startle Mindfulness meditation +2

Acute Mood-Elevating Properties of Microdosed Lysergic Acid Diethylamide in Healthy Volunteers: A Home-Administered Randomized Controlled Trial.

Biological Psychiatry September 15, 2023 Robin J Murphy, Rachael Sumner, William Evans et al. 69 citations

Microdosing psychedelic drugs is a widespread social phenomenon with diverse benefits claimed for mood and cognition. Randomized controlled trials have failed to support these claims, but the laboratory-based dosing in trials conducted to date may have limited ecological validity. Healthy male volunteers were randomized into lysergic acid diethylamide (LSD) (n = 40) and placebo (n = 40) groups...

DOI: 10.1016/j.biopsych.2023.03.013 Full text Anxiety LSD Micro-dosing Cognition +7

Lysergic Acid Diethylamide-Assisted Therapy in Patients With Anxiety With and Without a Life-Threatening Illness: A Randomized, Double-Blind, Placebo-Controlled Phase II Study.

Biological Psychiatry February 1, 2023 Friederike Holze, Peter Gasser, Felix Müller et al. 294 citations

This study aimed to investigate the efficacy and safety of lysergic acid diethylamide (LSD)-assisted therapy in patients who experienced anxiety with or without association with a life-threatening illness. The study is an investigator-initiated 2-center trial that used a double-blind, placebo-controlled, 2-period, random-order, crossover design with 2 sessions with either oral LSD (200 μg) or...

DOI: 10.1016/j.biopsych.2022.08.025 Full text Depression LSD Psilocybin Life-threatening-illness +7

Effective Connectivity of Functionally Anticorrelated Networks Under Lysergic Acid Diethylamide.

Biological Psychiatry February 1, 2023 Devon Stoliker, Leonardo Novelli, Franz X. Vollenweider et al. 49 citations

Classic psychedelic-induced ego dissolution involves a shift in the sense of self and a blurring of the boundary between the self and the world. A similar phenomenon is identified in psychopathology and is associated with the balance of anticorrelated activity between the default mode network, which directs attention inward, and the salience network, which recruits the dorsal attention network...

DOI: 10.1016/j.biopsych.2022.07.013 Full text Ego dissolution Anticorrelated networks Dynamic causal modeling Effective connectivity +8

Mindfulness Training Changes Brain Dynamics During Depressive Rumination: A Randomized Controlled Trial.

Biological Psychiatry February 1, 2023 Anne Maj van der Velden, Jacqueline Scholl, Else-Marie Elmholdt et al.

Depression is a leading cause of disability worldwide and its prevalence is on the rise. One of the most debilitating aspects of depression is the dominance and persistence of depressive rumination, a state of mind that is linked to onset and recurrence of depression. Mindfulness meditation trains adaptive attention regulation and present-moment embodied awareness, skills that may be...

DOI: 10.1016/j.biopsych.2022.06.038 Full text Depression Mindfulness Interoceptive awareness Mechanisms +2

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