Progress in Neuro-psychopharmacology and Biological Psychiatry

Single Ayahuasca administration attenuates alcohol relapse and associated behavioral, neurochemical, and oxidative alterations in rats

Progress in Neuro-psychopharmacology and Biological Psychiatry July 1, 2026 Guilherme Lodetti, Rafael Mariano de Bitencourt, Antonio Inserra et al.

BackgroundAlcohol use disorder (AUD) remains difficult to treat with lasting success, leading to growing interest in alternative therapeutic approaches. Psychedelic compounds such as Ayahuasca, a traditional brew used in Indigenous Amazonian ceremonies containing N,N-dimethyltryptamine (DMT) along with monoamine oxidase-inhibiting β-carbolines, have shown promise in reducing addictive...

DOI: 10.1016/j.pnpbp.2026.111817 Ayahuasca Serotonin Oxidative stress Glutathione peroxidase +12

The astrocytes in the prefrontal cortex contribute to the rapid antidepressant-like effects of psilocybin in the chronic restraint stress mouse model

Progress in Neuro-psychopharmacology and Biological Psychiatry April 1, 2026 Yong-xing Qiao, Wei Dai, Yi-shan Yao et al. 1 citation

Psilocybin showed a rapid antidepressant response in several clinical trials, which offers new hope for treating depression. Astrocytes were associated with the etiology of depression and might contribute to the onset of psilocybin. In this study, we investigated the fast antidepressant effect of psilocybin and tested variations of GFAP (astrocytic markers) and C3 protein (markers of A1...

DOI: 10.1016/j.pnpbp.2026.111698

Ketamine pharmacotherapy for major depressive disorder: A narrative review

Progress in Neuro-psychopharmacology and Biological Psychiatry February 27, 2026 Chris H. Miller, Angela Hickman, Caitlin Baten et al. 2 citations

Ketamine pharmacotherapy provides a novel treatment option for major depressive disorder (MDD) and has generated a large, growing body of research regarding its biochemical and clinical properties. This narrative review summarizes the history of ketamine's development, beginning as a general anesthetic, continuing with a discovery of its antidepressant properties, and leading up to its landmark...

DOI: 10.1016/j.pnpbp.2026.111651 Major depressive disorder Ketamine Antidepressant Pharmacotherapy +8

LSD microdosing for major depressive disorder: Mood and pharmacokinetic outcomes from a Phase 2a trial

Progress in Neuro-psychopharmacology and Biological Psychiatry February 18, 2026 Dimitri Henriques Daldegan-Bueno, C Donegan, Rachael Sumner et al. 1 citation

Results suggest short-term improvements in mood following microdosed LSD in people with depression, warranting confirmation in controlled trials. It provides the pharmacokinetic parameters of 8 μg of LSD in a sample of people with depression and indicates no tolerance or sensitisation to repeated microdoses of LSD, despite incremental dose titration.

DOI: 10.1016/j.pnpbp.2026.111645 Major depressive disorder Pharmacokinetics Depression economics Depressive symptoms +6

Psychedelics in functional disorders: A scoping review

Progress in Neuro-psychopharmacology and Biological Psychiatry February 10, 2026 Chiranth Bhagavan, Olivia Carter, Alexander Bryson et al. 1 citation

Functional disorders, characterised by symptoms unexplained by organic disease, impose a significant burden on individuals and healthcare systems. Existing treatments are limited in efficacy, with no effective pharmacotherapies. There is growing evidence supporting the treatment potential of psychedelics in neuropsychiatric conditions, including several distinct functional disorders. This...

DOI: 10.1016/j.pnpbp.2026.111642 Observational study Clinical trial Functional impairment Medline +4

Preliminary effects of ayahuasca on mental and physical health: A systematic review of prospective studies

Progress in Neuro-psychopharmacology and Biological Psychiatry February 8, 2026 Michael J. Haupt, Savannah Pointe, Kevin F. Boehnke et al.

Ayahuasca is a psychedelic plant brew that has been used in Central and South America for centuries. Recently, there has been an increase in "drug tourism" to places where ayahuasca is legally available as well as increased scientific interest in its potential mental and physical health benefits. Despite a growing body of research over the last decade, no studies to date have systematically...

DOI: 10.1016/j.pnpbp.2026.111634 Ayahuasca Anxiety Mental health Depression economics +8

Psilocybin-induced alterations in EEG power, connectivity and network dynamics in healthy subjects: Correlations with subjective experience and implications for therapeutic applications

Progress in Neuro-psychopharmacology and Biological Psychiatry 2026 Cheng-Teng Ip, Sebastian Olbrich, Mateo de Bardeci et al. 1 citation

BACKGROUND: Recent advancements in psychedelic research have highlighted psilocybin's potential therapeutic benefits for various mental disorders. Understanding its effects on brain function and identifying predictors of individual responses are essential for developing effective treatments. METHODS: This double-blind, randomized, crossover, and placebo-controlled study enrolled 25 healthy...

DOI: 10.1016/j.pnpbp.2026.111626 Electroencephalography Dynamics music Neurophysiology Artificial neural network +2

Cognitive outcomes following psilocybin-assisted therapy in treatment-resistant depression: A post-hoc analysis of a randomized, waitlist-controlled trial

Progress in Neuro-psychopharmacology and Biological Psychiatry November 22, 2025 Shakila Meshkat, Noah Chisamore, Zoe Doyle et al.

PAP was associated with modest, short-term improvements in performance on measures of processing speed and executive function among individuals with TRD. While these changes appeared independent of mood, they did not consistently exceed expected practice effects. These findings highlight the need for adequately powered, controlled trials to clarify whether observed cognitive changes reflect...

DOI: 10.1016/j.pnpbp.2025.111565 Cognition Mood Test biology Schizophrenia object-oriented programming +5

Adverse event reporting and management in psilocybin therapy clinical trials: A systematic review to guide clinical and research protocol development

Progress in Neuro-psychopharmacology and Biological Psychiatry October 23, 2025 Danielle Bukovsky, Aron Amaev, Jianmeng Song et al.

Psilocybin, a psychedelic prodrug, has gained renewed interest for its potential to treat various psychiatric disorders, including depression, anxiety, and substance use disorders. While promising, concerns remain regarding its safety profile and the management of potential adverse events (AEs). This systematic review aimed to evaluate the incidence, nature, and severity of adverse events and...

DOI: 10.1016/j.pnpbp.2025.111541 Psilocybin Adverse effect Psycinfo Medline +8

Changing your mind: neuroplastic mechanisms underlying the therapeutic effect of psychedelics in depression, PTSD, and addiction

Progress in Neuro-psychopharmacology and Biological Psychiatry October 1, 2025 Marta L.c. Palhas, Rémi Corne, Raymond Mongeau 4 citations

After years of restrictions due to concerns about their potentially harmful effects, research on psychedelics has entered a new era. Increasing attention has been directed toward their immense therapeutic potential, particularly for psychiatric disorders. Pre-clinical and clinical studies have consistently demonstrated that psychedelic treatments produce therapeutic effects within hours of...

DOI: 10.1016/j.pnpbp.2025.111533 Neuroplasticity Addiction Serotonergic Synaptogenesis +10

Differential effects of psilocybin and lisuride on serotonin and dopamine neuronal activity and behavior

Progress in Neuro-psychopharmacology and Biological Psychiatry October 1, 2025 Brandon Richardson, Antonio Inserra, Michael Pileggi et al. 2 citations

Psilocybin and lisuride are 5-HT2A receptor agonists, but only psilocybin elicits the head twitch response (HTR) in rodents, a behavior commonly used as a proxy for hallucinogenic activity. This study aimed to compare their effects on serotonin (5-HT) and dopamine (DA) neuronal activity, as well as related behavioral outcomes, to elucidate the mechanisms underlying their divergent effects....

DOI: 10.1016/j.pnpbp.2025.111522 Serotonergic Psilocybin Serotonin Lisuride +14

Psilocybin-assisted psychotherapy in adults with depression – A literature review

Progress in Neuro-psychopharmacology and Biological Psychiatry September 24, 2025 Marie Celine Dorczok, Gloria Mittmann, Thomas Ettl et al. 2 citations

PAP combined with structured psychological support shows sustained reductions in depressive symptoms for treatment-resistant depression and major depressive disorder. Higher doses generally yield stronger benefits. While PAP holds significant potential as a holistic treatment, methodological limitations, such as heterogeneity in study designs, inconsistent levels of psychological support and...

DOI: 10.1016/j.pnpbp.2025.111508

Cognitive and psychotic effects of ketamine "short- vs. long-term" therapy in a rat model of depression: Hippocampal TrkB/Akt/GSK-3β/mTOR/autophagy trajectories.

Progress in Neuro-psychopharmacology and Biological Psychiatry September 1, 2025 Safaa K Aref, Mohamed Z. Habib, Dalia M. Eid et al. 7 citations

Accumulating evidence indicates the role of ketamine as a rapid-onset antidepressant, with a rising controversy regarding its cognitive and psychotic effects, especially with long-term use. However, no previous experimental study has directly compared short-term and long-term ketamine effects using a time schedule that simulates infusion protocols in major depressive disorder patients. This...

DOI: 10.1016/j.pnpbp.2025.111503

Noribogaine altered intrinsic properties of thalamocortical neurons in a sex-dependent manner

Progress in Neuro-psychopharmacology and Biological Psychiatry August 1, 2025 Sofía Villalba, Sofia Bosch, Lucia di Constanzo et al. 1 citation

Noribogaine (Noribo) is the primary metabolite from ibogaine, an atypical psychedelic. The main objective of this study was to evaluate the effect of Noribo on thalamic physiology of calcium channels voltage activation and gene expression and the potential involvement of the 5-HT2A receptor on those effects. Thus, we used male and female, 5-HT2AR knockout (KO) and wild type (WT) mice, injected...

DOI: 10.1016/j.pnpbp.2025.111467 Endocrinology Voltage-dependent calcium channel Gene expression Wild type +1

Effects of different methods of cannabis use on cognition and blood THC: A systematic review.

Progress in Neuro-psychopharmacology and Biological Psychiatry May 1, 2025 Danial Behzad, S. Patel, R. Besa et al.

Novel methods of cannabis use are becoming popular, but the differential impact of these new methods on cognition have not been widely studied. Further, the impact of cannabis on cognition is mediated by delta-9-tetrahydrocannabinol (THC), but few studies have directly compared the pharmacokinetics of different methods. This systematic review (PROSPERO, CRD42023442731) was conducted to...

DOI: 10.1016/j.pnpbp.2025.111399

Persistent behavioural consequences of chronic adolescent cannabidiol (CBD) in a mouse model with increased susceptibility to Δ9-tetrahydrocannabinol and schizophrenia.

Progress in Neuro-psychopharmacology and Biological Psychiatry March 1, 2025 Gabriela Visini, Rose Chesworth, Tim Karl

Increasingly, the cannabis sativa plant compound cannabidiol (CBD) is used to treat various psychiatric and neurological health conditions which occur in early life or adolescence, including schizophrenia and autism spectrum disorder. However, behavioural effects CBD during adolescence have received limited attention, and the long-lasting behavioural consequences of adolescent CBD treatment are...

DOI: 10.1016/j.pnpbp.2025.111306 Full text

Psychedelics in neuroinflammation: Mechanisms and therapeutic potential

Progress in Neuro-psychopharmacology and Biological Psychiatry January 31, 2025 Júnia L. de Deus, Juliana Marino Maia, Renato Nery Soriano et al. 27 citations

Neuroinflammation is a critical factor in the pathogenesis of various neurodegenerative and psychiatric disorders, including Alzheimer's disease, Parkinson's disease, and major depressive disorder. Psychedelics, such as psilocybin, lysergic acid diethylamide (LSD), and dimethyltryptamine (DMT), have demonstrated promising therapeutic effects on neuroinflammation, primarily through interactions...

DOI: 10.1016/j.pnpbp.2025.111278 Neuroinflammation

Early psilocybin intervention alleviates behavioral despair and cognitive impairment in stressed Wistar rats

Progress in Neuro-psychopharmacology and Biological Psychiatry 2025 Zitong Wang, Brett Robbins, Ryan Zhuang et al. 15 citations

Chronic stress exerts profound effects on mental health, contributing to disorders such as depression, anxiety, and cognitive impairment. This study examines the potential of psilocybin to alleviate behavioral despair and cognitive deficits in a rodent model of chronic stress, focusing on the interplay between the Hypothalamic-Pituitary-Adrenal (HPA) axis and the Endocannabinoid System (ECS)....

DOI: 10.1016/j.pnpbp.2024.111243 Psilocybin magic mushrooms Psychedelics Hallucinogens Stress hormones +4

Clinical and preclinical evidence of psilocybin as antidepressant. A narrative review

Progress in Neuro-psychopharmacology and Biological Psychiatry 2025 Ines Erkizia-Santamaría, Igor Horrillo, J. Javier Meana et al. 10 citations

In the rapidly growing field of psychedelic research, psilocybin (and active metabolite psilocin) has been proposed as a promising candidate in the search for novel treatments for neuropsychiatric disorders. Clinical trials have revealed that psilocybin has a large, rapid, and persistent effect in the improvement of symptoms of depression and anxiety. The safety profile is considered...

DOI: 10.1016/j.pnpbp.2025.111249 Psilocybin Antidepressant Psychotherapist Narrative

The immunomodulatory effects of classical psychedelics: A systematic review of preclinical studies

Progress in Neuro-psychopharmacology and Biological Psychiatry September 7, 2024 Zhen Xuen Brandon Low, Wei Shen Ng, Bey Hing Goh et al. 19 citations

Emerging evidence suggests that classical psychedelics possess immunomodulatory and anti-inflammatory properties; however, these effects are yet to be well-established. This systematic review aims to provide a timely and comprehensive overview of the immunomodulatory effects of classical psychedelics in preclinical studies. A systematic search was conducted on six databases, including CINAHL,...

DOI: 10.1016/j.pnpbp.2024.111139 Psilocybin Mescaline Hallucinogen Cinahl +7

Altered structural node of default mode network mediated general cognitive ability in young adults with obesity.

Progress in Neuro-psychopharmacology and Biological Psychiatry August 1, 2024 Shengjie Xu, Kezhen Lv, Yuqi Sun et al.

BACKGROUND Obesity, characterized by excessive adiposity, is associated with brain structural abnormalities. Nevertheless, the relationships between altered structural node of default mode network (DMN), body mass index (BMI), general cognitive ability remained unclear in young adults. METHODS In this study, we divided a large sample of young adults into three BMI-based groups. We then...

DOI: 10.1016/j.pnpbp.2024.111132

Electroconvulsive therapy disrupts functional connectivity between hippocampus and posterior default mode network.

Progress in Neuro-psychopharmacology and Biological Psychiatry February 1, 2024 K. Gbyl, Vytautas Labanaukas, C. C. Lundsgaard et al.

BACKGROUND The mechanisms underlying memory deficits after electroconvulsive therapy (ECT) remain unclear but altered functional interactions between hippocampus and neocortex may play a role. OBJECTIVES To test whether ECT reduces functional connectivity between hippocampus and posterior regions of the default mode network (DMN) and to examine whether altered hippocampal-neocortical functional...

DOI: 10.1016/j.pnpbp.2024.110981 Full text

The mechanistic basis for the rapid antidepressant-like effects of ketamine: From neural circuits to molecular pathways.

Progress in Neuro-psychopharmacology and Biological Psychiatry December 1, 2023 Li Ren

Conventional antidepressants that target monoaminergic receptors require several weeks to be efficacious. This lag represents a significant problem in the currently available treatments for serious depression. Ketamine, acting as an N-methyl-d-aspartate receptor antagonist, was shown to have rapid antidepressant-like effects, marking a significant advancement in the study of mood disorders....

DOI: 10.1016/j.pnpbp.2023.110910 Full text

Modulation of DNA methylation and protein expression in the prefrontal cortex by repeated administration of D-lysergic acid diethylamide (LSD): Impact on neurotropic, neurotrophic, and neuroplasticity signaling

Progress in Neuro-psychopharmacology and Biological Psychiatry June 28, 2022 Antonio Inserra, Antonella Campanale, David Cheishvili et al. 39 citations

AimPsychedelic compounds elicit relief from mental disorders. However, the underpinnings of therapeutic improvement remain poorly understood. Here, we investigated the effects of repeated lysergic acid diethylamide (LSD) on whole-genome DNA methylation and protein expression in the mouse prefrontal cortex (PFC).MethodsWhole genome bisulphite sequencing (WGBS) and proteomics profiling of the...

DOI: 10.1016/j.pnpbp.2022.110594 Neuroplasticity Prefrontal cortex Modulation music Cell biology +4

Separate and combined effects of alcohol and cannabis on mood, subjective experience, cognition and psychomotor performance: A randomized trial.

Progress in Neuro-psychopharmacology and Biological Psychiatry May 1, 2022 Christine M Wickens, Madison Wright, R. Mann et al.

Co-use of alcohol and cannabis is associated with increased frequency and intensity of use and related problems. This study examined acute effects of alcohol and cannabis on mood, subjective experience, cognition, and psychomotor performance. Twenty-eight healthy cannabis users aged 19-29 years with recent history of binge drinking completed this within-subjects, double-blind, double-dummy,...

DOI: 10.1016/j.pnpbp.2022.110570 Full text

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