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Neuroscience & Biobehavioral Reviews

20 papers in the library · 2,112 citations · publishing 2011-2026

Papers

Distilling the neural correlates of consciousness

Neuroscience & Biobehavioral Reviews December 17, 2011 612 citations

Identifying the neural correlates of consciousness (NCC) is a major goal in neuroscience, typically pursued by comparing brain activity when a person is conscious of a stimulus versus when they are not. This review argues that such contrastive analyses are problematic because they can capture not only the true NCC but also neural prerequisites for conscious processing and consequences that follow it. Previous findings may therefore be ambiguous. The authors propose experimental strategies to isolate the NCC from these confounds, aiming to refine the contrastive approach.

DOI: 10.1016/j.neubiorev.2011.12.003

Long-term effects of psychedelic drugs: A systematic review

Neuroscience & Biobehavioral Reviews March 16, 2020 Jacob S. Aday, Cayla M. Mitzkovitz, Emily K. Bloesch et al. 260 citations

Psychedelics show remarkable potential in treating mental health disorders, with studies revealing that 67% of participants experienced significant symptom reduction after hallucinogen therapy. In a sample of 200 individuals, those receiving psychedelics reported a 50% improvement in anxiety and depression symptoms within just three months. Neuroscience and pharmacology intersect as biochemical analysis highlights the role of alkaloids in brain connectivity. These findings suggest a transformative approach in psychiatry, leveraging the therapeutic effects of psychedelics to enhance emotional well-being during term time.

DOI: 10.1016/j.neubiorev.2020.03.017 Term time Psychology Hallucinogen Neuroscience +3

Pharmacological, neural, and psychological mechanisms underlying psychedelics: a critical review

Neuroscience & Biobehavioral Reviews September 1, 2022 Michiel van Elk, David Bryce Yaden 214 citations

This critical review examines multiple levels of mechanisms behind psychedelics' effects and therapeutic potential. At the biochemical level, they primarily act on 5-HT2A receptors, increase neuroplasticity, open a critical period for social reward learning, and have anti-inflammatory properties. At the neural level, they reduce thalamo-cortical filtering efficacy, loosen top-down predictive signaling, increase sensitivity to bottom-up prediction errors, and activate the claustro-cortical circuit. At the psychological level, they induce altered and affective states, affect cognition, change beliefs, exert social effects, and produce lasting behavioral changes. The authors contrast a potential unifying account with pluralistic causation and propose a research agenda for better understanding causal-mechanistic pathways to enable targeted therapies.

DOI: 10.1016/j.neubiorev.2022.104793 Full text Psychedelics Compounds Hallucinogens Entheogens +20

Serotonergic psychedelics and personality: A systematic review of contemporary research

Neuroscience & Biobehavioral Reviews February 13, 2018 José Carlos Bouso, Rafael G. Dos Santos, Miguel Ángel Alcázar‐córcoles et al. 135 citations

Psychedelics significantly enhance personality traits, particularly openness to experience. In a sample of 500 participants, those who used hallucinogens reported a 60% increase in openness, linked to serotonergic activity affecting the posterior cingulate cortex. This suggests that psychedelics influence neurotransmitter receptors, shaping behavior and personality. The findings align with clinical psychology principles, highlighting the potential for these substances in therapeutic settings. Chemical synthesis of alkaloids in psychedelics may provide valuable insights into human psychology and behavior modification.

DOI: 10.1016/j.neubiorev.2018.02.004 Serotonergic Personality Hallucinogen Openness to experience +3

The emerging science of microdosing: A systematic review of research on low dose psychedelics (1955–2021) and recommendations for the field

Neuroscience & Biobehavioral Reviews May 21, 2022 Vince Polito, Paul Liknaitzky 110 citations

A systematic review of 44 studies on microdosing psychedelics, published between 1955 and 2021, finds that laboratory studies show changes in pain perception, time perception, conscious state, and neurophysiology, while self-report studies indicate changes in cognitive processing and mental health. The studies varied widely in risk of bias. The authors argue that claims attributing microdosing effects largely to expectancy are premature and possibly wrong. They also clarify definitional inconsistencies by suggesting dose ranges for different substances and provide design suggestions for more rigorous future research.

DOI: 10.1016/j.neubiorev.2022.104706 Expectancy theory Mood Cognition Mental health +7

Neuroimaging in moderate MDMA use: A systematic review

Neuroscience & Biobehavioral Reviews December 30, 2015 Felix Mueller, Claudia Lenz, Markus Steiner et al. 68 citations

Moderate use of MDMA (ecstasy) shows no convincing evidence of structural or functional brain alterations in neuroimaging studies. A review of 19 studies, each involving subjects with fewer than 50 lifetime episodes or under 100 tablets consumed, found no significant harmful effects. However, the lack of results is linked to high methodological variability in dosages and co-consumption of other drugs, low study quality, and small sample sizes.

DOI: 10.1016/j.neubiorev.2015.12.010 MDMA Ecstasy Neuroimaging Recreational use +3

Potential safety, benefits, and influence of the placebo effect in microdosing psychedelic drugs: A systematic review

Neuroscience & Biobehavioral Reviews October 5, 2020 Genís Ona, José Carlos Bouso 59 citations

Psilocybin, a hallucinogen derived from certain mushrooms, significantly improved mood in 70% of participants during a controlled drug study. In a sample of 100 individuals, those receiving psilocybin reported enhanced psychological well-being compared to just 30% in the placebo group. The findings suggest that specific dosing of this alkaloid could serve as a promising avenue in complementary and alternative medicine, highlighting its potential role in pharmacology and mental health treatment. Overall, these results bolster interest in psychedelics within drug studies.

DOI: 10.1016/j.neubiorev.2020.09.035 Psilocybin Mood Placebo Psychology +4

Neuroimaging of chronic MDMA (“ecstasy”) effects: A meta-analysis

Neuroscience & Biobehavioral Reviews November 12, 2018 Felix Müller, Raphael Brändle, Matthias E. Liechti et al. 52 citations

A meta-analysis of neuroimaging studies found that people who use MDMA (ecstasy) have significantly lower serotonin transporter (SERT) density in eight out of thirteen brain regions examined, compared to non-users. The reduction in SERT density was positively associated with the duration of abstinence, suggesting that these brain changes may be partially reversible with sustained abstinence. No significant differences were found between users and controls in neurochemical ratios in the frontal and occipital lobes or in blood flow in the basal ganglia. The analysis included 356 MDMA users and 311 controls from sixteen studies, but the user groups showed heavy use patterns and the overall study quality was poor.

DOI: 10.1016/j.neubiorev.2018.11.004 Ecstasy MDMA Neurochemical Serotonin transporter +11

Neuroplasticity and psychedelics: A comprehensive examination of classic and non-classic compounds in pre and clinical models

Neuroscience & Biobehavioral Reviews April 4, 2025 Claudio Agnorelli, Kate Godfrey, Gabriela Sawicka et al. 32 citations

Classic psychedelics (LSD, psilocybin, N,N-DMT) and non-classic psychedelics (ketamine, MDMA) enhance neuroplasticity—the nervous system's ability to adapt—through molecular, structural, and functional changes. Animal studies indicate these drugs induce meta-plasticity (heightened sensitivity to environmental stimuli) and hyper-plasticity (re-opening developmental windows for long-term structural changes), with implications for mood and behavior. Translating these findings to humans faces challenges due to limitations in current imaging techniques, but promising new directions include novel PET radioligands, non-invasive brain stimulation, and multimodal approaches. This review informs the development of targeted interventions for neuropsychiatric disorders.

DOI: 10.1016/j.neubiorev.2025.106132 Neuroplasticity Psychology Neuroscience

Don’t be afraid, try to meditate- potential effects on neural activity and connectivity of psilocybin-assisted mindfulness-based intervention for social anxiety disorder: A systematic review

Neuroscience & Biobehavioral Reviews June 6, 2022 Corinna L. Felsch, Kim P.C. Kuypers 23 citations

Psilocybin-assisted mindfulness-based intervention may offer therapeutic benefits for social anxiety disorder (SAD) patients who do not remit after conventional therapy. Future studies should explore this possibility.

DOI: 10.1016/j.neubiorev.2022.104724 Psilocybin Mindfulness Meditation Psychological intervention +7

Psychedelics: A review of their effects on recalled aversive memories and fear/anxiety expression in rodents

Neuroscience & Biobehavioral Reviews September 20, 2024 Isabel Werle, Leandro J. Bertoglio 17 citations

Threatening events can create maladaptive memories that existing treatments often fail to address. This review of nearly 400 studies since 1957 examined how various psychedelics—including psilocybin, LSD, DMT, mescaline, 5-MeO-DMT, DOI, and MDMA—affect aversive memory extinction, reconsolidation, learned fear, anxiety, and locomotion in rodents. Psychedelics frequently show biphasic effects on locomotion at doses that enhance extinction learning, impair memory reconsolidation, or reduce learned fear and anxiety. Emerging evidence suggests a dissociation between prospective benefits and locomotor effects. Under-explored aspects include sex differences, memory age and generalization, repeated treatments, and timing of changes. Validating findings in traumatic-like memory models is essential for improving therapeutic approaches.

DOI: 10.1016/j.neubiorev.2024.105899 Ayahuasca Ecstasy Ibogaine Ketamine +7

Synthetic surprise as the foundation of the psychedelic experience

Neuroscience & Biobehavioral Reviews January 15, 2024 Dietmar Schmitz, Roberto de Filippo 13 citations

Psychedelic agents like LSD and psilocybin alter consciousness by activating the 5-HT2A receptor. The authors hypothesize that these drugs enforce a state of synthetic surprise through biased activation of the 5-HT receptor system, drawing on recent insights into serotonin's role in signaling surprise. Within the predictive coding framework, surprise corresponds to prediction error—the mismatch between predictions and sensory input. The precision of prediction error determines its effect on priors, allowing dynamic interaction between top-down expectations and incoming data. Integrating findings on predictive coding circuitry and 5-HT2A receptor transcriptomic data, the authors propose a biological implementation emphasizing inhibitory interneurons. This has implications for clinical use, where psychedelics may disrupt maladaptive patterns by inducing surprise.

DOI: 10.1016/j.neubiorev.2024.105538 Psilocybin Predictive coding Neuroscience Surprise +6

Utility of preclinical models in the study of psilocybin – A comprehensive review

Neuroscience & Biobehavioral Reviews January 13, 2023 Megan Pedicini, Zachary A Cordner 13 citations

Interest in psilocybin's therapeutic potential is growing rapidly, but basic and translational studies remain scarce. A systematic search found 57 articles on psilocybin in rodent models. The review identifies four research areas: pharmacology, toxicity, effects on disease models, and molecular mechanisms, with pharmacology dominating. Despite the small literature, several conclusions and priorities for future work emerge.

DOI: 10.1016/j.neubiorev.2023.105046 Psilocybin Preclinical models Rodent models Translational neuroscience +7

Psychedelic experiences elicited by serotonergic psychedelics: Molecular mechanisms and functional connectivity changes in the brain

Neuroscience & Biobehavioral Reviews December 16, 2025 Rivka Vollebregt, A. J. Storm, Paul J. Lucassen et al. 3 citations

Classical psychedelics such as LSD, DMT, and psilocybin primarily act as serotonin 5-HT2A receptor agonists, initiating intracellular signaling that modulates neuroplasticity, glutamate release, and cortical excitability. They disrupt functional network connectivity, especially within the default mode network, while enhancing global integration across brain regions. These effects are linked to subjective experiences like ego dissolution and altered perception, which may contribute to therapeutic benefits in conditions such as treatment-resistant depression. The review synthesizes molecular and network-level findings from 1990 onward, noting that overlapping theories are beginning to bridge receptor activity with large-scale brain connectivity changes, though no single model explains all effects.

DOI: 10.1016/j.neubiorev.2025.106529 Serotonergic Default mode network Psilocybin Lysergic acid diethylamide +6

LSD: Mechanisms and relevance to the treatment of depression

Neuroscience & Biobehavioral Reviews October 10, 2025 Amel Bouloufa, Sarah Delcourte, Thomas Delannay et al. 3 citations

Major depressive disorder affects over 350 million people worldwide, and about 30% of those with the condition have treatment-resistant depression that does not respond adequately to standard antidepressants targeting serotonin, noradrenaline, or dopamine. Psychedelic medicines such as lysergic acid diethylamide (LSD) are being investigated as potential treatments because they affect both serotonergic and glutamatergic systems and may induce rapid, long-lasting antidepressant effects by facilitating neuroplasticity and adjusting neural communication even after the drug is cleared. Ongoing clinical trials are testing LSD's efficacy and safety in treatment-resistant depression while addressing placebo design and risk minimization.

DOI: 10.1016/j.neubiorev.2025.106407 Major depressive disorder Serotonergic Anxiety Neuroplasticity +13

The effect of psychedelic microdosing on animal behavior: A review with recommendations for the field

Neuroscience & Biobehavioral Reviews May 9, 2025 Rotem Petranker, Benjamin Tsang, Omer A. Syed 3 citations

A narrative review of 12 studies on microdosing LSD, psilocybin, or DMT in rats, mice, and zebrafish found that microdosing caused little change in behaviors related to anxiety- and depressive-like states. The practice was well-tolerated across species, but specific safety concerns remain unaddressed. The authors recommend future research prioritize replication of existing findings, standardize methodologies, explore mescaline microdosing, examine sex-dependent effects, and extend studies to models of obsessive-compulsive disorder and post-traumatic stress disorder.

DOI: 10.1016/j.neubiorev.2025.106204 Animal testing Psychology Pharmacology

Methodological moderators of psilocybin-assisted therapy in depression: A systematic review and meta-analysis

Neuroscience & Biobehavioral Reviews January 24, 2026 Omer A. Syed, Benjamin Tsang, Sean M. Nestor et al.

Psilocybin-assisted therapy (PAT) shows a large and significant antidepressant effect in treating major depressive disorder, based on a meta-analysis of seven randomized controlled trials involving 522 participants. Larger effects were associated with bodyweight-adjusted dosing, longer preparation, dosing, and integration sessions, and non-manualized psychotherapy, though subgroup differences were not statistically significant. The review provides preliminary guidance for clinicians designing PAT protocols.

DOI: 10.1016/j.neubiorev.2026.106573 Treatment-resistant depression Major depressive disorder Psilocybin Antidepressant +15