Neuroscience & Biobehavioral Reviews
December 17, 2011
Jaan Aru, Talis Bachmann, Wolf Singer et al.
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.
Neuroscience & Biobehavioral Reviews
June 5, 2011
Tom A. de Graaf, Po‐jang Hsieh, Alexander T. Sack
273 citations
The concept of 'consciousness' in the search for neural correlates of consciousness (NCC) is problematic, and the term 'correlates' is also confused. Brain events that covary with conscious experience can be neural substrates of the experience, but they can also be neural prerequisites or neural consequences. This work disentangles these different sorts of brain processes conceptually and proposes a concrete multi-pronged research program to distinguish them empirically in near-future consciousness research.
Neuroscience & Biobehavioral Reviews
March 16, 2020
Jacob S. Aday, Cayla M. Mitzkovitz, Emily K. Bloesch et al.
260 citations
A systematic review of 34 experimental studies on classic psychedelics with follow-up periods of at least two weeks found lasting changes in personality, attitudes, depression, spirituality, anxiety, wellbeing, substance misuse, meditative practices, and mindfulness. Psilocybin was the most commonly administered drug. Mystical experiences, connectedness, emotional breakthrough, and increased neural entropy were linked to these long-term psychological changes. With proper screening, preparation, supervision, and integration, participants reported few aversive side effects. The review calls for larger, more diverse samples, longer longitudinal designs, stronger control conditions, and standardized dosages in future research.
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.
Neuroscience & Biobehavioral Reviews
March 14, 2019
Benjamin Baird, Sérgio Mota‐rolim, Martin Dresler
196 citations
Lucid dreaming is becoming aware that one is dreaming while still asleep. This review of neuroscientific studies—including electroencephalographic, neuroimaging, brain lesion, pharmacological, and brain stimulation research—finds that evidence is limited and often mixed. Electroencephalographic studies are mostly underpowered and show inconsistent results. Neuroimaging data are scant but suggest involvement of prefrontal and parietal regions. Combining mental-set training with cholinergic stimulation shows promise for inducing lucid dreams, while electrical brain stimulation's effectiveness remains unclear. The review also covers best-practice measurement strategies for sleep laboratories. Lucid dreaming has clinical and scientific applications, especially for studying consciousness, but further research with larger samples and refined methods is needed.
Neuroscience & Biobehavioral Reviews
February 13, 2018
José Carlos Bouso, Rafael G. Dos Santos, Miguel Ángel Alcázar‐córcoles et al.
135 citations
Serotonergic psychedelics, which activate 5-HT2A receptors in the brain, can alter personality traits. A systematic review of 18 studies from 1985 to 2016 found that traits like Absorption and Self-Transcendence influence how people respond to these drugs. Users and nonusers differ in certain personality characteristics. When given in controlled settings, psychedelics may increase Openness and Self-Transcendence. Acute administration raises global brain entropy, which predicts changes in Openness. In long-term ayahuasca users, Self-Transcendence is negatively correlated with thinning of the posterior cingulate cortex. Both acute and long-term use appear to produce personality changes mediated by 5-HT2A receptors, suggesting therapeutic potential that warrants further randomized controlled trials.
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.
Neuroscience & Biobehavioral Reviews
May 10, 2021
Laith Alexander, Luke A. Jelen, Mitul A. Mehta et al.
79 citations
The anterior cingulate cortex (ACC), including its subgenual, perigenual, and dorsal zones, plays a key role in major depression and its treatment. Ketamine, a rapidly acting antidepressant, induces acute (over minutes) and post-acute (over hours to days) changes in subgenual and perigenual ACC activity, and these changes can correlate with antidepressant efficacy. The subgenual and dorsal ACC zones are specifically linked to ketamine's anti-anhedonic effects. The review emphasizes combining human neuroimaging with animal brain manipulations to understand causal relationships between brain activity and therapeutic outcomes. Circuit-based perspectives highlight ACC function in a central network mediating affective pain and its role as the anterior node of the default mode network.
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.
Neuroscience & Biobehavioral Reviews
May 5, 2015
Federico Turkheimer, Robert Leech, Paul Expert et al.
64 citations
The brain appears to use repeated computational building blocks—canonical computational motifs—that are similar across species, brain areas, and sensory modalities. These motifs, grounded in stereotyped neuronal circuits and inhibitory interneurons, operate at micro-, meso-, and macro-scales to form a multiplexing information system capable of encoding and transmitting increasingly complex information. Similar activation patterns are observed in primary sensory cortices via electrophysiology and in large-scale networks measured with fMRI. The authors apply this canonical model to unify evidence on the pathophysiology of schizophrenia and suggest it may extend to other brain disorders involving GABA interneuron dysfunction.
Neuroscience & Biobehavioral Reviews
December 6, 2019
Jasmine T. Ho, Katrin H. Preller, Bigna Lenggenhager
61 citations
The body continuously shapes cognition through sensory input and self-referential processing. In healthy individuals, predictive coding integrates multisensory information to form a coherent sense of self. Psychiatric disorders often involve distorted perceptions of the bodily self, linked to disrupted integration and updating of multisensory systems. Changes in functional connectivity between somatomotor and high-level association networks in these disorders may be remediated by 5-HT2A receptor agonism via psychedelics. Psychedelic experiences alter bodily self-awareness, suggesting a central role for the bodily self. The article proposes that psychedelic-induced desynchronization of predictive coding involves modulation of somatomotor, sensorimotor, and high-level association networks, potentially correcting aberrant bodily self-perceptions.
Neuroscience & Biobehavioral Reviews
October 5, 2020
Genís Ona, José Carlos Bouso
59 citations
Microdosing psychedelic drugs like LSD or psilocybin is increasingly common in Western societies, primarily for enhancing mood or creativity. This systematic review of human studies examined efficacy, safety, and the role of placebo effects. The evidence shows strengths such as large sample sizes and robust methods, but also limitations like gender bias and inconsistent dosing. Results are highly contradictory, with some studies reporting benefits and others reporting detriments to mood, creativity, and energy. The review offers an overview of methods to guide future research.
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.
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.
Neuroscience & Biobehavioral Reviews
December 16, 2021
Igor Elman, Amanda C. Pustilnik, David Borsook
26 citations
About 70% of chronic neuropathic pain patients do not respond to opioids or other conventional analgesics. A growing body of clinical observations over the past decade suggests that psychedelic drugs may help understand and treat chronic pain conditions. This review presents a theoretical framework for the neuroscience-based mechanisms of psychedelics' potential analgesic effects, covering studies on psychedelics for physical and emotional pain, neuro-restorative effects on impaired brain connectivity and dendritic plasticity, anti-neuroinflammatory and pro-immunomodulatory actions, and safety, legal, and ethical considerations. Including psychedelics in the analgesic toolkit could also deepen insights into comorbid psychiatric conditions like depression and anxiety.
Neuroscience & Biobehavioral Reviews
June 6, 2022
Corinna L. Felsch, Kim P.C. Kuypers
23 citations
Current first-line treatments for social anxiety disorder (SAD) have limited efficacy, prompting a need for novel approaches. This systematic review proposes combining meditation-based interventions with a psychedelic, such as psilocybin, as a future alternative. Thirty experimental studies on neural effects of meditation or psilocybin in healthy and patient samples suggest that psilocybin-assisted meditation could alter cognitive processes like biased attention to threat by modulating salience network connectivity, balancing cortical-midline structure activity, and increasing frontoparietal control over amygdala reactivity. The authors conclude that future studies should investigate whether this combination provides therapeutic benefits for SAD patients who do not remit with conventional therapy.
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.
Neuroscience & Biobehavioral Reviews
February 3, 2024
Ivana Solaja, Kate Haldane, Natasha L. Mason et al.
17 citations
A systematic review and meta-analysis of ten controlled studies involving 304 participants found no lasting changes in cognition, creativity, emotional processing, or personality from serotonergic psychedelics for most measures. However, faster reaction times were observed for recognizing disgust and sadness in active treatment groups. The authors call for larger samples and standardized methods to confirm these preliminary findings.
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.
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.
Neuroscience & Biobehavioral Reviews
October 19, 2025
Alessio Mosca, Gianluca Mancusi, Stefania Chiappini et al.
6 citations
Synthetic cannabinoids are the novel psychoactive substances most strongly associated with acute psychosis and, in some cases, persistent or relapsing psychotic disorders. Some cases show symptoms overlapping with schizophrenia, suggesting a possible risk of transition to chronic illness. Synthetic cathinones and phenethylamines are also linked to psychotic manifestations including thought disturbances and perceptual abnormalities. While many psychotic episodes are transient, a notable proportion evolve into persistent states, indicating that these substances may unmask latent vulnerabilities or directly contribute to chronic psychotic disorders. Clinicians should systematically assess NPS use in first-episode psychosis patients.
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.
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.
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.
Neuroscience & Biobehavioral Reviews
May 30, 2026
Raquel Kosted, Manoj K. Doss, Jennifer J. Donegan et al.
1 citation
Psychedelics may enhance cognitive flexibility, but findings are mixed, with some studies showing impairment. This review proposes that acute effects of psychedelics boost learning from reward receipt, which can lead to perseveration, while post-acute effects enhance learning from reward omission, counteracting that perseveration. Different serotonin receptor subtypes (5-HT2C, 5-HT2A, 5-HT1A) may support these distinct learning processes. This hypothesis explains when psychedelics improve flexible decision-making and why insights reached under their influence can be held strongly, and it suggests strategies to reduce maladaptive belief formation.