The International Journal of Neuropsychopharmacology
May 10, 2021
Natalie Gukasyan, David B. Yaden, Matthew W. Johnson et al.
56 citations
Psychedelic substances produce unusual changes in conscious experience, leading some to propose they offer unique insights into consciousness. However, psychedelics are unlikely to provide information relevant to the "hard problem of consciousness," which involves explaining how first-person experience emerges. Instead, they bear on multiple "easy problems of consciousness," involving relations between subjectivity, brain function, and behavior. This review discusses common meanings of "consciousness" regarding psychedelics and considers models of their effects on the brain linked to explanatory claims about consciousness. It calls for epistemic humility about psychedelic research's potential to explain the hard problem while noting ways psychedelics may advance study of specific aspects of consciousness.
Scientific Reports
October 2, 2020
Manoj K. Doss, Darrick G. May, Matthew W. Johnson et al.
52 citations
Salvinorin A, a κ-opioid receptor agonist and dissociative hallucinogen found in Salvia divinorum, alters human brain functional connectivity in ways similar to other hallucinogens. In a placebo-controlled, within-subject fMRI study, inhaled Salvinorin A tended to decrease functional connectivity within brain networks while increasing connectivity between networks, most notably attenuating the default mode network during peak effects. It reduced brainwide dynamic functional connectivity but increased brainwide entropic functional connectivity, though only the reduction survived statistical correction. Connectome-based classification models trained on dynamic connectivity accurately identified Salvinorin A scans, especially when using default mode network interactions. These findings suggest shared neural mechanisms across hallucinogen types.
ACS Chemical Neuroscience
August 24, 2022
Manoj K. Doss, Frederick S. Barrett, Philip R. Corlett
21 citations
A critique of a Nature Medicine paper claiming psilocybin therapy reduces brain network modularity in depressed patients, an effect not seen with the SSRI S-citalopram. The authors identify multiple problems: inconsistent reporting of the primary clinical outcome, statistical flaws including a one-tailed test and a nonsignificant interaction, regression to the mean, ambiguous interpretation of resting-state fMRI data, and a missing reference to a similar study that undermines the justification for a one-tailed test. These issues cast doubt on the uniqueness and impact of the original findings and the media hype they generated.
June 10, 2021
Drummond E-Wen Mcculloch, Gitte M. Knudsen, Frederick S. Barrett et al.
14 citations
preprint
Research into psychedelic drugs like psilocybin, LSD, and DMT is growing, with clinical trials showing promise for psychiatric conditions. Resting-state fMRI is a common method to study brain mechanisms in these contexts. A review of 42 articles from 17 datasets found high heterogeneity in methods and analyses; two datasets underlie over half the publications, and terms like "entropy" are used inconsistently. The authors suggest that the field needs greater methodological consistency and replicability to identify stable neural markers of psychedelic effects, and encourage development of new models and quantification methods.
July 3, 2023
Hugh McGovern, Hilary Jane Grimmer, Manoj K. Doss et al.
12 citations
preprint
Psychedelics can reorient beliefs, but they may also lead to false insights and false beliefs. A review of laboratory research on false insights and false memories is connected to belief formation under psychedelics through the active inference framework. Psychedelics increase both the quantity and subjective intensity of insights and beliefs, including false ones. Future research should aim to minimize the risk of false and potentially harmful beliefs arising from psychedelics. Understanding this risk is crucial for safely leveraging the therapeutic potential of psychedelics.
Psychedelic Medicine
June 1, 2023
Praachi Tiwari, Andrea Berghella, Ceyda Sayalı et al.
9 citations
Classic psychedelics may treat mood and substance use disorders by reversing learned helplessness, a well-studied phenomenon across mammals. The neural circuits underlying resilience to learned helplessness, including the dorsal raphe nucleus, overlap with those activated by psychedelics. Preclinical data show psychedelics improve performance in rodent behavioral despair tasks, supporting this hypothesis. The learned helplessness paradigm offers a robust model for investigating psychedelic mechanisms across behavioral, neurobiological, and clinical levels, potentially explaining transdiagnostic therapeutic effects.
bioRxiv (Cold Spring Harbor Laboratory)
May 24, 2022
Manoj K. Doss, Jason Samaha, Frederick S. Barrett et al.
6 citations
preprint
Different classes of psychoactive drugs—sedatives, dissociatives, psychedelics, stimulants, and cannabinoids—each produce unique patterns of effects on the conscious processes underlying episodic memory, depending on whether they act during encoding, consolidation, or retrieval. Reanalyzing confidence data from 10 published datasets (28 drug conditions) with signal detection models, the authors found that all drugs except stimulants impaired recollection when given at encoding; sedatives, dissociatives, and cannabinoids also impaired familiarity at encoding. Psychedelics at encoding enhanced familiarity and did not affect metamemory, while dissociatives and cannabinoids tended to enhance metamemory. Stimulants enhanced metamemory at encoding and retrieval but impaired it at consolidation. These distinct profiles may help explain drug-specific subjective phenomena such as sedative-induced blackouts or psychedelic déjà vu.
May 26, 2024
Hugh McGovern, Nick Wellman, Brendan Hutchinson et al.
2 citations
preprint
Psychedelics such as psilocybin show promise for treating anxiety, but how they work is unclear. This review proposes a model where anxiety disorders involve the hippocampus biasing the amygdala and salience network toward anxiety-related information, creating a self-perpetuating cycle. Psychedelics temporarily free cortical networks from this hippocampal constraint, and increased plasticity afterward allows the hippocampus to integrate new information into a less biased contextual frame, reducing anxious thoughts. The model highlights that psychedelics can acutely increase anxiety, and future research should determine optimal treatment approaches informed by cognitive neuroscience.
Neuroscience and biobehavioral reviews
July 1, 2026
Bruno Moses, Manoj K. Doss, Enzo Tagliazucchi
1 citation
The entropic brain hypothesis suggests that brain entropy—the uncertainty in brain state distributions—increases during psychedelic states and other states of expanded consciousness, while decreasing in states of diminished consciousness. Many neuroimaging studies have reported heightened entropy under psychedelics, leading some to consider entropy a reliable biomarker of the psychedelic state. This paper argues that view is oversimplified. It reviews evidence for entropy metrics, then identifies four challenges: entropy changes are not specific to psychedelics; current methods do not capture multidimensional conscious states; multiple entropy metrics exist with different interpretations and limited consistency; and there is little evidence linking brain entropy directly to phenomenal richness. The authors conclude the concept warrants further investigation and offer suggestions for future research.
Journal of Eating Disorders
December 4, 2025
Samuli Kangaslampi, Max Wolff, Manoj K. Doss et al.
1 citation
Psychedelics like psilocybin can trigger vivid memory-like experiences, but a recent case report claiming that two patients recovered dissociated traumatic memories during psilocybin treatment for anorexia nervosa may not have adequately considered alternative explanations. The cases do not necessarily show that psilocybin induces recovery of dissociated traumatic memories or could treat dissociative amnesia. The authors also caution against explicitly preparing patients for the emergence of forgotten material, as such suggestions warrant scrutiny.
April 28, 2022
Manoj K. Doss, Frederick S. Barrett, Philip R. Corlett
1 citation
preprint
A critical commentary identifies problems in a previously published study on psilocybin therapy. The authors argue that the original paper drew unsupported causal conclusions from correlational data, failed to account for placebo effects and participant expectations, and used statistical methods that inflated the apparent strength of the findings. The commentary suggests the original study's claims about psilocybin's therapeutic mechanisms are not justified by the evidence presented.