Scientific reports
February 10, 2020
Frederick S Barrett, Manoj K Doss, Nathan D Sepeda et al.
375 citations
A single 25 mg/70 kg dose of psilocybin temporarily reduced negative affect and amygdala response to negative facial expressions one week later in twelve healthy volunteers, while positive affect and prefrontal cortex responses to emotional conflict increased. One month later, negative affect and amygdala reactivity returned to baseline, but positive affect remained elevated and trait anxiety was lower. The number of resting-state functional connections across the brain increased from baseline to both one week and one month after dosing. These preliminary findings suggest psilocybin may enhance emotional and brain plasticity, with negative affect as a potential therapeutic target.
Translational psychiatry
November 8, 2021
Manoj K Doss, Michal Považan, Monica D Rosenberg et al.
343 citations
Psilocybin therapy increased cognitive flexibility for at least four weeks in 24 patients with major depressive disorder, though these improvements were not linked to antidepressant effects. One week after treatment, glutamate and N-acetylaspartate concentrations decreased in the anterior cingulate cortex (ACC), and functional connectivity dynamics increased between the ACC and posterior cingulate cortex. Surprisingly, larger increases in this neural flexibility were associated with smaller gains in cognitive flexibility. Baseline brain connectivity from the ACC predicted cognitive flexibility improvements, with greater baseline connectivity linked to better baseline flexibility but less improvement. The findings suggest that while some increase in neural dynamics may help shift from rigid states, larger persisting increases may be less beneficial.
Brain
October 22, 2021
Manoj K Doss, Maxwell B Madden, Andrew Gaddis et al.
196 citations
Classic psychedelic drugs like psilocybin and LSD may help treat psychiatric disorders by altering brain circuits. Two existing models—the cortico-striatal thalamo-cortical (CSTC) model and the relaxed beliefs under psychedelics (REBUS) model—highlight different subcortical structures in mediating these effects. This paper introduces a third circuit-level model, the cortico-claustro-cortical (CCC) model, focusing on the claustrum, a thin strip of grey matter that densely expresses serotonin 2A receptors. The CCC model proposes that the claustrum entrains canonical cortical network states, and psychedelic drugs disrupt 5-HT2A-mediated coupling between claustrum and cortex, attenuating these networks. Together, the three models may explain many phenomena of the psychedelic experience.
Neuroscience and biobehavioral reviews
July 1, 2023
Manoj K Doss, Harriet de Wit, David A Gallo
30 citations
Psychoactive drugs affect emotional episodic memory at three stages: encoding, consolidation, and retrieval. Drugs given before encoding can impair (e.g., alcohol, benzodiazepines, THC, ketamine), enhance (e.g., dextroamphetamine), or both impair and enhance (e.g., MDMA) emotional memories compared to neutral ones. Sedatives given after encoding can preferentially boost emotional memories during consolidation, but this selectivity may weaken or reverse over time. Retrieving memories under THC, dextroamphetamine, MDMA, or sedatives can distort memory, especially for positive emotional content. The review proposes neural mechanisms and discusses how these effects might influence drug use and abuse.
Psychological review
March 1, 2024
Manoj K Doss, Jason Samaha, Frederick S Barrett et al.
24 citations
Psychoactive drugs produce unique subjective states, but their effects on episodic memory often overlap. This reanalysis of 10 data sets (28 drug conditions) used signal detection models to separate three memory processes: recollection (retrieving specific details), familiarity (recognizing without details), and metamemory (introspecting about memory accuracy). Sedatives impaired both recollection and familiarity during encoding but enhanced recollection during consolidation. Dissociatives and cannabinoids impaired recollection during encoding, and cannabinoids increased false recollections during retrieval. Psychedelics impaired recollection during encoding but tended to enhance familiarity. Stimulants enhanced metamemory during encoding and retrieval but impaired metamemory during consolidation. These distinct patterns help explain drug-specific phenomena like sedative-induced blackouts and psychedelic presque vu, and suggest that memory quantity and stability influence metamemory.
Drugs
November 1, 2024
Manoj K Doss, Annamarie Demarco, Joseph E Dunsmoor et al.
14 citations
PTSD involves abnormalities in memory, and psychedelics may help treat it by affecting multiple memory systems. Most research has focused on fear conditioning and extinction, which are limited models. A review of 25 studies found that the acute effects of psychedelics can enhance extinction learning, which is impaired in PTSD, though they may also enhance fear conditioning. Post-acute effects may also boost extinction learning. PTSD and psychedelics both impair hippocampal-dependent episodic memory formation, but psychedelics may enhance cortical-dependent semantic learning, potentially helping integrate trauma memories and disrupt maladaptive beliefs. More research is needed on episodic memory consolidation, retrieval, and reconsolidation, and on post-acute effects across all memory phases.
Biological psychiatry. Cognitive neuroscience and neuroimaging
October 1, 2024
Manoj K Doss, Pablo Mallaroni, Natasha L Mason et al.
7 citations
Two psychedelics, psilocybin and 2C-B, impair the encoding of detailed recollections and distort feelings of familiarity for emotional memories. In a double-blind, placebo-controlled study with 20 participants, both drugs reduced estimates of recollection and familiarity the next day, but increased false alarms based on familiarity, especially for negative and positive images. The drugs also tended to impair metamemory for negative and neutral memories while enhancing it for positive ones, though these effects were less reliable. The similar pattern across both substances suggests a shared neurocognitive mechanism among psychedelics that may underlie other phenomena.
Journal of psychopharmacology (Oxford, England)
April 1, 2025
Manoj K Doss, Lilian Kloft, Natasha L Mason et al.
5 citations
In experienced users, ayahuasca acutely enhances recollection-based memory—the ability to recall specific details—without increasing false memories or affecting familiarity-based memory, a feeling of knowing. In an observational study of 24 Santo Daime members who had consumed ayahuasca over 500 times on average, participants completed a false memory task before and after taking a self-selected church dose. After ayahuasca, hit rates, memory accuracy, and recollection improved, while familiarity and false memory remained unchanged. The authors suggest that β-carboline activity in the brew may account for this recollection enhancement, which contrasts with past psychedelic research showing impaired recollection. Practice effects could not be ruled out, but multiple measures of false memory and metamemory did not improve across sessions.
Neuroscience and biobehavioral reviews
July 1, 2022
Drummond E-Wen Mcculloch, Gitte Moos Knudsen, Frederick Streeter Barrett et al.
A large group of psychedelic imaging researchers reviewed 42 articles from 17 unique studies that used resting-state functional magnetic resonance imaging (rs-fMRI) to examine psychedelic effects. They found that nearly all studies varied in data processing and analysis methods, two datasets underpin over half of the published literature, and key outcome terms are used ambiguously. The authors recommend guidelines to improve consistency and replicability in future research, arguing that the field must balance novel methods with standardized approaches to reliably understand the neural mechanisms of psychedelics.