Social Cognitive and Affective Neuroscience
September 5, 2012
Jennifer S. Mascaro, James K. Rilling, Lobsang Tenzin Negi et al.
225 citations
A randomized controlled trial tested whether an eight-week compassion meditation program (cognitive-based compassion training, CBCT) improves the ability to infer others' mental states from facial expressions. Twenty-one healthy adults completed the Reading the Mind in the Eyes Test during fMRI scans before and after either CBCT or a health discussion control group. Those who completed CBCT showed significantly greater improvement in empathic accuracy scores and increased brain activity in the inferior frontal gyrus and dorsomedial prefrontal cortex compared to controls. Changes in these brain regions correlated with changes in empathic accuracy. The findings suggest CBCT may enhance empathic accuracy and its underlying neural mechanisms.
Psychological Medicine
November 4, 2020
Simon B. Goldberg, Benjamin Shechet, Christopher R. Nicholas et al.
66 citations
Classical psychedelics such as psilocybin, ayahuasca, and LSD produce significant psychological effects lasting at least 24 hours after administration, according to a systematic review and meta-analysis of 34 experimental studies involving 549 participants. Large effects were observed for reducing targeted symptoms in psychiatric samples, improving negative and positive affect, social outcomes, and existential or spiritual well-being, with between-group effect sizes ranging from Hedges' g = 0.84 to 1.08. Effects may be larger in clinical samples. Evidence for changes in personality traits or mindfulness was weak. No post-acute adverse effects were found, but high risk of bias, heterogeneity, and possible publication bias underscore the need for larger, placebo-controlled trials.
Journal of Psychopharmacology
July 31, 2024
Roman Palitsky, Deanna M. Kaplan, John Perna et al.
32 citations
A multidisciplinary working group identified 54 potential adverse events that warrant systematic assessment in psychedelic-assisted therapies, finding that existing measurement tools substantially fail to cover these constructs. The group developed recommendations for when and how to assess these adverse events across preparation, dosing, integration, and follow-up phases, and demonstrated a preliminary assessment protocol. The framework addresses the need to capture post-acute dosing adverse events, accounting for both the pharmacotherapy and psychotherapy components of psychedelic-assisted therapy, as well as documented impacts on worldviews and spirituality.
PLoS ONE
January 2, 2024
Caroline Peacock, Erin Brauer, Ali John Zarrabi et al.
27 citations
Spiritual health practitioners bring unique expertise to psychedelic-assisted therapy based on their training and professional experience. Interviews with 15 such practitioners revealed seven themes in two domains: unique contributions (competency with spiritual material, awareness of power dynamics, familiarity with non-ordinary states, holding space, counterbalancing biomedical perspectives) and general contributions (using general therapeutic skills and supporting interdisciplinary collaboration). Their skills complement other clinical team members, and psychedelic-assisted therapy teams may benefit from including them. Further work is needed to define roles, qualifications, and training for these clinicians.
Frontiers in Psychiatry
November 29, 2022
Ana María Ortiz Bernal, Charles L. Raison, Rafael Lancelotta et al.
26 citations
Reactivations—similar to flashbacks—are common after using the psychedelic 5-MeO-DMT and are often neutral or positive rather than distressing. Analysis of survey data from 513 people who used 5-MeO-DMT outside clinical settings found that women, older age at first dose, higher education, and dosing in a structured group setting were linked to higher odds of reporting a reactivation. Higher mystical experience scores, greater personal wellbeing, and having had a non-substance-induced non-dual awareness experience were associated with neutral or positive emotional valence of the reactivation. The findings suggest reactivations are typically a benign byproduct of the experience, but more research is needed to identify those at risk for negative reactivations.
JAMA Psychiatry
April 27, 2022
Mazdak M. Bradberry, Natalie Gukasyan, Charles L. Raison
20 citations
No Summary
medRxiv
August 24, 2023
Subha Subramanian, Demetrius Perry, Caterina Gratton et al.
14 citations
preprint
Psilocybin disrupts connectivity across cortical networks and subcortical structures, producing more than three-fold greater acute changes in functional networks than methylphenidate. These changes are driven by desynchronization of brain activity across spatial scales, strongest in the default mode network (DMN), which is connected to the anterior hippocampus and thought to create our sense of self. Performing a perceptual task reduces psilocybin-induced network changes, suggesting a neurobiological basis for grounding during psychedelic therapy. Psilocybin induces a persistent decrease in functional connectivity between the anterior hippocampus and cortex (and DMN in particular), lasting for weeks but normalizing after six months. This persistent suppression of hippocampal-DMN connectivity represents a candidate neuroanatomical and mechanistic correlate for psilocybin's pro-plasticity and anti-depressant effects.
Psychedelics.
September 13, 2024
Syed F. Rab, Charles L. Raison, Elliot Marseille
5 citations
Between 24% and 62% of U.S. patients with major depressive disorder or treatment-resistant depression may be eligible for psilocybin-assisted therapy, depending on how strictly exclusion criteria are applied. The lower estimate uses stringent criteria from clinical trials; the mid-range (56%) reflects likely real-world scenarios; the upper bound (62%) accounts for patients with multiple comorbidities. The main reason for ineligibility is disqualifying conditions such as alcohol and substance use disorders. Actual demand will also depend on insurance coverage, state regulations, and availability of trained providers, highlighting the need for careful policy planning.
Pharmacology research & perspectives
August 1, 2024
Ari Brouwer, Robin L. Carhart‐Harris, Charles L. Raison
5 citations
Psychotomimetic drugs—such as amphetamines, cannabis, psychedelics, and dissociatives—can paradoxically relieve symptoms like attention deficits, pain, and depression, which themselves increase the risk of psychosis or co-occur with it. The authors propose two concepts to explain this paradox. Psychotomimetic compensation describes a short-term, drug-induced relief from stress, mediated by neurotransmitter systems including endocannabinoid, serotonergic, glutamatergic, and dopaminergic pathways. Psychotomimetic sensitization occurs after repeated stress or drug exposure, gradually intensifying psychotic-like experiences over time. The model has theoretical and practical implications.
Research Square (Research Square)
February 23, 2024
Ari Brouwer, Joshua K. Brown, Earth Erowid et al.
5 citations
Psychedelic therapy may work partly because its temporal structure mirrors the narrative arc of the Hero's Journey. A qualitative analysis of self-reported onset (comeup) and offset (comedown) phases of psilocybin experiences found that the comeup is more often characterized by negatively valenced feeling states, while the comedown is more often characterized by positively valenced feeling states resembling recovery from illness or adversity. This trajectory suggests that initially distressing altered states can ultimately resolve distress, offering a framework for understanding the therapeutic benefits of psychedelics.
March 5, 2024
Roman Palitsky, Deanna M. Kaplan, John Perna et al.
4 citations
preprint
A multidisciplinary working group identified 53 potential adverse events (AEs) specific to psychedelic-assisted therapies (PATs) that current assessment tools miss. Existing measures cover only a fraction of these constructs. The group recommends new assessment methods—including patient, clinician, and informant reports—and specifies when to measure AEs across preparation, dosing, integration, and follow-up phases. The framework addresses gaps in capturing post-acute dosing effects, including changes in worldview and spirituality, which distinguish PAT from other treatments.
Religion Brain & Behavior
July 11, 2024
Ari Brouwer, Charles L. Raison, F. Leron Shults
3 citations
A theory-building paper compares the trajectory of psilocybin mushroom experiences—aversive comeup, awe-inspiring peak, relief and clarity in the comedown—with spiritual and incipient psychotic experiences. It argues that these shared trajectories inform cognitive scientific perspectives on religion. The authors propose a causal pathway where stress, uncertainty, and arousal increase perception of extra agency (PEA), which may lead either to states that downregulate PEA or to states that perpetuate it. Religions could modulate this pathway to promote social cohesion. The paper emphasizes the need for phenomenological nuance when comparing psychedelic, spiritual, and psychotic experiences.
bioRxiv (Cold Spring Harbor Laboratory)
June 13, 2024
Christopher R. Nicholas, Matthew I. Banks, Richard Lennertz et al.
3 citations
preprint
Co-administering the amnestic benzodiazepine midazolam with psilocybin in 8 healthy participants partially impaired memory for the psychedelic experience while still allowing a conscious experience to occur. The degree of memory impairment was inversely associated with salience, insight, and well-being induced by psilocybin. These results suggest that memory of the acute psychedelic experience contributes to therapeutically relevant behavioral effects. Because midazolam blocks memory by blocking cortical neural plasticity, it may also help evaluate how the pro-neuroplastic properties of psychedelics contribute to their therapeutic activity.
bioRxiv (Cold Spring Harbor Laboratory)
July 29, 2025
May Kung Sutherland, Christopher R. Nicholas, Richard Lennertz et al.
preprint
Psilocybin, a serotonergic psychedelic, induces neural plasticity and alters consciousness, while midazolam, a benzodiazepine, blunts plasticity and causes sedation and amnesia. In an open-label pilot study, 25 mg of oral psilocybin was given alongside intravenous midazolam at doses that allowed a full psychedelic experience but reduced memory of it. EEG recordings showed that 15-30 minutes after dosing, when midazolam was at its target concentration, beta power increased and the spectral exponent decreased. As psilocybin's effects emerged over the next six hours, Lempel-Ziv complexity and spectral exponent increased while broadband power decreased. These findings suggest psilocybin's effects persist even with midazolam, supporting its use in mechanistic studies.
Psychedelics
March 8, 2024
Charles L. Raison
Charles Raison, a professor and researcher, discusses his career studying major depression and stress-related conditions. His work examines novel mechanisms in depression treatment, the effects of compassion training, and the potential of psychedelic medicines for major depression. He was recognized as one of the world's most influential researchers from 2010 to 2019.
Acta Psychiatrica Scandinavica
October 26, 2018
Charles L. Raison
The field of psychedelic medicine has undergone a dramatic transformation from fringe to mainstream psychiatry, driven by desperation for better treatments and promising research. Studies on psilocybin for cancer-related depression and anxiety show large effect size reductions, with over 50% of participants in clinical remission at 6 months after a single dose. In treatment-resistant depression, 47% achieved clinical response, with 66% maintaining response at 6 months. Psilocybin appears to produce lasting personality changes, decreasing neuroticism and increasing extraversion and openness. However, all studies are small, only two used randomized placebo-controlled designs, and blinding is difficult due to obvious acute effects. Larger trials are needed.