Neuropharmacology
December 27, 2022
Robin Carhart‐Harris, Shamil Chandaria, David Erritzøe et al.
106 citations
A theoretical model proposes that psychopathology arises from a defensive process called canalization, which narrows an individual's range of thoughts, feelings, and behaviors by increasing precision or reducing variance in neural responses. This contrasts with an early form of plasticity, TEMP (Temperature or Entropy Mediated Plasticity), which increases variance and learning rate. Canalization entrenches pathology as the agent develops expertise in their disorder, while TEMP, combined with gentle psychological support, may counter this entrenchment. The model distinguishes adaptive from maladaptive canalization and suggests concrete experiments to test its hypotheses.
Psychological medicine
June 1, 2024
Balázs Szigeti, Brandon Weiss, Fernando E Rosas et al.
74 citations
In a double-blind trial comparing escitalopram and COMP360 psilocybin for major depressive disorder, patients held higher expectations for psilocybin than for escitalopram. Higher pre-trial expectancy for escitalopram predicted better outcomes with escitalopram, but expectancy for psilocybin did not predict response to psilocybin. Pre-treatment trait suggestibility was linked to therapeutic response in the psilocybin arm but not the escitalopram arm. These findings suggest that psychedelic therapy may be less influenced by expectancy biases than previously thought, and that highly suggestible individuals may be especially responsive to psilocybin treatment.
Nature Reviews Psychology
September 3, 2024
David B. Yaden, Sean P. Goldy, Brandon Weiss et al.
57 citations
No Summary
Journal of Psychopharmacology
March 1, 2022
Gabrielle Agin-Liebes, Richard J. Zeifman, Jason B. Luoma et al.
51 citations
People who participated in ayahuasca retreats in Central and South America reported reduced negative mood and increased positive mood and psychological flexibility three months later. Acute experiences of cognitive reappraisal during the ceremony were the strongest predictor of improvements in positive mood and flexibility. Increases in psychological flexibility statistically accounted for the link between acute psychological factors, including reappraisal, and later mood improvements. The findings suggest that acute reappraisal and subsequent gains in psychological flexibility are key mechanisms behind psychedelic-assisted therapy's benefits, supporting the integration of mindfulness-based and third-wave therapy approaches with such interventions.
Frontiers in Psychology
November 25, 2021
Brandon Weiss, Victoria Amalie Nygart, Lis Marie Pommerencke et al.
47 citations
In an online volunteer sample, naturalistic use of psychedelic compounds was associated with reductions in Neuroticism and increases in Agreeableness and perceived social connectedness over four weeks. These changes covaried, suggesting shared emotion-regulation processes. Preliminary evidence pointed to a specific decrease in critical and quarrelsome interpersonal style, a component of Agreeableness. Baseline levels of Neuroticism, perspective taking, and social connectedness tentatively amplified adaptive changes in those respective traits. Demographic characteristics, social setting, and acute subjective factors showed limited moderating effects. The findings suggest psychedelics might help address interpersonal aspects of personality pathology and loneliness.
EClinicalMedicine
September 23, 2024
David Erritzoe, Tommaso Barba, Kyle T Greenway et al.
46 citations
In a clinical trial, psilocybin therapy showed comparable effectiveness to a common SSRI antidepressant for treating depression, with both treatments leading to significant reductions in depressive symptoms over a follow-up period. The findings suggest psilocybin may offer a viable alternative to standard antidepressant medication, though the study's design and sample size limit the strength of conclusions.
Psychological medicine
January 1, 2024
Brandon Weiss, Induni Ginige, Lu Shannon et al.
38 citations
In a trial comparing psilocybin therapy with the antidepressant escitalopram for moderate-to-severe major depressive disorder, both treatments led to personality changes in a direction consistent with improved mental health. Psilocybin was linked to decreases in neuroticism, introversion, disagreeableness, and impulsivity, and increases in absorption, conscientiousness, and openness at six weeks, with some changes lasting six months. Escitalopram was linked to decreases in neuroticism, disagreeableness, and impulsivity, and increases in openness at six weeks, with neuroticism remaining decreased at six months. No significant differences between the two treatments were observed, except that patients' pre-trial positive expectations for escitalopram moderated personality changes after that treatment, but not after psilocybin.
PCN reports : psychiatry and clinical neurosciences
December 1, 2023
Simon G D Ruffell, Max Crosland-Wood, Rob Palmer et al.
37 citations
Ayahuasca, a psychedelic plant brew from the Amazon made from Banisteriopsis caapi vine and a DMT-containing plant like Psychotria viridis, has attracted growing interest since the year 2000. This review covers its history, pharmacology, and the phenomenological responses it produces. Anecdotal reports range from positive to accounts of physical and psychological harm. The authors discuss effects on personality and mental health, and examine phenomenological analyses of the experience. They conclude that ayahuasca is a promising psychedelic agent deserving more empirical research into its neurochemical mechanisms and potential therapeutic use.
European journal of psychotraumatology
January 1, 2024
Richard J Zeifman, Hannes Kettner, Stephen Ross et al.
34 citations
Therapeutic alliance—the quality of the relationship between therapist and client—predicts improvement in PTSD symptoms after MDMA-assisted psychotherapy. Among 22 adults with chronic PTSD who received MDMA during a clinical trial, stronger therapeutic alliance measured at sessions 4 and 9 (but not before the third session) was associated with lower clinician-assessed PTSD severity after treatment, even after accounting for initial symptom severity. Self-reported PTSD severity was also predicted by alliance at baseline, session 4, and session 9, though the baseline finding did not survive correction for multiple comparisons. These results provide initial evidence that common psychotherapeutic factors like alliance contribute to outcomes in MDMA-assisted therapy.
Scientific reports
June 9, 2023
Brandon Weiss, Aleksandra Wingert, David Erritzoe et al.
32 citations
Ayahuasca ceremonies commonly trigger reexperiencing of adverse life events, with women more likely to reexperience sexual assault, veterans more likely to reexperience combat trauma, and individuals with PTSD showing higher prevalence of reexperiencing. Reexperiencing was associated with cognitive reappraisal, psychological flexibility, and discomfort during ceremonies. Participants who reexperienced adverse events showed greater reductions in trait neuroticism after ceremonies. The study tracked 33 military veterans and 306 non-veterans across three timepoints at ayahuasca centers in South and Central America.
International Journal of Mental Health and Addiction
March 7, 2024
Brandon Weiss, Leor Roseman, Bruna Giribaldi et al.
26 citations
Acute psychological experiences, particularly mystical experience and ego dissolution, partially account for how psilocybin therapy improves depression compared to escitalopram. In a phase 2 trial of patients with moderate-to-severe major depressive disorder, mystical experience and ego dissolution uniquely mediated the effect of treatment on depressive response. Higher levels of mystical experience, emotional breakthrough, and intense music-listening responses were also linked to greater antidepressant improvement. These findings suggest that acute psychological experiences play a causal mechanistic role in psilocybin therapy for depression.
Journal of Psychopharmacology
April 25, 2023
Brandon Weiss, David Erritzoe, Bruna Giribaldi et al.
24 citations
A reanalysis of data from a trial comparing psilocybin therapy (PT) to escitalopram (ET) for major depressive disorder found that 14 of 16 outcome measures favored PT, but the QIDS-SR-16 did not. The QIDS-SR-16 showed higher variance, imprecision from compound items and sum-scoring, vague response options, and lack of focus on a core depression factor. When the trial data were examined at item, facet, and factor levels, results suggested PT was superior in reducing depressed mood, anhedonia, a core depression factor, and specific symptoms like sexual dysfunction. This raises concerns about relying on individual scales that miss depression's multidimensional structure.
Psychological trauma : theory, research, practice and policy
December 1, 2024
Brandon Weiss, Lê-Anh L Dinh-Williams, Nick Beller et al.
16 citations
A mixed-methods case series of eight military veterans with moderate posttraumatic stress symptoms who participated in a three-day ayahuasca intervention in Central America found that most participants showed reliable or clinically significant reductions in PTSD symptoms after treatment, and most of those improvements were maintained at a three-month follow-up. Veterans also reported improvements in momentary PTSD symptoms and daily negative and positive affect. Perceived benefits included deep positive emotions, acceptance, and a sense of purpose, though adverse acute experiences were also reported. The study provides preliminary support for lasting benefits of a brief ayahuasca intervention on PTSD and mood symptoms in veterans.
Journal of personality disorders
April 1, 2023
Brandon Weiss, Chelsea Sleep, Joshua D Miller et al.
15 citations
After ceremonial use of ayahuasca, self-reported decreases in entitlement-exploitativeness and increases in leadership authority were observed among 314 adults, along with decreases in a proxy measure of narcissistic personality disorder. However, effect sizes were small, results varied across measures, and informants reported no significant changes. The findings offer modest support for adaptive change in narcissistic antagonism up to three months after the ceremonies, but meaningful changes in narcissism were not seen. More research is needed to evaluate psychedelic-assisted therapy for narcissistic traits, especially in individuals with higher antagonism and using antagonism-focused approaches.
Journal of Psychedelic Studies
December 8, 2023
Brandon Weiss, Chelsea Sleep, Nicholas M. Beller et al.
11 citations
People who use psychedelics tend to be more open and extraverted and less neurotic than non-users, and non-users interested in trying psychedelics are more open and neurotic than uninterested non-users. An online survey of 218 psychedelic users, 104 interested non-users, and 104 uninterested non-users identified 52 themes of perceived personality change attributed to the most intense psychedelic experience, which clustered into eight factors: Unitive Spiritual, Gratitude Absorption, Purpose Freedom, Compassion Understanding, Emotional Stability, Openness Perspective, Connection to Self, and Neuroticism Caution. The findings suggest that personality traits influence who uses psychedelics, and that setting and drug type moderate different types of personality changes.
Psychedelic Medicine
January 20, 2025
Marianna Graziosi, Gabrielle Agin-Liebes, Mary P Cosimano et al.
9 citations
Psilocybin and other serotonergic psychedelics are used in research settings with safety measures including controlled environments, staff presence, screening, and psychoeducation. An analysis of study materials from psilocybin trials over the past two decades found that psychoeducation documents varied but commonly emphasized biological and physical safety, psychological safety and well-being, aspects of setting, and the potential for expectancies. The materials prioritized biological and psychological safety across all sites. The authors also identified elements unrelated to safety that may contribute to participant expectancies and suggest these extrapharmacological factors be studied systematically to maximize safety while minimizing extraneous expectancies.
Research Square (Research Square)
November 30, 2020
Brandon Weiss, Joshua Miller, Nathan Carter et al.
7 citations
A longitudinal study of 256 participants at three ayahuasca healing centers in South and Central America found that ceremonial ayahuasca use was associated with a large reduction in Neuroticism, a key personality trait linked to emotional stability. This change was observed both in self-reports (effect size d = 1.00 from baseline to post-use, d = 0.85 at three-month follow-up) and in reports from informants (d = 0.62 at follow-up). The degree of personality change was moderated by participants' baseline personality, acute experiences during the ceremony, and purgative experiences. The findings suggest ayahuasca ceremonies may contribute to lasting personality change, particularly in reducing Neuroticism.
Neuroscience Applied
December 2, 2024
Kate Godfrey, Brandon Weiss, Joseph Peill et al.
5 citations
A single high dose of psilocybin (25 mg) given to healthy volunteers who had never used psychedelics reduced neuroticism one month later, consistent with prior research. The reduction was linked to how meaningful the experience felt and to the dread of ego dissolution during the drug's acute effects. Personality was measured with the Big Five Inventory and Big Five Aspect Scale; acute effects were tracked with the Altered States of Consciousness questionnaire and Psychological Insight Scale. Electroencephalography measured alpha power and Lempel-Ziv complexity. The findings suggest that acute psychedelic states can catalyze lasting personality changes in a beneficial direction, with implications for therapy and understanding personality.
Current Psychiatry Reports
November 1, 2024
Matthew J Reid, Hannes Kettner, Tessa F Blanken et al.
4 citations
Psilocybin is an emerging treatment for depression, but its effects on sleep are not well understood. Clinical trials show large improvements in depressive symptoms, but sleep quality or insomnia symptoms have not been directly studied. Preliminary data indicate that both depressive symptoms and sleep disturbances decreased significantly after psilocybin use, though sleep improvements were smaller than those for depression. More severe sleep disturbances at baseline were linked to a lower probability of depression remission, suggesting a potential interaction between sleep and psilocybin's efficacy. Addressing sleep disturbances could enhance therapeutic outcomes and lead to more personalized treatment strategies.
The International journal on drug policy
November 1, 2025
Liam O Jarvis, Alexander H Jack, Niall Galbraith et al.
1 citation
The UK public holds a neutral, slightly negative attitude toward psychedelic-assisted therapy (PAT) for depression, based on a cross-sectional survey of 951 adults. People who were younger, male, had used recreational drugs, and reported greater subjective knowledge about psychedelics were more likely to view PAT favorably. A history of depression itself did not shape attitudes or change how personal characteristics related to them. The findings suggest that low familiarity with PAT and concerns about its safety, efficacy, and social acceptability may explain the overall neutrality, highlighting the need for clear scientific communication to inform public understanding.
Psychological Medicine
July 19, 2023
Brandon Weiss, Induni Ginige, Lu Shannon et al.
1 citation
No Summary
bioRxiv Preprint Server
May 1, 2025
Claudio Agnorelli, Joseph Peill, Gabriela Sawicka et al.
preprint
A single psychedelic dose of ketamine (1 mg/kg, intravenous) alters brain chemistry and connectivity in healthy people for at least one to eight days. After the dose, glutamate levels in the anterior cingulate cortex rose significantly. Functional connectivity decreased within high-order networks such as the default mode network, while integration between low- and high-order networks increased. Increases in a PET marker of synaptic plasticity correlated with reduced intrinsic activity in default mode network regions and a diminished influence of the posterior cingulate cortex on global network dynamics. The posterior cingulate cortex appears to be a central hub through which ketamine may reshape brain hierarchies over the long term.