JAMA
August 31, 2023
Charles L Raison, Gerard Sanacora, Joshua Woolley et al.
493 citations
A single 25-mg dose of synthetic psilocybin, administered with psychological support, produced a clinically significant and sustained reduction in depressive symptoms and functional disability over 43 days in adults with major depressive disorder. In a phase 2 trial of 104 participants, those receiving psilocybin showed a mean 12.3-point greater improvement on the Montgomery-Asberg Depression Rating Scale at day 43 compared with those receiving a niacin placebo. Psilocybin also improved daily functioning and led to more sustained response, though not remission. No serious adverse events occurred, but psilocybin was associated with more overall and severe adverse events.
Nature
August 1, 2024
Joshua S Siegel, Subha Subramanian, Demetrius Perry et al.
241 citations
A single high dose of psilocybin (25 mg) massively disrupts functional connectivity in the human brain, causing more than threefold greater change than methylphenidate (40 mg). These changes are driven by desynchronization across spatial scales, dissolving network distinctions by reducing correlations within and anticorrelations between networks. The strongest effects occur in the default mode network, which is connected to the anterior hippocampus and is thought to create the sense of space, time, and self. Individual differences in connectivity changes are strongly linked to the subjective psychedelic experience. A persistent decrease in connectivity between the anterior hippocampus and default mode network lasts for weeks, suggesting a neuroanatomical correlate of the therapeutic and proplasticity effects of psychedelics.
JAMA psychiatry
July 1, 2023
Roman Palitsky, Deanna M Kaplan, Caroline Peacock et al.
86 citations
Spiritual, existential, religious, and theological components are important in psychedelic-assisted therapy, but they have not been systematically integrated into clinical practice. Research shows that spiritually integrated psychotherapies are effective and produce additional benefits on spiritually relevant outcomes, which are particularly relevant to psychedelic therapy. Established standards in spiritually integrated psychotherapy can be applied to psychedelic-assisted therapy. Integrating these topics is needed for culturally competent, evidence-based treatment aligned with high clinical standards, and neglecting them may undermine treatment success and increase risks for patients.
Frontiers in psychiatry
January 1, 2022
Charles L Raison, Rakesh Jain, Andrew D Penn et al.
75 citations
In a large online survey of 2,510 adults who had used psychedelics at least once, psychedelic use was linked to significant improvements in depression, anxiety, and emotional well-being. The benefits grew with more use but showed a ceiling effect; even a single use was associated with improvements. No single psychedelic agent proved clearly superior, but increases in mystical experiences and prosocial perspective-taking were tied to better mental health. However, 13% of participants (330 people) reported at least one harm from psychedelic use, and those individuals experienced less mental health benefit. The findings suggest that naturalistic psychedelic use may offer mental health benefits similar to those in clinical trials, while also posing some risk of harm for a minority.
JAMA psychiatry
January 1, 2023
Brian D Kiluk, Bethea A Kleykamp, Sandra D Comer et al.
22 citations
A review sponsored by a public-private partnership addresses clinical trial design for new opioid use disorder (OUD) treatments that target systems other than the μ-opioid receptor. The authors present consensus recommendations for evaluating novel therapies such as cannabinoids, psychedelics, sedative-hypnotics, and immunotherapeutics. Key design elements include specifying the treatment stage (e.g., early abstinence, long-term recovery), defining the treatment's role (adjunctive or independent), selecting patient-informed primary outcomes that assess opioid use patterns, retention, and quality of life, and monitoring adverse events like relapse or overdose, especially when patients are not on maintenance opioid agonist or antagonist medications. Incorporating input from people with lived experience is urged to accelerate development and uptake of effective therapeutics.
Psychotherapy
January 13, 2025
Roman Palitsky, Jessica L Maples-Keller, Caroline Peacock et al.
13 citations
In an open-label trial of psilocybin-assisted therapy for cancer-related demoralization and chronic pain, patients, facilitators, and caregivers identified key components and improvements for the treatment protocol. Using the Enhanced Critical Incident Technique, interviews revealed critical incidents, wish list items, and contributing factors related to therapy aspects like intention-setting and overall protocol transitions. The findings emphasize tailoring treatment to individual medical history, supporting common therapeutic factors, and ensuring collaborative care. Nine topic areas for protocol improvement emerged from the data.
Translational psychiatry
September 12, 2024
Christopher R Nicholas, Matthew I Banks, Richard C Lennertz et al.
10 citations
Psilocybin, a serotonergic psychedelic, can relieve symptoms in several psychiatric disorders and improve well-being, but it was unclear whether these benefits arise during the acute experience or depend on later memory of it. In 8 healthy participants, psilocybin (25 mg) was co-administered with the amnestic benzodiazepine midazolam at a dose that allowed a conscious psychedelic experience while partially impairing memory for it. Higher midazolam doses and greater memory impairment tended to associate with lower salience, insight, and well-being from psilocybin. These results suggest memory plays a role in therapeutically relevant behavioral effects of psilocybin.
International review of psychiatry (Abingdon, England)
December 1, 2024
Roman Palitsky, Nicholas K Canby, Nicholas T Van Dam et al.
6 citations
Research on adverse effects (AEs) of psychedelics has been limited, leading to underspecified profiles and potential undercounting. This article argues that meditation-related AE research, which shares phenomenological and contextual features with psychedelic AEs, offers valuable insights. An integrative review of both fields is presented, recommending that meditation AEs serve as a comparator condition. The authors propose adopting detailed, comprehensive, user-informed, impact-based, standardized, unbiased, and representative measures of AEs, along with examining factors that influence their impacts and trajectories, to advance psychedelic AE research.
Journal of psychiatric practice
September 1, 2023
Amir Garakani, Jeanne L Alexander, Calvin R Sumner et al.
6 citations
Public and clinical interest in psychedelics is growing, with many studies underway for depression, anxiety, PTSD, and substance use disorders. This paper focuses on psilocybin, explaining its mechanism, psychedelic effects, and dosing. It reviews treatment studies, primarily for treatment-resistant depression and cancer-related anxiety, and discusses future directions and potential limitations in studying and regulating psilocybin and other psychedelics.
Npj mental health research
February 7, 2025
Ari Brouwer, Joshua K Brown, Earth Erowid et al.
5 citations
Psychedelic therapy may work partly because of an overlooked temporal pattern: the initial 'come-up' phase often feels like an acute stress reaction, while the later 'come-down' phase brings positive feelings similar to recovery from illness or stress. A qualitative analysis of psilocybin experience reports from Erowid.org, using phenomenological, thematic content, and word frequency analysis, shows that negatively valenced states dominate the onset, and positively valenced states dominate the falling phase. This pattern helps explain how initially distressing altered states can ultimately resolve distress, with implications for therapeutic and theoretical understanding of psychedelic treatment.