Frontiers in Psychiatry
July 12, 2022
Kwonmok Ko, Gemma Knight, James Rucker et al.
296 citations
Mystical experience—characterized by oceanic boundlessness, ego dissolution, and universal interconnectedness—may be a psychological mechanism influencing outcomes in psychedelic therapy. A review of 12 studies using psilocybin, ayahuasca, or ketamine found that 10 reported a significant association (correlation, mediation, or prediction) between mystical experience and symptom reduction across cancer-related distress, substance use disorder, and depressive disorders including treatment-resistant depression. However, most studies had small, non-diverse samples, and half were open-label, introducing potential bias. Future research needs larger, more diverse randomized designs and deeper exploration of mystical experience's nature and predictors to maximize therapeutic benefits while minimizing anxiety.
Journal of Affective Disorders
February 1, 2023
Kwonmok Ko, Emma I Kopra, Anthony J. Cleare et al.
144 citations
A systematic review and meta-analysis of 14 studies (7 randomized controlled trials) examined the effects of classic psychedelics (psilocybin, ayahuasca, LSD) on depressive symptoms. The review found significant reductions in depressive symptoms at 1 day, 1 week, and 3-5 weeks after treatment with psychological support. Results at 6-8 weeks were less conclusive. Small sample sizes in most studies and lack of long-term follow-up data limited statistical power and interpretation. The findings suggest an association between psychedelic therapy and short-term symptom reduction, but more rigorous trials with larger, diverse samples are needed.
International Review of Psychiatry
June 5, 2020
Ben Carter, Rebecca Strawbridge, Muhammad Ishrat Husain et al.
45 citations
A network meta-analysis of 27 randomized trials found that NMDA-targeting medications (e.g., ketamine) are markedly more effective than placebo for augmenting treatment-resistant depression (effect size 0.91). Antipsychotics, mood stabilizers, and other pharmacological augmenters were also compared, but NMDA therapies had the highest probability of being effective. No psychological augmentation trials could be included due to the lack of a common comparator. The evidence is limited by few trials, heterogeneity, and inconsistent safety reporting.
Neuropsychiatric Disease and Treatment
January 1, 2023
Kwonmok Ko, Ben Carter, Anthony J. Cleare et al.
26 citations
In psychedelic therapy, both mystical and challenging experiences may affect treatment outcomes, but what predicts their intensity is not well understood. Analyzing data from a randomized, double-blind, placebo-controlled trial, 89 healthy volunteers received a placebo, 10 mg, or 25 mg of psilocybin. Higher dosage strongly predicted greater intensity of both mystical and challenging experiences. Older age was linked to less intense challenging experiences. Personality traits showed little correlation, except that neuroticism correlated with more intense challenging experiences at the higher dose. Positive or negative mood before dosing did not predict experience intensity. The analysis was exploratory and post hoc.
Npj Ment Health Res
July 2, 2024
Ronit Kishon, Nadav Liam Modlin, Yael M. Cycowicz et al.
22 citations
Before psychedelics were prohibited, clinical research with complex psychiatric patients developed diverse treatment methods and practices that remain relevant today. These early studies, though lacking modern rigor, recognized that the treatment context and clinician's role are essential for positive outcomes. This review examines pre-prohibition clinical narratives about the phenomenology of psychedelic treatment and non-pharmacological factors in patient experience. It also explores clinician perspectives and psychological interventions from that era to inform future research directions and best practice guidelines for modern psychedelic research and clinician training.
Journal of psychopharmacology (Oxford, England)
January 1, 2025
Gianmarco Ingrosso, Anthony J. Cleare, Mario F Juruena
20 citations
A review of 16 studies involving 2,174 patients found that addiction phenomena during ketamine treatment for depression are rare. Only four patients showed clear signs of tolerance or dependence, while the vast majority did not. The review included randomized controlled trials and other study designs using various routes of administration, including intravenous and intranasal esketamine. The findings suggest that medically supervised ketamine treatment is relatively safe for adult depression patients, though the authors emphasize the need for vigilant monitoring and careful dosing. Future research using standardized scales could further strengthen evidence for safe use.
European neuropsychopharmacology : the journal of the European College of Neuropsychopharmacology
April 1, 2025
Eduard Vieta, Nahida Ahmed, Celso Arango et al.
12 citations
Patients with treatment-resistant depression who received esketamine nasal spray experienced 43.2% more weeks with functional remission over 32 weeks compared to those taking quetiapine extended release, a difference of 2.0 weeks. Esketamine also led to an 11.9% reduction in productivity loss due to absenteeism and a 14.2% reduction in overall work productivity loss. Both treatments were taken alongside an ongoing SSRI or SNRI. The findings suggest that esketamine provides greater improvements in daily functioning and workplace productivity for this patient group.
Psychedelic Medicine
November 26, 2024
Nadav Liam Modlin, Tyler McPhee, Nira Zazon et al.
5 citations
People who use psychedelics and attend integration groups report that these groups provide essential community support and help process psychedelic experiences, but also face challenges such as managing group dynamics and ensuring facilitators are adequately trained. Three main themes emerged: reasons for attending, utility of the groups, and adverse factors affecting experience. While integration groups can reduce some risks of unregulated psychedelic use, research is needed to develop standardized protocols and facilitator training to improve their safety and effectiveness.
EClinicalMedicine
December 1, 2025
Nadav Liam Modlin, Victoria Williamson, Guy M. Goodwin et al.
2 citations
Psilocybin treatment for post-traumatic stress disorder, when delivered with standardized preparation and support, may allow patients to engage with trauma-related material indirectly through affective, somatic, and self-transcendent experiences, such as feelings of unity or dissolution of self, rather than requiring direct confrontation with traumatic memories as in standard therapies. This qualitative study, nested within a phase 2 trial involving 21 adults with PTSD, identified four core themes: non-pharmacological factors for psychological safety and trust, the experiential nature of psilocybin treatment, engagement with trauma-related material, and comparative reflections on prior therapies. The findings suggest psilocybin offers a meaningful therapeutic opportunity, but larger controlled studies are needed.
Therapeutic Advances in Psychopharmacology
June 8, 2025
Nadav Liam Modlin, Victoria Williamson, Carolina Maggio et al.
1 citation
PTSD is a common and debilitating condition that current treatments only partially address. This review examines psilocybin, a classical psychedelic, as a potential therapeutic agent. It synthesizes recent literature on psychedelic therapies for trauma-related conditions, including treatment-resistant depression and end-of-life anxiety. The authors propose a conceptual framework viewing PTSD as a maladaptive interpretive framework that psilocybin may disrupt through its psychopharmacological properties and subjective effects. A clinical narrative illustrates this process. Recommendations emphasize rigorous, trauma-informed protocols for safe administration in medical research settings.
Journal of Affective Disorders
January 5, 2024
Kwonmok Ko, Emma I Kopra, Anthony J. Cleare et al.
1 citation
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Psychiatry and Clinical Psychopharmacology
August 14, 2025
Nadav Liam Modlin, Jessica L Maples-Keller, Maria Sarang et al.
Among 873 people who reported trauma symptoms or a PTSD/CPTSD diagnosis, 94.8% had experienced psychological trauma and 73.4% had a formal diagnosis. Many had tried multiple medications and psychotherapies but were highly dissatisfied. Significant numbers used marijuana, psychedelics, or MDMA on their own to manage symptoms, with few physical or psychological complications. After learning about MDMA and psilocybin therapies, willingness to try them was high (0.81 and 0.83, respectively). Women and heterosexual individuals showed lower willingness, while younger and more educated respondents were more willing. The findings point to a need for further clinical research and public education about risks and harm reduction.