The International Journal of Neuropsychopharmacology
March 12, 2020
Erwin Krediet, Tijmen Bostoen, Joost J. Breeksema et al.
262 citations
Posttraumatic stress disorder (PTSD) often remains chronic after psychotherapy, and few effective medications exist. A promising new approach involves psychedelic drugs. This review discusses four compound types: MDMA, ketamine, classical psychedelics (psilocybin, LSD), and cannabinoids. It describes each compound's therapeutic rationale, administration setting, and current evidence for treating PTSD. Each offers unique qualities, from rapidly targeting symptoms to facilitating psychotherapy. The review outlines questions for future research.
CNS Drugs
August 17, 2020
Joost J. Breeksema, Alistair Niemeijer, Erwin Krediet et al.
217 citations
This review argues that qualitative research on psychedelic treatments can reveal unique features of different substances and uncover implications for treating specific psychiatric disorders that quantitative methods might miss. By examining subjective experiences, such studies can help tailor therapies to particular conditions and substances, offering insights into how psilocybin, LSD, or other compounds produce distinct psychological effects. The authors suggest that incorporating qualitative findings into clinical practice could enhance treatment precision and patient outcomes, highlighting the value of exploring personal narratives and emotional processes in psychedelic therapy.
Journal of Psychopharmacology
August 26, 2022
Joost J. Breeksema, Bouwe Kuin, Jeanine Kamphuis et al.
171 citations
A systematic review of 44 clinical studies (34 quantitative, 10 qualitative) involving 598 patients treated with MDMA or serotonergic psychedelics (psilocybin, LSD, ayahuasca) found that treatments were generally well tolerated, though adverse events were often not systematically assessed. Common acute adverse events across diagnoses and compounds included nausea, headaches, and anxiety. Late adverse events included headaches (psilocybin, MDMA), fatigue, low mood, and anxiety (MDMA). One serious adverse event occurred during MDMA administration (increased premature ventricular contractions requiring brief hospitalization); no other events required medical intervention. Qualitative studies suggested that psychologically challenging experiences may be therapeutically beneficial. The authors conclude that adverse events are poorly defined and likely underreported due to study design and sample selection.
ACS Pharmacology & Translational Science
July 16, 2021
Joost J. Breeksema, Michiel van Elk
69 citations
The authors argue that the concept of mystical experience should remain central to psychedelic science, countering a recent call to abandon it. They emphasize the need to recognize the diversity and strangeness of psychedelic experiences, drawing on a rich tradition and scientific tools for studying mystical-type experiences. These experiences are relevant for understanding the therapeutic effects of psychedelics. The authors also call for greater diversity in both the types of experiences and the participants included in future research.
Scientific Reports
February 5, 2024
Alistair Niemeijer, Erwin Krediet, Jeanine Kamphuis et al.
50 citations
Patients with treatment-resistant depression who received psilocybin in a clinical trial described challenges with trust-building and expectation management, the need to navigate intense experiences often guided by music, and a desire for a more comprehensive treatment including multiple psilocybin sessions and sustained therapy. Distrust in mental healthcare generally, but trust in study therapists, was a key subtheme. The findings suggest that optimizing psilocybin treatment for this population requires individualized preparation, investment in trust-building, additional sessions, and access to ongoing psychotherapy with trusted therapists.
Frontiers in Psychiatry
January 1, 2022
Joost J. Breeksema, Alistair Niemeijer, Bouwe Kuin et al.
41 citations
Patients with treatment-resistant depression undergoing oral esketamine treatment often find the experience overwhelming and struggle with whether to let go or maintain control. Their ability to let go is influenced by preparation, emotional support, and the treatment setting. Better preparation, an optimized environment, and psychological support during sessions may improve patients' experiences and outcomes. The study provides recommendations for improving quality of care, including training for nurses and support staff.
Nature Medicine
June 3, 2025
Chloé Pronovost-Morgan, Kyle T. Greenway, Leor Roseman et al.
26 citations
A Delphi consensus study with 89 experts from 17 countries identified 30 extra-pharmacological variables that are important or very important for reporting the setting in psychedelic clinical trials. These variables, forming the ReSPCT guidelines, cover physical environment, dosing session procedure, therapeutic framework and protocol, and subjective experiences. The findings reveal significant ambiguities in current conceptualizations of set and setting. The guidelines provide a new standard for designing and documenting contextual factors in psychedelic research.
The lancet. Psychiatry
January 1, 2025
Carolina Seybert, Nina Schimmers, Lucio Silva et al.
26 citations
Reporting on the psychological intervention component of psychedelic-assisted psychotherapy is mostly incomplete and inconsistent across studies, limiting replicability and clinical translation. A systematic review of 45 original studies on psilocybin, MDMA, LSD, or ayahuasca for mental disorders found that descriptions of psychotherapy varied widely and completeness of information was generally low, based on an adapted Template for Intervention Description and Replication checklist. Studies involving MDMA showed more homogeneous psychotherapy and more procedural details. Improved reporting on psychological interventions would support replicability, generalisability, and accurate interpretation of research, as well as enhance feasibility and safety of future clinical research and real-world implementation.
Psychopharmacology
July 1, 2023
Joost J. Breeksema, Alistair Niemeijer, Bouwe Kuin et al.
26 citations
The effects of oral esketamine for treatment-resistant depression are highly variable, and psychological distress is common. Patients report perceptual changes, detachment from body and emotions, stillness, mystical-type experiences, and fear. After sessions, many feel hungover and fatigued, while depressive mood is neutralized. Some effects, such as increased openness and detachment, may hold psychotherapeutic potential, but the frequent distress calls for additional patient support throughout treatment.
Psychiatr Res Clin Pract
February 11, 2025
Jules Evans, Marc Aixalà, Brian T Anderson et al.
18 citations
Thirty psychedelic researchers identified critical gaps in knowledge about harms from psychedelic use, including how to define those harms, predict them, and treat them effectively. They recommend better online information, peer support groups, affordable therapy, and psychiatric consultation for people experiencing post-psychedelic difficulties. The researchers also call for improved funding for a psychedelic safety net, suggesting that psychedelic philanthropists, investors, and companies commit 1% of their investment to support safety measures such as research and support services. The article outlines practical steps to make the field of psychedelic medicine safer.
International review of neurobiology
January 1, 2025
Stephan Tap, Tijmen Bostoen, Joost J. Breeksema et al.
4 citations
Patients with life-threatening disease often experience end-of-life distress—physical, psychological, emotional, and spiritual suffering linked to chronic illness and the prospect of death. Palliative care aims to improve quality of life, but current psychological and pharmacological interventions show inconclusive evidence with only short- to moderate effects and often require months to work. Over the past decade, psychedelic-assisted therapy has been investigated for addressing end-of-life distress, producing highly significant and sometimes sustained decreases in depression and death anxiety, along with improvements in meaning, spiritual well-being, optimism, life satisfaction, and attitudes toward disease. This chapter describes end-of-life distress, its prevalence, limitations of palliative interventions, the evidence for psychedelic-assisted therapy, why it may work for these patients, and future directions.
International review of neurobiology
January 1, 2025
Tijmen Bostoen, Stephan Tap, Joost J. Breeksema et al.
1 citation
MDMA-assisted therapy shows substantial and sustained reductions in PTSD symptoms, especially for patients resistant to conventional treatments. Over the past two decades, it has emerged as one of the most promising psychedelic treatments, with the FDA designating it a 'breakthrough therapy' in 2017. However, due to methodological concerns such as unblinding and potential expectancy effects, the FDA decided in 2024 not to approve it for clinical use, requiring additional research. The chapter examines psychological and neurobiological mechanisms of action, methodological challenges, and future directions for psychedelic-assisted therapies for PTSD.
Psychedelics
June 28, 2026
Joost J. Breeksema, Ulf Bremberg, Jens H van Dalfsen et al.
Psychedelic therapies face layered complexity from interactions between pharmacological and extra-pharmacological factors, and their embeddedness in societal, legal, and regulatory systems. This is compounded by epistemic fragmentation: dominant biomedical paradigms often clash with knowledge from social sciences, humanities, or Indigenous traditions. Though interdisciplinary engagement is increasingly recognized as necessary, existing calls rarely specify structural or pedagogical conditions for operationalizing it. Addressing these complexities requires moving beyond superficial collaboration; genuine interdisciplinary progress needs researchers capable of productive friction across epistemic cultures. The authors propose cultivating T-shaped competencies and intersectoral training as a structural response to these systemic challenges.
February 20, 2024
Joost J. Breeksema
Patients with treatment-resistant depression who received ketamine or psilocybin often had intense, overwhelming experiences that could cause temporary anxiety. Those who felt unprepared or unsupported struggled to surrender to the experience, increasing discomfort. Trust in therapists, realistic expectations, and emotional support made surrender easier and reduced anxiety. Ketamine produced effects like openness, detachment from negative thoughts, and mystical experiences. Recommendations include offering multiple psilocybin sessions, longer-term therapeutic support, and better staff training to improve patient comfort and possibly treatment outcomes.
Psychopharmacology
January 1, 2022
Nina Schimmers, Joost J. Breeksema, Sanne Y Smith-Apeldoorn et al.
Both classical psychedelics (DPT, LSD, psilocybin) and atypical psychedelics (MDMA, ketamine) show promise for reducing anxiety, depression, and existential distress in terminally ill patients, with recent controlled trials indicating positive effects on existential and spiritual well-being, quality of life, and acceptance while causing few adverse and no serious adverse effects. Early studies had serious methodological flaws, but newer trials are of higher quality. Larger high-quality studies are still needed for classical psychedelics and MDMA, and ketamine research should better address existential well-being and psychotherapeutic context.