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Psychoactives

48 papers in the library · 207 citations · publishing 2022-2026

Papers

Rapid and Prolonged Antidepressant and Antianxiety Effects of Psychedelics and 3,4-Methylenedioxy-methamphetamine—A Systematic Review and Meta-Analysis

Psychoactives October 4, 2024 Dimy Fluyau, Vasanth Kattalai Kailasam, Neelambika Revadigar 2 citations

Psilocybin rapidly and sustainably reduces depressive and anxiety symptoms in patients with major depressive disorder and those with life-threatening cancer. MDMA decreases depressive symptoms in patients with life-threatening cancer, autism spectrum disorder, and post-traumatic stress disorder, but its effect on generalized anxiety symptoms is negligible or negative, while it reduces social anxiety. Ayahuasca reduces depressive symptoms in treatment-resistant major depressive and personality disorders. LSD decreases anxiety in life-threatening cancer. Adverse effects include elevated blood pressure, headaches, panic attacks, and for MDMA, feeling cold.

From Adults to Adolescents: Bridging Scientific Potential and Evidence-Based Paths for Psychedelic-Assisted Interventions

Psychoactives January 6, 2026 Mayank Gupta, Aaron Krasner, Priyal Khurana 1 citation

Adolescent mental health conditions, especially treatment-resistant depression, pose a growing public health problem with high rates of illness, impairment, and suicide risk. Psychedelic-assisted therapies show strong antidepressant effects in controlled adult trials, but extending this work to adolescents is scientifically compelling yet ethically complex due to ongoing brain development and lack of pediatric data. This review examines the history of psychedelic use, summarizes adult findings on effectiveness and mechanisms, explores adolescent-specific opportunities and risks, and considers applications in co-occurring neurodevelopmental disorders. The authors do not advocate for premature clinical adoption but highlight translational gaps, developmental risks, and research priorities needed to responsibly assess these approaches in youth.

Digital Enablement of Psychedelic-Assisted Therapy in Non-Clinical Settings: A Systematic Review of Safety, Efficacy, and Implementation Models

Psychoactives December 24, 2025 Brendan Driscoll, Shaheen E. Lakhan 1 citation

A systematic review of six studies involving 12,731 participants examined digitally enabled psychedelic-assisted therapy delivered outside clinical settings, mostly at-home ketamine or esketamine supported by telehealth or mobile apps. Digital tools enabled high response rates for depression (56.4% to 62.8%) and rapid symptom improvement, particularly for depression and anxiety. Remote monitoring was feasible and acceptable, but serious safety concerns emerged, including psychiatric adverse events and one unintentional overdose, highlighting the need for strict oversight. One study on virtual ayahuasca rituals noted sociocultural potential and limitations. The field lacks controlled trials and has moderate to serious risk of bias across non-randomized studies, limiting confidence in findings.

“Becoming Your Own Psychologist”: Novel Psychoactive Substances (NPSs) for Mood and Anxiety Disorder Self-Medication

Psychoactives August 20, 2025 Tayler Holborn, Fabrizio Schifano, Emma Smith et al. 1 citation

People with depression and anxiety often self-medicate with novel psychoactive substances (NPS) such as bromazolam, etizolam, clonazolam, 1P-LSD, and 2-FDCK, perceiving these as more effective than conventional treatment. An online survey of 274 individuals (average age 29.8, 71% male, 18% female, 5% non-binary) and follow-up interviews with five participants revealed that self-medication typically follows failed conventional treatment. Themes included chronic, treatment-resistant depression with comorbidities, attempts to mimic existing treatments, high pharmacological knowledge, and difficulty controlling benzodiazepine use. The findings highlight the need for affordable emerging treatment options for depression and anxiety.

Psilocybin Use in an Intercollegiate Athlete with Persisting Symptoms After Concussion: A Case Report

Psychoactives July 1, 2025 David W. Lawrence, Alex P. Di Battista, Michael G. Hutchison 1 citation

A 22-year-old male athlete with persisting symptoms after a concussion took three 250 mg doses of dried Psilocybe cubensis (containing 2.5 mg of psilocybin) on days 42, 45, and 46 post-injury. He reported immediate relief from headache, noise sensitivity, and cognitive difficulties. His symptom severity score dropped from 25 to 11, and his emotional symptoms resolved completely, allowing a return to full activity with no adverse effects. This case suggests classic psychedelics might help treat persisting post-concussion symptoms, but more research is needed to confirm safety and effectiveness.

A Fully Validated LC-MS Quantitation Method for Psychoactive Compounds Found in Native South American Plant Species

Psychoactives November 8, 2024 Jonathan Tran, Aaron Elkins, Simone Vassiliadis et al. 1 citation

A validated analytical method using ultra-high performance liquid chromatography coupled to mass spectrometry (UHPLC-MS) was developed to measure six psychoactive compounds—tryptamine, N,N-dimethyltryptamine (DMT), 5-methoxy-N,N-dimethyltryptamine (5-MeO-DMT), tetrahydroharmine (THH), harmaline, and harmine—in raw plant material. The method achieved high sensitivity, with detection limits between 0.06 and 0.11 ng/mL and quantitation limits between 0.18 and 0.34 ng/mL, along with excellent extraction efficiency (>98%) and recovery (74.1–111.6%). Applied to Psychotria viridis, Psychotria carthagenensis, Banisteriopsis caapi, and Alicia anisopetala, all compounds eluted within nine minutes, enabling high-throughput analysis for potential agricultural and medicinal applications.

Producing Altered States of Consciousness, Reducing Substance Misuse: A Review of Psychedelic-Assisted Psychotherapy, Transcendental Meditation and Hypnotherapy

Psychoactives March 25, 2024 Agnieszka D. Sekula, Prashanth Puspanathan, Luke A. Downey et al. 1 citation

A review of three interventions that produce altered states of consciousness—psychedelic-assisted psychotherapy, Transcendental Meditation, and hypnotherapy—finds that the first two are linked to significant reductions in substance misuse and improvements in emotional, cognitive, and social functioning, motivation, self-identity, and meaning. Hypnotherapy, despite wider acceptance, shows mixed and minimal results for substance misuse treatment. The review notes common phenomenological, psychological, and neurobiological features among the interventions, suggesting possible convergent mechanisms, but also highlights mixed findings and methodological issues. Key research gaps and promising future directions are outlined.

Psychedelic-Assisted Psychotherapy for the Treatment of PTSD: A Systematic Review and Meta-Analysis

Psychoactives June 8, 2026 Fizza Mitter, Anton Sheptooha, Janni Leung et al.

Post-traumatic stress disorder (PTSD) is often not well treated by current medications or talk therapies, leading to interest in psychedelic-assisted psychotherapy. A systematic review and meta-analysis of 11 randomized controlled trials with 358 participants examined MDMA, ketamine, and cannabidiol. MDMA-assisted psychotherapy produced a moderate-to-large reduction in PTSD symptoms, with more participants achieving clinical response and loss of PTSD diagnosis. Ketamine showed a small, non-significant effect, and one trial of cannabidiol found no clear benefit. All agents were generally well tolerated. The evidence is dominated by MDMA trials, and safety data remain insufficient for strong comparisons. More studies with standardized outcomes and direct comparisons are needed.

Psychedelic Use and Missed Needed Mental Health Treatment: Gender Differences in Unmet Perceived Need for Care

Psychoactives May 12, 2026 Sean M. Viña

Analyzing 2008–2019 National Survey on Drug Use and Health data, lifetime psychedelic use is not independently linked to lower odds of missing needed mental health treatment after accounting for psychological distress. However, psychedelic exposure weakens the link between distress and missed care: as distress rises, those who have used psychedelics—especially men—show a smaller increase in unmet treatment needs compared to non-users. Among women, only MDMA shows a similar buffering effect. The findings indicate that psychedelic use does not uniformly improve care engagement but reveals gendered patterns in how distress leads to disengagement, with women experiencing diminished benefits despite comparable distress levels.

Psilocybin for Treatment of Prolonged Grief Disorder: An Open-Label Feasibility Study Protocol

Psychoactives April 13, 2026 J. Morgan Penberthy, Fatma Wise, Nicholas P. Cherup et al.

Prolonged grief disorder (PGD) affects about 10% of bereaved individuals and often does not respond well to traditional therapies. This manuscript describes the protocol for an early-stage open-label feasibility trial testing psilocybin as a treatment for PGD in 20 adults, with a focus on young adults. Participants receive a single 25 mg dose of psilocybin within a structured therapeutic process that includes preparation and integration sessions. The main aims are to assess safety, feasibility, and acceptability. Outcome measures include changes in PGD and trauma symptoms, cognitive flexibility, openness to experience, meaning in life, and subjective experiences. Functional MRIs are collected pre- and post-dosing during a standardized grief-elicitation task to evaluate neural activity.

Is Cannabidiol (CBD) a Non-Psychoactive Phytocannabinoid?

Psychoactives February 3, 2026 Eliana Rodrigues

Interest in psychoactive substances like psychedelics is growing in medicine and academia, but misclassifications of certain plants, animals, fungi, and their substances persist in media and scholarly circles. This opinion piece argues whether cannabidiol (CBD) is a non-psychoactive phytocannabinoid, noting that hundreds of robust studies support its clinical use for seizures, anxiety, psychosis, schizophrenia, post-traumatic stress disorder, and addiction. The text reviews historical classifications of psychoactive substances, reflects on terminology, and proposes a new classification for psychedelics.

Cautions on the Notion of Moral Enhancement with Psychedelics. Reply to Kähönen, J. Subjective Effects of Psychedelics Are the Plausible Mechanism of Psychedelic Moral Enhancement Rather than a Risk. Comment on “Tang, B.L. Psychedelics for Moral Bioenhancement in Healthy Individuals—A Violation of the Non-Maleficence Principle? Psychoactives 2025, 4, 5”

Psychoactives December 17, 2025 Bor Luen Tang

A scholar responds to criticism that the risks of psychedelics have been exaggerated and their potential for moral enhancement dismissed. The author maintains that claims about psychedelics improving moral character require far more scientific evidence and broader bioethical discussion before they can be accepted. The piece does not present new data but argues for caution and further debate on the topic.

A Comparative Neurophenomenology of the Psychedelic State and Autism: Predictive Processing as a Unifying Lens

Psychoactives November 14, 2025 William Roseby, Catriona Osborn Moar

Serotonergic psychedelics like psilocybin, LSD, and DMT help advance understanding of consciousness and brain activity, but little work connects psychedelic theory to experiential differences in autism. This narrative review compares the psychedelic state and autism in adults using predictive processing as a unifying framework. Both involve a shift toward sensory information over prior knowledge, but may affect opposite ends of the cortical hierarchy. The contrast refines concepts like psychological flexibility and suggests testable hypotheses, though neurobiological findings in autism are heterogeneous and comparing a transient state with a lifelong trait has inherent limitations.

Psilocybin-Assisted Psychotherapy for Chronic Somatoform Pain Disorder: A Case Report

Psychoactives September 1, 2025 M Mercier, Cédric Mabilais, Vasileios Chytas et al.

A patient with persistent somatoform pain disorder and recurrent depressive disorder underwent four sessions of psilocybin-assisted psychotherapy. The intervention was associated with reduced negative impact of pain on daily life, increased pain acceptance, improved quality of life, and fewer depressive symptoms. The case suggests that psychedelics combined with psychotherapy may offer a novel approach to chronic pain treatment, though controlled studies are needed.

Pilot Data on Salivary Oxytocin as a Biomarker of LSD Response in Patients with Major Depressive Disorder

Psychoactives August 1, 2025 L. Cazorla, S. Alaux, C. Amberger et al.

Salivary oxytocin levels changed significantly over time during a single LSD-assisted psychotherapy session in people with treatment-resistant major depressive disorder. Perceived psychedelic intensity also varied significantly. These findings suggest oxytocin may serve as a biomarker for the therapy's effects. The study was a small observational pilot; larger controlled trials are needed to confirm the results and clarify how oxytocin dynamics relate to changes in depressive symptoms and mental flexibility.

Ayahuasca, Pain, and Inflammation: A Systematic Review of Preclinical Studies

Psychoactives July 15, 2025 Bianca Villanova, Giordano Novak Rossi, Lorena Terene Lopes Guerra et al.

Ayahuasca, a psychoactive brew containing DMT and harmine, may reduce pain and inflammation. A systematic review of 29 preclinical studies found that ayahuasca and its alkaloids, especially harmine, produce antinociceptive effects and shift cytokine balance toward anti-inflammatory. More research is needed.

Increasing the Evaluation and Reporting Rigor of Psychotherapy Interventions in Treatments Involving Psychedelics

Psychoactives June 29, 2025 Mathieu Fradet

Psychedelic treatments show promise for mental health conditions but are delivered inconsistently across studies and clinics. Beyond differences in substances and doses, the psychotherapeutic interventions themselves vary greatly. A systematic review of clinical trials using psilocybin for depression reveals that the exact nature of these therapies is poorly defined in most scientific papers. This lack of documentation hinders the dissemination and improvement of evidence-based protocols. The field would benefit from optimized psychotherapeutic methods, but insufficient reporting currently blocks progress. The article offers ideas to encourage better documentation and advancement of research on psychedelic-assisted therapies.

The Use, Role, and Function of Music During Psychedelic-Assisted Therapy (PAT) with Ayahuasca: A Scoping Review Protocol

Psychoactives June 25, 2025 Guillermo Escobar-Cornejo, Fernando P. Cardenas, Diego Torres et al.

Music is considered crucial during ayahuasca experiences, yet its use in psychedelic-assisted therapy (PAT) lacks systematization and is poorly explored in scientific literature. This scoping review aims to provide a state of the art on the use, role, and function of music during PAT with ayahuasca. Following JBI methodology, the review will search multiple databases without year restrictions and include published literature in English, Spanish, and Portuguese that conceptualizes, defines, or describes music's role in PAT sessions with ayahuasca. Findings will be presented narratively, with a potential theoretical framework outlined for future research and clinical practice.

A Perspective for Enhancing the Supervision of Psychedelic-Assisted Therapy: Motivational-Interviewing-Enhanced Integration Supervision (MIE-IS)

Psychoactives June 25, 2025 Mitch Earleywine, Alyssa B. Oliva

Supervision in psychedelic-assisted therapy currently accounts for very little variance in treatment outcome, despite enthusiasm from trainees and supervisors. A proposed model, Motivational-Interviewing-Enhanced Integration Supervision (MIE-IS), aims to improve outcomes by having supervisors model Motivational Interviewing (MI) principles with trainees. Trainees then apply those same MI technical and relational skills to support clients in integrating psychedelic-induced insights into behavioral change. This approach is expected to enhance therapeutic alliances, improve self-care for clients, trainees, and supervisors, reduce burnout, and foster a culture of continuous learning and reflective practice, ultimately benefiting clients through more effective integration of psychedelic experiences.

Natural Guardians of the Balkans: Entheogens in Indigenous Practices and Their Implications for Well-Being and Therapy

Psychoactives June 25, 2025 Lucija Vejmelka, Damir Gašpar

Psychedelic plants and fungi have long been used in traditional rituals and medicine, including within Slavic cultural heritage, but knowledge of their use on the Balkan Peninsula is largely undocumented due to oral transmission. This review describes the ethnobotanical uses of native Balkan entheogens, outlines the pharmacological mechanisms of their active compounds, and discusses their impacts on social behavior, mental health, and well-being. It examines therapeutic potential and risks, aiming to bridge indigenous knowledge with contemporary psychedelic-assisted therapy and advocate for culturally respectful research practices.

Shamanism and Psychoactives: Theory, Practice and Paradoxes of a Field Study in India

Psychoactives April 1, 2025 Stefano Beggiora

The debate on the interaction between religions and psychoactive substances has been shaped more by prejudice, policy, and fashion than by scientific research, with entheogens alternately stigmatized and exalted in studies of shamanic phenomena worldwide. This article provides new epistemological insights from ethnographic fieldwork among Indigenous peoples of India, where producing alcoholic beverages—fermented and distilled, sometimes combined with other psychoactives—is a fundamental cultural trait. The discourse around these sacred substances, subject to political instrumentalization in both colonial and contemporary eras, now offers a key to understanding Indigenous ontology and traditional sustainability, extending beyond altered states of consciousness to local pharmacopeias and principles of fermentation and food preservation.

Integrating Psychedelics into Groupwork: A Culturally Responsive Model for the Counseling Profession

Psychoactives July 18, 2024 Isaac Burt

Psychedelics combined with talk therapy show promise for challenging clients, such as those with PTSD, and groupwork emphasizing social connections can be effective. However, integrating psychedelics into professional counseling, especially groupwork, has seen little progress due to societal perceptions and concerns about practicing outside one's scope. This article overviews the lack of implementation, explains inhibiting factors, and advocates for a psychedelic-assisted groupwork (PAG) model. The argument is that psychedelic approaches can be transformative for group facilitators. It concludes with an overview of what a PAG with an interdisciplinary team could entail, including recruitment, screening, selection, therapeutic processes, and termination.

Natural Hallucinogens in Mental Health

Psychoactives November 21, 2022 Rafael G. Dos Santos, Jaime E. C. Hallak

Ayahuasca, a traditional Amazonian brew containing the hallucinogen DMT, shows promise for treating mental health disorders. Over the past twenty years, research has increasingly explored its therapeutic potential, particularly for depression, anxiety, and addiction. The brew's active compounds interact with serotonin receptors in the brain, potentially promoting neuroplasticity and emotional processing. Clinical studies suggest that ayahuasca can produce rapid and sustained reductions in depressive symptoms, often after a single dose. However, the authors note that more rigorous randomized controlled trials are needed to confirm these effects and understand the underlying mechanisms. The cultural and spiritual context of ayahuasca use also plays a role in its therapeutic outcomes.