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Psychoactives

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

Papers

Mind the Psychedelic Hype: Characterizing the Risks and Benefits of Psychedelics for Depression

Psychoactives April 16, 2024 Daniel Meling, Rebecca Ehrenkranz, Sandeep M. Nayak et al. 26 citations

Psychedelic research has returned after a period of suppression, but media coverage now often overstates benefits as much as it once overstated risks. The actual evidence is more mixed than commonly portrayed, so conclusions about effectiveness remain preliminary. Poor communication may mislead patients and misinform policy. This article reviews studies on psychedelics for depression, noting that effect sizes for other depression treatments—cognitive behavioral therapy, mindfulness, SSRIs, and ketamine—have decreased over time as trials improved. The authors suggest the same may happen for psychedelics: larger, better-controlled trials will likely show smaller, more realistic benefits. Clear communication is essential to set public expectations and guide policy.

Transpersonal Ecodelia: Surveying Psychedelically Induced Biophilia

Psychoactives May 25, 2023 Alexander Irvine, David Luke, Freya Harrild et al. 22 citations

People who had used psychedelics reported that the experiences strengthened or created a passionate, protective connection with nature. Those already close to nature felt psychedelics re-established and deepened that bond; those without a prior connection said psychedelics helped them form one. Central to these shifts were transpersonal experiences, especially a sense of interconnectedness, which was most often linked to changes in attitudes and behaviors. Participants also noted benefits of having the experience in a natural setting. The findings suggest psychedelics can foster a caring relationship with nature even in people not previously nature-oriented.

Life after Ayahuasca: A Qualitative Analysis of the Psychedelic Integration Experiences of 1630 Ayahuasca Drinkers from a Global Survey

Psychoactives June 13, 2023 Tessa Cowley‐court, Richard Chenhall, Jerome Sarris et al. 19 citations

Integrating ayahuasca experiences can be challenging and take considerable time, though working through these challenges may facilitate positive growth. A global online survey of 1630 ayahuasca drinkers (50.4% male, mean age 43) identified three main themes in integration experiences: overall appraisal (easy, challenging, or long-term/ongoing), beneficial tools (like-minded community, yoga, meditation, journaling), and challenges (feeling disconnected, returning to old life with new understandings). Findings challenge individual psychotherapy as the primary integration tool, suggesting communal and somatic elements may also be useful. An expanded definition of psychedelic integration is proposed that includes working with challenges and adjusting to life changes.

Insights, Life Changes and Lifestyle Changes Reported by Individuals Consuming Ayahuasca in Naturalistic Settings: Nature, Frequency and Associations with Mental Health and Wellbeing

Psychoactives October 3, 2023 Daniel Perkins, Emérita Sátiro Opaleye, José Carlos Bouso et al. 18 citations

Ayahuasca drinkers almost universally report gaining insights during their experiences, and these insights strongly predict subsequent beneficial life and lifestyle changes, including improvements in psychological wellbeing and mental health. In a large international survey of 8,907 ayahuasca drinkers, common changes attributed to ayahuasca included personal, vocational, religious or spiritual, and health-related shifts, along with healthier behaviors. Demographic factors and drinking patterns also predicted these outcomes. The findings suggest that insights and resulting life changes are central to the transformative effects of ayahuasca, occurring across diverse contexts and groups.

‘Mind-Revealing’ Psychedelic States: Psychological Processes in Subjective Experiences That Drive Positive Change

Psychoactives September 27, 2024 Rúna F. E. Walther, Hein T. van Schie 14 citations

A narrative review argues that the therapeutic use of psychedelics should refocus on the subjective experiences they induce—the original meaning of 'mind-manifesting'—rather than solely on the substances themselves. It surveys psychedelic substances used in modern therapy and indigenous rituals, along with non-pharmacological methods like breathwork, meditation, and sensory deprivation that can produce similar states. While mystical experiences are the strongest predictor of positive outcomes, other processes—awe, perspective shifts, insight, emotional breakthrough, acceptance, memory re-experiencing, and certain challenging experiences—also contribute significantly. Changes in metaphysical and self-related beliefs further influence outcomes. The review concludes that a purely medical and neurobiological view is reductive and should not overshadow the importance of phenomenological experiences in understanding and treating psychological issues rooted in subjective realities.

The Effects of Psilocybin on Lipopolysaccharide-Induced Inflammation in THP-1 Human Macrophages

Psychoactives January 28, 2024 Esmaeel Ghasemi Gojani, Bo Wang, Dongping Li et al. 12 citations

Psilocybin, a compound from Psilocybe mushrooms known for activating serotonin 5-HT2A receptors, reduces inflammation in immune cells. In laboratory experiments, human THP-1 monocytes were turned into macrophages and then stimulated with lipopolysaccharide (LPS) to trigger an inflammatory response, followed by adenosine triphosphate (ATP) to activate the NLRP3 inflammasome. Psilocybin exposure produced a dose-dependent inverse correlation with the production of proinflammatory cytokines and proteins. The compound likely mediates these anti-inflammatory effects by influencing key signaling pathways, including NF-κB, IL-6/TYK2/STAT3, and TYK2/STAT1.

Minorities’ Diminished Psychedelic Returns: Gender, Perceived Stigma, and Distress

Psychoactives June 2, 2024 Sean Matthew Viña 9 citations

Psychedelics such as MDMA, psilocybin, DMT, ayahuasca, peyote/mescaline, and LSD do not consistently reduce the impact of psychological distress on internalized stigma. Among men, ayahuasca use was linked to reduced stigma perception associated with higher distress; among women, DMT use was linked to reduced stigma perceptions when experiencing higher distress. However, individuals who used MDMA or psilocybin reported heightened perceptions of stigma alongside increased psychological distress, especially among women. Overall, psychedelics may not help manage the internalized stigma that deters formal mental health treatment.

Tripping to Cope: Coping Strategies and Use of Hallucinogens during the COVID-19 Pandemic in Three Cultural Contexts

Psychoactives September 2, 2022 Genís Oña, Dóra Révész, Maja Kohek et al. 9 citations

Coping strategies are more closely linked to psychological well-being and psychopathology than to hallucinogenic drug use, according to a survey of 2,971 people from three cultural contexts followed for six months during the COVID-19 pandemic. Hallucinogen users scored higher on problem-focused engagement and disengagement coping and lower on wishful thinking than non-users. Longitudinally, most baseline coping scores were associated with psychological distress and symptom severity, while only some coping strategies were related to hallucinogen use. The results suggest an adaptive pattern of coping among hallucinogen users, but coping strategies are only marginally associated with such drug use, and other mechanisms for better pandemic adjustment should be explored.

The Clinical Potential of Dimethyltryptamine: Breakthroughs into the Other Side of Mental Illness, Neurodegeneration, and Consciousness

Psychoactives February 26, 2024 Frankie A. Colosimo, Philip Borsellino, Reese I. Krider et al. 8 citations

DMT, a naturally occurring psychedelic compound, promotes neuroplasticity—the brain's ability to remodel its neural connections—by stimulating neuritogenesis, the growth of new neuronal branches. It interacts with serotonergic, sigma-1, and trace amine-associated receptors and their signaling pathways. Evidence from animal models and clinical trials suggests DMT can improve mental well-being in depression, anxiety, and PTSD, and may aid learning, memory, and recovery from brain injuries. The compound's potential to enhance neurogenesis, particularly for neurodegenerative conditions, is also explored.

Ketamine and Esketamine in Psychiatry: A Comparative Review Emphasizing Neuroplasticity and Clinical Applications

Psychoactives June 23, 2025 Georgios Mikellides 7 citations

Ketamine and esketamine are fast-acting antidepressants for treatment-resistant depression, providing symptom relief within hours—an unprecedented speed in psychiatric care. Originally anesthetics, they work through neuroplastic effects on glutamate transmission and BDNF, offering particular value for suicidal ideation. Esketamine, the S-enantiomer, is FDA- and EMA-approved as an intranasal spray for treatment-resistant depression. This narrative review synthesizes evidence on their pharmacology, efficacy, safety, and regulatory status, bridging experimental research with clinical practice.

Regulatory Challenges of Integrating Psychedelics into Mental Health Sector

Psychoactives April 22, 2025 Kerem Kemal Soylemez, Emma Marie de Boo, Joanne Lusher 7 citations

Psychedelic substances like LSD, psilocybin, and MDMA show promise for treating depression, anxiety, and addiction when administered in controlled settings with psychological support. They can induce profound psychological insights that lead to long-lasting positive changes in mood, cognition, and behavior. However, ethical, social, and regulatory challenges across different countries influence societal beliefs about their efficacy and use. The review calls for further research to develop standardized administration protocols and understand societal implications and long-term outcomes, highlighting the need for rigorous scientific inquiry and ethical considerations.

Funding Success of United States Federal Grant Applications Proposing to Study Therapeutic Applications of Psychedelics: A Survey Study

Psychoactives February 5, 2025 Brian S. Barnett 7 citations

A survey of researchers who submitted NIH grant applications for therapeutic psychedelic research found that only 16.7% of 24 applications were funded, below the NIH's average 23.4% funding rate for R01-equivalent grants from 1998 to 2023. No applications submitted before 2006–2010 received funding, but the rate since then (19.05–22.2%) aligns with the NIH's annual average of 20.6 ± 1.9% from 2006 to 2023. Respondents perceived funding as more difficult to obtain than for other areas, though recent improvements were noted. The small sample and lack of public data on unfunded applications limit generalizability.

Neural Network Modulation of Ayahuasca: A Systematic Review of Human Studies

Psychoactives March 20, 2023 Guilherme Henrique de Morais Santos, Lucas Silva Rodrigues, Juliana Mendes Rocha et al. 6 citations

Ayahuasca, a serotoninergic hallucinogen used in Amazonian traditional medicine, alters brain connectivity in ways similar to other psychedelics. A review of 11 neuroimaging studies found that acute consumption expands local neural networks while reducing overall brain connectivity, with notable effects on the Default Mode Network suggesting short-term neuromodulation. In chronic users, anatomical changes in the cingulate cortex have been reported. The findings are preliminary and more research is needed.

The Legal Perspective on Psilocybin for Medical Use in Czechia: A Key Milestone and the Case for Broader Consideration Beyond the Clinical Setting

Psychoactives September 11, 2025 Tereza Dleštíková 4 citations

Czechia has approved the medical use of psilocybin, a key shift in drug policy that allows regulated therapeutic applications in clinical settings. This commentary places the reform within international trends, drawing on the publication "How to Regulate Psychedelics" and qualitative findings from a ketamine-assisted therapy program in the Czech Destigmatizing the Therapeutic Use of Psychedelics in Psychiatry project. It examines regulation of non-clinical psychedelic use and highlights legal ambiguity around the offence of "spreading toxicomania." The authors advocate for a rational, evidence-based regulatory approach, arguing that medicalization alone is incomplete without clear pathways for non-clinical use to ensure safety and legal clarity.

Long-Term Effects of Single and Repeated Ketamine Infusions on Treatment-Resistant Depression: A Retrospective Chart Review Study

Psychoactives October 12, 2024 Sofia Sakopoulos, Lisa D. Hinz 4 citations

For people with treatment-resistant depression, ketamine infusions may provide lasting relief from depressive symptoms. A retrospective chart review examined 14 patients who received either a single high-dose (1 mg/kg) intravenous ketamine infusion or six repeated infusions. Depressive symptoms were measured using the Beck Depression Inventory (BDI-II) before treatment and again 30 days after the last infusion. The results suggest that ketamine can be an effective and enduring intervention for treatment-resistant depression, offering a valuable option when other treatments have failed.

Exploring the Impact of Recreational Drugs on Suicidal Behavior: A Narrative Review

Psychoactives July 3, 2024 Rosa María Moret, Sergio Sanz‐gómez, Santiago Gascón et al. 4 citations

Substance use and suicide are closely linked through neurobiological, psychological, and social factors. This narrative review examines the relationship between suicidal behavior and common recreational drugs including alcohol, cannabis, cocaine, methamphetamine, heroin, nicotine, ketamine, psilocybin, MDMA, and LSD. Current research indicates that most substances increase the risk of suicidal behavior, except for ketamine and psilocybin, which may have a protective effect. The relationship between MDMA, LSD, and suicide remains unclear and requires further investigation.

Subjective Effects of a Single Dose of Ayahuasca among College Students with Harmful Alcohol Use: Qualitative Analysis of Participant Accounts

Psychoactives November 17, 2023 Anna Beatriz Vicentini, Lucas Silva Rodrigues, Giordano Novak Rossi et al. 4 citations

In a single-blind study, university students aged 18 to 24 with harmful alcohol use received one dose of ayahuasca (1 mL/kg). Twenty-one days later, semi-structured interviews with six participants identified psychological elements linked to reduced drinking. Content analysis revealed categories including Positive Impacts, Substance Use Pattern, and Insights. Together, these categories suggest that insights and positive emotions from the experience may foster internal transformation, potentially leading to decreased alcohol consumption.

Psychedelics for Moral Bioenhancement in Healthy Individuals—A Violation of the Non-Maleficence Principle?

Psychoactives February 6, 2025 Bor Luen Tang 3 citations

The author argues that using psychedelics such as psilocybin for moral bioenhancement lacks good justification from both neuropharmacological and bioethical perspectives. The hallucinogenic properties and risk of adverse psychosis undermine their suitability for enhancing morality. There is no sound bioethical basis for this use, and in healthy individuals it would violate the principle of non-maleficence. Unless new non-hallucinogenic derivatives are developed or unequivocal evidence of moral enhancement emerges, an indication for psychedelics in moral bioenhancement is untenable.

Self-Rated Effectiveness of Ayahuasca and Breathwork on Well-Being, Psychological Resilience, Self-Compassion, and Personality: An Observational Comparison Study

Psychoactives March 31, 2024 Rishma S. I. Khubsing, Martin van Leerdam, Eline Haijen et al. 3 citations

Both an ayahuasca retreat and a breathwork session led to sustained increases in well-being, resilience, and self-compassion over 12 weeks, with no difference between the two groups. Older participants reported higher resilience and self-compassion overall. The ayahuasca group showed higher self-compassion and lower neuroticism than the breathwork group. Neuroticism decreased in both groups, and agreeableness increased over time regardless of group, while extraversion, conscientiousness, and openness did not change. The findings suggest that improvements in psychological processes may be influenced by the social setting rather than solely by the substance.

Guidelines for Establishing Safety in Ayahuasca and Ibogaine Administration in Clinical Settings

Psychoactives December 11, 2023 Juliana Mendes Rocha, José Augusto Silva Reis, Giordano Novak Rossi et al. 3 citations

As psychedelic research expands to include more diverse participants with varied medical conditions, the risk of adverse events increases, yet specialized safety protocols for such trials are scarce. The LEAPS research group at the University of São Paulo developed standardized guidelines for managing adverse scenarios in clinical trials with ayahuasca and ibogaine. These protocols, based on the hospital's established philosophy, expert consultation, and literature review, address both psychiatric issues (panic attacks, suicidal behavior, psychotic episodes) and clinical issues (hypertensive crisis, hypoglycemia) to ensure volunteer safety.

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 Juuso Kähönen 2 citations

Classic psychedelics like psilocybin are unlikely to reliably foster moral growth in healthy individuals, according to a critical analysis. The argument challenges the idea of psychedelic moral bioenhancement (PMBE), contending that the subjective, context-dependent nature of psychedelic experiences makes them unsuitable as a dependable tool for moral enhancement. The author suggests that moral development requires sustained cognitive and social engagement rather than transient pharmacological effects. The analysis draws on existing evidence about psychedelics' mechanisms and effects to question the feasibility and ethical basis of using them for moral improvement in non-clinical populations.

Hormonal Influences on Psilocybin Responsivity Across the Female Lifespan: Toward Personalized Psychedelic-Assisted Therapy

Psychoactives November 2, 2025 Faith Ekoh, Shanice Rerrie, James Angud et al. 2 citations

Psilocybin shows therapeutic promise for mood, cognitive, and affective disorders, which are regulated by the serotonergic system. Sex hormones such as estrogen and testosterone can influence serotonin physiology, and females have a higher prevalence of affective disorders and may respond differently to drug therapy. A review of current literature discusses how fluctuating hormonal states across female reproductive phases could affect serotonin dynamics, synaptic plasticity, and the optimal timing of psilocybin treatment. The authors suggest that future research should examine sex hormone influences on psychedelic-assisted therapy to personalize treatment plans.

Psychedelics and Mental Health Treatment Seeking Among Asians and Hawaiians

Psychoactives September 4, 2025 Sean Matthew Viña 2 citations

Psychedelic use relates to mental health treatment-seeking differently across racial groups. Among White individuals, psychedelic use is associated with a lower likelihood of seeking formal mental health care. In contrast, among Native Hawaiian and Other Pacific Islander (NHOPI) individuals, psychedelic use is linked to increased odds of accessing mental health services. These patterns suggest that psychedelics may serve culturally distinct roles in coping with psychological distress, influenced by structural stigma and perceptions of the formal treatment system. The analysis uses national survey data from 2008 to 2019 with over 458,000 respondents.

Neuroplasticity and Neuro-Generation: The Promise of Psychedelics in Dementia Care

Psychoactives September 2, 2025 Kerem Kemal Soylemez, Emma Marie de Boo, Aysil Susuzlu et al. 2 citations

A narrative review of existing literature examines the potential of psychedelics such as psilocybin and LSD for treating dementia, a progressive neurodegenerative disease characterized by cognitive decline, memory loss, and behavioral changes. Psychedelics alter perception, mood, and cognition by affecting serotonin receptors and may promote neuroplasticity, reduce neuroinflammation, and enhance cognitive flexibility. These effects could slow disease progression and improve quality of life for patients, who often experience emotional distress, and may also help prevent dementia by fostering brain health. The review raises significant safety and ethical concerns and aims to critically raise awareness on the topic.

Exploring the role of psychedelic experiences on wellbeing and symptoms of disordered eating

Psychoactives March 4, 2025 Nadine Loh, David Luke 2 citations

Eight adults with chronic eating disorders (mean age of onset 13) reported their experiences with psychedelics in naturalistic and clinical settings. Seven of the eight reported lasting cessation or reduction of eating disorder symptoms, with two attributing full recovery to psychedelic use. Two participants relapsed months later due to environmental factors. Thematic analysis identified two overarching themes: 'Exploring' as a 'gateway to healing' covering mental, emotional, and transcendental aspects of the experience, and 'Transformation' enabling cognitive and behavioral changes alongside retrospective safety perceptions. The findings offer detailed insights into potential benefits and risks of psychedelic experiences for people with eating disorders and may guide future research into psychedelic-assisted therapy.