Psychoactives

Post-traumatic stress disorder (PTSD) remains inadequately treated by existing pharmacological and psychological interventions, prompting growing interest in psychedelic-assisted psychotherapy. Although randomised controlled trials have evaluated several psychedelic agents for PTSD, to our knowledge, no prior PTSD-specific synthesis has quantitatively examined multiple agent classes within a single review framework. This systematic review and meta-analysis searched PsycINFO, CINAHL, Embase, MEDLINE, and clinical trial registries to identify RCTs of psychedelic-assisted psychotherapy for PTSD. Risk of bias was assessed using the Cochrane Risk of Bias 2 tool, and random-effects meta-analyses were conducted for efficacy outcomes; safety and therapeutic protocols were synthesised narratively. Eleven RCTs involving 358 participants met inclusion criteria, evaluating MDMA, ketamine, and cannabidiol, of which eight contributed to meta-analyses. MDMA-assisted psychotherapy demonstrated a significant moderate-to-large reduction in PTSD symptom severity with negligible heterogeneity, and participants were significantly more likely to achieve clinical response and loss of PTSD diagnosis. The pooled effect for ketamine was small and non-significant, and a single cannabidiol trial showed no clear benefit. All agents were generally well tolerated. MDMA-assisted psychotherapy showed a promising efficacy signal for PTSD symptom reduction, although safety data were heterogenous and remain insufficient for strong comparative conclusions. Evidence for ketamine and cannabidiol remains too limited to support clinical implementation and it is noted that the current evidence base is dominated by MDMA trials. Further adequately powered trials with standardised outcomes and direct comparative studies across agents are needed. Full article

Acute pain is the most common presentation in the emergency department (ED), accounting for approximately 78% of visits and highlighting the need for rapid and effective pain management. Ketamine is a well-established analgesic that can serve as an alternative when opioids are contraindicated. Recently, low-dose ketamine (LDK), also known as sub-dissociative or subanesthetic ketamine, has emerged as a potential option for acute pain control in ED settings; however, evidence regarding its efficacy and safety remains inconsistent. This systematic review aimed to evaluate the effectiveness and safety of LDK for acute pain management in the emergency department. A comprehensive search of SCOPUS, PubMed, and Web of Science was conducted using predefined keywords related to ketamine, acute pain, and emergency care. Peer-reviewed randomized controlled trials (RCTs) published in English between 2015 and 2025 involving adults aged ≥ 18 years were included, and the risk of bias was assessed using the Cochrane Risk of Bias 2 (ROB-2) tool. Sixteen RCTs including 1908 adult patients met the inclusion criteria. The findings were heterogeneous: several studies demonstrated that LDK provided effective pain reduction within 30 min compared with commonly used analgesics such as morphine, ketorolac, and fentanyl, whereas others found no significant superiority, including one placebo-controlled trial. The analgesic effect appeared dose- and administration-dependent, with short intravenous infusions showing better tolerability than bolus dosing. Transient neuropsychiatric adverse effects were reported, but no serious adverse events were identified. Larger multicenter studies are needed to further clarify optimal dosing strategies and confirm the safety profile of LDK in ED pain management. Full article

While prior research links psychedelic use to improved psychological outcomes, less is known about whether psychedelic exposure relates to engagement with formal mental health care when treatment is recognized as needed. Using publicly available, de-identified pooled data from the National Survey on Drug Use and Health (2008–2019), this study examines whether lifetime psychedelic use is associated with missed needed mental health treatment and whether psychedelic exposure moderates the relationship between psychological distress and unmet care, with attention to gender differences. Regression analyses indicate that psychedelic use is not independently associated with lower odds of missing needed treatment once psychological distress is accounted for. However, psychedelic exposure is associated with a weaker relationship between distress and missed care: as psychological distress increases, individuals with prior psychedelic use—particularly men—exhibit a smaller increase in missed needed treatment compared to non-users. Gender-stratified analyses show that this buffering pattern is evident for men across multiple substances, whereas among women, only MDMA demonstrates a comparable moderating effect. These findings suggest that psychedelic use does not uniformly increase engagement with mental health care but is associated with gendered differences in how psychological distress translates into disengagement. Situated within the Medical Sociological and Social Epidemiological Psychedelics Paradigm, the results highlight how structural inequality shapes the behavioral translation of psychedelic experiences, producing diminished returns for women despite comparable levels of distress. Full article

This observational study examined the association between binge drinking and a binary measure of participation in physical activity (PPA) in veterans and nonveterans using pooled 2021–2023 Behavioral Risk Factor Surveillance System data (n = 107,498). Multivariable survey-weighted logistic regression models were stratified by veteran status and adjusted for sociodemographic and health characteristics. Veterans were older than nonveterans (mean age: 60.8 vs. 51.4 years) and slightly less likely to report PPA (80.8% vs. 83.4%). Among veterans, binge drinking days were inversely associated with PPA (aOR = 0.98, p = 0.01), indicating lower odds of physical activity with increasing binge drinking days. A similar but stronger association was observed among nonveterans (aOR = 0.98, p < 0.001). These findings suggest that binge drinking is associated with reduced PPA among veterans and nonveterans. Full article

Prolonged grief disorder (PGD) affects approximately 10% of bereaved individuals and is now formally recognized in both the DSM-5-TR and ICD-11. Despite its prevalence, PGD often responds poorly to traditional therapeutic approaches. This manuscript outlines the protocol for an early-stage open-label feasibility trial investigating the use of psilocybin, a psychedelic compound, in treating PGD in adults, with a focus on young adults. The study will involve 20 participants diagnosed with PGD. Each participant will undergo a structured therapeutic process that includes a preparatory session, a single 25 mg dose of psilocybin, and post-session integration. Throughout the study, participants will be monitored via symptom assessments, including qualitative and quantitative data, with the main aims related to safety, feasibility and acceptability. Functional MRIs will be obtained pre- and post-dosing and collected during a standardized grief-elicitation methodology. Key outcome measures include changes in the severity of PGD and trauma symptoms, cognitive flexibility, openness to experience, meaning in life and subjective experiences during the psilocybin session. Neural activity will also be evaluated through fMRI to better understand the neurobiological effects of the treatment. This research represents one of the first clinical protocols specifically focused on the potential of psilocybin for treating PGD. The goal is to assess feasibility and safety while laying the groundwork for future randomized controlled trials. Full article

Increasing rates of cannabis use among young adult college students is concerning, as research suggests that there may be a negative relationship between cannabis use and academic performance. The present study was conducted to investigate the relationships between cannabis use, harm reduction strategies, and college students’ grade point average (GPA). Participants (N = 125) completed an online survey that included a measure of Cannabis Use Frequency, Protective Behavioral Strategies (PBS) for Cannabis, and the New General Self-Efficacy scale. Hierarchical regressions were used to examine whether Cannabis Use Frequency or PBS for Cannabis were associated with GPA after controlling for covariates. Mediation analysis was conducted to determine whether Cannabis Use Frequency explained the relationship between PBS for Cannabis and GPA. Additionally, general self-efficacy was investigated as a potential moderator of the relationship between PBS for Cannabis and GPA. The results did not show a significant relationship between Cannabis Use Frequency or PBS for Cannabis and GPA after controlling for covariates. General self-efficacy did not significantly moderate the relationship between PBS for Cannabis and GPA. While PBS for Cannabis was indirectly related to Cumulative GPA via Cannabis Use Frequency, and its direct effect was associated with Cumulative GPA, the total effect was not significant, suggesting a suppressor effect. To our knowledge, this was the first study to investigate the relationship between PBS for Cannabis and academic performance with official GPA records. Future longitudinal studies are needed to identify strategies that may help students who engage in cannabis use succeed academically. Full article

Introduction: Chronic non-cancer pain represents a major global health challenge because of its high prevalence, functional impact, and limited response to conventional therapies, highlighting the need for alternative approaches. In this context, subanesthetic-dose ketamine has emerged as a promising therapeutic option because of its ability to modulate central sensitization and enhance analgesia through NMDA receptor antagonism. However, current evidence regarding its long-term efficacy and safety remains limited and heterogeneous. Objective: To evaluate the efficacy and safety of subanesthetic ketamine for the management of chronic non-cancer pain in adults, based on randomized controlled trials published between 2005 and 2025. Methods: A systematic review was conducted in accordance with the PRISMA 2020 guidelines. Randomized controlled trials involving adults with chronic non-cancer pain were included, comparing ketamine with placebo or other active agents. The databases searched were PubMed, ScienceDirect, and the Cochrane Library. Risk of bias was assessed using the Cochrane RoB-2 tool, and the certainty of evidence was evaluated using GRADE. Results: Five trials met the inclusion criteria. All included studies evaluated intravenous ketamine at doses ranging from 0.3 to 0.5 mg/kg. Overall, ketamine demonstrated significant short-term pain relief (p < 0.05), particularly in neuropathic conditions; however, the magnitude of this effect decreased progressively after the infusion ended. Reported adverse effects were mild and transient, with no evidence of severe toxicity. Heterogeneity in dosing protocols, pain phenotypes, comparator strategies, and follow-up duration limited cross-study comparability. Conclusions: Current evidence supports the short-term efficacy and safety of subanesthetic-dose ketamine as an analgesic option for chronic non-cancer pain, especially in neuropathic syndromes. However, the transient nature of its effects and the heterogeneity among studies underscore the need for standardized protocols and longer follow-up periods. Despite its generally favorable short-term safety profile, subanesthetic ketamine should be used with caution under strict clinical supervision, as the potential for long-term neurocognitive, urological, and hepatic adverse effects remains insufficiently defined. Full article

Synthetic cannabinoids are widely available in the United States, yet contemporary national data on who uses these products, and disparities in use, are limited. To assess disparities in lifetime and past-year synthetic cannabis use (each yes/no), we used 2022–2024 National Survey on Drug Use and Health data from adults aged ≥18 years (n = 139,532) and fit two multivariable logistic regression models adjusted for survey year and sociodemographic and policy characteristics. We also calculated proportions of lifetime and past-year use by various plant-based cannabis use modalities. The proportions of adults with lifetime and past-year synthetic cannabis use were 2.7% and 0.3%, respectively. Younger age, male sex, lower education and household income, and non-metropolitan residence were linked to both lifetime and past-year synthetic cannabis use. For example, past-year synthetic cannabis use was associated with living in non-metropolitan (vs. large metropolitan) areas (AOR = 1.54; 95% CI: 1.03–2.30). Past-year use was also linked to residence in states without medical cannabis law coverage (AOR = 1.45; 95% CI: 1.09–1.94). Finally, past-year synthetic cannabis use was most prevalent among adults who smoked (67.3%) or vaped (52.5%) plant-based cannabis. Synthetic cannabis use was uncommon overall but exhibited clear disparities, underscoring the need for continued surveillance amid evolving cannabinoid policies and markets. Full article

Background: Mitragynine pseudoindoxyl (MP) is a semi-synthetic kratom metabolite increasingly sold online and over-the-counter, marketed misleadingly as “kratom” or “7-OH,” despite lacking FDA approval and safety data in humans. Methods: This case report describes a 44-year-old male with polysubstance use history who developed opioid withdrawal symptoms after regular MP use (400 mg daily for pain management following neck injury). Vital signs, alcohol and opioid withdrawal scores and clinical outcomes were recorded. Results: The patient presented exhibiting symptoms of moderate opioid withdrawal in the absence of other opioid use. A buprenorphine macro-induction protocol was initiated. Following pre-treatment using chlorpromazine as an anti-emetic and diazepam to treat concomitant alcohol withdrawal, 32 mg buprenorphine were provided (16 mg × 2) on day one, with subsequent maintenance dosing and adjunctive medications. The patient demonstrated significant symptomatic improvement with decreased COWS scores and expressed interest in long-acting injectable buprenorphine maintenance therapy. Discussion: This represents the first documented case of suspected MP withdrawal successfully managed with buprenorphine macro-induction, demonstrating the potential efficacy of this approach for novel semi-synthetic kratom metabolites when standard withdrawal management protocols are insufficient. Further studies should evaluate long term outcomes and validate findings. Full article

Public debates about psychoactive substances have traditionally been organized around the pharmacology of compounds and the institutional control of supply. In digitally mediated societies, however, the pathways through which people encounter psychoactives are increasingly informational: search engines, recommender systems, social platforms, and—distinctively—conversational AI. These systems do not merely deliver neutral facts. They rank, frame, personalize, and conversationally validate claims in ways that can shape perceived norms, acceptable risk thresholds, and willingness to seek help. This opinion advances the concept of AI-mediated exposure to capture how algorithmic curation and interactive dialogue become upstream determinants of psychoactive-related harms and benefits across the continuum from everyday medicines to non-medical use. From a social-scientific ethics perspective, the central question is not whether AI is “good” or “bad,” but what obligations apply when AI performs interpretive authority in contexts characterized by vulnerability, stigma, and unequal access to trusted expertise. The paper argues for an ethics-centered governance framework grounded in four commitments: epistemic responsibility (how claims are generated, warranted, and communicated), relational responsibility (how users are treated in moments of uncertainty, distress, and stigma), distributive justice (who benefits and who bears risk under unequal conditions), and accountability (how behavior is evaluated, contested, and corrected over time). The aim is to treat conversational AI as a public-facing institution whose design choices must be ethically legible and publicly contestable, oriented toward harm reduction without intensifying surveillance, moralization, or inequity. Full article

Male-biased drug use is a consistent finding in contemporary epidemiology, yet most global evidence derives from urban and industrialized populations. As a result, little is known about gendered substance use in small-scale societies, leaving unresolved whether male-biased drug use reflects universal features of human behavior or is primarily a product of industrialization. To address this gap, we examine ethnographic evidence of female substance use across 171 societies in the Standard Cross-Cultural Sample using 1397 ethnographic cases from the Human Relations Area Files. We document the presence of male and female drug use descriptions, regional and subsistence-based variation, substances associated with women’s use, and the cultural contexts in which female consumption occurs. Results reveal that women’s drug use is consistently less frequent and more culturally regulated than men’s across all world regions and subsistence economies, with variation in magnitude. Exploratory factor and cluster analyses identify four domains structuring female drug-use contexts: prestige-regulated substances, ceremonial and social practices, medicinal use, and high-risk entheogenic rites. Together, these findings demonstrate that low female drug use is a cross-cultural regularity while highlighting patterned variation in the contexts of women’s consumption, providing a comparative foundation for evaluating biocultural, political–economic, and evolutionary explanations of gendered substance use. Full article

Interest in psychoactive substances, including psychedelics, is rapidly expanding in medical, academic, and other popular fields. Despite the classifications established within the psychopharmacological scientific community, certain plants, animals, and fungi, as well as the substances obtained from them, have been misclassified by both the media and academic circles. This opinion piece aims to present arguments to answer the following question: Is CBD a non-psychoactive phytocannabinoid? Hundreds of robust scientific studies published in recent years involving CBD have strengthened its clinical use in the treatment of seizures, anxiety, psychosis, schizophrenia, post-traumatic stress disorder, and addiction. As part of the arguments to answer the question posed, this text provides a historical overview of the classifications of psychoactive substances available to date, and offers reflections on these terminologies and a proposed classification of psychedelics. Full article

Cannabis is one of the most common intoxicants used worldwide. Cannabis is widely consumed worldwide and can lead to visual alterations. However, most of the available information on its effects comes from studies conducted in developed countries, while data remain limited in developing regions such as Morocco, despite its significant role in cannabis cultivation. The aim of this study was to explore multiple visual parameters and self-perceived eyesight in cannabis users in Morocco. A cross-sectional study was conducted between March 2022 and April 2023 in Marrakesh, Morocco, in cannabis consumers. Data collection was performed in two phases. First a hetero-administrated questionnaire was used to collect socio-demographics, intoxicant consumption habit information, and eye health information. Then, several visual acuity tests were performed, including a preliminary examination, a visual function assessment, and an eye health assessment. Ninety-five cannabis users participated in this study. The majority were single (62.1%) males (87.4%). All lived in the Marrakesh-Safi region (100%), and most had daily activities such as having a job or being a student (77.9%). Most had vision conditions like astigmatism or myopia (83.4%). The majority had multiple addictions (66.5%), mainly to tobacco (43.7%). Hashish was the main cannabis type used (57.9%), and smoked cannabis was the principal mode of consumption (94.7%). Many had a family history of cannabis addiction (58.9%). Day light sensitivity (66.3%) and appearance of eye symptoms after cannabis use (90.5%) were declared by the majority. In most cases, no impact on far or near vision or vision impairment due to cannabis use were declared. Our results showed that using cannabis could have significant adverse effects on visual functions. Full article

Adolescent mental health conditions, particularly treatment-resistant depression (TRD), represent a growing public health challenge associated with high morbidity, functional impairment, and elevated suicide risk. Psychedelic-assisted therapies have shown robust antidepressant and transdiagnostic effects in rigorously controlled adult trials. Extending this work to adolescents is scientifically compelling yet ethically complex, given neurodevelopmental vulnerabilities and the paucity of pediatric data. This review examines the historical context of psychedelic use, summarizes adult efficacy and mechanistic insights, explores adolescent-specific opportunities and risks, and considers applications in co-occurring neurodevelopmental disorders. Conventional treatments, including selective serotonin reuptake inhibitors and psychotherapy, are often inadequate for a narrow but substantial subset of clinical phenotypes, prompting interest in novel and rapid-acting interventions. Psychedelic-assisted therapies have shown promising results in adults with refractory mood disorders, yet their applicability to adolescents remains uncertain due to ongoing neurodevelopment and ethical constraints. This review critically examines evidence from adult psychedelic and psychedelic-adjacent interventions, including esketamine, and evaluates their potential relevance to adolescent populations through a developmental, mechanistic, and ethical lens. Rather than advocating for premature clinical adoption, we highlight translational gaps, developmental risks, and research priorities paramount to responsibly assess these approaches in youth. Full article

Cannabis and its derivatives are increasingly popular. The public perception of “cannabis” is commonly related to abuse potential with no sharp distinction to “marijuana”, “cannabinoids”, “hemp”, and cannabis derivatives. Delta 9-tetrahydrocannabinol (THC)—rich cannabis (“marijuana”), needs to be distinguished from hemp and cannabidiol (CBD)—rich; the former is psychotomimetic, while the latter is not, and it is increasingly used as a “health product”; the phytochemical composition makes the difference. However, this is still inadequately addressed. Without a detailed characterization of the components and effects conclusions cannot be generalized and are only applicable to the product used. Cannabis varieties have a highly variable phytochemical composition; the effects cannot always be attributed solely to the “main cannabinoids.” Growth conditions and processing methods also have a significant influence on the properties of the final product, even when the same cannabis variety is used. Therefore, the few comparative studies between extracts and the corresponding pure cannabinoids often produce conflicting results, as numerous preclinical and clinical examples demonstrate. They also show how little attention is paid to the phytochemical profile, even in scientific publications. Both in scientific research and consumer products, the phytochemical profile beyond the main cannabinoids should be disclosed in detail, especially since new cannabis products containing semi-synthetic CBD derivatives have recently entered the market. Full article

Kähönen argued that the harms associated with psychedelics have been overstated, while evidence for the latter’s moral enhancing effects was disregarded, in my earlier commentary. Here, I respond to these arguments and maintain that the notion of moral enhancement with psychedelics needs substantially more scientific evidence and extended bioethical debates. Full article

Background: This review examines the prevalence of substance abuse and related disorders in South Pacific nations. Methods: The review focused on data included in reports published since 2000 from countries like Samoa, Papua New Guinea, Fiji, and French Polynesia, excluding Hawaii, New Zealand, Australia, and American Samoa. Prevalence studies indexed in Medline, CINAHL, PsycInfo, Embase, and Cochrane were screened and retrieved. Joanna Briggs Institute critical appraisal tools were used to assess included studies. Results: Ten studies with diverse methods, such as national surveys, were analysed. Results show high variability in prevalence across countries, sexes, and ethnicities. Notably, tobacco and betel nut use are prevalent. Indigenous populations and men face higher SUD burdens. Discussion: inconsistencies in study methods and reliance on self-reporting limit direct comparison. Data on co-occurring disorders and polysubstance use are limited, highlighting research gaps. The review emphasises the need for culturally sensitive, standardised research to monitor emerging trends like synthetic drug use. Policy suggestions call for targeted interventions and improved surveillance to reduce disparities and support vulnerable populations in Pacific Island communities. Full article