Psychoactives, Volume 5, Issue 3 (September 2026) – 7 articles

The development of depression frequently impacts epileptic patients due to unmanaged central nervous system changes. This may severely reduce their quality of life. These mental conditions can lead to the administration of illicit drugs for self-medication. However, these substances may increase seizure frequency. The combination of this condition may both interacting brain disorders deeply aggravate each other, requiring simultaneous, comprehensive treatment. The aim will be to systematically evaluate the role of phytomedicine in managing comorbid depression and recreational substance use in people with epilepsy. The methods followed the PRISMA guidelines. This systematic review protocol outlines an evaluation of phytomedicine’s role in managing comorbid depression and recreational substance use in epilepsy patients. Data were searched using nine online databases for 2000–2026 primary studies, extracted data, assessed risk of bias, and performed a narrative or meta-analysis synthesis. It is well documented that depression and recreational substance use frequently coexist, with severity influenced by youth, homelessness, unemployment, childhood trauma, and prolonged substance dependence. Several evidence globally consistently demonstrates strong associations between depressive symptoms and heroin, cocaine, benzodiazepine, and alcohol use. The statistical analyses obtained indicate that substance use and depression reinforce each other, highlighting the need for integrated mental health, addiction, and psychosocial interventions to improve clinical outcomes. This highlighted a complex interaction among depression, epilepsy, and substance use. It emphasised an integrated management approach while cautiously evaluating phytomedicine’s efficacy, safety, and drug interactions. Therefore, the use of phytomedicine may complement integrated epilepsy care by addressing depression and substance use, although robust clinical evidence remains essential for validation. Full article

The global drug landscape is undergoing its most profound transformation since the emergence of the modern illicit drug market during the twentieth century. For decades, drug policies, analytical toxicology, forensic science, and public health responses have been developed around a relatively limited number of well-characterized substances, including heroin, cocaine, cannabis, and amphetamines such as 3,4-methylenedioxymethamphetamine (MDMA). Although new psychoactive substances (NPS) have received increasing attention over the last two decades, they are often considered an additional drug category rather than evidence of a much broader transformation affecting the entire drug ecosystem. This work argues that the contemporary challenge is no longer the emergence of isolated novel compounds but the transition from relatively stable drug markets to dynamic, synthetic, and continuously evolving psychoactive ecosystems. Drug production is increasingly detached from agricultural constraints, driven instead by advances in synthetic chemistry, global precursor markets, digital technologies, and highly adaptive criminal networks capable of rapidly modifying molecular structures to evade legislation and analytical detection. Simultaneously, counterfeit pharmaceuticals, semi-synthetic cannabinoids, highly potent synthetic opioids, novel stimulants, and complex patterns of polysubstance use are blurring traditional boundaries between illicit drugs, medicines, and consumer products. Future preparedness will depend less on identifying individual new substances than on developing integrated scientific predictive systems capable of anticipating rapidly evolving drug threats before they become widespread public health crises. Full article

Background: Alcohol use disorder (AUD) remains a leading contributor to global morbidity, yet conventional treatments often yield suboptimal outcomes and high relapse rates. Psilocybin-assisted therapy has re-emerged as a potential intervention for substance use disorders, but its effectiveness and safety in AUD specifically remain to be comprehensively evaluated. Objective: To review and synthesize available evidence on the efficacy and safety of psilocybin-assisted therapy in adults with AUD. Methods: A systematic search of PubMed, PsycNet, Cochrane Library, and EuropePMC was conducted on 16 June 2025 for studies published between January 2004 and 16 June 2025. Eligible studies included English-language clinical trials investigating psilocybin-assisted therapy in adults with AUD, including randomized controlled trials and proof-of-concept designs. Due to heterogeneity in study design and outcome measures, results were synthesized narratively. Results: Three eligible studies were identified. Overall, psilocybin-assisted therapy was associated with reductions in heavy drinking days and showed an acceptable safety profile in the context of controlled research settings with highly selected participants. However, findings on abstinence rates and relapse prevention were mixed, with some studies reporting no significant differences between psilocybin and control conditions. Conclusions: Preliminary evidence suggests that psilocybin-assisted therapy may reduce heavy alcohol consumption in some individuals with AUD, but the evidence base is very small and findings are inconsistent across studies. The available data are insufficient to establish clinical effectiveness or to support routine implementation. Larger randomized trials with standardized protocols, longer follow-up, and independent replication are required before conclusions about clinical utility can be drawn. Full article

Rotator cuff tears are common, and although surgical repair is frequently performed, re-tear and complication rates remain substantial. The impact of selective serotonin reuptake inhibitors (SSRIs) and serotonin–norepinephrine reuptake inhibitors (SNRIs) on postoperative outcomes after rotator cuff repair is not well understood. Using the TriNetX Research Network, adult patients undergoing arthroscopic rotator cuff repair were identified and stratified into SSRI/SNRI users (at least one prescription within 3 months preoperatively and continued use within 2 years postoperatively) and non-users. Propensity score matching was performed for demographic and medical comorbidities, yielding 2457 patients in each cohort. At 1-year follow-up, SSRI/SNRI users demonstrated lower rates of adhesive capsulitis compared with controls (3.1% vs. 5.8%; RR 0.53; 95% CI 0.41–0.70; p < 0.001), with similar revision rotator cuff repair rates. This pattern persisted at 2 years (3.6% vs. 6.1%; RR 0.58; 95% CI 0.45–0.75; p < 0.001), with comparable revision rates between groups. There were no differences in 30-day emergency department visits, readmissions, or 90-day postoperative infections. SSRI/SNRI users had lower early opioid use (21.0% vs. 29.5%; RR 0.71; p < 0.001) but higher prolonged (17.2% vs. 14.1%; RR 1.22; p = 0.003) and chronic opioid use (16.7% vs. 9.1%; RR 1.84; p < 0.001). In this large national cohort, SSRI/SNRI use was associated with lower rates of adhesive capsulitis and differences in postoperative opioid utilization, without differences in revision rotator cuff repair or short-term complications. These findings reflect associations rather than causation and highlight the need for further studies to clarify underlying mechanisms and clinical implications. Full article

Background/Objectives: In a recent meta-analysis of 1186 empirical studies, results showed that impulsivity may be one of the most important predictors of substance use. As such, the current study examined the association between an emerging psychological construct in the military veteran population, moral injury, and impulsivity—a construct found in high prevalence among military veterans. Methods: In this cross-sectional pilot study, 31 veterans completed the Moral Injury Purchase Task (MIPT), a behavioral economic assessment of sensitivity to moral injury–related relief, and the Monetary Choice Questionnaire. Demand indices for moral injury were derived, and delay discounting was quantified using area under the curve (AUC) and effective delay (ED50). Results: Participants were primarily White and male, with an average age of 38.55 years. Multivariable linear regression models adjusted for age, race, and sex. Higher moral injury intensity (b = 0.002, SE = 0.001, p = 0.04) and clinically significant moral injury (b = 0.17, SE = 0.07, p = 0.02) were associated with greater delay discounting AUCs, indicating increased preference for immediate outcomes. ED50 was not significantly associated with moral injury indices. Conclusions: Results suggest that moral injury may be linked to contextually driven shifts toward immediate reinforcement. Practitioners should consider including delay discounting in clinical settings. Full article

The nature of the psychedelic experience, and the distinctive phenomenological features it generates, leaves it susceptible to an unresolved epistemological tension between first-person phenomenological reports and claims about the fundamental nature of consciousness and reality. This tension is examined through the concept of ontological tourism: the practice of treating phenomenological data as sufficient grounds for ontological conclusions without adequate engagement with alternative mechanistic explanations or the philosophical requirements that such inferences demand. This practice, absent adequate epistemic scaffolding, poses a genuine threat to scientific integrity and clinical ethics. At the same time, reflexively dismissing phenomenological data as mere pharmacological artifacts represents an equally impoverished position. The tourist analogy cuts both ways: the tourist may be an unreliable cartographer, but the tourist has been somewhere. An alternative stance is proposed, one that takes subjective experience seriously as a form of evidence without overclaiming its metaphysical implications or dismissing its epistemic weight, along with a framework for achieving it. Ontological tourism risks bypassing the explanatory work that makes psychedelic phenomenology valuable to consciousness science. Full article

Cannabis use among adolescents and young adults has increased alongside legalization, commercialization, and higher product potency. However, evidence regarding the effectiveness of interventions to prevent or reduce cannabis use remains heterogeneous. To systematically synthesize evidence from randomized controlled trials (RCTs) evaluating behavioral, educational, psychosocial, family-based, and digital interventions targeting cannabis use among adolescents and young adults. Following PRISMA guidelines, MEDLINE, PsycINFO, CINAHL, Embase, and Web of Science were searched for randomized or cluster-randomized controlled trials involving participants aged 12–25 years. Study characteristics, intervention approaches, outcomes, and effectiveness were synthesized qualitatively. Of 973 records, 15 RCTs met the inclusion criteria. Studies varied in setting, intervention characteristics, delivery modality, and follow-up duration (2 months–7 years). School-based cognitive-behavioral interventions demonstrated the most consistent reductions in cannabis use and related harms by strengthening emotional regulation, problem-solving, coping skills, and social competence. Motivational interviewing, family-based, and digital interventions showed beneficial but variable effects. Behavioral interventions, particularly school-based cognitive-behavioral approaches, provide the strongest and most consistent evidence for reducing cannabis use and related harms among adolescents and young adults. However, methodological heterogeneity limits direct comparisons. Future well-powered RCTs with standardized outcome measures, longer follow-up, and implementation evaluations are needed to strengthen evidence-based prevention strategies. Full article