Psychoactives doi: 10.3390/psychoactives5020017

Authors: Daniel J. Kruger Mark Schlueter Nicholas J. Felicione Jessica S. Kruger

The label content on consumer products is important for communicating health-related information and promoting safety, which is especially important for psychoactive products such as legal cannabis. New York State (NYS) legalized cannabis for adult use in 2021 and implemented packaging and labeling requirements, including requiring NYS symbols and a Certificate of Analysis (COA). We conducted an online survey exploring consumer recognition of the required NYS symbols and the comprehension and utilization of information provided in COAs. Participants (N = 195) had low recognition of required NYS symbols, most frequently selecting a symbol required in California as being required in NYS. Most participants did not know what proportion of the products that they used had a required NYS symbol on them. Half of the participants did not know how often they viewed COAs, and those who did viewed them less than half of the time they purchased products on average. Participants’ perceptions of the clarity of COAs and the impact of a COA on product safety were mixed. Additionally, 14.9% of respondents reported not using a product because of the information contained in the COA, and 13.8% reported not using a cannabis product because it did not have a COA. These results demonstrate the need for consumer education regarding cannabis product labeling and safety.

Psychoactives doi: 10.3390/psychoactives5020016

Authors: Fizza Mitter Anton Sheptooha Janni Leung Sarangan Ketheesan Wole Akosile

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.

Psychoactives doi: 10.3390/psychoactives5020015

Authors: Nasser Almulhim Abdullah Alibrahim Ali Alajwad Hanan Alzahrani Ibrahim Aldandan Abdulelah Aldabbab Ahmad Aljaziri Mayar Ibrahim

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.

Psychoactives doi: 10.3390/psychoactives5020014

Authors: Sean M. Viña

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.

Psychoactives doi: 10.3390/psychoactives5020013

Authors: Samantha McCowen Kieleha Ingram Julie A. Partridge Justin T. McDaniel

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.

Psychoactives doi: 10.3390/psychoactives5020012

Authors: J. Kim Penberthy Fatma A. Wise Nicholas Cherup J. Morgan Penberthy Evaline Mitchell Madeline Burns Oluwafunmilayo Akinlade David Chung Harshit Parmar Jonathan Singer

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.

Psychoactives doi: 10.3390/psychoactives5020011

Authors: Christopher J. Mullin Anita Cservenka

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.

Psychoactives doi: 10.3390/psychoactives5020010

Authors: Esteban Zavaleta-Monestel Jeaustin Mora-Jiménez Paulina Quesada-Abarca Carolina Rojas-Chinchilla Jorge Arturo Villalobos-Madriz Sebastián Arguedas-Chacón Roberto Rodríguez-Miranda

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.

Psychoactives doi: 10.3390/psychoactives5020009

Authors: Delvon T. Mattingly Meman Diaby Osayande Agbonlahor Joy L. Hart

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.

Psychoactives doi: 10.3390/psychoactives5020008

Authors: Ricardo Jorge Dinis-Oliveira

In 2025, Psychoactives continued its clear upward trajectory, strengthening its position as an international, peer-reviewed, open-access journal dedicated to advancing the science of psychoactive substances, spanning pharmacology, clinical psychiatry, toxicology, neuroscience, forensic science, and public health [...]

Psychoactives doi: 10.3390/psychoactives5010007

Authors: TaReva Warrick-Stone Kate Fulton Phil Durney Dennis Goodstein Elise Paquin Gamal Fitzpatrick Maeve Montesi Christopher Martin Kory London

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.

Psychoactives doi: 10.3390/psychoactives5010006

Authors: Jaewon Lee

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.

Psychoactives doi: 10.3390/psychoactives5010005

Authors: Drake Rinks Casey J. Roulette

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.

Psychoactives doi: 10.3390/psychoactives5010004

Authors: Eliana Rodrigues

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.

Psychoactives doi: 10.3390/psychoactives5010003

Authors: Karima Raoui Elmhedi Wakrim Abdelmounaim Baslam René Combe Sarah Michaud Hajar Gebrati Mohamed Cherkaoui Chait Abderrahman

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.

Psychoactives doi: 10.3390/psychoactives5010002

Authors: Mayank Gupta Aaron Krasner Priyal Khurana

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.

Psychoactives doi: 10.3390/psychoactives5010001

Authors: Gerhard Nahler

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.

Psychoactives doi: 10.3390/psychoactives4040044

Authors: Bor Luen Tang

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.

Psychoactives doi: 10.3390/psychoactives4040043

Authors: Juuso Kähönen

In a recent Psychoactives article, Bor Luen Tang argues against psychedelic moral bioenhancement (PMBE)—the use of classic psychedelics such as psilocybin to foster moral growth in healthy individuals [...]

Psychoactives doi: 10.3390/psychoactives4040042

Authors: Wole Akosile Daniel McDonald Henry Aghanwa Bola Ola

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.

Psychoactives doi: 10.3390/psychoactives4040041

Authors: William Roseby Catriona Osborn Moar

Serotonergic psychedelics, particularly psilocybin, lysergic acid diethylamide (LSD), and dimethyltryptamine (DMT), are increasingly recognised as powerful tools to advance the understanding of consciousness and its relation to brain activity. Psychedelic research has informed neuroscientific theories that attempt to map neural observations of network connectivity and signal diversity to phenomenological qualities like psychological flexibility. Thus far, however, there have been relatively limited efforts to bridge the gap between psychedelic-informed theory and the experiential differences observed in neurodevelopmental conditions such as autism. In this narrative review and conceptual synthesis, we compare the psychedelic state and autism in adults from a neurophenomenological perspective. Predictive processing is invoked as a unifying framework. This procedure highlights both phenomena as involving a shift towards sensory information relative to prior knowledge, but potentially implicating alterations at opposite ends of the cortical hierarchy. This contrastive approach also reveals opportunities for refining concepts—including psychological flexibility—as well as interpretations of results across fields. However, neurobiological findings, especially in autism, are heterogeneous and there are inherent restrictions in comparing transient state and lifelong trait phenomena. Conclusions of this comparison are primarily conceptual and offer testable hypotheses for the neurophenomenology of the psychedelic state, autism, and their interaction.

Psychoactives doi: 10.3390/psychoactives4040040

Authors: Caroline Anastasia Fernando Akila Randika Jayamaha Nafeesa Noordeen Tibutius Thanesh Pramanayagam Jayadas Chinthika Gunasekara Chandima Jeewandara Neluka Fernando

Methamphetamine is a highly addictive stimulant with severe health and psychosocial consequences. Over recent decades, genetic and molecular research on methamphetamine use disorders has expanded considerably, yet a comprehensive synthesis of this growing body of literature is lacking. This study conducted a bibliometric analysis to map the scientific landscape of genetic and molecular biology research on methamphetamine use, identifying key contributors, influential publications, publication trends, and co-occurring keywords and citations. A systematic search of the Scopus database retrieved 1550 documents. After applying the inclusion criteria and manual screening, 449 peer-reviewed articles published between 1993 and 2025 were included. Performance analysis and scientific mapping were conducted using VOSviewer software through bibliographic coupling and keyword co-occurrence. The study followed the BIBLIO checklist for reporting bibliometric reviews in biomedical literature. Publication output increased markedly after 2005, peaking in 2022, followed by a decline that may reflect a shift in research priorities. The United States, China, and Japan emerged as leading contributors, underscoring their significant investment in addiction and molecular research. Keyword co-occurrence revealed strong emphasis on addiction, dopamine, neurotoxicity, gene expression, and genetic polymorphisms, highlighting their central role in the pathophysiology of methamphetamine use disorders. This bibliometric analysis demonstrates substantial growth and influence of genetic research on methamphetamine use. Despite a recent decline in publications, the field provides a solid foundation for future interdisciplinary research and funding priorities in addiction genetics.

Psychoactives doi: 10.3390/psychoactives4040039

Authors: Faith Ekoh Shanice Rerrie James Angud Ersilia Mirabelli

Today’s research highlights the therapeutic potential of the hallucinogen psilocybin in the treatment of pathologies associated with mood, cognitive, and affective dysregulation. These domains of function are regulated by the serotonergic system, which can be influenced by sex hormones, like estrogen and testosterone, and psychedelic compounds including psilocybin. Current evidence supports a higher prevalence of affective disorders in females, and a growing awareness of sex-based differences in response to drug therapy. Estrogen’s influence on serotonin physiology is an aspect that must be accounted for when planning a treatment regimen that includes a psychoactive drug such as psilocybin. A review of the current literature was conducted, and an analysis of how the fluid hormonal states in females across their different reproductive phases may impact serotonin dynamics, synaptic plasticity, and therapeutic timing of psilocybin use is discussed. Future research should focus on the influence of sex hormones on psychedelic-assisted therapy in the effort to further personalize treatment plans for these pathologies.

Psychoactives doi: 10.3390/psychoactives4040038

Authors: Sharmistha Roy Ashis Kumar Biswas Manoj Sharma

Opioid misuse and suicide among youth remain pressing public health challenges. This scoping review examined studies published between 2020 and 2024 on associations between opioid misuse and suicidal ideation, suicide attempts, or non-suicidal self-injury (NSSI) among adolescents and young adults aged 12–30, emphasizing sex and racial or ethnic differences. Guided by Arksey and O’Malley’s framework and PRISMA-ScR, we searched MEDLINE (PubMed), PsycINFO, Scopus, Embase, and CINAHL for peer-reviewed cross-sectional studies in English. Eligible studies assessed nonmedical prescription or illicit opioid use and excluded clinical or incarcerated samples and those with older participants. Seventeen studies met the inclusion criteria. Fifteen analyzed U.S. national or state data, one examined youth in the Northern Mariana Islands, and one used Canadian data. Sixteen studies identified a positive association between opioid misuse and suicide-related outcomes, while one showed a recency gradient, with current misuse carrying the highest risk. Other findings showed that frequent misuse increased risk, multiple substance use heightened danger, and females and youth from racial and ethnic minority groups were more vulnerable. Opioid misuse is strongly associated with suicide risk. Integrated, sex- and culturally responsive prevention strategies are needed, alongside further research clarifying mechanisms and protective factors.

Psychoactives doi: 10.3390/psychoactives4040037

Authors: Phil Durney Elise Paquin Gamal Fitzpatrick Drew Lockstein TaReva Warrick-Stone Maeve Montesi Sejal H. Patel-Francis Jamal Rashid Oluwarotimi Vaughan-Ogunlusi Kelly Goodsell Jennifer L. Kahoud Christopher Martin Keira Chism Paul Goebel Karen Alexander Dennis Goodstein Kory S. London

Medetomidine, a potent central acting α2 agonist, has emerged as a fentanyl adulterant in the non-medical opioid supply. Its use has been linked to a novel withdrawal syndrome that is often resistant to conventional treatment protocols. Four cases are presented exemplifying extreme, but increasingly common forms of this withdrawal syndrome. A literature review is provided demonstrating both the paucity of available literature as well as potential avenues for treatment and future research. As adulterants continue to proliferate in the illicit drug supply, clinicians should anticipate atypical withdrawal phenotypes and consider early intervention.

Psychoactives doi: 10.3390/psychoactives4040036

Authors: Rachel E. Thayer Juliamaria Coromac-Medrano Adrianna C. Neiderman

Cannabis use (CU) motives among older adults (OA) could be an important indicator of broader mental health. OA ages 60+ (N = 78) reported on CU, alcohol consumption, and mood and anxiety. Coping, enhancement, social, conformity, expansion, and routine motives were assessed. Relationships among CU, alcohol consumption, and screenings for Cannabis Use Disorder (CUD), Alcohol Use Disorder (AUD), depression, and anxiety were examined. OA who screened positive for CUD were not different in CU frequency or alcohol consumption, but did endorse higher routine, social, coping, and conformity motives than OA endorsing non-harmful CU (d = 1.01 to 1.70). Participants who screened positive for depression or anxiety endorsed higher coping (d = 1.87, 2.18) and routine (d = 0.83, 0.85) motives in the absence of higher alcohol or CU. Higher routine motives were particularly associated with positive CUD screening, beyond other motives and CU frequency. Healthcare providers serving OA with CU should ask about motives to help determine if further mental health evaluation is warranted.

Psychoactives doi: 10.3390/psychoactives4040035

Authors: Brendan Driscoll Shaheen E. Lakhan

Psychedelic-assisted therapy offers rapid and profound benefits for treatment-resistant psychiatric conditions but remains constrained by the need for intensive, clinic-based administration. Concurrently, advances in digital health technologies have introduced scalable tools. This systematic review evaluates the safety, efficacy, and implementation of digitally enabled psychedelic-assisted therapy delivered in non-clinical settings. A comprehensive search of five databases, registered in PROSPERO (CRD420251020968) and conducted in accordance with PRISMA guidelines, identified six eligible studies including real-world analyses, clinical trials, qualitative research, and case reports, representing a total of 12,731 participants. Most studies examined at-home ketamine or esketamine therapy supported by telehealth platforms or mobile applications. Data were synthesized narratively given the heterogeneity of designs and outcomes. Digital enablement was associated with high response rates (ranging from 56.4% to 62.8% for depression) and rapid symptom improvement, particularly in depression and anxiety. Remote monitoring and digital tools demonstrated feasibility and acceptability, but serious safety concerns—including psychiatric adverse events and one unintentional overdose—underscore the need for strict oversight. Risk of bias was moderate to serious across non-randomized studies, limiting confidence in the findings. One study on virtual ayahuasca rituals highlighted the sociocultural potential and limitations of online practices. Despite promising preliminary findings, the field is marked by low methodological rigor and absence of controlled trials. Digitally supported at-home psychedelic therapy represents a transformative but high-stakes frontier, requiring robust research and safeguards to ensure safe, equitable, and effective implementation. No funding was received for this review, and the authors declare no conflicts of interest.

Psychoactives doi: 10.3390/psychoactives4030034

Authors: Tereza Dlestikova

Czechia has recently approved the medical use of psilocybin, marking a pivotal shift in the country’s drug policy landscape. This development paves the way for regulated therapeutic applications of psilocybin within clinical settings, while simultaneously prompting a timely discussion on the potential uses of psychedelics beyond strictly medical contexts. This commentary first outlines the legal status of psilocybin for therapeutic use in Czechia and situates this reform within broader international policy trends. Drawing on the publication How to Regulate Psychedelics and qualitative findings from a ketamine-assisted therapy program conducted as part of the Czech Destigmatizing the Therapeutic Use of Psychedelics in Psychiatry project, it then examines the regulation of non-clinical psychedelic use, while also highlighting the persistent legal ambiguity surrounding the Czech offence of “spreading toxicomania.” The commentary advocates for a rational, evidence-based regulatory approach, arguing that while the medicalization of psilocybin constitutes a significant legal milestone, the framework will remain incomplete without clear pathways for non-clinical use to ensure safety and legal clarity.

Psychoactives doi: 10.3390/psychoactives4030033

Authors: Jiang-Hong Ye Wanhong Zuo Faraz Chaudhry Lawrence Chinn

Alcohol Use Disorder (AUD) profoundly impacts individuals and society, driven by neurobiological adaptations that sustain chronicity and relapse. Emerging research highlights neuroinflammation, particularly microglial activation, as a central mechanism in AUD pathology. Ethanol engages microglia—the brain’s immune cells—through key signaling pathways such as Toll-like receptor 4 (TLR4) and the NLRP3 inflammasome, triggering the release of proinflammatory cytokines (IL-1β, TNF-α, IL-6). These mediators alter synaptic plasticity in addiction-related brain regions, including the ventral tegmental area, nucleus accumbens, amygdala, and lateral habenula, thereby exacerbating cravings, withdrawal symptoms, and relapse risk. Rodent models reveal that microglial priming disrupts dopamine signaling, heightening impulsivity and anxiety-like behaviors. Human studies corroborate these findings, demonstrating increased microglial activation markers in postmortem AUD brains and neuroimaging analyses. Notably, sex differences influence microglial reactivity, complicating AUD’s neuroimmune landscape and necessitating sex-specific research approaches. Microglia-targeted therapies—including minocycline, ibudilast, GLP-1 receptor agonists, and P2X7 receptor antagonists—promise to mitigate neuroinflammation and reduce alcohol intake, yet clinical validation remains limited. Addressing gaps such as biomarker identification, longitudinal human studies, and developmental mechanisms is critical. Leveraging multi-omics tools and advanced neuroimaging can refine microglia-based therapeutic strategies, offering innovative avenues to break the self-sustaining cycle of AUD.

Psychoactives doi: 10.3390/psychoactives4030032

Authors: Sean Matthew Viña

States like Hawai‘i are decriminalizing psychedelics based on emerging evidence linking their use to improved psychological well-being. Yet, in many cultural contexts, stigma surrounding mental illness may lead individuals to pursue non-traditional forms of healing, including psychedelics, in place of formal care. This study examines how psychedelic use relates to mental health treatment-seeking behaviors among Asians and Native Hawaiians and Other Pacific Islanders (NHOPIs). Using the National Survey of Drug Use and Health (NSDUH) data from 2008 to 2019 (n = 458,372), the analysis compares Non-Hispanic Whites with Asian and NHOPI respondents to assess associations between MDMA and lifetime classic psychedelic use, psychological distress (K6 scale), and formal mental health service utilization. Nested logistic regression models conducted in Stata 18 indicate that psychedelic use among White individuals is associated with a lower likelihood of seeking formal treatment. In contrast, among NHOPI individuals, psychedelic use is associated with increased odds of accessing mental health care. These findings suggest that psychedelic use may serve culturally distinct roles in coping with distress, shaped by structural stigma and the perceived trustworthiness of formal treatment systems.

Psychoactives doi: 10.3390/psychoactives4030031

Authors: Kerem Kemal Soylemez Emma Marie de Boo Aysil Susuzlu Joanne Lusher

Dementia is a progressive neurodegenerative disease which is characterised by cognitive decline, memory loss, and behavioural changes. Patients suffering from dementia often experience emotional distress, sadness and depression which also impacts the wellbeing of their caregivers. Recent research has explored the potential of psychedelics, such as psilocybin and LSD, when treating various mental health conditions. Psychedelics are known to alter perception, mood and cognition by affecting serotonin receptors in the brain. Studies suggest that psychedelics may be a promising treatment for dementia patients and promote neuroplasticity, reduce neuroinflammation and enhance cognitive flexibility. These effects could potentially lead to a reduction in the progression of neurodegenerative diseases and improve the patients’ quality of life. Additionally, psychedelics might contribute to the prevention of dementia by fostering brain health and resilience against age-related decline. The application of psychedelics in dementia care might pose significant safety and ethical concerns. The present paper provides a narrative review of the existing literature on the use of psychedelics in treatment of dementia and its different types (Alzheimer’s) with the aim to raise awareness on the topic from a critical perspective.

Psychoactives doi: 10.3390/psychoactives4030030

Authors: Mathilda Mercier Cedric Mabilais Vasileios Chytas Leonice Furtado Federico Seragnoli Albert Buchard Tatiana Aboulafia-Brakha Gabriel Thorens Daniele Zullino Louise Penzenstadler

Psychedelic substances have experienced a resurgence of clinical interest in recent years, particularly for their promising effects in the treatment of psychiatric disorders such as depression and anxiety. While evidence regarding their role in chronic pain management remains limited, emerging studies suggest potential therapeutic benefits. This case report describes a patient with persistent somatoform pain disorder and recurrent depressive disorder who underwent four sessions of psilocybin-assisted psychotherapy. The intervention was associated with a reduction in the negative impact of pain on daily life, increased pain acceptance, improved quality of life, and reduction in depressive symptoms. These findings contribute to the growing body of literature suggesting that psychedelics, when combined with psychotherapy, may offer a novel and holistic approach to the treatment of chronic pain. Further controlled studies are needed to explore the safety, efficacy, and underlying mechanisms.

Psychoactives doi: 10.3390/psychoactives4030029

Authors: Erica Holliday Kawsar Ullah Chowdhury Kai Chen Bilal Saleem Abhinav Yenduri Vishnu Suppiramaniam

This review synthesizes preclinical evidence on the behavioral and neurobiological effects of cannabis exposure during prenatal and adolescent developmental periods, with a focus on anxiety, social behavior, learning and memory, and associated brain changes. Understanding the differential impact of cannabis exposure across these windows is critical, given the increasing prevalence of cannabis use and the rising potency of its primary psychoactive component, delta-9-tetrahydrocannabinol (THC). Both prenatal and adolescent periods represent vulnerable windows for disruption of the endocannabinoid system, which plays a central role in typical neurodevelopment. Exogenous activation of this system via THC can lead to atypical brain maturation and subsequent behavioral impairments. These impairments are associated with region-specific alterations in cortical and subcortical structures and are highly dependent on the timing of exposure. For instance, prenatal exposure may disrupt medial prefrontal cortex development, leading to long-term social deficits while sparing memory function. In contrast, adolescent exposure tends to impair hippocampal function, resulting in learning and memory deficits. The manuscript is organized developmentally, beginning with the effects of prenatal exposure and then discussing consequences of adolescent exposure. By delineating the distinct behavioral and neurobiological outcomes associated with the timing of cannabis exposure, this review highlights the importance of developmental stage in assessing the risks of exogenous cannabinoid use and identifies critical periods for targeted research and intervention.

Psychoactives doi: 10.3390/psychoactives4030028

Authors: Tayler Holborn Fabrizio Schifano Emma Smith Paolo Deluca

Numerous individuals suffer from mental health issues including depression and anxiety, resulting in substantial societal burden. Data suggests individuals are choosing to self-medicate with Novel Psychoactive Substances (NPS); however, this phenomenon is poorly understood. We aimed to investigate which NPS are being used to self-medicate, evaluate their perceived effectiveness and examine influencing factors. Data from respondents (n = 274) (Mean Age [SD] = 29.8 ± 9.1, Male = 71%, Female = 18%, non-binary 5%) were collected via an online survey, with five participants (male = 2; nonbinary = 3) undertaking further semi-structured interviews and the data examined using a Framework analysis. NPS used included bromazolam, etizolam, clonazolam, 1P-LSD and 2-FDCK. Individuals perceived self-medication to be more effective than conventional treatment (p < 0.001). A Framework analysis identified the following themes surrounding mood and anxiety disorder self-medication: (1) depression being chronic, treatment resistant and often comorbid; (2) individuals attempting to mimic existing treatments; (3) individuals having high levels of pharmacological knowledge; (4) difficulties in controlling benzodiazepine self-medication. This study brings important insight into self-medication practices with NPSs, adding to data demonstrating an increase in bromazolam use. Data suggests self-medication follows conventional treatment and, therefore, we outline the importance of affordable emerging treatment options for depression and anxiety.

Psychoactives doi: 10.3390/psychoactives4030027

Authors: Nibene H. Somé Sameer Imtiaz Yeshambel T. Nigatu Samantha Wells Claire de Oliveira Shehzad Ali Tara Elton-Marshall Jürgen Rehm Kevin D. Shield Hayley A. Hamilton

This study estimates the prevalence of co-use of alcohol and cannabis, assesses the sociodemographic risk factors of co-use, and examines the associations between mental health and heavy episodic drinking (HED) and alcohol–cannabis co-use in Canada during the early years of the COVID-19 pandemic. Nine successive cross-sectional surveys, held from May 2020 to January 2022, of adults (aged ≥18 years) living in Canada were pooled for 9011 participants. The prevalence of co-use was calculated across sociodemographic groups. Logistic regressions were used to assess associations. Alcohol–cannabis co-use was associated with a greater likelihood of engaging in HED and experiencing symptoms of anxiety, depression, and loneliness. The prevalence of co-use of alcohol was different across sociodemographic groups. The highest prevalence was among TGD people (35.5%), followed by individuals aged 18–39 years (14.5%). Additionally, being TGD (aOR = 3.61, 95% CI 2.09–6.25), separated/divorced/widowed (aOR = 1.60, 95% CI 1.23–2.07), living in an urban area (aOR = 1.26, 95% CI 1.07–1.56), and having a high household income (aOR = 1.41, 95% CI 1.09–1.82) increased the likelihood of reporting alcohol–cannabis co-use. These findings underscore the fact that developing public health and clinical interventions for preventing and treating excessive alcohol or cannabis use must consider both alcohol and cannabis use patterns and should be tailored to the highest-risk TGD and young adults.

Psychoactives doi: 10.3390/psychoactives4030026

Authors: Laure Cazorla Sylvie Alaux Caroline Amberger Cédric Mabilais Leonice Furtado Albert Buchard Gabriel Thorens Louise Penzenstadler Daniele Zullino Tatiana Aboulafia Brakha

Despite growing evidence supporting the efficacy of LSD-assisted psychotherapy in treating major depressive disorder (MDD), identifying reliable psychopharmacological biomarkers remains necessary. Oxytocin, a neuropeptide implicated in social bonding and flexibility, is a promising candidate due to its release following serotonergic psychedelic administration in healthy individuals; however, its dynamics in psychiatric populations are currently unexplored. This observational pilot study aimed to characterize salivary oxytocin dynamics during a single LSD-assisted psychotherapy session in our patients with treatment-resistant MDD. Participants received 100 or 150 µg LSD, and salivary oxytocin was measured at baseline, 60, 90, and 180 min post-LSD. Concurrently, participants rated subjective drug intensity (0–10 scale) at 60, 90, and 180 min. A linear mixed model revealed significant variation of oxytocin levels over time. Perceived psychedelic intensity also significantly varied over time. This supports oxytocin as a potential biomarker. Larger, controlled trials are warranted to replicate these findings and clarify the mechanistic links between oxytocin dynamics and clinical outcomes, including changes in depressive symptoms and mental flexibility.

Psychoactives doi: 10.3390/psychoactives4030025

Authors: Filippo Besana Stefano Pasquariello Attilio Negri Valentina Costa

Shaboo is a street name commonly used in parts of Asia, particularly the Philippines and Thailand, to refer to methamphetamine, a powerful and highly addictive stimulant. Its long-term effects are related to chronic exposure to the drug effects, primarily neurotoxicity phenomena, which could lead to cognitive impairment, or psychiatric symptoms. We aim to present one case of problematic shaboo use in a patient referring to an addiction outpatient clinic in Northern Italy. This case highlights that the treatment of these patients involves careful multidisciplinary management. An accurate knowledge of the physical and psychological effects of New Psychoactive Substances is essential, as well as the implementation of a tailored psychological and social support program.

Psychoactives doi: 10.3390/psychoactives4030024

Authors: Bianca Villanova Giordano Novak Rossi Lorena Terene Lopes Guerra José Carlos Bouso Jaime Eduardo Cecilio Hallak Rafael Guimarães dos Santos

Pain is a protective mechanism that can be classified into acute and chronic types. Ayahuasca is a psychoactive brew rich in dimethyltryptamine or DMT (a 5-HT2A receptor agonist), and harmine (a monoamine-oxidase (MAO) inhibitor) used for religious and therapeutic purposes. Previous preclinical and anecdotal evidence suggests that ayahuasca and its compounds have antinociceptive and anti-inflammatory effects due to 5-HT2A agonism and MAO inhibition. Thus, the current study aims to provide a systematic review of the antinociceptive and anti-inflammatory effects of ayahuasca and its alkaloids in preclinical models. All studies published up to December 2024 were screened and evaluated for eligibility. A total of 1535 publications were identified, of which 29 adhered to the predefined criteria. Reviewed articles reported antinociceptive effects of ayahuasca, harmine, and harmaline. Regarding anti-inflammatory effects, the compounds of ayahuasca, especially harmine, have demonstrated a reduction and an increase in pro-inflammatory and anti-inflammatory cytokines, respectively. Although there are promising results regarding the antinociceptive and anti-inflammatory effects of ayahuasca and its alkaloids, further investigation is needed.

Psychoactives doi: 10.3390/psychoactives4030023

Authors: Samuel Cholette-Tétrault Nissrine Ammari Mehrshad Bakhshi

Canada’s national surveillance shows an 11% year-over-year decline in deaths from opioid and other unregulated drug poisonings, and a 10% drop in related hospitalisations in 2024. In stark contrast, Québec, home to more than nine million residents, and Montréal, the country’s second-largest city, experienced a continued rise in suspected drug-poisoning mortality through 2024, with fentanyl or analogues detected in almost two-thirds of opioid deaths. We conducted a narrative synthesis of provincial coroner and public-health surveillance tables, Health Canada dashboards, and the 2022–2025 Québec Strategy on Psychoactive-Substance Overdose Prevention. Results indicate a 40% increase in opioid-related mortality since 2018, a parallel uptick in stimulant toxicity, and a five-fold rise in overdose reversals at Montréal supervised-consumption services during the COVID-19 pandemic recovery. We aim to summarise the key problems underlying this epidemic and offer province-specific public-health strategies while also sending a call to action for first-line clinicians and psychiatrists to integrate overdose-risk screening, take-home naloxone, and stimulant-use-disorder treatments into routine care. We further urge Québec healthcare professionals to deepen their knowledge of provincial services such as supervised-injection sites and stay up to date with the rapidly evolving substance-use-prevention literature. Québec’s divergent trajectory underscores the need for region-tailored harm-reduction investments and stronger policy-to-clinic feedback loops to reduce preventable deaths.

Psychoactives doi: 10.3390/psychoactives4030022

Authors: David W. Lawrence Alex P. Di Battista Michael G. Hutchison

Background: Persisting symptoms after concussion is a complex syndrome warranting exploration into further treatment options. Emerging research highlights the potential of classic psychedelics, such as psilocybin, in managing neuropsychiatric conditions and promoting neuroprotection. Case Report: A case is presented of a 22-year-old male intercollegiate athlete who sustained a concussion and developed persisting symptoms despite multidisciplinary standard care. The symptom burden remained relatively stable for the first month post-concussion. He independently administered three 250 milligram (mg) doses of the dried fruiting body of Psilocybe cubensis (2.5 mg of psilocybin) on days 42, 45, and 46 post-injury. He reported immediate symptom relief, including improvements in headache, noise sensitivity, and cognitive function. His symptom severity score decreased from 25 to 11 and his affective symptom burden resolved completely. Functional improvements allowed him to return to full activity. No adverse effects were reported. Conclusions: This case highlights the potential role of classic psychedelics as adjuvant agents in treating persisting symptoms after concussion. Clinicians should be aware that athletes may explore psychedelics as alternative treatments. Further research is needed to evaluate the efficacy and safety of psilocybin in concussion recovery.

Psychoactives doi: 10.3390/psychoactives4030021

Authors: Mathieu Fradet

Psychedelic treatments are emerging as promising interventions for many mental health conditions. These interventions are not offered in a standardized fashion across studies and between different healthcare centers. Beyond differences in substances and doses, there is also a great heterogeneity in the interventions provided by therapists. The current review offers a summary of important elements that should be reported when describing psychedelic-assisted therapies. Clinical trials involving psilocybin for depression are systematically reviewed to synthesize available descriptions of their interventions. This review demonstrates that the exact nature of these psychotherapeutic interventions tends to be poorly defined in most scientific papers on psychedelic treatments. This problem and its implications are examined. The field stands to gain from optimized psychotherapeutic methods; however, insufficient documentation in scientific papers currently hinders the dissemination and improvement of evidence-based protocols. This article offers ideas to encourage the progress of research on psychedelic-assisted therapies.

Psychoactives doi: 10.3390/psychoactives4030020

Authors: Georgios Mikellides

Ketamine and esketamine are two closely related compounds with fast-acting antidepressant properties that have reshaped the treatment landscape for individuals with treatment-resistant depression (TRD). Originally developed as anesthetic agents, both have since demonstrated rapid and robust antidepressant effects in patients who have not responded to conventional treatments such as selective serotonin reuptake inhibitors (SSRIs) or cognitive behavioral therapy. This narrative review synthesizes evidence on their pharmacology, mechanisms of action, clinical efficacy, safety profiles, and regulatory considerations, with a particular focus on their neuroplastic effects. While ketamine is a racemic mixture composed of equal parts R- and S-enantiomers, esketamine consists solely of the S-enantiomer and has been approved for intranasal use by the FDA and EMA for TRD. These agents have been shown to produce symptom relief within hours of administration—an unprecedented effect in psychiatric pharmacology. This rapid onset is particularly valuable in managing suicidal ideation, offering potential lifesaving benefits in acute settings. Furthermore, ketamine and esketamine’s influence on synaptic plasticity, brain-derived neurotrophic factor (BDNF), and glutamate transmission provides insights into novel therapeutic targets beyond monoaminergic systems. This review incorporates recent real-world findings and peer-reviewed literature to contextualize the clinical use of these agents in modern psychiatry, bridging experimental research with practical application.

Psychoactives doi: 10.3390/psychoactives4030019

Authors: Alfonso Balmori María Paz de la Puente

Food can help release and promote neurotransmitters. As a result, the food’s effect in this regard is of great interest to individuals who have experienced dysregulation of the brain reward circuit due to addiction to drugs or other substances. This is one of the chief reasons why dietary choices can influence the success of drug addiction programs. While the general importance of nutrition was known previously—although it has been applied on few occasions—this review provides new knowledge that has emerged in recent years, which reinforces earlier findings regarding food’s importance in overcoming addiction. In the last 15 years, there has been great progress in the understanding of the human intestinal microbiota, its importance for health, and its connections with the brain. However, since this area of nutrition is such a new field of study, it has rarely been applied to or considered in treatment programs. At the same time, it is important to avoid a diet based on ultra-processed foods, which deteriorate the microbiome and consequently harm the restoration of the natural reward system. Although ongoing research will undoubtedly provide a wealth of information in the coming years, the knowledge currently available is enough to confirm the importance of diet in a person’s addiction recovery process. For this reason, it is important for patients and programs to follow a diet that regulates the brain’s natural neurotransmitters through the microbiota and restores the natural functioning of the reward circuit, helping to overcome cravings.

Psychoactives doi: 10.3390/psychoactives4020018

Authors: Chesmi Kumbalatara Dollia Cortez Wasantha Jayawardene

Chronic pain is a prevalent public health concern in the United States, frequently managed with over-the-counter (OTC) painkillers without professional medical supervision. This study investigates household-level patterns of over-the-counter painkiller use utilizing a nationally representative dataset from NielsenIQ, focusing on how reported health conditions, whether self-identified or professionally diagnosed, affect purchasing behaviors. By linking consumer purchase data with self-reported ailment information, this study analyzed painkiller expenditures across different ailment types and demographic groups. Results show that over-the-counter painkiller purchases were highly symptom-driven, particularly for headache-related products, which were the most frequently purchased category across all household types. Nearly one-third of single-member households purchased over-the-counter painkillers for headaches, regardless of diagnosis type, indicating a strong role of perceived need in driving behavior. Females and older individuals more frequently reported ailments, with consistently higher proportions across both pain-related and other conditions. Nonetheless, a notable share of households reported over-the-counter painkiller use without any reported ailments. The findings suggest that diagnostic status plays a limited role in determining over-the-counter painkiller usage, emphasizing the need for improved public health messaging around safe self-medication. These insights can inform targeted education, labeling regulations, and policy interventions to support safer and more equitable pain management practices at the population level.

Psychoactives doi: 10.3390/psychoactives4020017

Authors: Ayodele Atolagbe Ekenedilichukwu Theresa Emembolu Stanley Nkemjika

Introduction: Cannabis use disorder (CUD) is being increasingly diagnosed in the United States, but access to treatment remains unequal, particularly in New York. Identifying the factors that contribute to disparities in receiving treatment for CUD among different population groups is essential for ensuring effective and targeted interventions. This study explores the sociodemographic factors influencing treatment utilization for CUD in New York. Methods: Data for this study were retrieved from the 2018 Treatment Episode Data Set—Discharges (TEDS-D) of the U.S. Substance Abuse and Mental Health Services Administration (SAMHSA). Sample size for the study is 422,319 people with CUD. Logistic regression analysis was performed to examine the odds of receiving treatment for CUD based on demographic and socioeconomic factors, as well as the type of treatment setting. Results: The results revealed significant disparities in treatment utilization. Asians/Pacific Islanders and Hawaiian Natives had lower odds of receiving treatment compared to African Americans (OR = 0.367, 95% CI 0.341–0.394). Similarly, Caucasians had the lowest odds of receiving treatment (OR = 0.270, 95% CI 0.266–0.275). Females were less likely to receive treatment compared to males (OR = 0.756, 95% CI 0.744–0.768). Those with higher educational attainment (over four years of college) had the lowest odds of receiving treatment, while individuals with 9–11th grade education had the highest odds. Employment status also influenced treatment access, with the unemployed having the highest odds, and full-time employees having the lowest. Additionally, individuals with no source of income had significantly lower odds of receiving treatment. Conclusions: This study highlights significant disparities in the provision of treatment for CUD in New York, influenced by sociodemographic factors such as race, gender, age, education, and employment status. These findings emphasize the need for targeted interventions to reduce these disparities and improve treatment access for underserved populations.

Psychoactives doi: 10.3390/psychoactives4020016

Authors: Michael T. Lynskey Alkyoni Athanasiou-Fragkouli Anne K. Schlag David J. Nutt

Obsessive–compulsive disorder (OCD) has an estimated prevalence between 1 and 2.3%. Existing treatments may not be suitable or effective for all people with OCD, and there is increasing interest in whether these individuals may benefit from the use of cannabis-based medical products (CBMPs). We document the characteristics of 257 people reporting a diagnosis of OCD within Project T21, a study of medical cannabis patients, and examined whether the use of prescribed cannabinoids improves quality of life. Individuals with OCD were prescribed an average of 2.2 CBMPs, with most products classified as THC-dominant flowers (73.7%). Three months after initiating treatment, there were substantial improvements in quality of life (Cohen’s d = 0.48; 95% CI = 0.29–0.65), general health (Cohen’s d = 0.43; 95% CI = 0.26–0.61), mood/depression (Cohen’s d = 0.85; 95% CI = 0.65–1.04), and sleep (Cohen’s d = 0.61; 95% CI = 0.43–0.79). There was a corresponding reduction in anxiety symptoms among the subsample who completed the GAD-7 (Cohen’s d = 1.14; 95% CI = 0.84–1.44). Eight individuals (5.7%) reported a total of 14 adverse effects, with the majority of these (57%) being described as mild. Given emerging evidence that those with OCD can benefit from CBMPs, coupled with the increased availability of these unlicensed products internationally, there is a need for more research, including clinical trials, to identify those who may benefit most from the use of these medicines.

Psychoactives doi: 10.3390/psychoactives4020015

Authors: Lucija Vejmelka Damir Gašpar

Psychedelic plants and fungi have been traditionally used in many cultures as part of ritual ceremonies and ancient medicinal treatments. In some regions, these psychoactive plants have already entered mainstream discourse through popular literature and art. Today, numerous academic and medical institutions are establishing dedicated departments to examine the benefits and risks of psychedelic-assisted treatments. Entheogens in healing practices and herbal medicine are part of Slavic cultural heritage. However, due to the predominantly oral transmission of this knowledge, there is a significant lack of written sources and a profound gap in documentation regarding entheogen use on the Balkan Peninsula, where many psychoactive plants and mushrooms grow in their natural habitat. Our work aims to bridge indigenous knowledge systems with contemporary therapeutic discourse, while advocating for sustainable, inclusive, and culturally respectful research practices. This review manuscript presents information on Slavic ancient entheogens, and calls for further multidisciplinary, integrative approaches in researching psychoactive plants and mushrooms of the Balkans. Our paper includes the ethnobotanical uses of native Balkan entheogens, outlines the pharmacological mechanisms of their main active compounds, and discusses their impacts on social behavior, mental health, and overall well-being. We also examine their therapeutic potential and risks, contributing to the contemporary understanding of psychoactive and psychedelic use in mental health treatment and beyond, as tools for life enhancement to improve quality of life and well-being.

Psychoactives doi: 10.3390/psychoactives4020014

Authors: Mitch Earleywine Alyssa B. Oliva

While research on psychedelic-assisted therapy (PAT) continues to show promise, challenges in its clinical application persist. One relevant domain includes how supervision might enhance both client and trainee outcomes. Current data suggest that, despite supervisor reports and the enthusiasm of trainees, supervision accounts for extraordinarily little variance in treatment outcome. We propose that as supervisors model relevant skills, these skills can also improve in the therapist, which should lead to enhanced alliances and improved self-care for the client, trainee, and supervisor. Thus, we propose a model of supervision that rests on key Motivational Interviewing (MI) principles and supports the integration process—a pivotal phase of PAT where clients translate psychedelic-induced insights into meaningful behavioral change. This Motivational-Interviewing-Enhanced Integration Supervision (MIE-IS) model bridges the gap between psychedelic experiences and personal growth by ensuring supervisors can effectively encourage trainees to support their clients through this crucial integration process. Supervisors would model the use of MI with trainees in supervision, who would, in turn, apply those same MI technical and relational skills to support clients’ integration experiences. Beyond enhancing client outcomes, this supervisory model could also increase each trainee’s motivation to personally engage with wellness-promoting integration behaviors, potentially enhancing professional development and minimizing burnout. By reinforcing a culture of self-care and reflective practice, this model might inspire better self-care in supervisors as well. By fostering an MI-informed supervisory relationship, the model promotes a culture of continuous learning and skill development, benefiting clients through the effective and meaningful integration of their psychedelic experiences.

Psychoactives doi: 10.3390/psychoactives4020013

Authors: Bradley M. Brooks Ashley M. Nettles Brandon M. Brooks

Both Type 2 Diabetes Mellitus (T2DM) and depression are leading causes of disability despite T2DM being largely preventable and depression being among the most treatable mental health conditions. Diabetes and depression have a bidirectional association, with each condition worsening the development and progression of the other. Depression in patients with diabetes is linked with poor glycemic control, reduced treatment adherence, and increased risk of diabetes complications. On the other hand, chronic hyperglycemia, systemic inflammation, insulin resistance, and neuroendocrine dysregulation are involved in the pathophysiology of depression. Antidepressants are often used to treat depression in diabetic patients, but their metabolic impact is still a matter of concern. While some antidepressants like fluoxetine and escitalopram increase insulin sensitivity and improve glycemic parameters, others such as especially tricyclic antidepressants (TCAs) and certain selective serotonin reuptake inhibitors (SSRIs) have been associated with an increased risk of diabetes, weight gain, and poor cardiometabolic outcomes. Considering such complexities, the prescribing of antidepressants must be done carefully. This review underscores the need for evidence-based and patient-centric pharmacological management. Further, the inclusion of psychiatry in multidisciplinary diabetes care teams has the potential to maximize both metabolic and psychological health benefits, as well as reduce the complications of T2DM.

Psychoactives doi: 10.3390/psychoactives4020012

Authors: Ricardo Jorge Dinis-Oliveira

Psychoactive substances, including illicit drugs, prescription medications, and novel psychoactive compounds, are frequently analyzed in biological and in non-biological samples. Interpreting results is paramount for ensuring proper medical treatments and judicial decisions. However, false-positive results—where a sample is incorrectly identified as containing a psychoactive substance—remain a persistent issue. In other words, it is important to invest in understanding the meaning of toxicological results. Cross-reactivity in immunoassays, sample contamination, analytical interference with certain endogenous and exogenous substances, inadvertent and accidental exposure due to environmental contamination, second-hand smoke inhalation, or unintentional dermal or mucosal contact with drug residues are some of the major issues to consider. This perspective highlights major sources of artifacts in interpreting amphetamine analytical results in order to provide proper toxicological interpretations.

Psychoactives doi: 10.3390/psychoactives4020011

Authors: Kerem Kemal Soylemez Emma Marie de Boo Joanne Lusher

Psychedelic substances have recently emerged as a promising method for treating mental health conditions, despite a history of stigmatization and restriction in use. The present review synthesizes existing literature on the therapeutic potential of psychedelics such as LSD, psilocybin, and MDMA in addressing specific mental health conditions like depression, anxiety, and addiction. On reviewing the existing literature, it became apparent that when administered in controlled settings with psychological support, psychedelics can induce profound psychological insights, leading to long-lasting and positive changes in mood, cognition, and behaviour. This review discusses the ethical, social, and regulatory challenges linked to using psychedelics within the mental health sector across different countries, and how these might influence societal beliefs towards their efficacy and use. Further research would be beneficial for eliciting a deeper understanding of the use of psychedelics in the field of mental health, leading to the development of standardized administration protocols and a thorough appreciation of societal implications and long-term outcomes. This review discusses the potential for psychedelics to revolutionize mental health treatment while underlining the urgent need for rigorous scientific inquiry on this topic and the ethical considerations surrounding the use of psychedelics for therapeutic purposes.

Psychoactives doi: 10.3390/psychoactives4020010

Authors: Lumír Ondřej Hanuš Leonid N. Maslov

The history of cannabis research spans centuries, with a focus on isolating and understanding its active compounds. Although plants like opium and coca yielded active alkaloids relatively early, cannabis posed unique challenges due to its active substances existing in oily mixtures that were difficult to isolate. Early studies in the 19th century, such as Ferdinand Tscheppe’s 1821 research, debunked claims of opioid-like substances in hemp, setting the stage for further exploration. In the late 19th and early 20th centuries, key figures like Sir William Brooke O’Shaughnessy and Robert Sidney Cahn made significant contributions to the understanding of cannabis’s chemical components, though major breakthroughs were delayed due to technical limitations. In the 1940s, Ghosh and Adams independently elucidated the structure of cannabinol, marking the first cannabinoid identified from cannabis. Subsequent work, including Šantavý’s 1964 and Mechoulam and Gaoni’s 1964 identification of ∆9-THC, confirmed the psychoactive compound’s structure and absolute configuration. This article traces these incremental advancements, highlighting the critical role of each researcher’s contributions in piecing together the puzzle of cannabinoid chemistry. It underscores that scientific progress thrives on collaboration and shared knowledge.

Psychoactives doi: 10.3390/psychoactives4020008

Authors: Stefano Beggiora

Since its origins, the debate on the interaction between religions and psychoactives has been strongly influenced, both positively and negatively, by prejudices, policies, fashions and trends that had little to do with scientific research. Stigma and exaltation in different historical moments have equally characterized the study of the presence and use of so-called entheogens in the different declinations of the shamanic phenomenon around the world. This article attempts to shed light on the various trends regarding the state of the art, providing new epistemological elements on the basis of an ethnographic investigation among some Indigenous peoples of India. The production of alcoholic beverages (fermented and distilled, but sometimes in combination with other psychoactive or hallucinogens among the starters) is a fundamental trait of the aboriginal (ādivāsī) cultures of the Indian subcontinent. Not immune from an attempt at political instrumentalization, which occurred both in the colonial period and in the contemporary era, the discourse on the natural production of these sacred substances is today the key to understanding indigenous ontology and its traditional idea of sustainability. Far beyond the mere documentation of the induction of altered states of consciousness, this investigation involves the discovery of local pharmacopeias, as well as principles of fermentation and food preservation.

Psychoactives doi: 10.3390/psychoactives4020009

Authors: Guillermo Escobar-Cornejo Fernando P. Cardenas Diego Torres Mario Valderrama Mark Ettenberger

Objective: To provide a state of the art on the use, role, and function of music during psychedelic-assisted therapy (PAT) with ayahuasca. Introduction: Ayahuasca is a medicinal brew with psychoactive qualities used by indigenous communities throughout the Amazon region, and music is deemed crucial during ayahuasca experiences. In PAT, music forms part of the set and setting, but it lacks systematization and is poorly explored in the scientific literature. Inclusion criteria: Published literature in English, Spanish, and Portuguese, focusing on conceptualizing, defining, or describing the use, role, and/or function of music in PAT sessions with ayahuasca. Methods: This review follows the JBI methodology for scoping reviews. We will search Web of Science, Scopus, Google Scholar, and PubMed databases without year restrictions, and a hand search of articles will be performed. Two reviewers will assess titles/abstracts, followed by independent reviews of included full texts. An Excel data extraction sheet will be used to tabulate the information. The findings will be presented narratively, including respective tables or figures. If feasible, a potential theoretical framework for the use, role, and function of music during PAT with ayahuasca will be outlined, including implications for future research and clinical practice.

Psychoactives doi: 10.3390/psychoactives4010007

Authors: Nadine Loh David Luke

Accumulating psychedelic research has demonstrated a potential for improving mental health and wellbeing, yet studies in the context of eating disorders (EDs) are limited. This study aims to explore the subjective effects of psychedelic experiences to gain insight into the benefits and risks for people with EDs. Semi-structured interviews were conducted with eight adults aged 25–54 (mean age = 36.9), reporting to have had experiences with EDs and psychedelics in both naturalistic and clinical settings. Participants had multiple diagnoses and suffered chronic EDs, (mean age of onset = 13), diagnosed (N = 7) and undiagnosed (N = 1). Reports of cessation or the reduction of ED symptoms were unanimous and long-lasting for seven, with two participants reporting recovery attributed to psychedelic use. Two participants reported relapsing, attributed to environmental factors in the months following. Thematic analysis resulted in two superordinate themes, each comprising three subordinate themes. The first superordinate theme, ‘Exploring’ via the ‘gateway to healing’, illustrates mental, emotional, and transcendental elements of psychedelic experiences. The second superordinate theme, ‘Transformation’ and being ‘able to do the work’, illustrates cognitive and behavioural outcomes, with retrospective safety perceptions. These findings may provide more in-depth information on what benefits and experiences people with EDs can obtain from the use of psychedelic drugs and may inform more robust investigations of psychedelic-assisted therapy for the treatment of EDs.

Psychoactives doi: 10.3390/psychoactives4010006

Authors: Renan Massanobu Maekawa Lorena Terene Lopes Guerra José Carlos Bouso Jaime Eduardo Cecilio Hallak Rafael Guimarães dos Santos

Depression is common among patients suffering from cancer, but is often challenging to diagnose due to the overlap of symptoms with cancer and its treatments. Additionally, treating depression in cancer patients is challenging because of the confusion between the adverse effects of antidepressants, cancer treatments, and cancer symptoms. This study aims to evaluate the safety and adverse effects of pharmacological interventions, focusing on antidepressants and psychedelics, in the treatment of depression in cancer patients. The review follows the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines, and includes studies published up to July 2024. We searched PubMed, Scielo, and Lilacs databases, and included randomized, double-blinded, controlled clinical trials involving cancer patients with depressive symptoms. A total of 1764 articles were identified, with 21 randomized controlled trials meeting the inclusion criteria. All studies involved cancer patients with depressive symptoms, and only one study included patients with other life-threatening conditions. Serious adverse events related to antidepressant treatment were reported in only two studies, indicating an acceptable safety profile. Most other adverse effects were mild to moderate, and generally well-tolerated. Serious adverse events were infrequent; however, the small sample sizes underscore the necessity of larger, placebo-controlled trials assessing the safety of antidepressants and psychedelics in cancer patients.

Psychoactives doi: 10.3390/psychoactives4010005

Authors: Bor Luen Tang

Several authors have advanced the idea that psychedelics such as psilocybin might be effective means for achieving moral bioenhancement (MBE). Here, I discuss some reservations on this assertion from both neuropharmacological and bioethical perspectives, and surmised that there is little, if any, good justification for such a claim. The indication of psychedelics for MBE is undermined by their hallucinogenic properties and the risk of adverse psychosis. There is also a lack of sound bioethical basis for using psychedelics to enhance morality. Based on our current understanding, the use of psychedelics specifically for MBE in healthy individuals would violate the ethical principle of non-maleficence. Unless there is unequivocal demonstration that psychedelics could enhance morality, or that new non-hallucinogenic derivatives become available, an indication for psychedelics in MBE would be untenable.

Psychoactives doi: 10.3390/psychoactives4010004

Authors: Brian S. Barnett

The author surveyed researchers about United States federal grant applications for therapeutic psychedelic research and their funding success. An anonymous survey was sent to corresponding authors of the 50 most-cited psychedelic research articles published after 2000 and also disseminated on Twitter. Ten researchers responded, reporting on 24 National Institutes of Health (NIH) grant applications for psilocybin, ibogaine, lysergic acid diethylamide (LSD), 3,4-methylenedioxymethamphetamine (MDMA), and other psychedelics, dating back to the early 1990s. Grant applications increased noticeably after 2006. Of the applications assessed, 16.7% were funded, below the NIH’s 23.4% average funding rate for R01-equivalent grants from 1998 to 2023. While no applications submitted before 2006–2010 were funded, the funding rate since then (19.05–22.2%) aligns with the NIH’s 20.6 ± 1.9% annual average for R01-equivalent grants from 2006 to 2023. Respondents generally perceived funding for psychedelic research as more difficult to obtain than for other areas, though recent improvements were noted. If the analyzed applications represent only a small subset of total submissions of applications proposing to study therapeutic applications of psychedelics, the findings may have limited generalizability and larger-scale validation studies would be required. However, this is difficult to determine since detailed data on unfunded NIH applications are not publicly available.

Psychoactives doi: 10.3390/psychoactives4010003

Authors: Hazer Khalifa Emily J. Hibbert Natalie Gauci Alison Poulton

Dexamphetamine (DEX) is widely used in treatments, but concerns persist about its potential for addiction. This review aimed to assess the risks of DEX addiction by examining the existing literature. Originally planned as a systematic review, it was adjusted to a narrative review due to a lack of qualifying studies. A search of the literature on addiction to DEX was conducted on three databases including PubMed, Scopus, and Embase. Seven articles consisting of three reviews and four papers with original data were identified and reviewed. In total, four poorly documented cases of possible DEX addiction were found. The commonly cited papers on prescription DEX addiction did not hold up to scrutiny. Overall, the evidence that DEX is addictive is limited and inconclusive, highlighting the need for more rigorous research to clarify its true addiction risk.

Psychoactives doi: 10.3390/psychoactives4010002

Authors: Adeola Y. Akosile Babangida Tiyatiye Wole Akosile

Background: To estimate the prevalence of co-occurring obsessive–compulsive disorder (OCD) with substance use disorder (SUD) in the general population. Methods: A comprehensive literature search was conducted on the prevalence of comorbid OCD and SUD in the general population using MEDLINE, PsycINFO, EMBASE and CINAHL. Using the keywords, relevant studies published between 1993 and 2021 were identified. These studies were analysed using the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines and the guidelines for Meta-analysis for Observational Studies in Epidemiology. Results: Fourteen studies met the inclusion criteria and had a total combined sample size of 47,850 participants. The lifetime prevalence of any identified SUD in patients with OCD ranged between 4.3% and 62.4%. Among co-occurring OCD with AUD, prevalence ranged between 14.1% and 35.9%; cannabis use disorder and OCD, between 11.5% and 24.4%; and tobacco use disorder and OCD, between 15% and 23.1%. Alcohol was the commonest psychoactive substance used in most of the studies reviewed and the prevalence of co-occurring substance use was highest in males. Conclusions: In conclusion, this review highlights the variable prevalence of co-occurring SUDs in individuals with OCD, emphasizing that the association differs based on the type of substance. Overall, the prevalence rate of co-occurring OCD and SUDs underscores the need for further research on the relationship between these conditions and the development of effective treatment strategies that address both disorders concurrently.

Psychoactives doi: 10.3390/psychoactives4010001

Authors: Abdelmounaim Baslam Samia Boussaa Karima Raoui Hamid Kabdy Abdelfatah Aitbaba Loubna El Yazouli Rachida Aboufatima Abderrahman Chait

Adolescence is a phase characterized by reckless and risky behaviors, including the initiation and use of various illicit substances such as cannabis and alcohol. When ingested or administered, these substances affect mental processes by delivering pleasure, inner peace, and satisfaction. The aim of this study was to determine the prevalence and associated factors of psychoactive substance (PAS) use among adolescents. A cross-sectional study was conducted, including 300 participants surveyed using a structured questionnaire. Data were collected using the Mediterranean School Survey Project on Alcohol and Other Drugs (MedSPAD) to assess substance use, the Diagnostic and Statistical Manual of Mental Disorders (DSM-5) to diagnose substance use disorders (SUDs), and the Early Trauma Inventory Self-Report Short Form (ETISR-SF) to identify childhood maltreatment, as well as socio-demographic characteristics. During the study period, 300 secondary school students participated. Their mean age was 17.92 ± 1.40 years, ranging from 15 to 22. There were slightly more males (56.7%) than females. A total of 40.67% of participants admitted to using at least one PAS at least once, while the prevalence of current use was 26%. Tobacco was the most commonly used substance (22.1%), followed by cannabis (7.33%). According to the DSM-5, 40.2% of users met the criteria for severe addiction. Factors associated with PAS use included the father’s level of education; place of use (e.g., home); poor relationships with parents, siblings, and teachers; and childhood maltreatment. Psychoactive substance use was found to be prevalent among adolescents in this study.

Psychoactives doi: 10.3390/psychoactives3040034

Authors: Alexander Irvine David Luke Freya Harrild Sam Gandy Rosalind Watts

The authors would like to make the following corrections to this published paper [...]

Psychoactives doi: 10.3390/psychoactives3040033

Authors: Luis Manuel Menéndez-Quintanal Jose Manuel Matey Violeta del Fresno González Begoña Bravo Serrano Francisco Javier Hernández-Díaz Félix Zapata Gemma Montalvo Carmen García-Ruiz

In post-mortem (PM) investigations, forensic toxicologists attempt to identify legal or illegal substances present before death and determine how they contributed to the cause of death. A critical challenge is ensuring that PM sample concentrations accurately reflect those at the time of death, as postmortem redistribution (PMR) can alter these levels due to anatomical and physiological changes. The PMR phenomenon is called a ‘toxicological nightmare’. PMR significantly affects post-mortem drug concentrations, particularly for lipophilic drugs and those with a high volume of distribution. The emergence of new psychoactive substances (NPSs) has led to a growing recognition of their role as a significant public health concern, frequently associated with fatalities related to polydrug use. These substances are renowned for their ability to induce intoxication at low doses, which has led to the continuous updating of toxicological and forensic methods to improve detection and adopt new analytical standards. The comprehensive detection of NPS metabolites, some of which are still undiscovered, presents an additional analytical challenge, as do their metabolic pathways. This complicates their identification in fatal cases using standard analytical methods, potentially leading to an underestimation of their actual prevalence in toxicological results. Furthermore, the interpretation of analytical results is hindered by the absence of data on PM blood levels and the specific contributions of NPS to causes of death, exacerbated by the lack of knowledge of whether the PMR phenomenon influences them. This paper presents a comprehensive review of the literature on post-mortem cases involving various NPS, categorized according to classifications by the United Nations Office on Drugs and Crime (UNODC) and the European Union Drugs Agency (EUDA). These categories include cathinones, phenylethylamines, arylalkylamines, phencyclidine-type substances, phenmetrazines, piperazines, phenidates, aminoindanes, LSD-like NPSs, tryptamines, fentanyl analogs, designer benzodiazepines, synthetic cannabinoids, and nitazenes. This review covers not only postmortem blood levels but also the stability of the substances studied, the methods of analysis, and attempts to shed some light on the PMR phenomenon. This review used various key terms, such as PMR, NPS, and the names of previously categorized substances and drug analyses across multiple peer-reviewed journals and databases, including Scopus, Google Schoolar, Springer, PubMed, and Wiley Online Library. In addition, references from retrieved articles were examined to identify additional relevant research. Interpreting post-mortem toxicological results is complex and lacks definitive guidelines, requiring a nuanced understanding of its challenges and potential pitfalls. As a result, post-mortem toxicology is often regarded as an art. The primary aim of this review is to provide forensic toxicologists with a comprehensive framework to assist in the evaluation and interpretation of NPS analysis. This guide is intended to complement the existing knowledge and practices applied in forensic laboratories within the toxicological analysis of post-mortem cases.

Psychoactives doi: 10.3390/psychoactives3040032

Authors: Jonathan Tran Aaron C. Elkins Simone Vassiliadis Noel O. I. Cogan Simone J. Rochfort

Psychoactive drugs are compounds that alter the function of the central nervous system, resulting in changes in perception, mood, cognition, and behavior. A subclass of psychoactive drugs, psychedelics, are hallucinogenic drugs that can trigger psychedelic experiences and possible changes in mental perception. The potential use of psychedelics as a therapeutic has led to an increase in clinical research focusing on the treatment of mental disorders including anxiety and depression. There are numerous species belonging to Psychotria and Banisteriopsis which have been reported to contain psychedelic and psychoactive compounds; however, there is a lack of validated analytical methods for raw plant material, which is crucial if these plants are to be commercially cultivated for medicines. This study provides a fully validated method using ultra-high performance liquid chromatography (UHPLC) coupled to mass spectrometry (MS) for the following six compounds: tryptamine, N,N-dimethyltryptamine (DMT), 5-methoxy-N,N-dimethyltryptamine (5-MeO-DMT), tetrahydroharmine (THH), harmaline, and harmine. The validated method was used to determine the psychoactive concentrations in Psychotria viridis, Psychotria carthagenensis, Banisteriopsis caapi, and Alicia anisopetala. Validation parameters were established; linearity (R2 = 0.988–0.999), limit of detection (LOD) (0.06–0.11 ng/mL), limit of quantitation (LOQ) (0.18–0.34 ng/mL), accuracy, precision, extraction efficiency (>98%), recovery (74.1–111.6%), and matrix effect (70.6–109%) were all evaluated. All six compounds eluted within nine minutes, with a total analysis time of 20 min including column equilibration. This method establishes a high-throughput method for the robust analysis of psychedelics which may see future use in agricultural research and industry.

Psychoactives doi: 10.3390/psychoactives3040031

Authors: Sofia Sakopoulos Lisa D. Hinz

Treatment-resistant depression (TRD) is a substantial public health burden with limited treatment options. Recent evidence suggests that single and repeated-dose ketamine infusions have rapid and significant antidepressant effects on individuals with TRD. Few studies have compared single or repeated (6) ketamine infusions past 14 days post-treatment. This retrospective chart review study investigated the long-term effects of single (n = 9) and repeated (6) (n = 5) high-dose (1 mg/kg) intravenous ketamine infusions on TRD 30 days post-infusion(s) (N = 14). Changes in depressive symptoms were measured by comparing Beck Depression Inventory (BDI-II) scores pre- and 30 days post-treatment for an understanding of long-term efficacy in clinical practice. Results indicated that ketamine has the potential to be an effective and enduring intervention for TRD, adding treatment and management options that are currently limited.

Psychoactives doi: 10.3390/psychoactives3040030

Authors: Willi Schirmer Stefan Schürch Wolfgang Weinmann

Δ9-Tetrahydrocannabiphorol (Δ9-THCP, THCP) a psychoactive cannabinoid recently found in Cannabis sativa L., is widely used as a legal marijuana substitute. THCP is encountered in sprayed Cannabis, edibles, and vape liquids. The distributors of such products claim that the THCP in use originates from a natural source. The legal status of this substance varies from country to country. THCP and similar cannabinoids with a dibenzoyprane structure have been banned in Switzerland since October 2023. A vape liquid, which contains 90% THCP and 10% terpenes according to the distributor, was analyzed by gas chromatography coupled with mass spectrometry (GC-MS). Besides CBP, CBDP, Δ9-THCP and Δ8-THCP and some terpenes, other compounds were found which probably result from a synthetic procedure. This sample contained 5-heptylresorcinol, the heptyl homologue of olivetol, a common precursor for the synthesis of tetrahydrocannabinol (THC). Bisalkylated compounds (m/z 476) were found as a result of the reaction of one equivalent of 5-heptylresorcinol with two equivalents of (+)-p-mentha-1,8-dien-4-ol or another precursor. Similar bisalkylated compounds are known as undesired side products of the synthesis of THC. The sample contained unidentified isomers of Δ9-THCP, presumably abnormal cannabinoids (abn-Δ9-THCP; abn-Δ8-THCP) and iso-cannabinoids (iso-THCP). Chiral derivatization with Mosher acid chlorides revealed that the Δ9-THCP in the sample was enantiopure.

Psychoactives doi: 10.3390/psychoactives3040029

Authors: Dimy Fluyau Vasanth Kattalai Kailasam Neelambika Revadigar

Background: There is ongoing research into the potential use of psychedelics and 3,4-methylenedioxy-methamphetamine (MDMA) as alternatives to commonly used medications for treating major depressive and anxiety disorders. Aims: We aimed to assess the efficacy of psychedelics and MDMA in managing depressive and anxiety symptoms and evaluate their safety profiles. Methods: We searched five databases for randomized controlled trials of psychedelics and MDMA targeting depressive and anxiety symptoms and conducted a meta-analysis using a random effects model when possible. The review protocol is registered in PROSPERO under CRD42022341325. Results: Psilocybin induced a rapid and sustained reduction in depressive and anxiety symptoms in patients with major depressive disorder and in patients with life-threatening cancer. MDMA induced a decrease in depressive symptoms in patients with life-threatening cancer, autism spectrum disorder, and post-traumatic stress disorder. MDMA’s effect size was either negligible or negative in reducing generalized anxiety symptoms, but MDMA reduced social anxiety symptoms. Ayahuasca induced a reduction in depressive symptoms in individuals with treatment-resistant major depressive and personality disorders. Lysergic acid diethylamide (LSD) induced a decrease in anxiety symptoms in individuals with life-threatening cancer. Psilocybin’s adverse effects were noticeable for elevated blood pressure, headaches, and panic attacks. For MDMA, elevated blood pressure, headaches, panic attacks, and feeling cold were noticeable. Conclusions: Psychedelics (psilocybin, ayahuasca, and LSD) and MDMA have the potential to induce a reduction in depressive and anxiety symptoms. Adverse effects are noticed. Rigorous randomized controlled studies with larger sample sizes utilizing instruments with better reliability and validity are warranted.

Psychoactives doi: 10.3390/psychoactives3040028

Authors: Promethi Das Deep Nitu Ghosh Catherine Gaither Md. Shiblur Rahaman

Adolescents and young adults are particularly susceptible to substance abuse. They have yet to solidify their sense of self to the degree necessary to effectively resist temptations from negative peer pressure. It is vital for mental health counselors to understand the factors affecting substance abuse in adolescents/young adults and to comprehend the effectiveness of common intervention strategies fully. This paper produces a narrative literature review of 27 international journal publications from 2004 through June 2024 related to causal factors and interventions effective for treating substance abuse in adolescents and young adults. The results indicate that adolescents who idolize antisocial peers and lack a strong sense of self, family attachment, parental monitoring, and role models are more likely to suffer from substance abuse. Successful interventions include those that help strengthen the adolescent’s sense of self, a mental-health-friendly school environment staffed with professional mental health counselors, and interactive programs that engage students in positive behaviors. Positive family and peer role models can also assist in helping adolescents/young adults build a strong self-image and resist substance use. Positive peer influence is another critical factor, but more work must be undertaken to fully assess its effectiveness as an intervention.

Psychoactives doi: 10.3390/psychoactives3040027

Authors: Rosamond Goodson Justin Poklis Harrison J. Elder D. Matthew Walentiny William Dewey Matthew Halquist

Synthetic opioids such as fentanyl are key drivers of the opioid crisis, contributing to approximately 68% of the nearly 108,000 deaths linked to drug overdose in 2022 (CDC). Though fentanyl is a μ opioid receptor agonist, it demonstrates enhanced lipophilicity, heightened potency to induce respiratory depression, and more rapid central nervous system entry compared to certain other opioids, i.e., morphine. However, there are relatively few biodistribution comparison studies of fentanyl and classical opioids like morphine in mice, despite the use of mice as preclinical models of opioid effects, i.e., respiratory depression. Therefore, the current study compared acute fentanyl (0.3 mg/kg) and morphine (30 mg/kg) biodistribution in blood and 12 tissues at doses causing respiratory depression in male Swiss Webster mice. Whole-body plethysmography was used to select fentanyl and morphine doses producing comparable respiratory depression, and an LC/MS-MS protocol was developed to quantify fentanyl, morphine, and metabolites in diverse tissue samples. Drug distribution time courses varied by tissue, with fentanyl and morphine displaying similar time courses in the lung, stomach, and small intestine, but differing in the brain and spleen. Fentanyl exhibited greater distribution out of the blood and into the brain, liver, lung, and heart than morphine early after administration and out of the blood into fat at later time points after administration. The ratios of total drug distribution (area under the curve) in tissue–blood over time suggest that fentanyl accumulation in tissue relative to blood in several areas, such as lung, heart, kidney, spleen, fat, and small intestine, is greater than morphine. These findings indicate that fentanyl administration may affect several organs to a larger degree than morphine.

Psychoactives doi: 10.3390/psychoactives3030026

Authors: Rúna F. E. Walther Hein T. van Schie

This narrative review explores the utilization of psychedelic states in therapeutic contexts, deliberately shifting the focus from psychedelic substances back to the experiential phenomena which they induce, in alignment with the original meaning of the term “mind-manifesting”. This review provides an overview of various psychedelic substances used in modern therapeutic settings and ritualistic indigenous contexts, as well as non-pharmacological methods that can arguably induce psychedelic states, including breathwork, meditation, and sensory deprivation. While the occurrence of mystical experiences in psychedelic states seems to be the strongest predictor of positive outcomes, the literature of this field yields several other psychological processes, such as awe, perspective shifts, insight, emotional breakthrough, acceptance, the re-experiencing of memories, and certain aspects of challenging experiences, that are significantly associated with positive change. Additionally, we discuss in detail mystical experience-related changes in metaphysical as well as self-related beliefs and their respective contributions to observed outcomes. We conclude that a purely medical and neurobiological perspective on psychological health is reductive and should not overshadow the significance of phenomenological experiences in understanding and treating psychological issues that manifest in the subjective realities of human individuals.

Psychoactives doi: 10.3390/psychoactives3030025

Authors: Nathan S. Makarewicz Brent G. Albertson Twan Sia Anuj Aggarwal

Alkyl nitrites (“poppers”) are a diverse class of volatile chemical compounds with a varied legal and medical history. Though once commonly prescribed to treat angina, popper use is now almost exclusively recreational. Currently, poppers are widely available and sold legally under labels like “solvent cleaner”, despite marketing suggesting they are meant to be consumed. As a result, there is little incentive for producers to implement robust quality controls to protect users. In this study, nine common popper brands were analyzed using hydrogen-1 and carbon-13 nuclear magnetic resonance spectroscopy to assess the presence of impurities. Physical labels on all nine samples indicated the contents were “pure” isobutyl nitrite, despite contradictory online marketing in several cases. Spectral results showed isobutyl nitrite was present in all popper samples. However, there was evidence that various unlabeled compounds were also present in all samples. The identity and concentration of these contaminants were not clear, but the seemingly ubiquitous presence of impurities and lack of consistency in the tested samples are concerning and may represent a threat to users’ health. We hope the results of this study draw attention to the potential dangers of recreational popper use and the need to reassess how these compounds are regulated.

Psychoactives doi: 10.3390/psychoactives3030024

Authors: Samantha Banbury Chris Chandler Simon Erridge Javier del Rio Olvera John Turner Joanne Lusher

Research on the use of cannabis rectal suppositories for analgesia is limited. Few trials have evaluated the combined use of mindfulness and cannabis suppositories for anodyspareunia in men who have sex with men (MSM). This preliminary study, including a randomised control trial (RCT) and content analysis, assessed the effectiveness of an online mindful-compassion and cannabis suppository intervention among 52 British MSM (aged 18–50) who predominantly identified as bottoms (recipients of anal sex). Participants were randomly allocated to one of four groups based on whether they were using cannabis suppositories: adjunct cannabis suppository and mindful-compassion (CSMF), cannabis suppository only (CS), mindful compassion only (MF) and care as usual/control (CAU). Assessments measuring mindful compassion, sexual functioning, sexual self-efficacy, well-being, and anodyspareunia levels were completed at weeks 0, 4, and 12. Anodyspareunia levels were lower in the CSMF group compared to the other groups (CS/MF/CAU), p = 0.031. Feedback revealed that participants felt mindful compassion potentiated the effects of cannabis suppositories during sexual intimacy, reducing pain and enhancing sexual self-efficacy, sexual functioning, and well-being. This preliminary study warrants larger-scale investigation to establish the role of cannabis suppositories and mindful compassion in reducing anodyspareunia.

Psychoactives doi: 10.3390/psychoactives3030023

Authors: Lucy R. Thomsen Rhonda J. Rosengren Michelle Glass

Synthetic cannabinoids are a rapidly evolving, diverse class of new psychoactive substances. Synthetic cannabinoid use results in a higher likelihood of adverse events and hospitalization when compared to cannabis use. The mechanisms behind synthetic cannabinoid toxicity remain elusive. Furthermore, poly-substance use may be a significant contributing factor in many cases. This scoping review aimed to identify the key characteristics of synthetic cannabinoid co-exposure cases and discuss the potential implications of poly-substance use in humans. There were 278 human cases involving 64 different synthetic cannabinoids extracted from the databases. Cases involved a total of 840 individual co-exposures, with an average of four substances involved in each case. The most common co-exposures were alcohol (11.4%), opioids (11.2%), and cannabis (11.1%). When analyzed by case outcome, co-exposure to either antipsychotics/antidepressants, alcohol, or tobacco were significantly associated with mortality as an outcome (p < 0.05). Drug-use history (63.4%), mental illness (23.7%), and hypertensive and atherosclerotic cardiovascular disease (20.1%) were prevalent patient histories in the case cohort. There are several potential pharmacodynamic and pharmacokinetic interactions between co-exposure drugs and synthetic cannabinoids that could worsen clinical presentation and toxicity in synthetic cannabinoid users. Individuals with substance-use disorders or psychiatric illness would be especially vulnerable to these multi-drug interactions. Further research into these complex exposures is needed for the successful prevention and treatment of synthetic cannabinoid-related harms.

Psychoactives doi: 10.3390/psychoactives3030022

Authors: Isaac Burt

Psychedelics, combined with talk therapy, indicate promise with challenging clients, such as those struggling with PTSD. Furthermore, groupwork, with the emphasis on social connections, can be an effective modality. There appears, however, little movement with integrating psychedelics with professional counseling and even less in groupwork. Societal perceptions of psychedelics and the concern of practicing outside one’s scope may cause practitioners to hesitate. This article provides a brief overview for the lack of progression in implementing psychedelics in group counseling. I explain what potentially inhibits the utilization of psychedelics, then offer a resolution to these issues by advocating for a psychedelic-assisted groupwork (PAG) model. The argument is that psychedelic approaches can be an innovative and transformative method for group facilitators. I conclude with an overview depicting what a PAG with an interdisciplinary team could entail, including recruitment, screening, selection, therapeutic processes, and termination.

Psychoactives doi: 10.3390/psychoactives3030021

Authors: Rosa Maria Moret Sergio Sanz-Gómez Santiago Gascón-Santos Adrián Alacreu-Crespo

Substance use/abuse and suicide are two closely related phenomena, mostly due to neurobiological, psychological, and social impairments. In the present narrative review, the relationship between suicidal behavior (SB) and the use and abuse of common recreational drugs, such as alcohol, cannabis, cocaine, methamphetamine, heroin, nicotine, ketamine, psilocybin, MDMA, and LSD, has been explored. Furthermore, potential mechanisms linking the two have also been examined. According to current research, all substances appear to have a deleterious effect on SB except for ketamine and psilocybin, which could potentially confer a protective effect. Further studies are needed to understand the relationship between MDMA, LSD, and suicide.

Psychoactives doi: 10.3390/psychoactives3030020

Authors: Shadab Forouzan Kristi L. Hoffman Therese A. Kosten

Methamphetamine use disorder (MuD) is a global health problem, with no FDA-approved medications. Our prior work demonstrated that repeated methamphetamine exposure alters the gut microbiota in male rats and results in depressive-like behaviors. In this study, we extend our findings to females and determine whether probiotics block these effects. Male and female rats were administered methamphetamine (2 mg/kg; SC) or saline twice daily with either a combination of two probiotics (Lactobacillus helveticus R0052 and Bifidobacterium longum R0175) or placebo solution for 14 days. Fecal samples were collected at baseline and other days after treatment cessation. Tests of anxiety- and depressive-like behaviors were conducted using open-field and forced-swim assays. Methamphetamine induced anxiety-like behavior in females and anxiety-like and depressive-like behaviors in males. Probiotics blocked the depressive-like effect in males but did not alter anxiety-like effects in either sex. Methamphetamine exposure decreased levels of alpha diversity in both sexes, but sex differences were seen in the ability of probiotics or methamphetamine to alter levels of various bacteria. These findings support the role of the gut–brain microbiome in the depressive effects of repeated methamphetamine exposure in males, suggesting that probiotics may be a viable treatment option for MuD.

Psychoactives doi: 10.3390/psychoactives3020019

Authors: Sean Matthew Viña

Because psychedelics have been found to increase psychological traits like openness, mental flexibility, and interpersonal perceptiveness, some researchers believe that psychedelics could help individuals cope with the psychological effects of discrimination. However, it is still unclear whether psychedelic use can help manage the internalized stigma that deters formal mental health treatment. This study investigates the impact of six measures of psychedelic use (MDMA, psilocybin, DMT, ayahuasca, peyote/mescaline, and LSD) on psychological distress (Kessler Psychological Distress Scale) and internalized stigma. The study used data from the National Survey of Drug Use and Health (NSDUH) from 2008 to 2019, with a sample size of 458,372 participants. Ordinary least square regression models were conducted using Stata 18. Gender analysis found that among men, ayahuasca use was linked to reduced stigma perception associated with higher distress. For women, DMT use was linked to reduced stigma perceptions when experiencing higher distress. However, results find that individuals who have used MDMA and psilocybin reported heightened perceptions of stigma associated with increased psychological distress. Among women, MDMA and psilocybin use was associated with a higher perception of stigma when they experienced distress. These findings suggest that, overall, psychedelics may not reduce the impact of distress on the perception of stigma, especially for women.

Psychoactives doi: 10.3390/psychoactives3020018

Authors: Inês C. Santos Daniela Maia Ricardo Jorge Dinis-Oliveira Daniel José Barbosa

Drug abuse represents a significant public health problem with a growing tendency. As a way of circumventing the strict national and international control of psychoactive substances by regulatory agencies, there is a market release of new substances with psychoactive activity, called New Psychoactive Substances (NPSs). This group of substances encompasses a diverse range of synthetic compounds designed to mimic the effects of traditional illicit substances. As NPSs show stronger psychoactive effects than classical drugs, they pose unique challenges to public health and regulatory frameworks. Additionally, some substances are considered NPSs in some countries but not in others. Therefore, based on a given legal definition, manufacturers can create an NPS that does not fall under that definition and thus is not prohibited. This review critically explores the multifaceted dimensions of the criminal and legal contexts associated with NPSs. It examines the trends of abuse, the intricate network of criminal and legal aspects surrounding these substances, and the crucial warning signs that indicate their emergence, highlighting the health risks posed by these substances. In conclusion, this manuscript addresses the intricate interplay between the pharmacology, risks, and regulatory responses. These multifaceted challenges associated with NPSs will likely provide valuable insights for future research.

Psychoactives doi: 10.3390/psychoactives3020017

Authors: Christiano dos Santos Aline Thais Bruni

Novel psychoactive substances (NPSs) are compounds plotted to modify the chemical structures of prohibited substances, offering alternatives for consumption and evading legislation. The prompt emergence of these substances presents challenges in health concerns and forensic assessment because of the lack of analytical standards. A viable alternative for establishing these standards involves leveraging in silico methods to acquire spectroscopic data. This study assesses the efficacy of utilizing infrared spectroscopy (IRS) data derived from density functional theory (DFT) for analyzing NPSs. Various functionals were employed to generate infrared spectra for five distinct NPS categories including the following: amphetamines, benzodiazepines, synthetic cannabinoids, cathinones, and fentanyls. PRISMA software was conceived to rationalize data management. Unsupervised learning techniques, including Hierarchical Cluster Analysis (HCA), Principal Component Analysis (PCA), and t-distributed stochastic neighbor embedding (t-SNE), were utilized to refine the assessment process. Our findings reveal no significant disparities among the different functionals used to generate infrared spectra data. Additionally, the application of unsupervised learning demonstrated adequate segregation of NPSs within their respective groups. In conclusion, integrating theoretical data and dimension reduction techniques proves to be a powerful strategy for evaluating the spectroscopic characteristics of NPSs. This underscores the potential of this combined methodology as a diagnostic tool for distinguishing IR spectra across various NPS groups, facilitating the evaluation of newly unknown compounds.

Psychoactives doi: 10.3390/psychoactives3020016

Authors: Laurencia Bonsu Timothy J. Grigsby Christopher Johansen Asma Awan Sidath Kapukotuwa Manoj Sharma

College students are a primary population for risky alcohol use behaviors, with one of every eleven students grappling with severe alcohol-related issues. The objective of this scoping review was to synthesize the existing literature to identify factors influencing the prevalence of drinking and driving (DAD) behaviors among college students. A scoping review was conducted using Medline (PubMed), ERIC, The American Journal on Addictions, and the NCHA databases. Criteria for article selection included being published in English and focused on DAD behaviors among college students. Articles excluded from the review were systematic reviews and discussion pieces without empirical findings related to college DAD. Of the included studies (n = 23), most identified a range of factors as being influential in college students’ DAD behavior including a family history of alcohol misuse, the use of other substances such as marijuana, age of initial alcohol consumption, place of residence, propensity for sensation seeking, affiliation with sorority/fraternity groups, and the perception of associated risks. Effective strategies may include education on the risks of combined alcohol and substance use, screening and brief interventions tailored to at-risk students, and the implementation of campus policies that promote responsible alcohol consumption and deter DAD.

Psychoactives doi: 10.3390/psychoactives3020015

Authors: Val Bellman

Meldonium, a promising pharmacological agent initially developed for cardiovascular indications, has sparked considerable interest in recent years due to its potential performance-enhancing effects. This review manuscript delves into the multifaceted roles of meldonium, examining its pharmacological mechanisms, therapeutic applications, and controversial implications in medicine. Beyond its cardiovascular applications, emerging research has shed light on meldonium’s neuroprotective properties and its potential for mitigating various psychiatric conditions. Moreover, recent investigations have explored meldonium’s potential in treating neurodegenerative disorders, alcohol use disorder, and even enhancing cognitive function. However, meldonium’s journey extends beyond the realm of medicine, as its use among athletes has stirred debates surrounding performance enhancement and fair competition. The substance’s inclusion in the World Anti-Doping Agency’s (WADA) prohibited list has intensified scrutiny and raised ethical considerations regarding its use in sports. This manuscript aims to provide a comprehensive resource for researchers, clinicians, and enthusiasts alike, fostering a deeper understanding of meldonium’s complex biological interactions and its potential contributions to psychiatry.

Psychoactives doi: 10.3390/psychoactives3020014

Authors: Daniel Meling Rebecca Ehrenkranz Sandeep M. Nayak Helena D. Aicher Xaver Funk Michiel van Elk Marianna Graziosi Prisca R. Bauer Milan Scheidegger David B. Yaden

Rationale: Psychedelic research re-emerged from a period of suppression into the so-called psychedelic renaissance. In parallel, most media reporting has shifted from the overstatement of the risks of psychedelics to overly positive hype. As the empirical evidence is more equivocal than frequently portrayed, the conclusions about the effectiveness of psychedelics should be considered preliminary. Poor science communication about psychedelics’ therapeutic potential may lead potential participants or patients to feel misled and policy decisions to be misinformed. An evidence-informed characterization of their risks and benefits is needed. Objectives: This article assesses the state of psychedelic research for treating depression and the effect sizes of psychedelics on therapeutic outcomes, the risk of bias, and the prevalence of adverse effects. We review research on the risks and benefits of psychedelics and discuss how the following depression treatments have shown decreasing effect sizes over time: (1) cognitive behavioral therapy, (2) mindfulness interventions, (3) selective serotonin reuptake inhibitors, and (4) ketamine. We speculate that a similar trend may occur for psychedelic treatments. Results and conclusions: It is likely that larger and better-controlled psychedelic trials will demonstrate smaller effect sizes that are more comparable to other conventional and emerging treatments for mood disorders. Clear science communication is critical for setting public expectations and psychedelic policy. With this evidence-based assessment, we aim to cut through the misinformation about the benefits, risks, and future prospects of psychedelic treatments.

Psychoactives doi: 10.3390/psychoactives3020013

Authors: Cecilia Ilaria Belfiore Valeria Galofaro Deborah Cotroneo Alessia Lopis Isabella Tringali Valeria Denaro Mirko Casu

We explored the intricate interplay of biological, social, and psychological factors contributing to substance use disorder (SUD) and co-occurring psychiatric symptoms. Drug misuse is a global concern, with increasing prevalence rates affecting mental well-being and safety. The spectrum of SUD includes polysubstance users, posing challenges for treatment and associated health outcomes. Various psychoactive substances like cannabis, hallucinogens, opioids, and stimulants impact addiction vulnerability, with marijuana being widely used globally. Gender differences in SUD prevalence have narrowed, with women escalating drug consumption rapidly once initiated. Age disparities in substance use highlight regional variations among adolescents. Comorbidities with psychiatric symptoms are common, with mood and anxiety disorders frequently observed. This study aimed to analyze factors influencing SUD development and maintenance to inform prevention strategies and treatment recommendations. By conducting a systematic search of databases, sixty articles were reviewed, revealing diverse methodologies and geographic locations. Biological factors, including neurotransmitter systems like endocannabinoid and dopaminergic systems, play a significant role in addiction. Genetic and neurobiological factors contribute to cannabis addiction susceptibility. Social factors such as childhood experiences and parenting styles influence substance use behaviors. Psychological factors like personality traits and mental health conditions interact with SUD development. Understanding these multifaceted interactions is crucial for designing effective interventions to address the complexities of SUD and co-occurring psychiatric symptoms.

Psychoactives doi: 10.3390/psychoactives3020012

Authors: Samantha M. Ayoub Erin M. Rock Cheryl L. Limebeer Marieka V. DeVuono Linda A. Parker

(1) Background: Intraperitoneal injections of the endogenous N-acyl amino acid N-Oleoyl alanine (OlAla) effectively reduces both the affective and somatic responses produced by opioid withdrawal in preclinical models. To increase the translational appeal of OlAla in clinical drug applications, the current experiments tested whether oral OlAla pretreatment also attenuates opioid withdrawal in rats. (2) Methods: In Experiment 1, to assess its impact on affective withdrawal behavior, OlAla (0, 5, 20 mg/kg) was orally administered during the conditioning phase of an acute naloxone-precipitated morphine withdrawal conditioned place avoidance task. In Experiment 2, to assess its impact on somatic withdrawal behavior, OlAla (5–80 mg/kg) was orally administered prior to naloxone-precipitated withdrawal from chronic heroin exposure. (3) Results: Pretreatment with oral OlAla at the higher (20 mg/kg), but not lower (5 mg/kg) dose, reduced the establishment of an acute morphine withdrawal-induced conditioned place aversion. Instead, the lower dose of oral OlAla (5 mg/kg) reduced heroin withdrawal-induced abdominal contractions and diarrhea, whereas higher doses were without effect. (4) Conclusions: The results suggest a dose-dependent reduction of opioid withdrawal responses by orally administered OlAla, and further highlight the potential utility of this compound for opioid withdrawal in clinical populations.

Psychoactives doi: 10.3390/psychoactives3020011

Authors: Rishma S. I. Khubsing Martin van Leerdam Eline C. H. M. Haijen Kim P. C. Kuypers

Background: In recent years, there has been a growing interest in the therapeutic potential of classical psychedelics like ayahuasca for mental health improvement. Naturalistic studies at ayahuasca retreats have shown (short-term) improvements in mental well-being but understanding the psychological mechanisms is crucial. We are interested in psychological processes such as resilience, self-compassion, and personality traits. Additionally, it is unclear whether changes are solely due to ayahuasca or influenced by the social setting. To address this, a control group participating in a breathwork session, similar to ayahuasca retreats, was included. Methods: In this observational study, individuals who attended an ayahuasca retreat (n = 69) and individuals who participated in a breathwork session (n = 30) completed an online survey one week before (baseline) and one, six, and twelve weeks after they entered the retreat/session. The survey included a series of questionnaires, i.e., the World Health Organisation-Five Well-Being Index, 14-item Resilience Scale, Self-Compassion Scale–Short Form, and Big Five Inventory-10. A linear mixed model (LMM) was used to analyze the outcome data. Results: It was shown that well-being, resilience, and self-compassion increased and remained stable over 12 weeks compared to baseline, regardless of group (ayahuasca or breathwork). Older participants generally reported higher resilience and self-compassion. Self-compassion was also higher in the ayahuasca group overall. Neuroticism decreased in both groups, with lower scores in the ayahuasca group. Agreeableness increased over time, also not influenced by group membership, while there were no changes in extraversion, conscientiousness, or openness. Discussion: Both interventions improved well-being, aligning with prior research. Importantly, this study unveils a novel finding: both interventions enhance resilience and self-compassion for up to three months, offering promise for conditions marked by low well-being, resilience, and self-compassion like depression and anxiety-related disorders. While acknowledging its limitations (e.g., self-selected sample, no specific information of the ayahuasca brew or the breathwork technique), it emphasizes the need for controlled studies with control groups, attention to social contexts in research on these interventions, and to assess other variables like depth of altered states of consciousness that might explain improvement in psychological processes and wellbeing.

Psychoactives doi: 10.3390/psychoactives3020010

Authors: Agnieszka D. Sekula Prashanth Puspanathan Luke Downey Paul Liknaitzky

A set of interventions that can produce altered states of consciousness (ASC) have shown utility in the treatment of substance misuse. In this review, we examine addiction-related outcomes associated with three common interventions that produce ASCs: psychedelic-assisted psychotherapy (PP), Transcendental Meditation (TM) and hypnotherapy (HT). While procedurally distinct, all three interventions are associated with some common phenomenological, psychological, and neurobiological features, indicating some possible convergent mechanisms of action. Along with addiction and mental health outcomes, these common features are reviewed, and their impact on substance misuse is discussed. While our review highlights some mixed findings and methodological issues, results indicate that PP and TM are associated with significant improvements in substance misuse, alongside improvements in emotional, cognitive and social functioning, behavior-change motivation, sense of self-identity, and meaning. In contrast, and despite its broader acceptance, HT has been associated with mixed and minimal results with respect to substance misuse treatment. Authors identify key research gaps in the role of ASC interventions in addiction and outline a set of promising future research directions.

Psychoactives doi: 10.3390/psychoactives3010009

Authors: Ricardo Jorge Dinis-Oliveira

The world of drugs of abuse is a complex clinical and forensic topic since their misuse can lead to devastating consequences [...]

Psychoactives doi: 10.3390/psychoactives3010008

Authors: Chandni Sakthi Amanda Adolfo Umme Shefa Warda Asmaa Khaled Mary-Lynn Brecht Mary Rezk-Hanna

Heavily advertised as a harmless tobacco alternative, hookah (i.e., waterpipe)-flavored tobacco smoking has contributed to the wider epidemic of smoking, especially amongst marginalized sexual minority (SM) populations. Evidence regarding the concurrent use of substances and other drugs, among SM current hookah smokers, is scarce. We utilized nationally representative data from the Population Assessment of Tobacco and Health (PATH) Study (2016–2019) to examine patterns of the concurrent use of substances (i.e., marijuana, painkillers, sedatives, tranquilizers, cocaine, stimulants (specifically methamphetamines), and others), in SM adult hookah smokers and their heterosexual counterparts. Current hookah smoking is higher among SM adults (Wave 4: 4.22% [95% CI = 2.94–5.94] and Wave 5: 2.65% [95% CI = 1.81–3.48]) than heterosexuals (Wave 4: 1.31% [95% CI = 1.13–1.50] and Wave 5: 1.07% [95% CI = 0.89–1.25]). Among current SM hookah users, the co-use of substances, including alcohol, marijuana, and cocaine, is comparable to heterosexuals (p = ns). Adjusting for gender alone and all covariates, including age, sex, race/ethnicity, education, income, and education, no differences in concurrent substance use were observed between SM and heterosexual hookah users. While the co-use of substances is comparable between SM and heterosexual hookah smoker adults, the prevalence of current hookah use more than doubled among SM individuals than heterosexual individuals during 2018–2019. Our findings highlight the critical value of prevention efforts directed to increase education and awareness about hookah smoking use and known health effects, particularly tailored towards sexual minorities.

Psychoactives doi: 10.3390/psychoactives3010007

Authors: Frankie A. Colosimo Philip Borsellino Reese I. Krider Raul E. Marquez Thomas A. Vida

The human brain is an extraordinarily complex organ responsible for all aspects of cognition and control. Billions of neurons form connections with thousands of other neurons, resulting in trillions of synapses that create a vast and intricate network. This network is subjected to continuous remodeling that adapts to environmental and developmental changes. The resulting neuroplasticity is crucial to both healthy states and many forms of mental illness and neurodegeneration. This narrative review comprehensively examines N,N-dimethyltryptamine (DMT), a naturally occurring hallucinogen and psychedelic compound, focusing on its implications in promoting neuroplasticity via neuritogenesis. We examine DMT’s pharmacology, including its interaction with serotonergic, sigma-1, and trace amine-associated receptors and their associated signaling pathways. The therapeutic potential of DMT in both animal models and clinical trials is discussed with impacts on perception, cognition, emotion, and consciousness. We uniquely focus on current directions centered on unveiling the direct mechanisms of DMT’s therapeutic effects that demonstrate transformative effects on mental well-being, particularly for conditions like depression, anxiety, and post-traumatic stress disorder. We discuss the connection between DMT and neuroplasticity, offering the potential for forming new neural connections, improving learning, memory, and aiding recovery from brain injuries, including neurorehabilitation and neuroregeneration. The ultimate potential of DMT’s therapeutic efficacy to enhance neurogenesis, especially for neurodegenerative conditions, is also discussed.

Psychoactives doi: 10.3390/psychoactives3010006

Authors: Lívia Salviano Mariotto Caio Henrique Pinke Rodrigues Aline Thais Bruni

The identification of new psychoactive substances (compounds that mimic the effects of outlawed substances) poses a significant challenge due to their rapid emergence and continuous modifications. This phenomenon results in these molecules escaping legal regulation, allowing them to circumvent legislation. The phenethylamine class has garnered attention because its molecules replicate the effects of LSD and are associated with numerous cases of intoxication. In this study, we focused on three phenethylamines—2C-H, 25H-NBOH, and 25I-NBOMe—with crystallographic structures available in the Cambridge Crystallographic Data Center (CCDC) database. We conducted a systematic conformational analysis and compared the structural information obtained. Subsequently, we compared the spectra derived from this analysis with experimental details from the ENFSI database. Structural comparisons were made based on the RMSDs between the lower energy conformations and experimental crystallographic structures. Additionally, structures obtained from direct optimization were compared. We then simulated the spectra based on the X-ray structures and compared them with those in the experimental database. Interpretation was carried out using heat maps and PCA in Pirouette software. Combining in silico methods with experimental approaches provides a more comprehensive understanding of the characterization process of new psychoactive substances (NPSs).

Psychoactives doi: 10.3390/psychoactives3010005

Authors: Wasantha Jayawardene Chesmi Kumbalatara Alsten Jones Justin McDaniel

Background: Correctional officers’ life expectancy in the U.S. is 59 years, compared to the population average of 75 years. Correctional officers have higher suicide rates than others and carry a higher risk for substance use. This study examined relationships between work stress, psychoactive substance use, and preferred venues for treatment. Methods: Secondary analysis was conducted on 2017–2018 data from interviews with correctional officers, randomly sampled from prisons within Massachusetts and Texas. Independent sample t-test, multinomial logistic regression, and mediation effect model were used for analysis. Results: Of the 1083 participants (mean age = 38.6), 71.4% were males, 62.9% were White, 17.0% were veterans, and 46.7% worked in maximum-security prisons, among which 70.8% used alcohol and 17.2% sedatives in the last month. While 52.3% did not prefer receiving stress management services from the department, 32.9% did not prefer receiving from outside. Alcohol and sedative use were associated positively with work stress and counterproductive workplace behaviors, and negatively with organizational citizenship and task performance. Preferred treatment varied based on work stress and substance use. Conclusions: Work stress and psychoactive substance use among correctional officers are multifactorial. Interventions should be tailored to officers’ needs and preferred treatment venues. Prison reform should address the needs of not only inmates, but also officers.

Psychoactives doi: 10.3390/psychoactives3010004

Authors: Esmaeel Ghasemi Gojani Bo Wang Dongping Li Olga Kovalchuk Igor Kovalchuk

Psilocybin, an innate compound produced by mushrooms belonging to the Psilocybe genus, is primarily known for its agonistic effects on the serotonin 5-HT2A receptor. This receptor’s functioning is involved in many neurological processes. In the context of this research, our primary aim was to comprehensively investigate the influence of psilocybin as a serotonin receptor agonist on the intricate cascade of events involved in THP-1 macrophages stimulated by lipopolysaccharide (LPS). THP-1 monocyte cells were subjected to differentiation into macrophages through a controlled incubation with phorbol 12-myristate 13-acetate (PMA). The next step involved the induction of an inflammatory response by exposing THP-1 macrophages to 500 ng/mL LPS for 4 h. Subsequently, we triggered the activation of the second phase of the NLRP3 inflammasome by introducing adenosine triphosphate (ATP) immediately following LPS stimulation. Our findings have revealed a dose-dependent inverse correlation between psilocybin exposure and the production of LPS-induced proinflammatory cytokines and proteins. Our work indicates that psilocybin likely mediates these responses by influencing key signaling pathways, including NF-κB, IL-6/TYK2/STAT3, and TYK2/STAT1.

Psychoactives doi: 10.3390/psychoactives3010003

Authors: Carmen Ferrer-Pérez Sandra Montagud-Romero María Carmen Blanco-Gandía

It is essential to develop theories and models that enable us to understand addiction’s genesis and maintenance, providing a theoretical and empirical framework for designing more effective interventions. Numerous clinical and preclinical research studies have investigated the various brain and physiological mechanisms involved in addictive behavior. Some researchers have gone a step further, developing what we may refer to as “neurobiological theories of addiction”, which are scientific models that can explain and predict different addiction phenomena. Many of these neurobiological theories are not mutually exclusive but rather extensions and refinements of earlier theories. They all share a similar definition of addiction as a chronic disease characterized by a loss of control over substance consumption, with the brain being identified as the principal organ involved. Most propose a multifactorial causation in which both biological and environmental factors interact, accentuating or causing neurobiological dysfunction in structures and brain circuits involved in behavior and motivation. This review delves into primary neurobiological theories of addiction, commencing with the opponent-process theory—one of the earliest comprehensive explanations of the addictive process. Subsequently, we explore more contemporary formulations connecting behavioral alterations in the addictive process to changes and disruptions in various brain systems.

Psychoactives doi: 10.3390/psychoactives3010002

Authors: Novonil Deb Debankur Dey Poulami Roy

Psychotropic medications, commonly prescribed for psychiatric disorders, can have underappreciated dermatological side effects. This in-depth review explores the intricate relationship between psychotropic drugs and the skin, emphasizing the significance of recognizing and managing these side effects in clinical practice. It categorizes the dermatological side effects associated with different classes of psychotropic medications. These include antidepressants, antipsychotics, mood stabilizers, and anxiolytics. We delve into the spectrum of dermatological conditions, from mild issues like dry skin and acne to severe complications such as Stevens–Johnson syndrome and drug-induced lupus erythematosus. In conclusion, a comprehensive understanding of the dermatological side effects of psychotropic medications is essential for healthcare providers, enabling a holistic approach to patient care. This review is a valuable resource for clinicians, researchers, and educators, facilitating better-informed decision-making in the treatment of mental health disorders while prioritizing skin health and overall well-being.

Psychoactives doi: 10.3390/psychoactives3010001

Authors: Anjali Priyadarshani Rishit Bhatia Muniba Shan

Noscapine is a naturally occurring alkaloid isolated from Papaver somniferum, commonly known as opium poppy or bread seed poppy. It edges over other opioids as it lacks addictive, sedative or euphoric effects. This review chronicles the saga of endeavours with noscapine, from modest efforts in the mid-1950s to its present anticancer potential and futuristic hope in combating COVID-19. We comprehensively searched for publications including noscapine- and noscapinoid-relevant keywords in different electronic databases such as PubMed, Google Scholars, Elsevier, Springer Link and Science Direct up to June 2023. We excluded those in a language other than English. Noscapine has long been used as an antitussive and suppresses coughing by reducing the activity of the cough centre in the brain. A great number of water-soluble noscapine analogues have been found to be impressive microtubule-interfering agents with a superior antiproliferative activity, inhibiting the proliferation of cancer cell lines with more potency than noscapine and bromo-noscapine. With enhanced drug delivery systems, noscapine has exerted significant therapeutic efficacy in animal models of Parkinson’s disease, polycystic ovary syndrome, multiple sclerosis and other disorders. Furthermore, the merit of noscapine in crossing the blood–brain barrier makes it a putative candidate agent against neurodegenerative and psychiatric diseases. Its long safety record, widespread availability and ease of administration make it an ideal candidate for fighting several life-threatening conditions. Recent promising docking studies onnoscapine with main protease (Mpro) of SARS-CoV-2 paves the way for combinatorial drug therapy with anti-viral drugs and is hopeful in fighting and triumphing over any future COVID-19 pandemic.

Psychoactives doi: 10.3390/psychoactives2040024

Authors: Juliana M. Rocha José Augusto S. Reis Giordano N. Rossi José Carlos Bouso Jaime E. C. Hallak Rafael G. dos Santos

As the research field with psychedelic substances grows, it is expected to encompass a more extensive cohort of individuals presenting a spectrum of medical conditions, comorbidities, and unique physiological traits, thereby increasing the likelihood of potential adverse events. Furthermore, it is worth noting that there is a scarcity of the specialized literature regarding procedures to ensure the safe management of clinical trials involving psychedelics. Acknowledging this, our research team designed a series of protocols to standardize the care and management of adverse scenarios, ensuring the safety and well-being of research volunteers included in clinical trials conducted by the LEAPS (Laboratory for Studies with Hallucinogens and Psychedelics in Mental Health, linked to the University of São Paulo). These guidelines have been meticulously crafted based on the established guideline philosophy of Hospital das Clínicas de Ribeirão Preto (the university hospital of Universidade de São Paulo), consultation with specialists in the field, and a thorough review of the existing literature. The process resulted in protocols that have been tailored to specifically address the unique requirements and particularities of clinical research with psychedelic substances (in this case, ayahuasca and ibogaine). As a result, these guidelines aim to cover a range of potential issues, encompassing both psychiatric manifestations (e.g., panic attacks, suicidal behavior, and psychotic episodes) and clinical manifestations (e.g., hypertensive crisis and hypoglycemia).

Psychoactives doi: 10.3390/psychoactives2040023

Authors: Maraine Catarina Tadini Antônio José Ipólito Marcelo Firmino de Oliveira

(1) Background: 3,4-Methylenedioxymethamphetamine (MDMA) is an illicit drug that is sold as ecstasy. We aimed to develop a voltammetric method based on a chemically modified electrode (CME) to analyze MDMA. (2) Methods: The CME was evaluated with respect to the percentage of modifier, pre-concentration time, electroanalytical parameters, and selectivity. Then, the performance of the new voltammetric method was compared to the performance of color tests and chromatographic analyses (GC-MS and UPLC-MS) during the analysis of 11 seized ecstasy batches. (3) Results: The modifier percentage (v/v) of 1.5% provided the best CME. The electroanalytical parameters were in a linear range from 4.06 to 25.42 µmol L−1, SD = 0.018 µA, m = 84.0 × 103 µA L mol−1, r = 0.999, LD = 0.64 µmol L−1, and LQ = 2.17 µmol L−1. The CME was selective for MDMA. The MDMA concentration in the analyzed ecstasy lots ranged from 0 (without MDMA) to 63% (w/w). The voltammetric method developed for quantifying MDMA in ecstasy lots proved feasible and accurate (with a relative percentage error of ≤ ±13.2%). (4) Conclusions: The CME developed herein showed greater sensitivity (m) and lower LD and LQ for quantifying MDMA traces, paving the way for the use of voltammetric methods during forensic investigations.

Psychoactives doi: 10.3390/psychoactives2040022

Authors: Anna Beatriz Vicentini Lucas Silva Rodrigues Giordano Novak Rossi Juliana Mendes Rocha Lorena T. L. Guerra José Augusto Silva Reis Renan Massanobu Maekawa Flávia de Lima Osório José Carlos Bouso Fabiana Pereira Santos Beatriz Aparecida Passos Bismara Paranhos Mauricio Yonamine Jaime Eduardo Cecilio Hallak Rafael Guimarães dos Santos

Alcohol is the recreational drug most frequently consumed, and its high frequency of use can lead to worsening social, psychological, and domestic issues. The age group most susceptible to alcohol dependence is 18- to 24-year-old youths, demanding interventional tools to target early involvement risks. Ayahuasca seems to be a promising therapeutic tool since evidence suggests it presents potential for the treatment of depression, anxiety, and substance abuse, among other disorders. This study aimed to analyze subjective reports of university students with harmful alcohol use participating in a single-blind study evaluating the effects of one ayahuasca dose (1 mL/kg). Twenty-one days after ayahuasca administration, semi-structured interviews were conducted (n = 6) to identify peer psychological elements linked to its therapeutic potential. Subsequently, content analysis methodology was employed to define the main categories: Self-perception of experience, Positive Impacts (PI), Substances Use Pattern (SUP), Insights (I), Visual Effects, Transient Derealization, and Sleep Pattern. Among these, the most pertinent categories for this study were PI, SUP, and I, as, together, they suggest a potential link between insights and/or positive emotions and reduced alcohol consumption due to their internal transformation potential, which could be linked to a decrease in consumption.

Psychoactives doi: 10.3390/psychoactives2040021

Authors: Anil Bachu Padma Kotapati Tejasvi Kainth Garima Yadav Sahar Ashraf Bhavani Nagendra Papudesi Kristina Kennedy Sakshi Prasad Nagy A. Youssef

Background: Delirium is a complex neuropsychiatric syndrome common in all medical settings. An acute change in cognition characterizes a disturbance of consciousness, usually resulting from an underlying medical condition or withdrawal from medications or drugs. Three different subtypes of delirium have been identified based on the motor symptoms exhibited by the patient: hyperactive, hypoactive, and mixed. This study aims to review the use of methylphenidate for treating hypoactive delirium. Methods: The review was conducted in accordance with the guidelines of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. We performed a literature search of PubMed, MEDLINE, Cochrane, and clinical trial registries from 1990 to 15 March 2023. Results: A total of 115 articles were identified. After removing duplicates, 68 abstracts were reviewed by all the authors. Then, 13 full-text articles were assessed for eligibility. Three articles were deemed eligible for the systematic review. These included one prospective clinical study, one case series, and one case report. The total number of participants was 17, with multiple comorbidities. Most studies reported using methylphenidate for hypoactive delirium in terminally ill patients. All reviewed studies reported symptomatic benefits in individuals with hypoactive delirium. Conclusions: Methylphenidate may be beneficial in treating hypoactive delirium in terminally ill patients. Clinical trials are needed to assess the safety and efficacy of methylphenidate in Hypoactive delirium.

Psychoactives doi: 10.3390/psychoactives2040020

Authors: Toine Pieters

The ravaging COVID-19 pandemic has almost pushed into oblivion the fact that the United States is still struggling with an immense addiction crisis. Drug overdose deaths rose from 16,849 in 1999 to nearly 110,000—of which an estimated 75,000 involved opioids—in 2022. On a yearly basis, the opioid casualty rate is higher than the combined number of victims of firearm violence and car accidents. The COVID-19 epidemic might have helped to worsen the addiction crisis by stimulating drug use among adolescents and diverting national attention to yet another public health crisis. In the past decade, the sharpest increase in deaths occurred among those related to fentanyl and fentanyl analogs (illicitly manufactured, synthetic opioids of greater potency). In the first opioid crisis wave (1998–2010), opioid-related deaths were mainly associated with prescription opioids such as Oxycontin (oxycodone hydrochloride). The mass prescription of these narcotic drugs did anything but control the pervasive phenomenon of ‘addiction on prescription’ that played such an important role in the emergence and robustness of the US opioid crisis. Using a long-term drug lifecycle analytic approach, in this article I will show how opioid-producing pharmaceutical companies created a medical market for opioid painkillers. They thus fueled a consumer demand for potent opioid drugs that was eagerly capitalized on by criminal entrepreneurs and their international logistic networks. I will also point out the failure of US authorities to effectively respond to this crisis due to the gap between narcotic product regulation, regulation of marketing practices and the rise of a corporate-dominated health care system. Ironically, this turned the most powerful geopolitical force in the war against drugs into its greatest victim. Due to formulary availability and regulatory barriers to accessibility, European countries have been relatively protected against following suit the US opioid crisis.