Psychoactives

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. Full article

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. Full article

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-HT_2A 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-HT_2A 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. Full article

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. Full article

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. Full article

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. Full article

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. Full article

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. Full article

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. Full article

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. Full article

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. Full article

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. Full article

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. Full article

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. Full article

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. Full article

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. Full article

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. Full article

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. Full article

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. Full article