Psychoactives, Volume 4, Issue 3 (September 2025) – 8 articles

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