Psychoactives, Volume 2, Issue 4 (December 2023) – 8 articles

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). Full article

(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. Full article

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. Full article

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. Full article

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. Full article

Background: Cannabis is one of the most popular drugs of the 21st century, especially among adolescents and young adults. Evidence of a variety of lasting neuropsychological deficits as a result of chronic cannabis use has increased. Furthermore, regular cannabis use is found to be a predictor of mental health problems, less motivation in school, and school dropout. Aim: Our goal is to propose a theoretical model of adolescent cannabis use disorder (CUD) based on Zinberg’s drug, set, and setting model and explicated by a review of the literature on adolescent cannabis use to improve the prevention and treatment of CUD for adolescents. Methods: PubMed and Web of Science were searched for relevant publications as part of a hypothesis-based and model-generating review. Results: Individual (set) and environmental (setting) risk factors play important roles in the development of CUD in adolescents. School performance, motivation, and attendance can be negatively influenced by persistent cannabis use patterns and adolescent brain development can consequently be impaired. Thus, cannabis use can be understood as both being the cause of poor school performance but also the consequence of poor school performance. To prevent and reduce adolescent CUD the drug, set, and setting must all be considered. It is important to notice that the multiple feedback loops (indicated in our dynamic interaction model) are not mutually exclusive, but offer important intervention focus points for social workers, addiction professionals, parents, and other care takers. Conclusion: We argue that the three dimensions of drug, set, and setting contribute significantly to the eventual manifestation of CUD. Based on our dynamic interaction model, recommendations are made for possible preventive and therapeutic interventions for the treatment of adolescents and young adults with CUD. Full article

Psychedelics could have revolutionary potential in psychiatry, although, until recently, the pharmacodynamic properties of such compounds have not seemed to differ much from those of serotonin, whose levels are raised by Serotonin Reuptake Inhibitors (SSRI). The cardinal point is that serotonergic compounds, such as antidepressive drugs, do not have the potential to induce long-lasting neuroplasticity as psychedelics do. Therefore, the biological underpinnings of the peculiar effect of such compounds had not been fully understood until new astonishing molecular findings came out this year to shed new light on them. Specifically, the phenomena of neuroplasticity are triggered by the stimulation of a peculiar type of receptors: the intracellular 5-HT2A receptors. Interestingly, psychedelics can reach this pool of intracellular receptors due to their lipophilic properties, as they can cross the lipophilic neuronal membrane while serotonin cannot. The importance of such a discovery should not be underestimated as the specific mechanisms involved have not yet been elucidated and a better understanding of them could pave the way to the development of new drugs (and/or new tailored therapeutic strategies) able to sustain neuroplasticity while minimizing side effects. Full article

Background: In the context of increasing scientific interest in the potential therapeutic use of psychedelic agents and their underlying psychotherapeutic mechanisms, we undertake the first detailed assessment of insights and life and lifestyle changes associated with ayahuasca consumption. Methods: An international cross-sectional study of ayahuasca drinkers in a variety of settings was performed (n = 8907). Bivariate analysis and multivariate linear and logistic regressions were used to explore associations between a range of covariates and insights, life changes and lifestyle changes. The least absolute shrinkage and selection operator variable selection method (LASSO) was used to select the variables most relevant for inclusion in models assessing broader wellbeing and mental health associations. Results: Insights are almost universally reported as part of the ayahuasca experience and are highly valued by drinkers and strongly predictive of subsequent beneficial life and lifestyle changes. A range of personal, vocational, religious/spiritual and health-related life changes (attributed to ayahuasca) are also commonly identified, as are various beneficial lifestyle and health behavior changes. Demographic and ayahuasca drinking variables that are predictive of such phenomena are reported, along with associations between insights, life and lifestyle changes and perceived growth in psychological wellbeing and current mental health status (Kessler 10 and SF-12 MCS). Conclusion: Insights and subsequent life and lifestyle changes appear to have a central role in the transformative effects reported by individuals consuming ayahuasca, with these occurring across contexts of use and demographic groups. Full article