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). Full article

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. 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

Objective: To explore the perceived influence of psychedelic experiences on participants’ relationship with the natural world. Method: A total of 272 participants reporting previous use of psychedelics completed free-text response requests via an online survey. Thematic analysis was used to explore group participant responses. Results: Participants who described a pre-existing relationship with nature reported that psychedelics acted to re-establish and bolster their connection to nature. Those reporting no previously established connection to nature described psychedelics as helping them bond with the natural world. Underlying both of these were reports of transpersonal experiences, of which ‘interconnectedness’ was most frequently linked to shifts in attitudes and behaviours. Participants were also asked to reflect on previous psychedelic experiences that took place in nature and reported a range of benefits of the natural setting. Conclusions: These findings suggest that psychedelics have the capacity to elicit a connection with nature that is passionate and protective, even among those who were not previously nature oriented. More research is needed to explore the potential implications of psychedelic use outside laboratory-controlled settings in order to enhance these important effects. Full article

The COVID-19 pandemic has made evident the need to develop effective strategies to cushion the psychological consequences of social catastrophes. Preliminary evidence suggests that the use of hallucinogens is a protective factor that mitigates against such stressors. However, the underlying mechanisms must be further explored. This study specifically focused on the potential role of coping strategies in this regard, analyzing them through an online survey completed by a total of 2971 subjects who were followed up with from the beginning of the COVID-19 pandemic until six months after baseline. The survey was published in three different cultures (English, Spanish, and Portuguese), allowing for the collection of data from three different cultural contexts. The results show that coping strategies were generally more related to psychological well-being and psychopathology than to hallucinogenic drug use. However, regarding the latter, users of hallucinogens had higher scores on problem-focused engagement and disengagement and lower scores on wishful thinking than non-users. Longitudinally, while most baseline coping scores were associated with psychological distress and the severity of psychological symptoms, some coping strategies were related to the use of hallucinogens. These results show an adaptive pattern of coping strategies among hallucinogen users. Further research should take into account that coping strategies are only marginally associated with hallucinogenic drug use. Other underlying mechanisms explaining the better adjustment of users of hallucinogens to pandemics should be explored. Full article

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. Full article

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. 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

1,3-dimethylamylamine (1,3-DMAA) is a simple straight-chain aliphatic sympathomimetic amine, which was used as a nasal decongestant between 1948 and 1983. It reappeared in both dietary supplements as a substitute for ephedrine, and in party pills as an alternative to 3,4-methylenedioxymethamphetamine and/or 1-benzylpiperazine, after these substances were banned. Following its introduction to the market, it became one of the most widely used stimulants, and several case reports started to raise concerns about the safety and adverse effects of 1,3-DMAA. As a result, many countries banned or restricted the sale of 1,3-DMAA. Nevertheless, despite the efforts of regulating agencies, it has been reported that 1,3-DMAA is still found in dietary supplements and has been identified in doping controls. Therefore, the objective of this work is to review both the clinical and forensic aspects of 1,3-DMAA. 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

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

Exposure to psychoactive substances is undoubtedly a serious public health issue that should be carefully analyzed from different perspectives. Regarding the types of toxic effects inflicted by these xenobiotics, it is already known that many of the common abused psychoactives have shown positive genotoxicity findings in complementary genetic toxicology assays. Nevertheless, while there are several experimental articles and reviews on this topic, it is also clear that additional information, particularly mechanistic studies, is still needed. This article addresses these issues, pointing out some aspects of the potential genotoxicity of psychoactive substances that should be further explored, and suggests some possible approaches that could be valuable in future toxicological studies. Full article

This technical clinical and forensic note is designed to interpret the influence that psychoactive (or psychotropic) substances may have on driving. The present interpretation is restricted to the four groups of substances (i.e., cannabinoids, cocaine and metabolites, opiates and amphetamines and derivatives) outlined in Annex V of Ordinance No. 902-B/2007 of 13 August and it is expected that can be extrapolated to other jurisdictions besides Portugal. This work is presented in a pragmatic and objective way, avoiding the clinical, physiological, pathophysiological, and toxicological aspects that would hinder understanding and impair the usefulness and applicability of its content. The evaluation of the state of influence by psychotropic substances is a complex clinical and forensic subject especially due interindividual variability and concomitant consumption of other substances that may predispose to pharmacological interactions. Full article