Psychoactives

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

(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. Full article

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. 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

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. Full article

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. Full article

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

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. Full article

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. Full article

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. Full article

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. Full article

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