Psychoactives, Volume 3, Issue 1 (March 2024) – 9 articles

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