Search

Undesirable behaviors of dogs and cats may reduce their quality of life and may cause harm to their owners. Such behaviors have been treated with medications as well as behavioral training and environmental modifications. Finnish veterinarians answered a web-based questionnaire to characterize the treatment of undesirable behaviors in dogs and cats by medications. Fourteen indications related to undesirable behaviors were defined in the questionnaire. Most psychoactive medications authorized for veterinary or human use in Finland and allowed to be prescribed for animal use according to the national legislation were listed. In addition, some sedative and analgesic agents were included. Canine and feline undesirable behaviors were treated by the respondents with a wide variety of medications. In many cases, none of the remedies used could be demonstrated to be a clear favorite for a certain indication. Off-label use of psychoactive medications was common. Many medications were used without research-based evidence of their efficacy for the indication in those species in question. Treatment of dogs was more often associated with advice for behavioral training in addition to medications than treatment of cats. Both the common off-label use of medications and the wide variety of substances used for the particular behavioral problem reveal the need for further clinical evidence of the efficacy of medications to treat various canine and feline undesirable behaviors. • Undesirable behaviors of dogs and cats were treated with a wide variety of medicines. • Off-label use of psychoactive medicinal substances was common. • Some drugs were used with no evidence of their efficacy for the indication. • Dog owners were advised for behavioural training more often than cat owners. [ABSTRACT FROM AUTHOR]

Adolescents living in peri‐urban communities are more vulnerable to risky behaviours such as substance use. This was a cross‐sectional study carried out to determine the prevalence, risk and protective factors of adolescent substance use in peri‐urban communities in Abuja. Data on lifetime and current substance use were collected using the Youth Risk Behaviour Survey Instrument. Data on risk and protective factors of adolescent substance use, based on the Problem Behaviour Theory, were also collected. Using the SPSS software, descriptive analysis was conducted to summarise the data. Bivariate analysis was conducted using chi‐square and independent t‐tests, and multivariate analysis was conducted using logistic regression. A p‐value of less than 0.05 was considered statistically significant. The prevalence of lifetime substance use was 22.8%, whilst current substance use was 18.5%. The consumption of mixed drinks was the most currently used form substance at 8.1%, followed by alcohol (5.7%) and shisha (4.7%). Multivariate analysis showed that self‐esteem (0.007), delinquency (p < 0.001) and parent alcohol use (p = 0.045) were independently associated with adolescent substance use. There is a high prevalence of substance use amongst adolescents living in peri‐urban communities in Abuja, Nigeria, as well as a new pattern of substance use consumption. The findings showed that some risk factors identified by the problem behaviour theory were independently associated with adolescent substance use, whilst the protective factors were not. There is a dire need for adolescent substance use interventions in peri‐urban communities that addresses certain risk factors. [ABSTRACT FROM AUTHOR]

Psychoactive mushrooms in the genus Psilocybe have immense cultural value and have been used for centuries in Mesoamerica. Despite the recent surge of interest in these mushrooms due to the psychotherapeutic potential of their natural alkaloid psilocybin, their phylogeny and taxonomy remain substantially incomplete. Moreover, the recent elucidation of the psilocybin biosynthetic gene cluster is known for only five of ~165 species of Psilocybe, four of which belong to only one of two major clades. We set out to improve the phylogeny of Psilocybe using shotgun sequencing of fungarium specimens, from which we obtained 71 metagenomes including from 23 types, and conducting phylogenomic analysis of 2,983 single-copy gene families to generate a fully supported phylogeny. Molecular clock analysis suggests the stem lineage of Psilocybe arose ~67 mya and diversified ~56 mya. We also show that psilocybin biosynthesis first arose in Psilocybe, with 4 to 5 possible horizontal transfers to other mushrooms between 40 and 9 mya. Moreover, predicted orthologs of the psilocybin biosynthetic genes revealed two distinct gene orders within the biosynthetic gene cluster that corresponds to a deep split within the genus, possibly a signature of two independent acquisitions of the cluster within Psilocybe. [ABSTRACT FROM AUTHOR]

Peyote (Lophophora williamsii) is a cactus that contains various biologically active alkaloids—such as pellotine, anhalonidine, hordenine and mescaline. Here, mescaline induces the psychoactive effects of peyote through the activation of the serotonin 5-HT2A receptor and the subsequent release of calcium (Ca2+) from the endoplasmic reticulum (ER). Moreover, an evaluation of the therapeutic benefits of mescaline is also currently the subject of research. It is important to consider that the outcome of taking a psychedelic drug strongly depends on the mindset of the recipient and the context (set and setting principle), including ceremonies and culture. This overview serves to summarise the current state of the knowledge of the metabolism, mechanism of action and clinical application studies of peyote and mescaline. Furthermore, the benefits of the potential of peyote and mescaline are presented in a new light, setting an example for combining a form of treatment embedded in nature and ritually enriched with our current highly innovative Western medicine. [ABSTRACT FROM AUTHOR]

BackgroundSynthetic cannabinoids are a significant public health concern, especially among incarcerated populations due to increased reports of abuse. Recent news reports have highlighted the severe consequences of K2/Spice, a synthetic cannabinoid, among the prison population in the United States. Despite regulations against cell phone use, inmates use TikTok to post K2/Spice-related content.ObjectiveThis study aimed to examine TikTok posts for use and illicit distribution of psychoactive substances (eg, K2/Spice) among incarcerated populations.MethodsThe study collected TikTok videos associated with the #k2spice hashtag and used a data collection approach similar to snowball sampling. Inductive coding was used to conduct content analysis of video characteristics. Videos were manually annotated to generate binary classifications related to the use of K2/Spice as well as selling and buying activities associated with it. Statistical analysis was used to determine associations between a video's user engagement and an intent to buy or sell K2/Spice.ResultsA total of 89 TikTok videos with the hashtag #k2spice were manually coded, with 40% (n=36) identified as displaying the use, solicitation, or adverse effects of K2/Spice among the prison population. Of them, 44.44% (n=16) were in a prison-based setting documenting adverse effects including possible overdose. Videos with higher user engagement were positively correlated with comments indicating an intent to buy or sell K2/Spice.ConclusionsK2/Spice is a drug subject to abuse among prison inmates in the United States, including depictions of its harmful effects being recorded and shared on TikTok. Lack of policy enforcement on TikTok and the need for better access to treatment services within the prison system may be exacerbating substance use among this highly vulnerable population. Minimizing the potential individual harm of this content on the incarcerated population should be a priority for social media platforms and the criminal justice system alike.

The purpose of this community service activity is to carry out mental health screening as an effort to detect mental health problems in adolescents early. The method of implementing the activities consists of 3 stages: the preparation stage, the implementation of screening with the SRQ-29 instrument (Self-Reporting Questionnaire 29), and education. One hundred seventy-six teenage students in one of the Padang City State Senior High Schools participated in this activity. Adolescents who participated consisted of grades 10, 11, and 12. The results of these activities found that more than half of adolescents (56.8%) were identified as having symptoms of neurosis (anxiety and depression), more than half of adolescents (63.6%) were identified with psychotic symptoms, most of the adolescents (77.3%) were identified PTSD symptoms, and about 0.6% of adolescents were identified as using psychoactive substances. The results illustrate that most adolescents experience mental health problems in the form of anxiety and depression, psychotic, and PTSD symptoms that require further attention and treatment. For this reason, the attention and active participation of all parties, such as the government (education office, health office, schools) and families, overcome seriously adolescent mental health problems. Improving the function of guidance and counseling services (BK) in schools is very important. Counseling and scheduled mental health education can increase adolescent awareness and understanding of mental health.

Iman Khan,1 Taimoor Asif Jaura,2 Alaa Tukruna,3 Aabiya Arif,1 Sameer Saleem Tebha,4 Sameen Nasir,5 Dattatreya Mukherjee,6 Nadia Masroor,7 Abubakr Yosufi8 1Department of Medicine, Ziauddin Medical University, Karachi, Sindh, Pakistan; 2General Adult Psychiatry, Southwest London and Saint George’s Mental Health Nhs Trust, London, UK; 3Department of Medicine, Batterjee medical college, Jeddah, Kingdom of Saudi Arabia; 4Department of Neurosurgery and Neurology, Jinnah Medical and Dental College, Karachi, Pakistan; 5Medical College, Aga Khan University Hospital, Karachi, Pakistan; 6Department of Medicine, International School, Jinan University, Jinan, People’s Republic of China; 7Department of Medicine, Liaquat University of medical and health Sciences, Jamshoro, Sindh, Pakistan; 8Medical School, Kabul University of Medical Sciences, Kabul, AfghanistanCorrespondence: Abubakr Yosufi, Kabul University of Medical Sciences, Kabul, Afghanistan, Tel +93 747236767, Email abubakr.educational@gmail.comAbstract: About 40% of the people with the obsessive-compulsive-disorder do not experience the desired outcome after the existing treatment, and its several side effects were reported. This systematic review was conducted to evaluate the efficacy and tolerability of alternative drugs and assess the possibility of their use as treatment options for obsessive-compulsive-disorder. The Scientific databases PubMed, Science Direct, Google Scholar, Cochrane, Directory of Open Access Journals, MedRxiv and BioRxiv, were searched from inception to March 2022, using appropriate search strategies for each drug and following the Prisma guidelines 2020. Studies were selected according to the already set criteria and assessed for bias. Data were extracted, and descriptive and continuous data were analyzed and presented as frequency/percentage and mean. A total of 16 observational and interventional studies were included for data extraction. The studies focused on four drugs, Psilocybin (n=4), Cannabis (n=7), Nicotine (n=3), and Morphine (n=2), that were used to test out their effect on OCD symptoms. Overall, the majority of the studies showed promising results by documenting a reduction in Y-BOCS scores. However, few subjects, specifically those using nicotine or Cannabis, did not affect their condition or self-reported worsening symptoms. Few side effects were also noticed. This systematic review found that the drugs mostly showed a positive response. All Psilocybin and morphine users, 88.2% and 74.1% of the nicotine and Cannabis users, respectively, reported experiencing the positive effect of these drugs, indicating that these drugs have the potential to be used in the management of OCD. However, further research is required in this arena to thoroughly understand the mechanism of action by which these drugs produce their therapeutic effect. Policies to destigmatize and encourage clinical trials with these drugs are crucial for exploring the use of these drugs as a treatment option for OCD.Keywords: psychedelic, psychoactive, psychoneurotic disorders, obsessions, compulsions

The aim of this study was to identify the sociodemographic factors associated with emotional distress and determine if the quality of family relationships and the perception of social isolation can protect those who transacted sex or used psychoactive substances from emotional distress during the COVID-19 pandemic. Data for 426 people who transacted sex and 630 persons who used psychoactive drugs during the COVID-19 pandemic were extracted from a database of participants recruited from 152 countries. The extracted data were the dependent (emotional distress), independent (age, sex, education status, employment status, HIV status, the perception of social isolation, and the quality of family relationships), and confounding (country income level) variables. Multivariable logistic regression analyses were conducted to determine the associations between the dependent and independent variables after adjusting for confounders. Students who transacted sex (AOR:2.800) and who used psychoactive substances (AOR:2.270) had significantly higher odds of emotional distress. Participants who transacted sex, lived with HIV (AOR:2.582), or had the same/better quality of family relationships (AOR:1.829) had significantly higher odds of emotional distress. The participants who used psychoactive substances, had tertiary education (AOR:1.979), were retired (AOR:2.772), were unemployed (AOR:2.263), or felt socially isolated (AOR:2.069) had significantly higher odds of emotional distress. Being a student was the only sociodemographic risk indicator common to both populations. The risk indicators and protective factors for emotional distress differed for both populations despite both being at high risk for emotional distress.

Copyright of Artnodes is the property of Universitat Oberta de Catalunya and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Background and aimsThe Psychoactive Surveillance Consortium and Analysis Network (PSCAN) is a national network of academic emergency departments (ED), analytical toxicologists and pharmacologists that collects clinical data paired with biological samples to identify and improve treatments of medical conditions arising from use of new psychoactive substances (NPS). The aim of this study was to gather clinical data with paired drug identification from NPS users who presented to EDs within PSCAN during its first year (2016-17).DesignObservational study involving patient records and biological samples.SettingSeven academic emergency medical centers across the United States.ParticipantsED patients (n = 127) > 8 years of age with possible NPS use who were identified and enrolled in PSCAN by clinical providers or research personnel.MeasurementsClinical signs, symptoms and treatments were abstracted from the patients' health records. Biological samples were collected from leftover urine, serum and whole blood. Biological and drug samples, when available, were tested for drugs and drug metabolites via liquid chromatography-quadrupole time-of-flight mass spectrometry (LC-QTOF/MS).FindingsPatients in whom synthetic opioids were detected (n = 9) showed higher rates of intubation (four of nine), impaired mental status (four of nine) and respiratory acidosis (five of nine) compared with the rest of the cohort (nine of 118, P-value

Introduction: The consumption of psychoactive substances has become a public health problem, having great consequences on the health, economy, academic performance, family, and social coexistence of the consumer. Objective: To determine the risk factors influencing the consumption of psychoactive substances in university students during COVID-19. Materials and Methods: Research with quantitative correlational, cross-sectional descriptive type, with a sample of 272 university students of a University of Barranquilla of the Nursing program of fourth, fifth, sixth, seventh, and eighth semesters. The instrument used was a virtual survey divided into five sections, comprising identification and sociodemographic data, individual, sociocultural, family, and psychological factors. Results: In the statistical analysis, the predominant sex was female with 69%, and 74% of them aged 17-20 years. Seventy-nine percent stated that they had consumed psychoactive substances, and 58% indicated that the type of psychoactive substance they had consumed for the first time was alcohol. Discussion: In contrast to a study conducted by Fernández et al, in 2021, it was found that the frequency of consumption of psychoactive substances in the students of the Simón Bolívar University was higher with a percentage of 74%, on the other hand the study in question only 41.8% consumed some type of psychoactive substance (alcohol, tobacco, etc.). Through the research carried out, it was possible to evaluate each of the factors that significantly influence the consumption of psychoactive substances, taking into account each of the variables evaluated (sociodemographic, consumption, individual, family, psychological, sociocultural) in times of COVID-19. [ABSTRACT FROM AUTHOR]

The aim of this study was to identify the sociodemographic factors associated with emotional distress and determine if the quality of family relationships and the perception of social isolation can protect those who transacted sex or used psychoactive substances from emotional distress during the COVID-19 pandemic. Data for 426 people who transacted sex and 630 persons who used psychoactive drugs during the COVID-19 pandemic were extracted from a database of participants recruited from 152 countries. The extracted data were the dependent (emotional distress), independent (age, sex, education status, employment status, HIV status, the perception of social isolation, and the quality of family relationships), and confounding (country income level) variables. Multivariable logistic regression analyses were conducted to determine the associations between the dependent and independent variables after adjusting for confounders. Students who transacted sex (AOR:2.800) and who used psychoactive substances (AOR:2.270) had significantly higher odds of emotional distress. Participants who transacted sex, lived with HIV (AOR:2.582), or had the same/better quality of family relationships (AOR:1.829) had significantly higher odds of emotional distress. The participants who used psychoactive substances, had tertiary education (AOR:1.979), were retired (AOR:2.772), were unemployed (AOR:2.263), or felt socially isolated (AOR:2.069) had significantly higher odds of emotional distress. Being a student was the only sociodemographic risk indicator common to both populations. The risk indicators and protective factors for emotional distress differed for both populations despite both being at high risk for emotional distress. [ABSTRACT FROM AUTHOR]

Throughout this text we will analyze some human concerns that are the subject of analysis in different fields of knowledge such as philosophy, art, science and technology. These concerns revolve around what is reality? what is fiction? what are the effects of hallucination? and what is virtuality? through different cultural products such as art, literature, cinema, psychoactive or entheogenic experiences, up to the most recent proposals of Virtual Reality and their forms of interaction. We will try to envision and propose new ways of perceiving reality, seeking a balance between the real and the virtual world. We will take a tour from the way we process reality and create fictions around it, to the illusionism that has constituted an important part of our search for consciousness, mediating between rationality and experimentation in the construction of new realities to finally make a proposal on Virtual Reality based on the therapeutic use of hallucinogens

Peyote (Lophophora williamsii) is a cactus that contains various biologically active alkaloids—such as pellotine, anhalonidine, hordenine and mescaline. Here, mescaline induces the psychoactive effects of peyote through the activation of the serotonin 5-HT2A receptor and the subsequent release of calcium (Ca2+) from the endoplasmic reticulum (ER). Moreover, an evaluation of the therapeutic benefits of mescaline is also currently the subject of research. It is important to consider that the outcome of taking a psychedelic drug strongly depends on the mindset of the recipient and the context (set and setting principle), including ceremonies and culture. This overview serves to summarise the current state of the knowledge of the metabolism, mechanism of action and clinical application studies of peyote and mescaline. Furthermore, the benefits of the potential of peyote and mescaline are presented in a new light, setting an example for combining a form of treatment embedded in nature and ritually enriched with our current highly innovative Western medicine.

Harmful usage of tobacco is a global public health problem associated with adverse health effects and addiction. Yet, in the Peruvian Amazon, the native region of Nicotiana rustica L., this plant is used in remarkably different manners: it is considered a potent medicinal plant, applied in liquid form for oral ingestion to treat mental health problems, a common and ancient healing practice in this region. Using a transdisciplinary field research approach with mixed ethnopsychological methods, this work aimed to report for the first time a case study in this context. The intervention took place in the Peruvian Amazon (Loreto) and involved ritual tobacco ingestion in a weeklong retreat-like frame, administered by a specialized traditional Amazonian healer. The patient was a 37-year-old woman with diagnosed mood, anxiety, and attention deficit disorders, as well as a chronic somatic condition. We applied qualitative experience-sampling during and quantitative symptom assessments pre- and post-treatment. Our findings offer a detailed description of the experiential therapeutic process during the treatment week and suggest clinically relevant improvements in patient well-being. This work is significant in view of the globally prevalent harmful uses of tobacco and the current scientific trend of revisiting herbal psychoactives (e.g., cannabis, psilocybin) for their therapeutic potentials. [ABSTRACT FROM AUTHOR]

Use of Psychoactive substances by young people poses an important public health threat despite mass campaigns and education. There have been documentations of rise in prevalence and use of psychoactive substances by Nigerian adolescents in urban areas of Nigeria. Few reports exist on in-school adolescents in rural areas, and differences in their sociodemographic profile such as public/private school attendance, day/boarding status and socioeconomic status of students. The study determined the rate and sociodemographic profile of psychoactive substance use among secondary school students in selected rural communities in Anambra state, Nigeria. This was a cross-sectional study in which multistage sampling was used to select 494 students from selected secondary schools in Anambra state. Data on age, gender, socioeconomic status, student status, school category, alcohol, tobacco and intravenous drug use were obtained using pretested semi-structured questionnaires. Analysis of data was done using IBM SPSS statistics software version 20.0, frequency, percentages and means were calculated, with cross-tabulation done for variables (Chi-square and Fishers exact test where applicable). Level of significance for tests of association set at 5%. A total of 494 participants were studied of which 48.8% (n=241) were males. The mean age was 14.5 ± 1.8 years. The prevalence of lifetime use of psychoactive substance was 22.5%. Prevalence for individual substances were 21.9% (n=108), 1.8% (n=9) and 0.8% (n=4) respectively for alcohol, tobacco and illicit intravenous drugs. Neither gender {6 males (2.5%), 3 females (1.2%), p=0.890}, age {10–13 years (1.3%), 14–16 years (2.1%), >16 years (1.7%), p=0.329}, student status {day (2.6%), boarding (1.2%), p=0.320}, social class {upper (0.9%), middle (0.6%), lower (3.1%), p=0.208 } nor school category {private (1.5%), public (2.1%), p=0.742} of students was significantly associated with smoking and respectively. More males (73/241=30.3%, p<0.001) took alcohol than females (35/253 = 13.8%) and this was statistically significant. Participants from the lower socioeconomic class (30.3%, p<0.001) had a significantly higher rate of alcohol consumption than those from the upper (11.8%) and middle classes (16.7%) respectively. Higher rate was noted among those who attended public schools (30.8%, p<0.001) compared to those who attended private schools (13.8%). Day students (30.2%, p<0.001) indulged more in alcohol than boarding students (14.3%). There was no association between either the class (junior=22.5%, senior=21.3%, p=0.759) or age of participants (10–13 years=20.7%, 14–16 years=20.1%, >16 years=33.3%, p=0.071) and alcohol consumption. No association was found between age (0.7%, 1.1%, p=1.000), gender (male=1.2%, female=0.4%, p=0.362), social class (lower=1.3%, upper=0.9%, p=0.443), student status (day=0.9%, boarding=0.8%, p=1.000), school category (junior=0.8%, senior=0.8%, p=1.000) and intravenous drug use. The rate of about 22% alcohol use by secondary school students in rural south eastern Nigeria, which is strongly associated with male gender, low socioeconomic status, day student status and public school attendance is high. [ABSTRACT FROM AUTHOR]

Ethnopharmacological Relevance: The use of "Mexican calea" (Calea zacatechichi Schltdl.) in ritualistic ceremonies, due to its dream-inducing effects, was until recently limited to indigenous communities in Mexico. However, the plant has recently gained popularity in Western societies being commonly used in recreational settings. Despite the traditional and recreational uses, mechanisms underlying its reported oneirogenic effects remain unknown, with no data available on its neurotoxic profile., Aim of the Study: The scarcity of toxicological data and the unknown role of major neurotransmitter systems in the dream-inducing properties of the plant prompted us to investigate which neurotransmitters might be affected upon its consumption, as well as the potential cytotoxic effects on neurons and microglial cells. Furthermore, we aimed to explore a relationship between the recorded effects and specific constituents., Materials and Methods: Effects on cholinergic and monoaminergic pathways were investigated using enzymatic assays, with the latter also being conducted in neuronal SH-SY5Y cells along with the impact on glutamate-induced excitotoxicity. Investigation of the neurotoxic profile was approached in neuronal SH-SY5Y and microglial BV-2 cells, evaluating effects on metabolic performance and membrane integrity using MTT and LDH leakage assays, respectively. Potential interference with oxidative stress was monitored by assessing free radical's levels, as well as 5-lipoxygenase mediated lipid peroxidation. Phenolic constituents were identified through HPLC-DAD-ESI(Ion Trap)MS n analysis., Results: Based on the significant inhibition upon acetylcholinesterase (p < 0.05) and tyrosinase (IC 50  = 60.87 ± 7.3 μg/mL; p < 0.05), the aqueous extract obtained from the aerial parts of C. zacatechichi interferes with the cholinergic and dopaminergic systems, but has no impact against monoamine oxidase A. Additionally, a notable cytotoxic effect was observed in SH-SY5Y and BV-2 cells at concentrations as low as 125 and 500 μg/mL (p < 0.05), respectively, LDH leakage suggesting apoptosis may occur at these concentrations, with necroptosis observed at higher ones. Despite the neurocytotoxic profile, these effects appear to be independent of radical stress, as the C. zacatechichi extract scavenged nitric oxide and superoxide radicals at concentrations as low as 62.5 μg/mL, significantly inhibiting also 5-lipoxygenase (IC 50  = 72.60 ± 7.3 μg/mL; p < 0.05). Qualitative and quantitative analysis using HPLC-DAD-ESI(Ion Trap)MS n enabled the identification of 28 constituents, with 24 of them being previously unreported in this species. These include a series of dicaffeoylquinic, caffeoylpentoside, and feruloylquinic acids, along with 8 flavonols not previously known to occur in the species, mainly 3-O-monoglycosylated derivatives of quercetin, kaempferol, and isorhamnetin., Conclusions: Our findings regarding the neuroglial toxicity elicited by C. zacatechichi emphasize the necessity for a thorough elucidation of the plant's toxicity profile. Additionally, evidence is provided that the aerial parts of the plant inhibit both acetylcholinesterase and tyrosinase, potentially linking its psychopharmacological effects to the cholinergic and dopaminergic systems, with an apparent contribution from specific phenolic constituents previously unknown to occur in the species. Collectively, our results lay the groundwork for a regulatory framework on the consumption of C. zacatechichi in recreational settings and contribute to elucidating previous contradictory findings regarding the mechanisms underlying the dream-inducing effects of the plant., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier B.V.)

Although the tobacco plant has been employed as a medicinal and sacred herb by Indigenous cultures across the Americas, its usage drastically changed after the 15th-century colonial arrival; its large-scale commodification and global marketing once brought to Europe lead to hedonic and addictive uses harmful to health. As a consequence, tobacco smoking is now one of the largest public health problems worldwide. However, in the Peruvian Amazon, a region of origin of tobacco species, Indigenous healers still know how to use the plant for therapeutic purposes. Due to a general disregard of Indigenous knowledge and stigma, these uses have however not so far been clinically investigated. We hence conducted for the first time a clinical field study assessing a sample of patients treated by a traditional healer specialized in tobacco in the Peruvian Amazon (observational design, pilot study, N = 27). The study was conducted within a transdisciplinary and multi-epistemic medical frame, in close partnership with an Amazonian healer. We used validated self-report scales to quantitatively assess mental health variables before and after the weeklong treatment, and mixed-methods to report experienced effects. Paired-samples t-tests comparing pre- and post-treatment scores revealed significant reductions in anxiety, depression, perceived stress, and general symptom indicators. Experienced effects included initial physical discomfort, followed by psychologically or existentially/spiritually significant insights. Our findings point to a sophisticated therapeutic approach based on Indigenous knowledge of tobacco applications, which should be further investigated. The study also contributes to the burgeoning scientific field on therapeutic uses of contentious psychoactive plants., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: The authors declare that there is no conflict of interest. In keeping with the transdisciplinary approach, the Indigenous healer that provided the traditional Amazonian treatment is the second author of this work; data collection and analysis were performed independently by the scientific authors.

Abstract Background Globally, there is growing concern over the impacts of pharmaceuticals and drug manufacturing on aquatic animals, and pharmaceuticals are now recognized as contaminants of emerging environmental concern. In recent years, scientists, environmental managers, and policymakers have been interested in using behavioural endpoints for chemical regulation, given their importance for fitness and survival. The body of research on whether and how pharmaceutical exposure alters the behaviour of aquatic animals has grown exponentially, making it difficult to get an overview of the results. With an international spotlight on the management of these environmental threats, synthesizing the currently available data is vital to inform managers and policymakers, as well as highlighting areas where more research is needed. This is a protocol for a systematic evidence map (SEM) and serves as an a priori record of our objectives and methodological decisions. Our objectives are to identify, catalogue, and present primary research articles on the effects of human and veterinary pharmaceuticals on aquatic animal behaviour. Methods The literature search will be conducted using two electronic databases: Web of Science and Scopus, and we will supplement these searches with additional sources. The search string has been developed using a Population–Exposure–Comparison–Outcome (PECO) framework, to capture articles that used an aquatic organism (P, population) to test the effects of a pharmaceutical (E, exposure) on behaviour (O, outcome). Eligible articles must also have a control group (C, comparison). Articles will be screened in two stages, title and abstract, followed by full-text screening before data extraction. Decision trees have been designed a priori to appraise articles for eligibility at both stages of screening. At both stages, screening each article will be completed by two independent reviewers. Study validity will be appraised but not used as a basis for article inclusion. The information extracted from the eligible articles, along with bibliometric data, will be mapped and displayed. All data associated with this SEM will be publicly available through the Open Science Framework (OSF) and a future project webpage.

The scourge of substance abuse among the youths seems to be escalating globally in recent times with the resultant increase in crimes and various antisocial behaviors that are of public health concern. Substance abuse refers to the illicit use of drugs, alcohol and tobacco with no recourse to medical prescription. However, the fact remains that substances commonly abused are generally mind altering. This study therefore investigated psycho-social determinants of substance abuse among adolescents in order to reduce the burden of psychoactive drugs in Nigeria. A descriptive research design was adopted for the study. A total sample of 500 participants between ages 14-18 years were selected through multistage sampling technique. A self-designed questionnaire was used to collect data and the data collected was analyzed using descriptive and inferential statistics. The hypotheses postulated were tested at 0.5 level of significance. The result revealed that there was significant relationship between psycho-social factors and substance abuse among adolescents. The findings also revealed that out of the three psychosocial variables reviewed (poor parenting, poor academic performance and negative peer influence), poor parenting is the best predictor of substance abuse among secondary school adolescents. It was recommended that parents should be proactive in close supervision and use of appropriate anti-drug communication strategies to prevent the onset of substance abuse among adolescents. [ABSTRACT FROM AUTHOR]

Despite the recent promising results of MDMA (3,4-methylenedioxy-methamphetamine) as a psychotherapeutic agent and its history of misuse, little is known about its molecular mode of action. MDMA enhances monoaminergic neurotransmission in the brain and its valuable psychoactive effects are associated to a dual action on the 5-HT transporter (SERT). This drug inhibits the reuptake of 5-HT (serotonin) and reverses its flow, acting as a substrate for the SERT, which possesses a central binding site (S1) for antidepressants as well as an allosteric (S2) one. Previously, we characterized the spatial binding requirements for MDMA at S1. Here, we propose a structure-based mechanistic model of MDMA occupation and translocation across both binding sites, applying ensemble binding space analyses, electrostatic complementarity, and Monte Carlo energy perturbation theory. Computed results were correlated with experimental data (r = 0.93 and 0.86 for S1 and S2, respectively). Simulations on all hSERT available structures with Gibbs free energy estimations (ΔG) revealed a favourable and pervasive dual binding mode for MDMA at S2, i.e., adopting either a 5-HT or an escitalopram-like orientation. Intermediate ligand conformations were identified within the allosteric site and between the two sites, outlining an internalization pathway for MDMA. Among the strongest and more frequent interactions were salt bridges with Glu494 and Asp328, a H-bond with Thr497, a π-π with Phe556, and a cation-π with Arg104. Similitudes and differences with the allosteric binding of 5-HT and antidepressants suggest that MDMA may have a distinctive chemotype. Thus, our models may provide a framework for future virtual screening studies and pharmaceutical design and to develop hSERT allosteric compounds with a unique psychoactive MDMA-like profile. [ABSTRACT FROM AUTHOR]

Herbal drugs of abuse are being practiced for ages. Old-fashioned addictive substances, such as opium, and cannabis are mainly imitated or altered from the ingredients likely based on crude drugs. Cannabinoids and cathinone are derived from natural derivatives. Safety and efficacy altogether is a matter of concern that needs to be discussed and awareness related to that must be spread. In this review, we briefly, discuss some plants such as khat, kratom, salvia, and mandrake, with the perception that experts and common people alike are aware of the possible glitches caused by regular and synthetic derivatives, and appropriate resistor procedures will be taken. Some "herbal plants" should be termed as injurious drugs since chronic management has been connected with addiction and cognitive deficiency, and findings inspecting these features are deficient. This paper discusses toxicity issues and main safety concerns regarding plant-derived products. Safety persists as the major concern with the use of herbal remedies, it becomes imperious, to ensure that all herbal constituents are safe and reliable. [ABSTRACT FROM AUTHOR]

Recreational use of piperazine designer drugs is a serious threat to human health. These compounds act on the body in a similar fashion to illegal drugs. They induce psychostimulatory effects as well as visual and auditory hallucinations to varying degrees. In many cases of poisoning and deaths, the presence of two or even several psychoactive substances have been demonstrated. Piperazine derivatives are often found in such mixtures and pose a great analytical problem during their identification. Additionally, some piperazine derivatives can be detected in biological material as a result of metabolic changes to related drugs. Therefore, it is necessary to correctly identify these compounds and ensure repeatability of determinations. This article presents a comparison of the methods used to detect abused piperazine designer drugs using liquid chromatography in combination with a diode-array detector (LC-DAD) or mass spectrometer (LC-MS). Each of methods can be used independently for determinations, obtaining reliable results in a short time of analysis. These methods can also complement each other, providing qualitative and quantitative confirmation of results. The proposed methods provide analytical confirmation of poisoning and may be helpful in toxicological diagnostics. [ABSTRACT FROM AUTHOR]

Introduction: Current methods to detect recent delta-9-tetrahydrocannabinol (THC) use cannot objectively quantify its psychoactive effects (PE). The Cognalyzer®, an electroencephalography (EEG)-based method, detects and quantifies the strength of THC-induced PE on a scale from 0 to 100%. This study assesses the relationship between the magnitude of Cognalyzer® PE predictions and reported subjective drug effects for 4-h post-cannabis inhalation. Methods: Seventy-five participants were enrolled in the study. Prior to ad libitum cannabis inhalation, an EEG recording episode was completed. Immediately after inhalation, the Drug Effects Questionnaire (DEQ) was administered and another EEG recording performed. For 25 participants, the study ended. For 50 participants, assessments were repeated at 30-min intervals for 4 h. EEG files were blinded and analyzed using two versions of the Cognalyzer® algorithm. The relationship between the Cognalyzer® PE level results and the DEQ was assessed using generalized linear models and multiple regression. Results: There were significant PE increases from pre-cannabis for up to 3.5 h. Mean reports of feeling drug effects were > 0 at all post-inhalation time points (p ≤ 0.024). Furthermore, there were significant relationships between the Cognalyzer® PE and self-reported perception of drug effects (p ≤ 0.001). Subgroup analysis showed that Cognalyzer® PE levels were impacted by cannabis use history, subjective ratings of drug effects, oral fluid THC concentration and the cannabis product inhaled. Conclusion: The findings show that the Cognalyzer® can be used to objectively determine the strength of cannabis psychoactive effects that cannabis products create on consumers and how it changes depending on their experience with cannabis. The Cognalyzer® can be used to conduct scientific consumer research to generate trustworthy informational material about the psychoactive experience of cannabis products. For clinical research, the Cognalyzer® can be used to study the pharmacodynamics of cannabinoids or delivery systems, such as nano-emulsifications. [ABSTRACT FROM AUTHOR]

Substance Abuse among youths is a major public health challenge globally. Complications associated with drug abuse include psychiatric disorders, sexual violence, drug dependence and criminal tendencies. The study set out to determine the prevalence and sociodemographic characteristics associated with Substance abuse among the young in Edo State, Nigeria. A descriptive cross-sectional study design and multi-stage sampling technique was used with a structured interviewer administered questionnaire among 412 study respondents who gave informed consent. All relevant data such as socio-demographic information, substance abuse was collected and analyzed using SPSS 23. The mean age (SD) of the study subjects was 19.03(3.09) years. The age group with the highest use of drugs was 19-22 years. Among drug abusers, male subjects (10.8%) had a higher rate of substance use compared to females (6.2%). In all, 29(8.3%) of the respondents satisfied the criteria for defining substance abuse. Cannabis was the most named substance abused accounting for 86 (20.9%) followed by alcohol and tramadol respectively (19.7% and 11.2%). Alcohol was the most commonly abused substance accounting for 17(58.6%). This was closely followed by Tramadol 41.4%. 52.4% of the respondents had no knowledge about the definition of substance abuse. About 32.3% of the subjects got information about Substance abuse from friends. The commonest reason for illegal drug use was peer influence which accounted for 50% of the respondents. Majority of the substance abusers (62.5%) who continued to abuse drugs did so because of the euphoric feeling they got from its use. Alcohol is still the most commonly abused substance among young persons in our environment as shown in this study and all effort be made the relevance authorities to control the illicit use of this substance in our society. [ABSTRACT FROM AUTHOR]

Background: The stimulant, empathogenic, euphoric, and hallucinogenic properties of 3,4-methylenedioxymethamphetamine (MDMA), also known as 'Ecstasy,' make it a popular drug among teenagers. These effects are thought to be caused by significant increases in dopamine, serotonin, and glutamate neurotransmission. However, little is known about Garcinia kola extract's (GKE) neuroprotective activities against MDMA-induced neurotoxicity. Thus, the purpose of this study was to investigate GKE's neuroprotective activities against MDMA-induced neurotoxicity in rat models. Method: Sixty (60) healthy adult male Wistar rats (120–150 g) were randomly divided into six ten-animal groups (A, B, C, D, E, and F). Group A served as the control, while groups B and C were given 100 mg/kg and 200 mg/kg (low and high) daily doses of GKE for 21 days, respectively. Group D was given a 20 mg/kg intermittent dose of MDMA, while groups E and F were given 100 mg/kg and 200 mg/kg (low and high) daily doses of GKE along with 20 mg/kg intermittent doses of MDMA for 21 days. 24 h after the last administration, the rats were sacrificed. Five rats from each group were anesthetized with a diether and perfused intracardially, after which the brains were excised and fixed in 10% neutral buffered formalin for histology and immunohistochemistry. Graph Pad Prism5 was used for the statistical analysis, which included one-way analysis of variance (ANOVA). The number of lines crossed increased significantly in MDMA-treated rats, as did the frequency of rearing and the number of lines crossed. The increase in grooming frequency observed in conjunction with a slight decrease in the number of center square entries and defecation was not statistically significant. Interestingly, dopamine, serotonin, and glutamate levels were slightly elevated in MDMA-induced psychostimulant animals, correlating with anxiolytic (animal anxiety reduction) activity. Similarly, an increase in the expression of G6PDH and Cytochrome c-oxidase was observed, indicating that MDMA has the ability to upregulate mitochondrial metabolism, which accounts for the release of more energy. As a result of MDMA treatment, histological and GFAP results revealed neuronal degeneration and astrogliosis/glia scar formation, respectively. Conclusion: This finding demonstrates MDMA's neurotoxic damage to neurons in the prefrontal cortex, its ability to cause behavioural deficits, and how GKE administration was able to slow down MDMA's neurotoxic damage and behavioural deficits.

Cannabis sativa , widely known as 'Marijuana' poses a dilemma for being a blend of both good and bad medicinal effects. The historical use of Cannabis for both medicinal and recreational purposes suggests it to be a friendly plant. However, whether the misuse of Cannabis and the cannabinoids derived from it can hamper normal body physiology is a focus of ongoing research. On the one hand, there is enough evidence to suggest that misuse of marijuana can cause deleterious effects on various organs like the lungs, immune system, cardiovascular system, etc. and also influence fertility and cause teratogenic effects. However, on the other hand, marijuana has been found to offer a magical cure for anorexia, chronic pain, muscle spasticity, nausea, and disturbed sleep. Indeed, most recently, the United Nations has given its verdict in favour of Cannabis declaring it as a non-dangerous narcotic. This review provides insights into the various health effects of Cannabis and its specialized metabolites and indicates how wise steps can be taken to promote good use and prevent misuse of the metabolites derived from this plant. [ABSTRACT FROM AUTHOR]

5-Methoxy-N,N-Dimethyltryptamine (5-MeO-DMT) is a tryptamine with ultra-rapid onset and short duration of psychedelic effects. Prospective studies for other tryptamines have suggested beneficial effects on mental health outcomes. In preparation for a study in patients with depression, the present study GH001-HV-101 aimed to assess the impact of four different dose levels of a novel vaporized 5-MeO-DMT formulation (GH001) administered via inhalation as single doses of 2 (N = 4), 6 (N = 6), 12 (N = 4) and 18 mg (N = 4), and in an individualized dose escalation regimen (N = 4) on the safety, tolerability, and the dose-related psychoactive effects in healthy volunteers (n = 22). The psychedelic experience was assessed with a novel Peak Experience Scale (PES), the Mystical Experience Questionnaire (MEQ), the Ego Dissolution Inventory (EDI), the Challenging Experience Questionnaire (CEQ), and the 5-Dimensional Altered States of Consciousness Questionnaire (5D-ASC). Further aims were to assess the impact of 5-MeO-DMT on cognitive functioning, mood, and well-being. Higher doses of 5-MeO-DMT produced significant increments in the intensity of the psychedelic experience ratings as compared to the lowest 2 mg dose on all questionnaires, except the CEQ. Prominent effects were observed following single doses of 6, 12, and 18 mg on PES and MEQ ratings, while maximal effects on PES, MEQ, EDI, and 5D-ASC ratings were observed following individualized dose escalation of 5-MeO-DMT. Measures of cognition, mood, and well-being were not affected by 5-MeO-DMT. Vital signs at 1 and 3 h after administration were not affected and adverse events were generally mild and resolved spontaneously. Individualized dose escalation of 5-MeO-DMT may be preferable over single dose administration for clinical applications that aim to maximize the experience to elicit a strong therapeutic response. [ABSTRACT FROM AUTHOR]

5-Methoxy-N,N-Dimethyltryptamine (5-MeO-DMT) is a tryptamine with ultra-rapid onset and short duration of psychedelic effects. Prospective studies for other tryptamines have suggested beneficial effects on mental health outcomes. In preparation for a study in patients with depression, the present study GH001-HV-101 aimed to assess the impact of four different dose levels of a novel vaporized 5-MeO-DMT formulation (GH001) administered via inhalation as single doses of 2 (N = 4), 6 (N = 6), 12 (N = 4) and 18 mg (N = 4), and in an individualized dose escalation regimen (N = 4) on the safety, tolerability, and the dose-related psychoactive effects in healthy volunteers (N = 22). The psychedelic experience was assessed with a novel Peak Experience Scale (PES), the Mystical Experience Questionnaire (MEQ), the Ego Dissolution Inventory (EDI), the Challenging Experience Questionnaire (CEQ), and the 5-Dimensional Altered States of Consciousness Questionnaire (5D-ASC). Further aims were to assess the impact of 5-MeO-DMT on cognitive functioning, mood, and well-being. Higher doses of 5-MeO-DMT produced significant increments in the intensity of the psychedelic experience ratings as compared to the lowest 2 mg dose on all questionnaires, except the CEQ. Prominent effects were observed following single doses of 6, 12, and 18 mg on PES and MEQ ratings, while maximal effects on PES, MEQ, EDI, and 5D-ASC ratings were observed following individualized dose escalation of 5-MeO-DMT. Measures of cognition, mood, and well-being were not affected by 5-MeO-DMT. Vital signs at 1 and 3 h after administration were not affected and adverse events were generally mild and resolved spontaneously. Individualized dose escalation of 5-MeO-DMT may be preferable over single dose administration for clinical applications that aim to maximize the experience to elicit a strong therapeutic response.

Background: Globally, there is growing concern over the impacts of pharmaceuticals and drug manufacturing on aquatic animals, and pharmaceuticals are now recognized as contaminants of emerging environmental concern. In recent years, scientists, environmental managers, and policymakers have been interested in using behavioural endpoints for chemical regulation, given their importance for fitness and survival. The body of research on whether and how pharmaceutical exposure alters the behaviour of aquatic animals has grown exponentially, making it difficult to get an overview of the results. With an international spotlight on the management of these environmental threats, synthesizing the currently available data is vital to inform managers and policymakers, as well as highlighting areas where more research is needed. This is a protocol for a systematic evidence map (SEM) and serves as an a priori record of our objectives and methodological decisions. Our objectives are to identify, catalogue, and present primary research articles on the effects of human and veterinary pharmaceuticals on aquatic animal behaviour. Methods: The literature search will be conducted using two electronic databases: Web of Science and Scopus, and we will supplement these searches with additional sources. The search string has been developed using a Population–Exposure–Comparison–Outcome (PECO) framework, to capture articles that used an aquatic organism (P, population) to test the effects of a pharmaceutical (E, exposure) on behaviour (O, outcome). Eligible articles must also have a control group (C, comparison). Articles will be screened in two stages, title and abstract, followed by full-text screening before data extraction. Decision trees have been designed a priori to appraise articles for eligibility at both stages of screening. At both stages, screening each article will be completed by two independent reviewers. Study validity will be appraised but not used as a basis for article inclusion. The information extracted from the eligible articles, along with bibliometric data, will be mapped and displayed. All data associated with this SEM will be publicly available through the Open Science Framework (OSF) and a future project webpage. [ABSTRACT FROM AUTHOR]

The popular recreational drug MDMA (3,4-methylenedioxy-methamphetamine) has a documented potential as a psychopharmacological clinical and research tool. This is due to its unique ability to promote reprocessing of traumatic memories, empathetic and pro-social states. Although it is established that MDMA exerts its behavioural effects via the serotonin transporter (SERT), the ligand-protein molecular interplay remains elusive. In order to shed light on the binding of MDMA and its primary congeneric entactogens (MDA, MBDB and MDAI), we first combined induced fit with Monte Carlo simulations. The computed interaction energies of the models correlated well with experimental activities (adjR2 = 0.78). Then we carried out ‘ensemble binding space docking’ on trajectories generated by interpolation of experimentally derived structures of the hSERT from the outward-open, and the occluded, to the inward-open states. This approach revealed low-energy alternative binding modes, suggesting high occupancy of the central site, yet considerable MDMA mobility within it, favouring the paroxetine-like orientation. Finally, we designed a pharmacophore that may be used to recognise hSERT-mediated serotonin releasers and uptake inhibitors of diverse chemical structure, identifying their active conformations and interacting residues. We conclude that the conserved amine-Asp98 ionic and edge-to-face π-π interactions are crucial to the mode of action of MDMA on the hSERT, underscoring the contributions of Tyr95 and gating residues Phe341, Tyr176 and Phe335. Amenable to experimental testing, our modelling may aid the rational design of novel entactogenic compounds and contribute to the understanding of an action mechanism, common and typical of psychotropic agents.

Background: Rural areas have increased injury mortality with a high pre-hospital death rate. Knowledge concerning the impact of psychoactive substances on injury occurrence is lacking for rural arctic Norway. These substances are also known to increase pre-, per- and postoperative risk. The aim was by prospective observational design to investigate the prevalence and characteristics of psychoactive substance use among injured patients in Finnmark county.Methods: From January 2015 to August 2016, patients ≥18 years admitted to hospitals in Finnmark due to injury were approached when competent. Blood was analysed for ethanol, sedatives, opioids, hypnotics and illicit substances in consenting patients, who completed a questionnaire gathering demographic factors, self-reported use/behaviour and incident circumstances.Results: In 684 injured patients who consented to participation (81% consented), psychoactive substances were detected in 35.7%, alcohol being the most prevalent (23%). Patients in whom substances were detected were more often involved in violent incidents (odds ratio 8.92 95% confidence interval 3.24-24.61), indicated harmful use of alcohol (odds ratio 3.56, 95% confidence interval 2.34-5.43), reported the incident being a fall (odds ratio 2.21, 95% confidence interval 1.47-3.33) and presented with a reduced level of consciousness (odds ratio 3.91, 95% confidence interval 1.58-9.67). Subgroup analysis revealed significant associations between testing positive for a psychoactive substance and being diagnosed with a head injury or traumatic brain injury.Conclusion: A significant proportion of injured patients had used psychoactive substances prior to admission. Use was associated with violence, falls, at-risk alcohol consumption, decreased level of consciousness on admittance and head injury. [ABSTRACT FROM AUTHOR]

Objective: Driver monitoring systems (DMS) are the next generation of vehicle safety technology. Broadly, these refer to the embedded, aftermarket wearable or vehicle-mounted devices that collect observable information about the operator to make real-time assessment of their capacity to perform the driving task. Integrating biobehavioral monitoring (primarily ocular metrics) with driving performance assessments, these systems function to infer driver state in real time to identify operator conditions that negatively affect driving (such as fatigue, inattention, or distraction).Method: We review available methods used to infer driver state, as referenced against accepted models for optimal performance. Modeling our observations on deviation from predetermined performance thresholds used to trigger graded safety alerts, we suggest that many psychoactive substances produce alterations to biobehavioral processes including attentional and motor control, which affect performance indices in a manner already arguably captured by these technologies.Results: Using these existing frameworks, there is considerable potential to similarly catalogue the effect of many common intoxicants known to negatively affect driving ability. This will provide safety-relevant and practical biological models for the development of next-generation multimodal DMS that integrate ocular and physiological variables sensitive to the effects of common and emergent psychoactive substances.Conclusion: These devices have tangible potential application across all areas of transportation, including aviation, rail, and all commercial and private vehicle systems. [ABSTRACT FROM AUTHOR]

The consumption of energy drinks poses significant risks to minors' health, and strict regulations are urgently needed to protect them. The high caffeine, high sugar, and high caloric content of energy drinks have drawn concern from health professionals. The consumption of energy drinks has been linked to unhealthy dietary behaviors, obesity, and mental health problems in adolescents. The psychoactive and stimulant effects of energy drinks are particularly worrisome, and the marketing of these drinks on social media platforms is also a cause for alarm. In light of these concerns, we strongly recommend policy measures, such as restrictions on the sale of energy drinks to minors, to prevent their health risks. The evidence clearly suggests that energy drinks pose significant risks to minors' health and well-being, and regulatory standards must be implemented without further delay. • Energy drinks have become popular among children and adolescents. • The high caffeine, sugar, and caloric content of many energy drinks have drawn concern from health professionals. • The United States urgently needs to adopt policies to reduce energy drink consumption by adolescents. [ABSTRACT FROM AUTHOR]

Despite the recent promising results of MDMA (3,4-methylenedioxy-methamphetamine) as a psychotherapeutic agent and its history of misuse, little is known about its molecular mode of action. MDMA enhances monoaminergic neurotransmission in the brain and its valuable psychoactive effects are associated to a dual action on the 5-HT transporter (SERT). This drug inhibits the reuptake of 5-HT (serotonin) and reverses its flow, acting as a substrate for the SERT, which possesses a central binding site (S1) for antidepressants as well as an allosteric (S2) one. Previously, we characterized the spatial binding requirements for MDMA at S1. Here, we propose a structure-based mechanistic model of MDMA occupation and translocation across both binding sites, applying ensemble binding space analyses, electrostatic complementarity, and Monte Carlo energy perturbation theory. Computed results were correlated with experimental data (r = 0.93 and 0.86 for S1 and S2, respectively). Simulations on all hSERT available structures with Gibbs free energy estimations (ΔG) revealed a favourable and pervasive dual binding mode for MDMA at S2, i.e., adopting either a 5-HT or an escitalopram-like orientation. Intermediate ligand conformations were identified within the allosteric site and between the two sites, outlining an internalization pathway for MDMA. Among the strongest and more frequent interactions were salt bridges with Glu494 and Asp328, a H-bond with Thr497, a π-π with Phe556, and a cation-π with Arg104. Similitudes and differences with the allosteric binding of 5-HT and antidepressants suggest that MDMA may have a distinctive chemotype. Thus, our models may provide a framework for future virtual screening studies and pharmaceutical design and to develop hSERT allosteric compounds with a unique psychoactive MDMA-like profile.

IntroductionHarmful usage of tobacco is a public health problem of global concern and, in many countries, the main risk factor for non-communicable diseases. Yet, in the Peruvian Amazon, the geographical region believed to be tobacco’s historical birthplace, this plant is associated with a strikingly different usage and repute: Tobacco (especially Nicotiana rustica L.) in this area is described as a potent medicinal plant, used topically or via ingestion to treat a variety of health conditions. The goal of this transdisciplinary field study was to investigate clinical applications of the tobacco plant as per Amazonian medicine exemplified in the practice of a reputed Maestro Tabaquero, an Amazonian traditional healer whose medical specialization focuses on tobacco-based treatments.MethodsUsing a transdisciplinary clinical approach, we conducted in-depth interviews with the tabaquero applying the systematizing expert interview method, in order to map modes of preparation and administration, indications, contraindications, effects, risks, adverse effects, and systemic aspects of tobacco-based remedies.ResultsThe informant’s descriptions revealed refined knowledge on this plant’s therapeutic properties and scope, safety profile, and application techniques. The main indications mentioned included “problems of the mind,” of the respiratory system, parasitic illnesses (intestinal/skin), gout, and Amazonian epistemic conditions described as spiritual-energetic in nature. A liquid remedy taken orally was his most commonly used preparation, with acute/sub-acute effects involving a pronounced psychoactive component (altered state of consciousness) and physiological response (emesis, nausea). A skilled tabaquero that knows how to dose, administer, and intervene in case of adverse effects was considered imperative for safe treatment delivery.ConclusionsTo our knowledge, this is the first study employing a transdisciplinary clinical approach to examine therapeutic applications of tobacco by an Amazonian tabaquero. Our findings significantly contribute to the growing research literature on Amazonian medicine and emergent psychedelic-assisted therapies and could, in the long-term, open new treatment avenues in several domains. Forthcoming studies should assess toxicity/safety and clinical outcomes of patients receiving Amazonian tobacco-based treatment.

Sildenafil is a widely used drug for the treatment of erectile dysfunction in a dosage ranging from 50 to 100 mg per day. Recreational use is reported among youth for its sexual function enhancing effects. To date, however, no study has reported the use of sildenafil for its nonsexual, psychoactive effects. We report a case of a 38-year-old male with opioid and sedative use disorder who self-administered sildenafil orally in a dose of up to 2000 mg per day for its psychoactive effects (primarily) for 10 years before seeking treatment and discuss the literature relevant to the case. [ABSTRACT FROM AUTHOR]

Introduction: Harmful usage of tobacco is a public health problem of global concern and, in many countries, the main risk factor for non-communicable diseases. Yet, in the Peruvian Amazon, the geographical region believed to be tobacco's historical birthplace, this plant is associated with a strikingly different usage and repute: Tobacco (especially Nicotiana rustica L.) in this area is described as a potent medicinal plant, used topically or via ingestion to treat a variety of health conditions. The goal of this transdisciplinary field study was to investigate clinical applications of the tobacco plant as per Amazonian medicine exemplified in the practice of a reputed Maestro Tabaquero , an Amazonian traditional healer whose medical specialization focuses on tobacco-based treatments. Methods: Using a transdisciplinary clinical approach, we conducted in-depth interviews with the tabaquero applying the systematizing expert interview method, in order to map modes of preparation and administration, indications, contraindications, effects, risks, adverse effects, and systemic aspects of tobacco-based remedies. Results: The informant's descriptions revealed refined knowledge on this plant's therapeutic properties and scope, safety profile, and application techniques. The main indications mentioned included "problems of the mind," of the respiratory system, parasitic illnesses (intestinal/skin), gout, and Amazonian epistemic conditions described as spiritual-energetic in nature. A liquid remedy taken orally was his most commonly used preparation, with acute/sub-acute effects involving a pronounced psychoactive component (altered state of consciousness) and physiological response (emesis, nausea). A skilled tabaquero that knows how to dose, administer, and intervene in case of adverse effects was considered imperative for safe treatment delivery. Conclusions: To our knowledge, this is the first study employing a transdisciplinary clinical approach to examine therapeutic applications of tobacco by an Amazonian tabaquero. Our findings significantly contribute to the growing research literature on Amazonian medicine and emergent psychedelic-assisted therapies and could, in the long-term, open new treatment avenues in several domains. Forthcoming studies should assess toxicity/safety and clinical outcomes of patients receiving Amazonian tobacco-based treatment. [ABSTRACT FROM AUTHOR]

In recent years, the use of natural psychoactive drugs (NPDs) has grown rapidly. They are classified as new psychoactive substances (NPSs), despite the reality that they have been used for centuries. We are lacking information regarding patterns of use or characteristics of users, but some evidence suggests that NPDs substantially differ from NPSs in terms of both their safety profile and patterns of use. The aim of this study was to investigate patterns of use and user characteristics by collecting data from a sample of NPD users. We designed an online questionnaire that was shared through social media. A sample of 564 NPD users was recruited from 52 different countries, with the United States being the most common (19%), followed by Spain (14.9%). The typical user in our sample is a well-educated adult individual who uses NPDs sporadically. The most used substances were Psilocybe mushrooms (88.5%) and ayahuasca (51%). Users reported that the use of NPDs positively influenced their lives, and they showed a good mental health status. Stakeholders should consider these results particularly when deciding on legal classifications for these substances, as the study findings suggest that NPDs should not be in the same class as NPSs. [ABSTRACT FROM AUTHOR]

Psychoactive alcoholic herbal mixture is popularly consumed because of the belief on its stimulant and curative effects. This study investigated the neurobehavioral, biochemical and histopathological consequences following its single and repeated co-administration with ethanol to mice. Mice were assessed for sensorimotor, anxiety and memory functions following acute and repeated administration of alcohol herbal mixture (AHM). Alterations in brain acetylcholineterase, nitrite, reduced glutathione (GSH) and malondialdehyde levels were assessed in striatum, prefrontal cortex (PFC) and hippocampus. Neuronal cells counts were determined in the prefrontal cortex and hippocampal tissues. In the acute study, AHM significantly impaired locomotor activity and motor coordination in mice. Repeated administration of AHM and AHM combined with ethanol caused significant impairment of locomotor and motor coordination, increased anxiety-like behavior and impaired memory in mice. Acetylcholinesterase activity was significantly increased in the PFC while nitrite level was elevated in the striatum and PFC. There was significant elevation of malondialdehyde and depletion of GSH in all brain regions as well as reduced neuronal cell counts in the PFC and hippocampus. This study showed evidences of behavioral perturbation and brain biochemical changes in mice, hence repeated consumption of alcoholic herbal mixture might produce substance-attributable harm and quicken neurodegenerative diseases in humans. [ABSTRACT FROM AUTHOR]

Synthetic cathinones are new designer drugs that possess hallucinogenic and psychostimulant properties, and are designed to mimic the effects of illegal substances such as cocaine, amphetamines, and 3.4-methylenedioxymethamphetamine (ecstasy) and to produce rewarding effects, circumventing existing laws and penalties. Synthetic cathinones, also referred to as 'bath salts', have become popular particularly among young people since the mid-2000s. Similar to other psychomotor stimulants, synthetic cathinones have the potential to increase monoamine concentration in the synaptic cleft by targeting the plasma membrane transporters of dopamine, norepinephrine, and serotonin. Because of their structural similarities to amphetamines, it has been suggested that synthetic cathinones may have a neurotoxicity profile similar to that of their amphetamine congeners. Therefore, it has been hypothesized that synthetic cathinones may induce neurotoxicity on monoamine nerve endings in the striatum, hippocampus, and cortex. To date, with regard to synthetic cathinone neurotoxicity, parameters such as monoamine depletion, biosynthetic enzyme inhibition, cytotoxicity, generation of reactive oxygen species, pro-oxidation status, and the ability to induce neuroinflammation were investigated in both in vitro and in vivo experimental studies. Compared with amphetamines, synthetic cathinones appear to have more moderate effects than their amphetamine congeners in terms of neurotoxic effects. However, many synthetic cathinone users take these substances simultaneously with other substances such as benzodiazepines, amphetamines, ecstasy, tetrahydrocannabinol, and ethanol and this abuse can modify their neurotoxic effects. Hence, it is important to understand the underlying mechanism of early neurotoxic effects in case of polysubstance use. In this review, we aimed to present up-to-date information on the abuse potential of synthetic cathinones, their legal status, mechanism of action, and particularly their neurotoxic effects. [ABSTRACT FROM AUTHOR]

Copyright of Dilemas Contemporáneos: Educación, Política y Valores is the property of Dilemas Contemporaneos: Educacion, Politica y Valores and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)