Illicit Psychoactive Substances Research Articles

Role of MARK4 in methamphetamine-induced acute kidney injury.

Methamphetamine (METH) is an illicit psychoactive substance that can damage various organs, with the urinary system being one of its significant targets. This study aims to explore the role of microtubule affinity-regulating kinase 4 (MARK4) in METH-induced acute kidney injury (AKI). A total of 10 healthy adult male C57BL/6 mice were randomly divided into a control group and a METH group, 5 mice in each group. The METH group was administered METH (20 mg/kg, intraperitoneally, once daily for 3 consecutive days), while the control group received an equal volume of physiological saline. The mice were executed 24 hours after the final injection, and the success of the AKI model was detected by blood serum creatinine, blood urea nitrogen, and renal HE staining. Proteins differentially expressed between kidney tissues with METH-induced AKI and normal kidney tissues were screened by proteomics techniques and subjected to gene ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) and bioinformatics analysis. The accuracy of proteomic data was validated using Western blotting, and the expression levels of MARK4 and cleaved caspase-3 in mouse kidneys were measured. We further explored the role of MARK4 in METH-induced AKI. Firstly, a METH toxicity model was established in BUMPT cells to screen the appropriate concentration and time of METH treatment; the viability of BUMPT cells after METH treatment and the expression of cleaved caspase-3 were detected by interfering with MARK4 expression through inhibitors. The proteomic analysis of kidney tissues from METH and control groups screened for a total of 17 differentially expressed proteins, of which 11 were up-regulated and 6 were down-regulated (all P<0.05). The expression levels of MARK4 and cleaved caspase-3 were elevated in the kidneys of METH-treated mice (both P<0.05). The activity of BUMPT cells gradually decreased with increasing METH treatment concentration (all P<0.05), where the viability of BUMPT cells decreased to about 60% after METH treatment at 4 mmol/L. Compared with the control group, expression levels of MARK4 and cleaved caspase-3 were increased with higher METH concentrations and longer exposure times in a concentration- and time-dependent manner (all P<0.05). Inhibition of MARK4 expression improved METH-induced decrease in BUMPT cell activity, down-regulated the expression of cleaved caspase-3, and decreased the apoptosis of BUMPT cells induced by METH. MARK4 is highly expressed in a mouse model of METH-induced AKI, and MARK4 mediates METH-induced AKI by regulating cell apoptosis.

Trends in the nonmedical misuse of benzodiazepines and Z-hypnotics among school-aged adolescents (2016-2021): gender differences and related factors.

The misuse of psychotropic medication has increased during the past decade, especially among adolescents. The aim of our study was to describe the prevalence and patterns of the nonmedical use of benzodiazepines (BDZ) and Z-hypnotics among school-aged adolescents through the lens of sex. In addition, we sought to analyze the temporal evolution of the nonmedical use of these drugs during the period 2016-2021. The temporal evolution of the nonmedical use of these drugs was analyzed based on survey data collected in 2016, 2018 and 2021, which includes the first years of the COVID-19 pandemic. To assess the possible effect of the COVID-19 pandemic, the year at survey was conducted was introduced as a categorical variable. We used data from the Spanish State Survey on Drug Use in Secondary Education, which covers drug use among students aged 14-18 years. Using multivariate logistic regression models, we estimated the independent effect of different variables (sociodemographic data, use of other psychoactive substances, risk perception and availability) on the nonmedical use of BDZ and Z-hypnotics. In total, survey data from 95,700 adolescents were included in our analysis. The nonmedical use of BDZ and Z-hypnotics increased among adolescents during the study period. The adjusted odds ratio (AOR) from 2016 to 2018 was 1.11 (95% CI 0.94-1.31) and from 2018 to 2021 the AOR was 1.26 (95% CI 1.08-1.46), using 2016 and 2018, respectively, as reference years. The nonmedical use of BDZ and Z-hypnotics was more likely in adolescent girls than boys (AOR = 2.11). The nonmedical use of prescription opioids (AOR = 3.44), novel psychoactive substances and other illicit psychoactive drugs (AOR = 4.10) were risk factors for the nonmedical use of BDZ and Z-hypnotics in both sexes. Use of cannabis (AOR = 1.38) was a predictor of nonmedical use in female adolescents only. This study shows that the trend of the nonmedical use of BDZ and Z-hypnotics among school-aged adolescents in Spain increased between 2016 and 2021. Among adolescents aged 14 to 18, the probability of nonmedical use of these psychoactive substances was twice as high for female adolescents as for male adolescents.

Suicidal thoughts and behaviors among untreated illicit substance users: a population-based study.

Research regarding the contribution of specific psychoactive substances to suicidality has yielded equivocal results. The present study examined the prevalence and factors associated with suicidal thoughts and behaviors among a population-based sample of untreated illicit substance users. A total of 616 illicit substance users who were recruited from high-risk areas of Shiraz using snowball sampling participated in the study. Eligible participants were individuals aged 18 years and older who regularly used one illicit psychoactive substance (e.g., opioids, heroin, cannabinoids, stimulants, hallucinogens) for at least one year and who had received no treatment for their drug use during the past year. Data were collected regarding socio-demographic characteristics, mental history, and substance use habits. Data regarding suicidal thoughts and behaviors were assessed using the Beck Suicidal Ideation Scale (BSIS) and self-reports of previous suicide attempts. Multiple logistic regression analysis was used to identify independent variables associated with suicidality. Among the participants, 23.6% reported having had suicidal thoughts during the past week and 6.7% reported having attempted suicide during the past year. Methamphetamine was reported as the primary substance of use among approximately half of the participants who attempted suicide during past year (49.2%). Multiple logistic regression analysis showed that current suicidal thoughts were independently associated with having no job, a history of mental health condition, previous suicidal attempts, concurrent use of more than one substance, and using methamphetamine and heroin as the primary substances. Suicidal thoughts were not associated with increased odds of regular opium and cannabis use. Both methamphetamine and heroin use are significantly associated with current suicidal thoughts. Evaluation of the risk of suicidality by physicians and mental health care professionals in both community and outpatient settings would be especially appropriate among those individuals using these psychoactive substances.

Gender Differences in the Co-Use of Tranquilizers, Sedatives, Sleeping Pills and Alcohol among Spanish Adolescents: A Nationwide Population-Based Study.

Adolescence is a critical developmental stage for the initiation of substance use worldwide, which is one of the main risk-taking behaviors that may impact adolescents' physical and mental well-being. The aims of this study were to (1) assess the prevalence of the co-use of tranquilizers, sedatives, and sleeping pills with alcohol (TSSp&AC) by gender in the Spanish adolescent population in 2018 and (2) identify the variables associated with TSSp&AC. An observational cross-sectional study following STROBE guidelines was conducted. We analyzed data from 38,010 adolescents aged 14 to 18 years old (18,579 males and 19,431 females) who participated in ESTUDES (Survey on Drug Use in Secondary Education in Spain) 2018. Female adolescents reported a higher prevalence of TSSp&AC than males (p < 0.001). The factors associated with female co-use were being 16-18 years of age (OR 1.65); the consumption of tobacco (OR 1.73), cocaine (OR 1.84), other illicit psychoactive drugs (OR 1.89); and novel illicit psychoactive drugs (OR 1.74); no perceived health risk from the consumption of TSSps (OR 2.45); and the perceived availability of TSSps (OR 2.23) and alcohol (OR 2.09). There are several factors associated with TSSp&AC in Spanish female adolescents with potential implications for healthcare providers.

Sex differences and driving impairment related to psychoactive substances

Objective The first aim of the study was to identify sex differences in the use of psychoactive substances among subjects with a previous driving under the influence (DUI) episode. The secondary objective was to propose specific strategies for medico-legal improvements. Methods This was a retrospective observational study that took place between June 1, 2019, and August 31, 2023. It was conducted on DUI subjects examined for reinstatement of their driver’s license using an integrated medico-legal and toxicological approach. Ethyl glucuronide (EtG) and illicit psychoactive substances were determined from hair samples. We performed descriptive statistical analyses for the entire sample as well as separately by sex. Additionally, we conducted binary logistic regression analyses separately for males and females to identify protective/risk factors associated with previous road accidents and judgments of unfitness to drive due to excessive alcohol consumption (EtG ≥ 30 pg/mg). Results The study included 2,221 subjects, comprising 1,970 men and 251 women. Men exhibited a higher prevalence of tobacco, alcohol, and illicit psychoactive substance use. Women were more frequently co-users of alcohol and psychoactive substances and involved in road accidents at the time of DUI. Among the men, being married or having a partner was found to be a protective factor concerning past traffic accidents. For both sexes, a DUI episode with a blood alcohol concentration (BAC) exceeding 1.5 g/L or the co-ingestion of alcohol and drugs was identified as a risk factor for road accident involvement. For men, smoking more than 20 cigarettes per day and, for women, having a DUI episode with a BAC over 1.5 g/L were the main factors indicating unfitness to drive, as determined through high hair EtG levels (> 30 pg/mg). Women with a previous history of road accidents were less likely to have EtG levels of 30 pg/mg or more. Conclusions The study confirmed sex differences in subjects with a previous DUI episode. A BAC exceeding 1.5 g/L or the simultaneous use of alcohol and drugs at the time of DUI necessitate careful assessment of both men and women seeking driver’s license reinstatement. In women, a BAC exceeding 1.5 g/L is considered a risk factor for a subsequent judgment of unfitness to drive. The medico-legal assessment should also involve a thorough investigation of smoking habits in men, as these habits could be related to an increased risk of excessive alcohol consumption.

Effects of Herpud1 in Methamphetamine-Induced Neuronal Apoptosis.

Methamphetamine (METH) is an illicit psychoactive substance that can damage various organs in the body, especially the nervous system. We hypothesized that expression of homocysteine-inducible endoplasmic reticulum-resident with ubiquitin-like domain member 1 (Herpud1) protein would alleviate the induction of apoptosis following METH administration. To test this hypothesis, we analysed the changes in Herpud1 expression and apoptosis in PC12 cells under different concentrations and exposure times of METH. Moreover, we examined the effects of Herpud1 knockdown on METH-induced neuronal apoptosis. Flow cytometry and Western blot analyses were used to evaluate apoptosis levels and the expression of apoptotic markers (cleaved caspase-3) in PC12 cells following Herpud1 knockdown by synthetic small interfering RNA (siRNA). Our results showed that Herpud1 expression was upregulated in PC12 cells following METH treatment, while endoplasmic reticulum stress (ERS) and apoptosis were also increased. Conversely, Herpud1 knockdown reduced METH-induced ERS and apoptosis levels in vitro. These results suggest that Herpud1 plays an essential role in METH-induced neuronal ERS and apoptosis and may represent a potential therapeutic gene target in METH-induced neurotoxicity.

Metabolic memory of Δ9-tetrahydrocannabinol exposure in pluripotent stem cells and primordial germ cells-like cells

Cannabis, the most consumed illicit psychoactive drug in the world, is increasingly used by pregnant women. However, while cannabinoid receptors are expressed in the early embryo, the impact of phytocannabinoids exposure on early embryonic processes is lacking. Here, we leverage a stepwise in vitro differentiation system that captures the early embryonic developmental cascade to investigate the impact of exposure to the most abundant phytocannabinoid, Δ9-tetrahydrocannabinol (Δ9-THC). We demonstrate that Δ9-THC increases the proliferation of naive mouse embryonic stem cells (ESCs) but not of their primed counterpart. Surprisingly, this increased proliferation, dependent on the CB1 receptor binding, is only associated with moderate transcriptomic changes. Instead, Δ9-THC capitalizes on ESCs’ metabolic bivalence by increasing their glycolytic rates and anabolic capabilities. A memory of this metabolic rewiring is retained throughout differentiation to Primordial Germ Cell-Like Cells in the absence of direct exposure and is associated with an alteration of their transcriptional profile. These results represent the first in-depth molecular characterization of the impact of Δ9-THC exposure on early stages of germline development.

Metabolic memory of Δ9-tetrahydrocannabinol exposure in pluripotent stem cells and primordial germ cells-like cells.

Cannabis, the most consumed illicit psychoactive drug in the world, is increasingly used by pregnant women. However, while cannabinoid receptors are expressed in the early embryo, the impact of phytocannabinoids exposure on early embryonic processes is lacking. Here, we leverage a stepwise in vitro differentiation system that captures the early embryonic developmental cascade to investigate the impact of exposure to the most abundant phytocannabinoid, Δ9-tetrahydrocannabinol (Δ9-THC). We demonstrate that Δ9-THC increases the proliferation of naive mouse embryonic stem cells (ESCs) but not of their primed counterpart. Surprisingly, this increased proliferation, dependent on the CB1 receptor binding, is only associated with moderate transcriptomic changes. Instead, Δ9-THC capitalizes on ESCs' metabolic bivalence by increasing their glycolytic rates and anabolic capabilities. A memory of this metabolic rewiring is retained throughout differentiation to Primordial Germ Cell-Like Cells in the absence of direct exposure and is associated with an alteration of their transcriptional profile. These results represent the first in-depth molecular characterization of the impact of Δ9-THC exposure on early stages of germline development.

Subtle Structural Modification of a Synthetic Cannabinoid Receptor Agonist Drastically Increases its Efficacy at the CB1 Receptor.

The emergence of synthetic cannabinoid receptor agonists (SCRAs) as illicit psychoactive substances has posed considerable public health risks, including fatalities. Many SCRAs exhibit much higher efficacy and potency compared with the phytocannabinoid Δ9-tetrahydrocannabinol (THC) at the cannabinoid receptor 1 (CB1R), leading to dramatic differences in signaling levels that can be toxic. In this study, we investigated the structure-activity relationships of aminoalkylindole SCRAs at CB1Rs, focusing on 5F-pentylindoles containing an amide linker attached to different head moieties. Using in vitro bioluminescence resonance energy transfer assays, we identified a few SCRAs exhibiting significantly higher efficacy in engaging the Gi protein and recruiting β-arrestin than the reference CB1R full agonist CP55940. Importantly, the extra methyl group on the head moiety of 5F-MDMB-PICA, as compared to that of 5F-MMB-PICA, led to a large increase in efficacy and potency at the CB1R. This pharmacological observation was supported by the functional effects of these SCRAs on glutamate field potentials recorded in hippocampal slices. Molecular modeling and simulations of the CB1R models bound with both of the SCRAs revealed critical structural determinants contributing to the higher efficacy of 5F-MDMB-PICA and how these subtle differences propagated to the receptor-G protein interface. Thus, we find that apparently minor structural changes in the head moiety of SCRAs can cause major changes in efficacy. Our results highlight the need for close monitoring of the structural modifications of newly emerging SCRAs and their potential for toxic drug responses in humans.

Detection of illicit psychoactive substances in the urine of mothers and newborn infants at a public hospital. Comparison between the 2009-2013 and 2014-2018 five-year periods.

Introduction. The use of illicit psychoactive substances during pregnancy is a growing problem. Few Latin American maternity centers implement a screening strategy, and published data are scarce. Objectives. To compare the outcomes of 2 five-year periods of a postpartum strategy to screen for illicit psychoactive drugs. Population and methods. This was a cross-sectional study. Immunoassay detection in urine of mother-newborn infant dyads in an Argentine public hospital between 2009 and 2018. Results. Substances were detected in 76/191 dyads over 10 years. The most frequent detection criterion was reporting or history of drug use: 25/37 and 32/39 in each five-year period. Cannabis (21/37 and 26/39) and cocaine (19/37 and 16/39) predominated in both periods. No differences were observed in demographic, gynecological, pregnancy, or neonatal data between both five-year periods. Conclusions. No differences were found in the frequency or type of substances detected over 10 years.

Socio-demographic profile and clinical co-morbidities of cannabis users attending a tertiary care hospital in India: A retrospective case record study.

Cannabis use has been the most commonly used illicit psychoactive substance in India. Increasing use of cannabis has been associated with an increased risk of co-morbid psychotic spectrum disorders with worse outcomes. This risk increases with increased use in a dose-dependent manner. A very complex association exists between cannabis use and mental illness hence it is essential to understand the relationship between the two to facilitate better care and management. The present study was conducted to assess the socio-demographic profile and psychiatric co-morbidities of cannabis users attending a tertiary mental health establishment in Goa. A retrospective case record study was carried out among self-reported cannabis users attending services at a tertiary mental health establishment from June 2021 to June 2022. Data regarding cannabis use, clinical profile, and socio-demographic profile of the individuals was obtained and analyzed using appropriate statistical tests. One hundred and sixty-four cannabis users were evaluated which consisted of 140 males and 24 females, the mean age being 28 years with a standard deviation of 7.68. Ganja was the most commonly used form smoked as joints. The median age of initiation was 18 with females starting at a later age than males. Later initiation was associated with using lower quantities. Concurrent alcohol and nicotine use was present in 90% of the cases. The most commonly associated diagnosis was substance-induced psychosis. Cannabis use in individuals with mental illness is more common in males and an early age of initiation was linked to earlier age of onset of psychiatric illness.

Maternal, Fetal and Neonatal Outcomes Related to Recreational Cannabis Use during Pregnancy: Analysis of a Real-World Clinical Data Warehouse between 2010 and 2019.

Cannabis is the main illicit psychoactive substance used in French childbearing women and very few data are available about adverse events (AEs) related to its use during pregnancy. The aim of this study was to evaluate the association between recreational cannabis use during pregnancy and adverse outcomes from a real-world clinical data warehouse. Data from the Poitiers University Hospital warehouse were analyzed between 1 January 2010 and 31 December 2019. Logistic regression models were used to evaluate associations between outcomes in three prenatal user groups: cannabis alone ± tobacco (C ± T) (n = 123), tobacco alone (T) (n = 191) and controls (CTRL) (n = 355). Pregnant women in the C ± T group were younger (mean age: 25.5 ± 5.7 years), had lower pre-pregnancy body mass index (22.8 ± 5.5 kg/m2), more psychiatric history (17.5%) and were more likely to benefit from universal free health-care coverage (18.2%) than those in the T and CTRL groups. Cannabis use increases the occurrence of voluntary interruption of pregnancy, at least one AE during pregnancy, at least one neonatal AE, the composite adverse pregnancy outcome over 28, prematurity and small for gestational age. Given the trivialization of recreational cannabis use during pregnancy, there is an urgent need to communicate on AEs of cannabis use during pregnancy.

Synthetic Anti-Cocaine Nanoaccine Successfully Prevents Cocaine-Induced Hyperlocomotion.

Cocaine is one of the most widely used and increasingly popular illicit psychoactive drugs. Unlike other commonly used substances of abuse, cocaine has no pharmacological therapies to treat addiction or aid in rehabilitation. Immunopharmacology has long been touted as a possible avenue to develop effective anticocaine therapies; however, lack of efficacy and designs which are not consistent with simple large-scale production have hindered vaccine translation. We have designed and synthesized a peptide-based anti-cocaine immunogen which we have shown is capable of inducing physiologically relevant immune responses in mice as part of a self-adjuvanting delivery system or in combination with the human-approved commercial adjuvant MF59. We have demonstrated that immunization with the reported vaccine elicits high titers of anti-cocaine IgG and prevents cocaine-induced hyperlocomotion in an in vivo murine model. This peptide-hapten immunogen along with self-adjuvanting liposomal-based delivery system provides a platform for the development of effective anti-drug vaccines.

Nail analysis for the assessment of caffeine abuse in Northwest China: A population-based study.

Caffeine is the most widely consumed psychoactive agent worldwide and has the potential for abuse, but studies monitoring caffeine abuse in China are scarce. This study aims to estimate the prevalence of caffeine abuse in northwest China and investigate the correlation between caffeine and other drugs in hair and nails using an ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). Fingernail clippings were collected from 376 participants in northwest China to detect caffeine and 13 other illicit psychoactive drugs and their metabolites. Paired hair and nail samples were collected from 39 participants to investigate the correlation between caffeine and other drugs in hair and nails. The samples were decontaminated, pulverized, and extracted by a high-throughput nail sample preparation method and analyzed by UPLC-MS/MS. The results showed a risk of caffeine abuse in northwest China, with concentrations ranging from 0.43 to 10.6 ng/mg for healthy volunteers, 0.49-246 ng/mg for caffeine abusers, and 0.25-363 ng/mg for drug addicts in community rehabilitation centers. Caffeine was detected together with other illicit psychoactive drugs and their metabolites. Furthermore, positive detection correlations were found between hair and nail samples. This study provides a current perspective on caffeine abuse in northwest China and demonstrates the practical use of UPLC-MS/MS for the simultaneous detection of caffeine and 13 illicit psychoactive drugs and their metabolites in hair and nails. The results highlight the potential of nails as a supplementary matrix when hair samples are unavailable and emphasize the need for handling caffeine carefully given its potential for abuse.

Cannabis regulatory system in European Union countries, forensic concept of "doping dose" and medico-legal implications.

Cannabis is the most widely used illicit psychoactive substance in the world. In recent years, in many European Union countries, there has been a decriminalisation of the use and personal possession of cannabis for recreational purposes. There has been a spread of medical cannabis, as well as marketing of cannabis products at low concentrations of delta-9-tetrahydrocannabinol (Delta-9-THC), the major chemical to which cannabis owes its psychotropic effect. The percentage limit of this substance, only recently set by the European Court of Justice, must be distinguished from the "doping dose" of Delta-9-THC, namely, the dose which causes psychotropic effect in the consumer. Our study analyses and summarises the regulations in the countries of the European Union on the penalisation of recreational cannabis, the legalisation of medical cannabis and limits on percentage of THC imposed locally. Based on the analysis of a recent judgment of the Italian Supreme Court of Cassation, we discuss the importance of the role of the forensic toxicologist in the scientific definition of "doping dose". The distinction between the doping dose of THC and the percentage of THC contained in the marketed cannabis product is vital when establishing fair punishment in the event of a crime.

Review: Christ Returns from the Jungle: Ayahuasca Religion as Mystical Healing, by Marc G. Blainey

Review: <i>Christ Returns from the Jungle: Ayahuasca Religion as Mystical Healing</i>, by Marc G. Blainey

Comparative Harm/Benefit Analysis of Various Psychotropic Substances from the Perspective of German Drug Users and Addiction Medicine Experts - A Contribution to Psychoeducation of Substance-Addicted Individuals and Restriction/Legalization Debates

To date, we cannot find any current international comparative study on the assessment of a benefit/harm profile of various licit and illicit psychoactive substances conducted by adult drug users and addiction experts as well. Particularly, there is no study from the German-speaking area of Western Europe. In addition to the data already published by 101 German addiction medicine experts (published in this journal, [1]), we carried out interviews using a structured questionnaire with 100 German substance dependent users, residing in acute and rehabilitation clinical setting, to evaluate 34 psychoactive substances regarding their health and social harm potential for users and others as well as their potential benefit. Both, users and experts estimated traditional illicit drugs, such as heroin, crack/cocaine and methamphetamine, to be particularly harmful. Synthetic cannabinoids, alcohol and benzodiazepines were in the upper midfield, cannabis and psychotropic mushrooms in the lower midfield, and gabapentinoids at the bottom of the harm rankings of both, users and experts. In comparison with the experts, the users estimated methadone and benzodiazepines to be significantly more harmful. In the benefit analysis, users rated traditional illicit drugs including cannabis and psychotropic mushrooms as well as nicotine as significantly more useful than the experts. In contrast to the experts (traditional illicit drugs), the users did not assess any substance as very harmful and very useless at the same time. Only a few users reported to have experiences with opioid analgesics which, however, did not differ between the users´ and experts´ harm/benefit-assessments. Neither users nor experts predicted cannabis-legalization to change the overall risk potential of cannabis. Specific cognitive valuation biases seemed to be prominent in both groups. This study presents first harm/benefit assessments of psychotropic substances from the perspective of German addiction medicine experts and drug users. The results can be valuable to the psychoeducation of substance-addicted individuals and to current restriction or legalization debates.

Risky sexual behaviours among Ugandan university students: A pilot study exploring the role of adverse childhood experiences, substance use history, and family environment.

University students are known to have risky sexual behaviours (RSBs). The severity of the RSB is influenced by many factors, including the family environment, exposure to adverse childhood events (ACEs), and the use of addictive substances. However, there is limited information about the influence of ACEs and the family environment of these students in low-and medium-income countries (LMICs). Therefore, a pilot study was conducted among university students from a LMIC, Uganda. The present study comprised a cross-sectional online survey among Ugandan students at a public university (N = 316; 75% male; 52.2% aged between 18-22 years). The survey included questions relating to socio-demographic information, family environmental information, the Sexual Risk Survey (SRS), and the Adverse Childhood Experiences-International Questionnaire (ACE-IQ). Over half (53.8%) reported having had sexual intercourse. Males reported over two times higher mean total SRS score compared to females (χ2 = 4.06, p = 0.044). Approximately one-sixth of the sample had drunk alcohol or used illicit psychoactive substances in the past six months (16.1%). Among four regression analysis models, sociodemographic variables predicted the highest variance (13%), followed by family environment variables (10%), and both psychoactive substance use history (past six months) and ACEs individually explained approximately 5% variance in total SRS score, with the final model predicting 33% of the variance in RSB. The present study demonstrated a gender disparity with males involved in more RSB than females, as has been reported in most previous RSB studies. Family environment, sociodemographic factors, substance use, and ACEs all appear to contribute to RSB among university students. These findings will benefit other researchers exploring factors associated with RSB among university students and will help develop interventions to reduce RSB to protect students from unwanted pregnancies, sexually transmitted diseases, and HIV/AIDS.

Differences between users' and addiction medicine experts' harm and benefit assessments of licit and illicit psychoactive drugs: Input for psychoeducation and legalization/restriction debates.

There is a lack of benefit/harm assessments of illicit and licit psychoactive substances performed by substance-dependent users in comparison to addiction medicine experts. We extended the analyses of substance harm/benefit assessments of German addiction medicine experts (N = 101), in parts reported recently in this journal [doi.org/10.3389/fpsyt.2020.59219], by the perspectives of substance-addicted persons. The same questionnaire as used for the abovementioned "experts-study" was handed out to inpatient detoxification or rehab treatment seeking German substance-dependent adults (N = 117) for a subsequent structured interview about harms and benefits of 33 new and traditional psychoactive substances comprising also prescription drugs. Both, users and experts, ranked the traditional illicit psychoactive substances heroin, cocaine and amphetamines within the top overall harm level group. Synthetic cannabinoids, alcohol and benzodiazepine were in a subordinate top-harm level position. Both cohorts also ranked methadone, nicotine and cannabis within the midrange and buprenorphine as well as psychotropic mushrooms within the lowest harm level positions. Experiences with prescription drugs (including opioidergic analgesics and gabapentinoids), cathinones, GHB, methamphetamine and methylphenidate was not prevalent in our user population. The same applied to barbiturates, propofol, kratom, ayahuasca with nearly zero assessments for each substance. The most user-experiences (>50% per assessed substance) were reported with nicotine, cannabis, alcohol, cocaine, heroin, amphetamine and methadone (core group). The user's overall harm ratings in terms of these psychoactive substances were similar to those of the experts with the exception of the methadone assessment which was rated by the experts to be significantly less harmful if compared with the users' estimation (supposed "treatment bias" of experts). The users' benefit ratings for the traditional illicit psychoactive substances, cannabis as well as for nicotine were significantly more positive in comparison to those of the experts (supposed "attraction bias" of users). Both, experts and users, ranked the harms arising from the use of alcohol or benzodiazepines (usually unregulated substances) higher than the harms caused by the use of methadone, cannabis or psychotropic mushrooms (regulated by most Western narcotic acts). Users attributed the most benefits to buprenorphine, methadone and cannabis. This might reflect a main limitation of the study as the data are from an user population comprising over 50% patients who sought detoxification-treatment of opiates where methadone and buprenorphine are usual transient medications (supposed "selection bias"). This study addressed current trends of psychoactive substance abuse (e.g., synthetic cannabinoids, prescription drugs) and provides from both perspectives (that of the user and that of the addiction medicine experts) robust harm/benefit evaluations at least of a core group of psychoactive substances (traditional illicit psychoactive substances, cannabis, methadone, alcohol and nicotine). The results of this study can be valuable to the psychoeducation of substance-addicted individuals and to current restriction/legalization debates, especially in the Western-EU.

Cannabis use in Tunisian adolescents: Alarming trends from 2013 to 2021

Abstract Background Cannabis is the most widely used illicit psychoactive substance worldwide. In Tunisia, the prevalence of cannabis use and its association with other risky behaviours were reported in several publications interesting mainly early adolescence. However, no publications exploring trends based on national epidemiological data are available yet. Our purpose was to determine cannabis prevalence in Tunisian high school adolescents and assess significant trends from 2013 to 2021. Methods Pooled data from Mediterranean school surveys on alcohol and other drugs conducted in 2013, 2017, and 2021, were used. Based on three-stage stratification sampling method, first and second grade secondary education students were enrolled. Were not included students enrolled in vocational training centers and out-of-school adolescents. Self-administered standardized questionnaire was used in data collection. We studied weighted lifetime prevalence of cannabis use and chi square test for trend was used for global, by gender and by sector (private/public) trends assessement. STATA software was used for statistical analysis. Results A total of 14.723 students were enrolled with sex ratio (M/F) equal to 0.61 and mean age of 16.2±0.8 years. The prevalence of cannabis use increased from 1.4%, to 3.8% then to 7.9% for 2013, 2017 and 2021 respectively. Trend assessement concludes to significant increase in overall cannabis use (p &amp;lt; 10-3). Besides, there was a significant increase in both public and private schools, and among both boys and girls. However, the greatest increase was among male students (3.5% in 2013, 9.2% in 2017 and 16.1% in 2021) (p &amp;lt; 10-3). Conclusions Despite the reinforcement of restrictive legislative measures, the prevalence of cannabis use among Tunisian high school adolescents is significantly increasing. Moreover, it’s important to further investigate problematic cannabis use and its effects on adolescents’ physical and mental health. Key messages • Trend assessement confirmed the significant increase in lifetime cannabis use in high school adolescents in Tunisia, for both sexes and for both private and public sector. • This alarming public health issue requires urgent legislation review and close multisectoral collaboration to control supply and demand.