An initial exploration of machine learning for establishing associations between genetic markers and THC levels in Cannabis sativa samples.

Cannabis sativa, a globally commercialized plant used for medicinal, food, fiber production, and recreation, necessitates effective identification to distinguish legal and illegal varieties in forensic contexts. This research utilizes multivariate statistical models and Machine Learning approaches to establish correlations between specific genotypes and tetrahydrocannabinol (Δ9-THC) content (%) in C. sativa samples. 132 cannabis leaves samples were obtained from legal growers in Piedmont, Italy, and illegal drug seizures in Turin. Samples were genetically profiled using a 13-loci STR multiplex and their Δ9-THC content was detected through quantitative GC-MS analysis. This study aims to assess the use of supervised classification modelling on genetic data to distinguish cannabis samples into legal and illegal categories, revealing distinct clusters characterized by unique allele profiles and THC content. t-distributed Stochastic Neighbor Embedding (t-SNE), Random Forest (RF) and Partial Least Squares Regression (PLS-R) were executed for the machine learning modelling. All the tested models resulted effective discriminating between legal samples and illegal. Although further validation is necessary, this study presents a novel forensic investigative approach, potentially aiding law enforcement in significant marijuana seizures or tracking illicit drug trafficking routes.

Medical Cannabis Prescription Practices and Quality of Life in Thai Patients: A Nationwide Prospective Observational Cohort Study.

Introduction: The legalization of cannabis in Thailand has renewed interest in its traditional medical use. This study aimed to explore the prescribing patterns of traditional practitioners and assess the impact of cannabis oil on patients' quality of life, with a specific focus on comparing outcomes between cancer and non-cancer patients. Methods: We conducted a prospective observational cohort study across 30 sites in 21 Thai provinces to analyze the use of "Ganja Oil," a cannabis extract in 10% coconut oil, prescribed for symptoms like pain, anorexia, and insomnia across a diverse patient group, including cancer and migraines. Quality of life was assessed using the Edmonton Symptom Assessment Scale (ESAS) and EQ-5D-5L at baseline, 1, 2, and 3 months. The study included a predefined subgroup analysis to compare the effects on cancer versus non-cancer patients. Data management was facilitated through Research Electronic Data Capture (REDCap), with statistical analysis performed using Stata/MP. Results: Among 21,284 participants, the mean age was 54.10 ± 15.32 years, with 52.49% being male. The baseline EQ-5D-5L index was 0.85 ± 0.24. Significant differences in EQ-5D-5L indices were seen between cancer patients (0.79 ± 0.32) and non-cancer patients (0.85 ± 0.23; p < 0.001). ESAS scores also differed significantly between these groups for all symptoms, except anxiety. The most frequent prescription of Ganja Oil was oral administration at bedtime (88.26%), with the predominant dosage being three drops daily, approximately 0.204 mg of tetrahydrocannabinol in total. Posttreatment, significant improvements were noted: the EQ-5D-5L index increased by 0.11 points (95% CI: 0.11, 0.11; p < 0.001) overall, 0.13 points (95% CI: 0.12, 0.14; p < 0.001) for cancer patients, and 0.11 points (95% CI: 0.10, 0.11; p < 0.001) for non-cancer patients. ESAS pain scores improved by -2.66 points (95% CI: -2.71, -2.61; p < 0.001) overall, -2.01 points (95% CI: -2.16, -1.87; p < 0.001) for cancer patients, and -2.75 points (95% CI: -2.80, -2.70; p < 0.001) for non-cancer patients, with similar significant improvements in other symptoms. Conclusion: Our study indicates potential benefits of Ganja Oil for improving quality of life among Thai patients, as a complementary treatment. These findings must be viewed in light of the study's design limitations. Further controlled studies are essential to ascertain its efficacy and inform dosing guidelines.

Cannabinoid Awareness, Reporting Use to Health Care Providers, and Perceptions Regarding Safety - Pennsylvania, March 2023-April 2023.

Introduction: With the continued societal and policy interest in cannabinoids, the Penn State Harrisburg Center for Survey Research (CSR) conducted a web survey (Cannabinoid Lion Poll) for adult-aged Pennsylvanians between March 6 and April 2, 2023. Methods: The Lion Poll omnibus survey asked questions of adult-aged Pennsylvanians to assess awareness of cannabidiol (CBD) and products containing tetrahydrocannabinol (THC), including marijuana, the likelihood of reporting cannabinoid use to health care providers (HCPs), and perceptions regarding safety. Results: Of these 1,045 respondents, 51.2% were female; 83.0% were white, non-Hispanic; and 48.6% and 27.5% were within the 35-64-year and 18-34-year age ranges, respectively. Of the respondents, 52.1% and 53.9% told their HCPs they took CBD or products containing THC, respectively. Alcohol was perceived by the large proportion of respondents as unsafe (47.3%), followed by products containing THC (25.2%), anxiety/depression medications (21.7%), CBD (16.1%), and over-the-counter (OTC) pain medications (8.1%). Most combinations were perceived to be unsafe when asked to consider the safety of taking them with other prescription medications. Again, alcohol was perceived to be unsafe by the largest proportion (77.4%), followed by anxiety/depression medications (43.2%), products containing THC (42.6%), CBD (33.4%), and then OTC pain medications (24.8%). Conclusions: Adult-aged Pennsylvanians perceive CBD and THC containing products as safer than alcohol. There is considerable underreporting of cannabinoid use to HCPs, and therefore significant implications for patient safety. It remains vital that HCPs have open communications with their patients about cannabinoid use.

Semen Cannabis and Oleum Hyperici: Antileishmanial activity against Leishmania tropica promastigotes and intracellular amastigotes.

The exploration of alternative agents and novel drug candidates for the effective treatment of cutaneous leishmaniasis has garnered significant attention, driven by the high cost, toxic effects, and the emergence of drug resistance associated with current therapeutic options. Plant extracts derived from Semen Cannabis, the seeds of the Cannabis sativa L. (hemp) plant, and Oleum Hyperici, the oily macerate of Hypericum perforatum L. (St. John's Wort) plant, were prepared by using solvents of varying polarity (n-hexane, chloroform, ethanol, and 60% aqueous ethanol). The primary objective of this study was to research in vitro and ex vivo antileishmanial efficacy of Semen Cannabis and Oleum Hyperici plant extracts against Leishmania tropica promastigotes and intracellular amastigotes. The efficacy of plant extracts against promastigotes were assessed using the cell counting by hemocytometer and the CellTiter-Glo assay. Additionally, their impact on infected THP-1 macrophages and the quantity of intracelluler amastigotes were investigated. Cytotoxicity was evaluated in THP-1 macrophages. Among the tested plant extracts, chloroform extract of Oleum Hyperici demonstrated significant antileishmanial activity against promastigotes (SI: 12.6) and intracellular amastigotes (SI: 16.8) of L. tropica without inducing cytotoxic effects and hold promise for further investigation as potential antileishmanial agents.

Trends in cannabis and tobacco co-use in the United States, 2002-2021.

BACKGROUND: Co-use of cannabis and tobacco poses greater risks than use of either substance individually and may be becoming more prevalent with increasing cannabis medicalization and legalization. We aimed to assess trends in the prevalence of cannabis and tobacco co-use between 2002-2019 and identify the updated prevalence and correlates of co-use in 2021 among US adults. METHODS: This study used data from the 2002-2021 National Survey on Drug Use and Health, a nationally-representative, cross-sectional survey in the US. We assessed prevalence trends in past 30-day cannabis and tobacco co-use, exclusive cannabis use, and exclusive tobacco use overall and by sociodemographic group using joinpoint regression. Additionally, multinomial models identified correlates of co-use in 2021. RESULTS: In 2021, the weighted prevalence of cannabis and tobacco co-use was 6.38 %, the weighted prevalence of exclusive cannabis use was 7.28 %, and the weighted prevalence of exclusive tobacco use was 15.01 %. From 2002 to 2019, the prevalence of past 30-day co-use of cannabis and tobacco increased significantly (annual percentage change [APC]: 1.9 [1.4-2.4], P<0.05) among the overall US population. All subgroups of sex, race/ethnicity, and age also saw significant increases in co-use, other than young adults ages 18-25, for whom co-use was stagnant between 2002-2014 and then decreased significantly between 2014-2019. CONCLUSION: This study identified increasing cannabis and tobacco co-use overall and among most sociodemographic strata in the US. As cannabis policy changes rapidly, co-use requires closer surveillance, clinical screening, and dedicated research.

A mixed method study exploring similarities and differences in general and social services-specific barriers to treatment-seeking among individuals with a problematic use of alcohol, cannabis, or gambling.

INTRODUCTION: The treatment gap for addictive disorders is one of the largest in health care. Several studies have investigated barriers to treatment for different addictive disorders, but very few studies conducted have explored whether the barriers differ depending on substance or behavior or if they are common among all addictive disorders. In Sweden, addiction care is provided both by the healthcare and social services, where the latter is common, but also less popular. To our knowledge, there are no studies exploring whether the barriers are different depending on where the treatment is given. AIM: The aim was to thoroughly explore both which general and social services-specific barriers to treatment that are common, which barriers that differs, and how the barriers are described among individuals with a problematic use of alcohol, cannabis and/or gambling. METHOD: A mixed method convergent parallel design was conducted. For the quantitative measures, surveys including the validated Barriers to Treatment Inventory as well as questions regarding barriers in the Swedish multi-provider landscape, were collected from individuals with a problematic use of alcohol (n = 207), cannabis (n = 51), and gambling (n = 37). In parallel, 17 semi-structured interviews from the same population were conducted and analyzed with thematic analysis. Thereafter, the quantitative and qualitative data was compared, contrasted, and at last, interpreted. RESULTS: The quantitative data showed that the largest general barriers in all groups were privacy concern and poor availability, and the largest barriers for seeking help from the social services was stigma, unawareness of what is offered, and fear of consequences for all groups. The qualitative data resulted in five general barriers: stigma, ambivalence, accessibility, fear of consequences, and lack of knowledge about addiction and its' treatments, and three barriers specifically towards social services: social services reputation, fear of meeting acquaintances, and lack of knowledge. The themes were developed from data from all groups, but different aspects of the themes were mentioned by different groups. CONCLUSION: There are details and aspects that differentiates both the general and social service-specific barriers to treatment between individuals with a problematic use of alcohol, cannabis, and gambling, but in large they perceive similar barriers.

Discriminative validity of a substance use symptom checklist for moderate-severe DSM-5 cannabis use disorder (CUD) in primary care settings.

Background: The prevalence of cannabis use disorder (CUD) is increasing in the US and primary care providers need tools to identify patients with moderate-severe CUD to facilitate treatment. A single-item screen for cannabis (SIS-C) has outstanding discriminative validity for CUD. However, because the prevalence of moderate-severe CUD is typically low, the probability that an average patient who screens positive for daily cannabis has moderate-severe cannabis use disorder is low, making follow-up assessment important. Methods: This study reports the discriminative validity of a DSM-5 Substance Use Symptom Checklist ("Checklist") for moderate-severe CUD among 498 primary care patients who reported daily cannabis use on the SIS-C. We evaluated the performance of the Checklist (score 0-11) completed during routine care, compared to ≥4 DSM-5 CUD symptoms (moderate-severe CUD) on the Composite International Diagnostic Interview Substance Abuse Module from a confidential survey (reference standard). We estimated areas under receiver operating curve (AUROC), sensitivities, specificities, and post-test probabilities. Results: Of 498 eligible patients, 17 % met diagnostic criteria for moderate-severe CUD. The Checklist's AUROC for moderate-severe CUD was 0.77 (95 % CI: 0.71-0.83), and Checklist scores of 1-2 balanced sensitivity and specificity. Among patients from a population with average prevalence of CUD before screening (~6 % prevalence) and daily use on the SIS-C, a Checklist score of 3 indicated a post-test probability of 82.1 %. Conclusion: Overall performance of the Checklist was good and the high specificity made it useful for identifying patients likely to have moderate-severe CUD among those at average risk.

A mobile health intervention for emerging adults with regular cannabis use: A micro-randomized pilot trial design protocol.

BACKGROUND: Emerging adult (EA) cannabis use is associated with increased risk for health consequences. Just-in-time adaptive interventions (JITAIs) provide potential for preventing the escalation and consequences of cannabis use. Powered by mobile devices, JITAIs use decision rules that take the person's state and context as input, and output a recommended intervention (e.g., alternative activities, coping strategies). The mHealth literature on JITAIs is nascent, with additional research needed to identify what intervention content to deliver when and to whom. METHODS: Herein we describe the protocol for a pilot study testing the feasibility and acceptability of a micro-randomized trial for optimizing MiWaves mobile intervention app for EAs (ages 18-25; target N = 120) with regular cannabis use (≥3 times per week). Micro-randomizations will be determined by a reinforcement learning algorithm that continually learns and improves the decision rules as participants experience the intervention. MiWaves will prompt participants to complete an in-app twice-daily survey over 30 days and participants will be micro-randomized twice daily to either: no message or a message [1 of 6 types varying in length (short, long) and interaction type (rate message, rate message + click additional resources, rate message + fill in the blank/select an option)]. Participants recruited via social media will download the MiWaves app, and complete screening, baseline, weekly, post-intervention, and 2-month follow-up assessments. Primary outcomes include feasibility and acceptability, with additional exploratory behavioral outcomes. CONCLUSION: This study represents a critical first step in developing an effective mHealth intervention for reducing cannabis use and associated harms in EAs.

Illicit Cannabis Use to Self-Treat Chronic Health Conditions in the United Kingdom: Cross-Sectional Study.

Background: In 2019, it was estimated that approximately 1.4 million adults in the United Kingdom purchased illicit cannabis to self-treat chronic physical and mental health conditions. This analysis was conducted following the rescheduling of cannabis-based medicinal products (CBMPs) in the United Kingdom but before the first specialist clinics had started treating patients. Objective: The aim of this study was to assess the prevalence of illicit cannabis consumption to treat a medically diagnosed condition following the introduction of specialist clinics that could prescribe legal CBMPs in the United Kingdom. Methods: Adults older than 18 years in the United Kingdom were invited to participate in a cross-sectional survey through YouGov between September 22 and 29, 2022. A series of questions were asked about respondents' medical diagnoses, illicit cannabis use, the cost of purchasing illicit cannabis per month, and basic demographics. The responding sample was weighted to generate a sample representative of the adult population of the United Kingdom. Modeling of population size was conducted based on an adult (18 years or older) population of 53,369,083 according to 2021 national census data. Results: There were 10,965 respondents to the questionnaire, to which weighting was applied. A total of 5700 (51.98%) respondents indicated that they were affected by a chronic health condition. The most reported condition was anxiety (n=1588, 14.48%). Of those enduring health conditions, 364 (6.38%) purchased illicit cannabis to self-treat health conditions. Based on survey responses, it was modeled that 1,770,627 (95% CI 1,073,791-2,467,001) individuals consume illicit cannabis for health conditions across the United Kingdom. In the multivariable logistic regression, the following were associated with an increased likelihood of reporting illicit cannabis use for health reasons-chronic pain, fibromyalgia, posttraumatic stress disorder, multiple sclerosis, other mental health disorders, male sex, younger age, living in London, being unemployed or not working for other reasons, and working part-time (P<.05). Conclusions: This study highlights the scale of illicit cannabis use for health reasons in the United Kingdom and the potential barriers to accessing legally prescribed CBMPs. This is an important step in developing harm reduction policies to transition these individuals, where appropriate, to CBMPs. Such policies are particularly important considering the potential risks from harmful contaminants of illicit cannabis and self-treating a medical condition without clinical oversight. Moreover, it emphasizes the need for further funding of randomized controlled trials and the use of novel methodologies to determine the efficacy of CBMPs and their use in common chronic conditions.

Assessment of frontal lobe functions in a sample of male cannabis users currently in abstinence: correlations with duration of use and their functional outcomes.

BACKGROUND: Previous research literature reported different results regarding the long-term effects that cannabis use can exert on the frontal lobe neurocognitive functions of its users. Another body of research suggested that cannabis use negatively affects the person's general level of occupational and psychosocial functioning consequently to these alterations. Some other research results did not support these findings. To date, it is still debatable whether chronic cannabis use triggers negative neurocognitive effects in chronic users even after a period of abstinence. Research data exploring consequent adverse outcomes on the general individual occupational and psychosocial functioning is not yet conclusive. RESULTS: We conducted this study to examine the residual neurocognitive effects of cannabis use, whether it is affected by duration of cannabis use before abstinence, and its relation to individual's global assessment of functioning exhibited in the person's occupational and social life whether it's family or friends. Our sample comprised 80 male participants (18-45 years old) who were grouped into 4 groups (3 groups with different durations of use and a control group), with no significant difference between the four studied groups regarding age, education, and socioeconomic level. The Kruskal Wallis test was used to test the significance of differences in the distribution of total frontal lobe battery results and the general assessment of function scores using GAF scores between study groups. Post hoc testing was performed to adjust for multiple comparisons using Bonferroni method. CONCLUSION: Data analysis showed that cannabis users experienced general functional disturbances that encompass impairments in social and occupational life aspects. These impairments in function are correlated with the presence of neurocognitive deficits even after a period of abstinence. Both having significant positive correlation with longer duration of cannabis use.

CANDI: A Web Server for Predicting Molecular Targets and Pathways of Cannabis-Based Therapeutics.

Background: Cannabis sativa with a rich history of traditional medicinal use, has garnered significant attention in contemporary research for its potential therapeutic applications in various human diseases, including pain, inflammation, cancer, and osteoarthritis. However, the specific molecular targets and mechanisms underlying the synergistic effects of its diverse phytochemical constituents remain elusive. Understanding these mechanisms is crucial for developing targeted, effective cannabis-based therapies. Methods: To investigate the molecular targets and pathways involved in the synergistic effects of cannabis compounds, we utilized DRIFT, a deep learning model that leverages attention-based neural networks to predict compound-target interactions. We considered both whole plant extracts and specific plant-based formulations. Predicted targets were then mapped to the Reactome pathway database to identify the biological processes affected. To facilitate the prediction of molecular targets and associated pathways for any user-specified cannabis formulation, we developed CANDI (Cannabis-derived compound Analysis and Network Discovery Interface), a web-based server. This platform offers a user-friendly interface for researchers and drug developers to explore the therapeutic potential of cannabis compounds. Results: Our analysis using DRIFT and CANDI successfully identified numerous molecular targets of cannabis compounds, many of which are involved in pathways relevant to pain, inflammation, cancer, and other diseases. The CANDI server enables researchers to predict the molecular targets and affected pathways for any specific cannabis formulation, providing valuable insights for developing targeted therapies. Conclusions: By combining computational approaches with knowledge of traditional cannabis use, we have developed the CANDI server, a tool that allows us to harness the therapeutic potential of cannabis compounds for the effective treatment of various disorders. By bridging traditional pharmaceutical development with cannabis-based medicine, we propose a novel approach for botanical-based treatment modalities.

Ten-year cardiovascular disease risk and related factors in lifetime marijuana use with comorbid methamphetamine-associated psychotic disorder: a QRISK®3 study.

BACKGROUND: Methamphetamine use and related direct and indirect problems are increasing all over the world. The coexistence of lifetime marijuana use (LMU) and methamphetamine use disorder (MUD) may also be accompanied by psychotic symptoms (MAP). Methamphetamine and marijuana use are known to pose risks for cardiovascular diseases (CVDs). However, ten-year CVD risk and inflammation markers of LMU-MUD (non-psychosis group) and LMU-MAP (psychosis group) subjects and the relationship of various sociodemographic and clinical variables with these markers have not yet been examined. METHODS: Thirty-two male subjects were included in non-psychosis group and 72 male subjects in psychosis group. Sociodemographic and clinical characteristics were recorded. Psychotic symptom severity of psychosis group subjects was measured. The ten-year CVD risk was calculated using QRISK®3 model. RESULTS: Age, cigarettes/pack-years, alcohol use onset age, drug use onset age, methamphetamine use onset age, duration of methamphetamine use, education and marital status of the groups were similar (p > 0.05). There was a statistical difference between the non-psychosis and psychosis groups in terms of self-mutilation history (p < 0.001), suicidal attempt history (p = 0.007), homicidal attempt history (p = 0.002), psychiatric hospitalization history (p = 0.010). Ten-year QRISK®3 score was 4.90 ± 9.30 in the psychosis group, while it was 1.60 ± 1.43 in the non-psychosis group (p = 0.004). The mean heart age of the psychosis group was 14 years higher than their chronological age, while the mean heart age of the non-psychosis group was 8 years higher. Neutrophil to lymphocyte ratio (NLR) (p = 0.003) was higher in the psychosis group. A significant correlation was detected between ten-year QRISK®3 and positive psychotic symptoms in the psychosis group (r = 0.274, p = 0.020). Regression analysis showed that self-mutilation history, NLR and relative risk obtained from QRISK®3 can be used to distinguish non-psychosis group and psychosis group subjects (sensitivity = 91.7; Nagelkerke R2 0.438; p = 0.001). CONCLUSIONS: This study is important as it demonstrates for the first time that among the subjects using marijuana and methamphetamine, those with psychotic symptoms have a higher NLR and ten-year CVD risk.

Utility of a brief measure of cannabis demand: Day-level associations with cannabis use.

BACKGROUND: Cannabis demand (i.e., relative value) is usually assessed as a trait-level risk-factor for cannabis use and consequences. This study examined within-person variability in day-level intensity (i.e., amount consumed at zero cost) and Omax (i.e., maximum cannabis expenditure) and tested hypotheses that demand would be positively associated with day-level cannabis use. METHODS: Young adults (n=85) reporting past-month simultaneous alcohol and cannabis use completed two daily surveys for 30 days. Morning surveys assessed prior-day cannabis use and evening surveys assessed day-level demand (i.e., intensity, Omax). Multilevel models tested day-level effects of intensity and Omax on any cannabis use and flower use frequency and quantity (i.e., grams). RESULTS: Approximately 52 % and 46 % of variability in intensity and Omax, respectively, was due to within-person change. At the day-level, higher intensity and Omax were associated with higher likelihood of any cannabis use, regardless of formulation; Omax was associated with use of flower in particular; and intensity was associated with the highest quantity of use. At the person-level, only Omax was associated with flower use likelihood, and only intensity was associated with flower quantity across days. CONCLUSIONS: Cannabis demand demonstrated day-to-day variability, conceivably in response to various internal states and external factors. Intensity and Omax were related to elevated likelihood of using any cannabis, particularly flower, at the day-level. Overall, these data illustrate the validity and utility of brief cannabis demand measures, which might be used to further understand cannabis' reinforcing value at a fine-grained level.

Cannabis use patterns and association with hyperemesis: A comprehensive review.

BACKGROUND: Cannabis use in the general population is prevalent and is rising because of increased acceptance of its use, legalization in most US states, and perceived health benefits. Cannabis product potency has dramatically increased with higher delta-9-tetrahydrocannabinol content. Cannabis has documented antiemetic properties and cannabinoid pharmaceuticals are used in disorders like chemotherapy-induced nausea and vomiting. PURPOSE: Forty to eighty percent of cyclic vomiting syndrome (CVS) patients use cannabis products, which reportedly reduce stress as well as nausea and vomiting. Cannabinoid hyperemesis syndrome (CHS) has a presentation similar to CVS, but is associated with longstanding, high dose cannabis use, and is thought to be relieved by sustained cannabis abstinence. Most CHS patients have used cannabis on a daily or near-daily basis for more than 2 years. Compulsive hot-water bathing behaviors are reported by most CHS patients, but are not specific for this disorder as they are also noted by about half of CVS patients. Episodic vomiting associated with cannabis use contributes to extensive health resource use, including emergency department visits and inpatient hospitalizations, and impacts patients and their families negatively. Treatment for CHS overlaps with CVS although cannabis abstinence remains the cornerstone of its management. Challenges associated with cannabis use cessation in CHS include patient skepticism of the role of cannabis as a cause of symptoms, perceived benefits of cannabis, and a lack of other effective therapies. In this review, we highlight cannabis use patterns in the US and discuss diagnosis and management of CHS and gaps in knowledge about this disorder.

Alcohol and Cannabis Use by Adolescents with Special Educational Needs: A Systematic Review Focused on Students with Emotional and Behavioral Disorders.

Aim: As most substance use prevention programs are offered at school, it is important to explore which group of students might be at increased risk. Both researchers and educators have often maintained that students with special educational needs due to emotional and behavioral disorders (SENs-EBD) are particularly vulnerable. Hence, the aim of the current systematic review was to examine the alcohol and cannabis use by students with SENs-EBD in comparison to students without SENs or other types of SENs. Methods: Adhering to the PRISMA guidelines, the review was registered on PROSPERO (CRD42023375799) and search terms were entered in Web of Science, Scopus, ERIC, and PubMed in December 2022. Publications were required to report on empirical quantitative studies (primary data) that assessed alcohol and/or cannabis use by adolescent students with SENs-EBD and a comparison group, and be published in English-language journal articles, conference papers, or book chapters from 2000 onwards. The QuADS tool was used for quality assessment. Results: Based on these criteria, six articles (sample sizes N = 61 to N = 122,180) were included for the thematic narrative synthesis. The studies revealed that the percentage of students with SENs-EBD consuming alcohol and cannabis was higher compared to students who did not have SENs or attended mainstream schools. Conclusion: The small number of heterogeneous studies, with limitations concerning the sample size, missing effect sizes, and influence of control variables, demonstrates the need for more research. The systematic review provides guidance for such future research endeavors, as well as preliminary notions for practical implications.

Can the THC concentration predict the number of patients with cannabis-related diagnoses?

INTRODUCTION: The use of high-potency cannabis products is associated with an increased risk of mental disorders. This study investigates whether the rising THC concentration in Germany is associated with an increase in cannabis-related diagnoses. METHODS: The number of insured persons with at least one cannabis-related ICD-10 F12 diagnosis (e.g., harmful use, dependence) in outpatient care was provided by statutory health insurance funds between 2009 and 2021. The dependent variable is the ratio of (a) the number of insured persons with at least one F12 diagnosis to (b) all insured persons who have used cannabis in the last year. Information on THC concentration in cannabis flower was provided by law enforcement agencies. Using generalised mixed linear models, the dependent variable was predicted by the median THC concentration in cannabis flower. RESULTS: The regression results show that an increase in THC concentration by one percentage point is significantly associated with an increase in the proportion of diagnoses (women: +0.17; men: +0.42). THC concentration positively predicted the proportion of diagnoses in all 16 federal states for men and in 15 federal states for women. DISCUSSION AND CONCLUSIONS: Compared to low-potency products, using high-potency products may pose additional health risks, which may be particularly pronounced in men. Acknowledging the limitations of the ecological study design and uncertainties inherent to the analysed data, further investigations on the sex-specific impact of THC exposure are required. Limiting the THC concentration in cannabis products and closely monitoring THC consumption in the population appears necessary.

Cannabis therapy in rheumatological diseases: A systematic review.

Cannabis has been used in rheumatic diseases as therapy for chronic pain or inflammatory conditions. Herein, the authors systematically review the rheumatological diseases in which cannabis has been studied: systemic sclerosis, fibromyalgia, osteoarthritis, rheumatoid arthritis, osteoporosis, polymyalgia rheumatica, gout, dermatomyositis, and psoriatic arthritis. We systematically searched PubMed for articles on cannabis and rheumatic diseases between 1966 and March 2023. Twenty-eight articles have been selected for review. Most of them (n=13) were on fibromyalgia and all of them but one showed important reduction in pain; sleep and mood also improved. On rheumatoid arthritis, two papers displayed decrease in pain and in one of them a reduction in inflammatory parameters was found. In scleroderma there was a case description with good results, one study on local use for digital ulcers also with good outcomes and a third one, that disclosed good results for skin fibrosis. In dermatomyositis a single study showed improvement of skin manifestations and in osteoarthritis (3 studies) this drug has demonstrated a good analgesic effect. Several surveys (n=5) on the general use of cannabis showed that rheumatological patients (mixed diseases) do use this drug even without medical supervision. The reported side effects were mild. In conclusion, cannabis treatment is an interesting option for the treatment of rheumatological diseases that should be further explored with more studies.

Inter-strain variability in responses to a single administration of the cannabidiol-rich cannabis extract in mice.

Cannabidiol (CBD) has gained widespread popularity; however, its pharmacological and toxicological profiles in the context of human genetic diversity remain largely unexplored. Here, we investigated the variability in metabolism and toxicity of CBD-rich cannabis extract (CRCE) in genetically diverse mouse models: C57BL/6J, B6C3F1/J, and NZO/HlLtJ strains. Mice received a single dose of CRCE containing 57.9% CBD at dosages of 0, 246, 738, and 2460 mg/kg of CBD. At 24 h after treatment, no appreciable histomorphological changes were detected in the liver. Plasma bilirubin levels increased markedly in all strains at the highest CBD dose. Mice in all treatment groups displayed significant but distinct increases in ALT and AST levels. While B6C3F1/J and NZO/HlLtJ mice had negligible plasma CBD levels at 738 mg/kg, C57BL/6J mice exhibited levels exceeding 7000 ng/mL. At 2460 mg/kg, high CBD concentrations were found in B6C3F1/J and C57BL/6J mice, but markedly lower levels were seen in NZO/HlLtJ mice. Gene expression profiling showed significant increases in Cyp2b10 across all strains but varying responses in Cyp1a1 expression, indicating strain-specific CYP dysregulation. Genetically diverse mice exhibited differential pharmacological and toxicological responses to CRCE, suggesting a high potential for inter-individual variability in the pharmacology and toxicology of CBD in humans.

Longitudinal patterns of alcohol and cannabis use among US young adults: Correlates and implications for problematic health outcomes.

INTRODUCTION: Alcohol and cannabis use are common during young adulthood. Less is known regarding correlates of alcohol-cannabis use patterns and related problematic health outcomes. METHODS: Using longitudinal survey data (Fall 2018, 2019, 2020) from 2,194 young adults (YAs; ages 18-34), bivariate analyses and multivariable logistic regressions examined: (1) Wave 1 (W1) sociodemographics and psychosocial factors (i.e., adverse childhood experiences [ACEs], depressive symptoms, personality traits, parent and peer alcohol and cannabis use) in relation to W3 past-month use group (i.e., use of neither, alcohol only, cannabis only, both/co-use); and (2) W3 use group in relation to W5 problematic alcohol use (Alcohol Use Disorder Identification Test), problematic cannabis use (Cannabis Use Disorder Identification Test), and depressive/anxiety symptoms (Patient Health Questionnaire - 4 item). RESULTS: Overall, 42.3% reported W3 alcohol-only use, 34.9% co-use, 17.8% no use, and 5.0% cannabis-only use. Those reporting W3 co-use reported greater W1 extraversion, openness, friend alcohol/cannabis use, and were more likely to report parent cannabis use (vs. no use); reported less conscientiousness, greater friend cannabis use, and were more likely to report depressive symptoms and parent cannabis use (vs. alcohol-only use); and reported greater friend alcohol use, and were more likely to report parent alcohol use (vs. cannabis-only use). W3 co-use was associated with higher odds of W5 problematic alcohol use (vs. alcohol-only use) and problematic cannabis use (vs. cannabis-only use). CONCLUSIONS: Substance use messaging and interventions should consider YAs' alcohol-cannabis co-use and the unique correlates of such use.

Cannabis use disorder and substance use treatment among U.S. adults.

INTRODUCTION: Recent expansion of cannabis legalization in multiple states calls for reexamination of the prevalence of cannabis use, cannabis use disorder (CUD), and the associations between CUD severity and substance use treatment. We used Andersen's behavioral model of healthcare use as the conceptual/analytic framework for examining treatment use. METHODS: We used data from the 2022 National Survey on Drug Use and Health (NSDUH; N = 47,100, age 18+) to describe the prevalence of past-year cannabis use, CUD and CUD severity, other substance use disorders, and substance use treatment. We compared sociodemographic, mental health, healthcare use, and cannabis and other substance use characteristics by CUD severity. Finally, we used logistic regression models to examine the associations between CUD severity and substance use treatment. RESULTS: Of the U.S. adult population, 23.0 % used cannabis in the past year; 7.0 % had a CUD (3.9 % mild, 1.9 % moderate, and 1.2 % severe CUD); and 4.7 % received substance use treatment. Of past-year cannabis users, 30.3 % had CUD (16.9 % mild, 8.4 % moderate, and 5.0 % severe CUD), and 9.6 % received substance use treatment. Cannabis users had 3-4 times higher rates of other substance use disorders than nonusers. Of those with CUD, 38.4 % had moderate/severe mental illness, 52.4 % had other substance use disorders, and 16.5 % received substance use treatment. Among all cannabis users, moderate (aOR [adjusted odds ratios] = 1.48, 95 % CI = 1.03-2.13) and severe (aOR = 2.57, 95 % CI = 1.60-4.11) CUDs were associated with greater odds of substance use treatment. Among cannabis users without nicotine dependence and alcohol, opioid, tranquilizer/sedative, and stimulant use disorders, only severe CUD (aOR = 6.03, 95 % CI = 3.37-10.78) was associated with greater odds of substance use treatment. CONCLUSIONS: This study shows increased prevalence of cannabis use and CUD among U.S. adults, and with or without other substance use disorders, CUD was associated with greater odds of substance use treatment. However, the overall low rate of treatment use among those with CUD is concerning. Healthcare providers need to provide education for both medical and recreational users on the development of tolerance and dependence. Harm reduction strategies to minimize the negative consequences of CUD are also needed.