Search Results (357)

Background: Poor appetite, a major contributor to malnutrition, is highly prevalent among older adults and associated with adverse clinical outcomes. Nevertheless, there are currently no widely accepted or consistently effective pharmacological treatments targeting appetite that are routinely recommended alongside nutritional interventions. Medical cannabis has been proposed as a potential appetite stimulant in older adults with poor appetite through modulation of appetite-regulating hormones such as glucagon-like peptide-1 (GLP-1) and total ghrelin, but the evidence remains limited. Aims: To investigate the effects of Sativex^® versus placebo on postprandial GLP-1 and total ghrelin concentrations following a single dose (8.1 mg Δ9-tetrahydrocannabinol (THC) and 7.5 mg cannabidiol (CBD)), and on subjective appetite following two separated doses, in older adults with poor appetite, and to investigate the associations between plasma concentrations of THC and its metabolites on these outcomes. Methods: This protocolized secondary analysis included 17 participants (≥65 years) with poor appetite from a double-blind, randomized, placebo-controlled crossover trial. Participants received Sativex^® or placebo on two separate study days. GLP-1 and total ghrelin were measured following one dose of Sativex^®/placebo and a standardized breakfast, and subjective appetite was assessed repeatedly using visual analog scales throughout the administration of two separate doses of Sativex^®/placebo, the consumption of a standardized breakfast, and an ad libitum lunch meal. Effects/associations were analyzed using linear mixed-effects models. Results: Compared with placebo, Sativex^® produced an estimated 2.38 pmol/L (95% confidence intervals (CI): −0.71 to 5.46; Bonferroni-corrected p = 0.274) reduction in mean GLP-1 and time-dependent changes in mean total ghrelin (Bonferroni-corrected p = 0.054). Compared with placebo, Sativex^® produced minimal changes in separate subjective appetite sensations (all Bonferroni-corrected p = 1.00) and a slightly lower combined appetite score (−5.2 mm; 95% CI: −24.4 to 4.0; Bonferroni-corrected p = 1.00). Increased plasma concentrations of THC and metabolites were associated with reduced estimates of mean GLP-1 concentrations and subjective appetite, as well as increased mean total ghrelin concentrations. However, no statistically significant differences were detected for any analyses, and estimates had wide CIs, warranting cautious interpretation. Conclusions: In conclusion, no statistically significant differences were detected between Sativex^® and placebo in postprandial GLP-1, total ghrelin, or subjective appetite over time in older adults with poor appetite. Similarly, no statistically significant associations were observed between plasma concentrations of THC and its metabolites and GLP-1, total ghrelin, or subjective appetite. Trial registration: ClinicalTrials.gov ID: NCT05503147; EudraCT nr.: 2021-002318-15. Full article

Background: Online communities such as Reddit can reveal critical information needs (CINs) among people who discuss opioid use for chronic or acute pain under conditions of stigma and uncertainty. Methods: We used a mixed-method design to analyze 3428 unique Reddit posts from 1 January to 31 December 2022. Sentence-BERT embeddings and K-means clustering identified eight dominant themes, followed by qualitative analysis of a random subsample of 400 posts. Results: The most prevalent theme was seeking alternatives to opioids for pain relief (28.00%), followed by medications for chronic pain (19.84%) and kratom use experiences (14.64%). Qualitative findings showed recurrent concerns about addiction, stigma in clinical encounters, withdrawal, treatment access, and peer-to-peer discussion of kratom, tianeptine, cannabis, and other substitute substances. Conclusions: The study suggests an unmet need for accessible, nonstigmatizing, and clinically grounded information on pain management, tapering, and lower-risk alternatives to opioid use. These results have implications for addiction prevention, harm reduction, and patient-facing communication strategies for clinical practice and community health. Full article

Background: Adolescence is a sensitive period for brain maturation during which exposure to Δ⁹-tetrahydrocannabinol (THC) can induce long-lasting neurobehavioral alterations. Yet, preclinical and clinical studies report inconsistent long-term outcomes of adolescent THC exposure, ranging from clear impairments to apparently normalizing effects. We hypothesize that these discrepancies reflect stable individual differences in stress-coping abilities. Methods: To test this, selectively bred Dominant (Dom; stress-resilient, risk-prone) and Submissive (Sub; stress-vulnerable, depressive-like) Sabra mice received THC or vehicle during adolescence and were assessed in adulthood. Results: Anxiety-like and exploratory behavior, measured in the hole-board test, were differentially affected by THC as a function of stress vulnerability: in Sub mice, THC increased exploration and reduced anxiety-like behavior, whereas in Dom mice THC produced the opposite pattern. Recognition memory, evaluated by the novel object recognition test, showed modest, line-dependent alterations. Sensitivity to N-methyl-D-aspartate (NMDA) receptor hypofunction, a widely used index of vulnerability to schizophrenia-like symptoms, was examined using MK-801-induced locomotion. Adolescent THC potentiated MK-801-evoked hyperlocomotion in Dom mice but attenuated it in Sub mice. Conclusions: In the context of increasing medical and recreational cannabis exposure, these in vivo findings suggest that stress-vulnerability-related traits may be an important variable to consider in future preclinical and translational studies of adolescent THC exposure. Full article

Introduction: Medical cannabis is increasingly used to manage post-traumatic stress disorder (PTSD), a condition frequently linked to high healthcare utilization, particularly for acute services. Methods: We conducted a retrospective cohort study using data from Leafwell among patients with PTSD who either used medical cannabis for at least one year (treated group) or were cannabis-naïve (untreated group). The primary outcomes were urgent care, emergency department (ED), or hospitalization visits in the past six months. We applied inverse probability weighting with regression adjustment (IPWRA) to estimate the average treatment effect (ATE) of medical cannabis exposure, adjusting for demographics, PTSD severity, and other health factors. Sensitivity analyses were performed to assess robustness. Results: Out of 1946 participants, 1261 were in the treated group and 685 in the untreated group. The treated group had a 35.6% lower probability of urgent care visits (coefficient = −0.024, SE = 0.0117) and a 35.1% lower probability of ED visits (coefficient = −0.027, SE = 0.0124). Although hospitalization rates were 26.3% lower, this difference was not statistically significant. Findings remained consistent across multiple ATE estimation methods, and adjusting the IPWRA model’s tolerance levels strengthened these associations. Fewer than 2% of the treated group reported adverse events. Conclusions: Medical cannabis use among patients with PTSD was associated with reduced urgent care and ED visits. These results were robust across analytical methods, supporting the potential role of medical cannabis in lowering acute healthcare needs. Further longitudinal research is warranted to assess causality and clarify effects on hospitalization. Full article

Background/Objectives: Chronic low back pain (CLBP) affects approximately 20% of the global population and is a leading cause of years lived with disability. Long-term, real-world evidence for inhaled cannabis in patients refractory to conventional multimodal therapy remains scarce. We assessed the five-year efficacy and safety of inhaled cannabis in CLBP patients who had documented failure of ≥1 year of opioid analgesics, anticonvulsants, antidepressants, NSAIDs, and physiotherapy, with each patient serving as their own historical control. Methods: We analyzed prospectively collected clinical data from 241 consecutive adults with treatment-refractory CLBP (mean age 49.3 ± 14.9 years; 37.8% female; mean pain duration 15.1 years) initiated on inhaled medical cannabis (predominantly smoking, THC 4–22%, CBD 2–22%) in a single-center tertiary orthopedic clinic between 2020 and 2025 (Hasharon Hospital, Rabin Medical Center, Israel; IRB protocols 0807-21-RMC and 0634-25-RMC). Year-0 outcomes during conventional therapy were compared with outcomes at Years 1–5 on cannabis. Primary outcomes were the Numeric Rating Scale (NRS), Oswestry Disability Index (ODI), and Brief Pain Inventory severity/interference (BPI-S/BPI-I). Concomitant-medication trajectories were a secondary outcome. The primary analysis was a mixed model for repeated measures (MMRM) with random intercept and slope, REML estimation, and time as a categorical fixed effect. Multiple imputation (MAR, m = 20, Rubin’s rules) was the primary missing-data approach; complete-case and tipping-point pattern-mixture sensitivity analyses were used. A multivariate Hotelling T² provided a joint test across the four correlated PROMs. Concomitant-medication discontinuation was modeled with GEE logistic regression and exact McNemar tests. Time to discontinuation was estimated by Kaplan–Meier and Cox regression. The Bonferroni-adjusted significance threshold for the four primary outcomes was α = 0.0125. BioWell gas-discharge-visualization (GDV) parameters were exploratory only. Results: Of 241 patients, 238 (98.8%) provided Year-5 data and 224 (92.9%) remained on cannabis at Year 5; only five patients (2.1%) discontinued for adverse events or inefficacy. All four primary PROMs improved markedly and durably. MMRM-estimated Year-5 minus Year-0 changes were: NRS −5.36 (95% CI −5.65, −5.07), ODI −17.68 (95% CI −19.73, −15.63), BPI-S −6.73 (95% CI −6.99, −6.47), and BPI-I −3.41 (95% CI −3.65, −3.16); all four contrasts had |z| ≥ 16.9 and p < 10⁻²⁰. MI-pooled estimates were within 0.05 of MMRM (FMI < 0.03 for all outcomes). Hotelling T² was F(4, 232) = 872.8, p < 10⁻²⁰. At Year 5, 89.2% achieved ≥30% NRS reduction, 77.2% ≥ 50%, and 93.4% met the NRS minimum clinically important difference (MCID); ODI MCID 65.6%, BPI-S MCID (≥1 pt) 98.3%, BPI-I MCID (≥1 pt) 91.3%. Concomitant opioid use fell from 100% at baseline to 4.6% at Year 5 (within-patient absolute risk reduction 95.4%, McNemar exact p = 1.16 × 10⁻⁶⁹), NSAID from 100% to 7.1%, SSRI/SNRI from 80.5% to 5.4%, and gabapentinoid from 38.6% to 2.5%. The ARR-derived NNT for opioid discontinuation was 1.05; this NNT is referenced to each patient’s own documented maximal-conventional-therapy state and is not equivalent to a between-arm randomized-trial NNT. Cannabis dose × time interaction was consistent with no pharmacological tolerance (β = −0.0044 per gram-month per year, p = 0.074). Across 1205 patient-years of cannabis exposure (calculated as 241 patients × 5 follow-up years from Year 1 through Year 5; baseline Year 0 represents pre-cannabis state and is not included in person-time on cannabis), 1338 organ-system AE events were recorded at 1.110/patient-year (Poisson 95% CI 1.05–1.17); 99.8% of graded events were mild (grade 1), with ocular (476 events, 0.40/PY), cognitive (460, 0.38/PY), and gastrointestinal (368, 0.31/PY) reactions predominating. The Year-3 retention dip reflected a documented telemedicine-clinic phenomenon during 2022–2024, with patients returning to in-person follow-up by Year 4–5. BioWell GDV discriminated NRS ≥ 4 only at chance level (BWS AUC 0.574, 95% CI 0.54–0.60; BWV AUC 0.51). Conclusions: In a treatment-refractory CLBP cohort with five-year longitudinal follow-up, inhaled cannabis was associated with large, sustained, and statistically robust improvements in pain, disability, and pain interference, accompanied by near-total displacement of opioids, NSAIDs, antidepressants, and gabapentinoids. These observational associations, although mechanically less susceptible to bias for the binary medication-discontinuation outcomes than for self-reported PROMs, cannot be interpreted causally in the absence of a concurrent randomized control arm and may reflect a combination of pharmacological effect, regression to the mean from a high pre-treatment baseline, expectancy and self-selection effects intrinsic to an actively chosen open-label therapy, and secular trends in pain reporting. The within-patient benefit-risk profile—ARR-derived NNT ≈ 1 for opioid sparing against a predominantly mild adverse-event burden—supports consideration of cannabis as a potentially clinically meaningful, opioid-sparing option in patients who have failed multimodal conventional therapy, pending confirmation in randomized comparative trials. Full article

Cannabis sativa L. is a multipurpose crop of increasing agricultural and medical relevance, whose productivity and phytocannabinoid profile are influenced not only by genotype and environmental factors but also by the composition of its microbiota. This review synthesizes current knowledge (2020–2026) on the rhizosphere and endophytic microbiota of hemp, with particular emphasis on plant growth-promoting bacteria (PGPB) and their mechanisms of action. Molecular studies indicate that hemp-associated bacterial communities are dominated by Proteobacteria, Actinobacteriota, Firmicutes and Bacteroidota, with genotype-, tissue- and developmental-stage-dependent variation. PGPB influence plant performance through direct mechanisms, including biological nitrogen fixation, phosphate solubilization, siderophore production and phytohormone synthesis (indole-3-acetic acid (IAA), gibberellins, cytokinins, and 1-aminocyclopropane-1-carboxylate (ACC) deaminase), as well as indirect mechanisms such as antibiosis, enzyme-mediated pathogen inhibition and induction of systemic tolerance to abiotic stress. Experimental studies demonstrate that inoculation with selected strains or consortia can enhance biomass accumulation, improve germination and root architecture, increase resistance to Fusarium oxysporum and modulate cannabinoid and terpene profiles. Importantly, plant responses are cultivar-specific, highlighting the need for genotype-tailored microbial formulations. Full article

The pharmaceutical development of cannabis-based medicinal products is challenged by significant variability in the quality, composition, and standardization of plant-derived active pharmaceutical ingredients (APIs). In Ukraine, despite recent legislative liberalization, a substantial shortage of standardized raw materials continues to limit the development of innovative dosage forms. This study analyses international practices among API manufacturers to identify technological parameters necessary to overcome domestic market barriers and support the implementation of advanced drug delivery systems. Content analysis was conducted on regulatory documentation, professional literature, and manufacturers’ technical specifications. Candidate evaluation followed predefined inclusion and exclusion criteria. The study assessed compliance with Good Manufacturing Practice (GMP) requirements, extraction and purification technologies, the extent of analytical characterization, and batch-to-batch reproducibility. Purposive sampling enabled a comparative analysis of various technological approaches. Marked heterogeneity was observed in API standardization and analytical control indicators among manufacturers. Possession of a GMP certificate was found necessary but may be insufficient to ensure the pharmaceutical equivalence of materials. Differences in extraction methods and purification levels may affect stability profiles, pharmaceutical development strategies, and risk management related to final product quality. The findings demonstrate that manufacturer selection is a critical decision point in pharmaceutical development, with substantiated supplier choice directly influencing dosage form development and regulatory compliance. Full article

Hemp (Cannabis sativa L.) is a multipurpose crop with significant industrial and therapeutic potential. This article reviews the various uses of hemp in production, building, food, cosmetics and medicine, focusing on its economic, environmental and health benefits. Industrially, hemp has been used for making fabrics, paper, bioplastics, construction materials and biofuels, because of its strong fibres, fast growth and low impact on the environment. Hemp seed oil and protein in the food and beauty industries are gaining more recognition for their nutritional and functional characteristics. Medically, compounds extracted from hemp, especially cannabidiol (CBD) and other non-psychoactive phytochemicals, have been shown to possess significant anti-inflammatory, pain-relieving, neuroprotective, antioxidant and antibacterial properties. This article talks about how better cultivation methods, processing technologies, and extraction techniques can help improve product quality, marketability, regulatory frameworks, safety standards and the quality control measures that are in place to monitor hemp production and utilization, as well as the focus on new policies in developing nations. Even though hemp has a wide range of potentials, the industry still faces difficulties in the form of laws, lack of infrastructure, unequal product standardization, and lack of scientific proof in certain areas of application. This article further identifies research gaps and points out potential areas for innovation, policymaking, and market development to be explored in the future. If backed up by proper regulations and research, hemp has great potential to contribute to the development of environmentally friendly industries, the improvement of public health and the socio-economic upliftment of communities. Full article

Non-medical use of cannabis (NmC) and/or opioids (NmO) can lead to adverse health effects (AHEs), yet the proportion of these harms attributable to adverse childhood experiences (ACEs) remains unclear. This study estimated the contribution of ACEs to AHEs from NmC and/or NmO among adults aged ≥18 years using 2019–2020 Behavioral Risk Factor Surveillance System data from Arizona and Massachusetts. We conducted a retrospective cohort analysis of 24,739 respondents, linking past ACE exposure to self-reported NmC/NmO/NmC&NmO and related AHEs. Generalized linear models with a log link and binomial distribution adjusted for socio-demographic, healthcare access, and geographic factors were used to estimate associations and population-attributable fractions (PAFs). Propensity score methods matched respondents with and without ACEs on demographic and location characteristics. Among all the adults, 17.9% reported NmC, 5.8% reported NmO, and 2.4% reported NmC&NmO; among users of NmC/NmO/NmC&NmO, 5.0%/13.2%/36.0% reported AHEs. Among the respondents reporting AHEs from non-medical substance use, exposure to ≥2 ACEs was common (NmC: 89%; NmO: 82%; NmC&NmO: 84%). Compared to adults without ACEs, those with ≥2 ACEs had a higher likelihood of AHEs for NmC (adjusted relative risk [aRR] = 3.54, 95% CI: 1.65–7.59) and NmO (aRR = 3.64, 95% CI: 1.99–6.66) but not NmC&NmO (aRR: 1.86, 95% CI: 0.84–4.09). PAFs indicated that 63% (NmC) to 64% (NmO) of AHEs among the adults reporting NmC or NmO were attributable to ≥2 ACEs. Preventing childhood adversity may substantially reduce substance-related harms in adulthood. Full article

Synthetic cannabinoids are widely available in the United States, yet contemporary national data on who uses these products, and disparities in use, are limited. To assess disparities in lifetime and past-year synthetic cannabis use (each yes/no), we used 2022–2024 National Survey on Drug Use and Health data from adults aged ≥18 years (n = 139,532) and fit two multivariable logistic regression models adjusted for survey year and sociodemographic and policy characteristics. We also calculated proportions of lifetime and past-year use by various plant-based cannabis use modalities. The proportions of adults with lifetime and past-year synthetic cannabis use were 2.7% and 0.3%, respectively. Younger age, male sex, lower education and household income, and non-metropolitan residence were linked to both lifetime and past-year synthetic cannabis use. For example, past-year synthetic cannabis use was associated with living in non-metropolitan (vs. large metropolitan) areas (AOR = 1.54; 95% CI: 1.03–2.30). Past-year use was also linked to residence in states without medical cannabis law coverage (AOR = 1.45; 95% CI: 1.09–1.94). Finally, past-year synthetic cannabis use was most prevalent among adults who smoked (67.3%) or vaped (52.5%) plant-based cannabis. Synthetic cannabis use was uncommon overall but exhibited clear disparities, underscoring the need for continued surveillance amid evolving cannabinoid policies and markets. Full article

Background/Objectives: Rheumatoid arthritis (RA) is a chronic, inflammatory, autoimmune disease that primarily affects the joints. Current treatments aim to relieve pain and limit joint damage; however, many are associated with significant side effects or high costs. Neutrophils play a critical role in RA development and progression by driving synovial inflammation and tissue damage, yet no approved therapies directly target neutrophil-mediated pathogenic mechanisms. Cannabinoids have demonstrated anti-inflammatory potential. Although cannabinoids have been studied in RA, the direct modulation of neutrophil-driven mechanisms by purified CBG has not been systematically addressed. To harness the cannabinoid potential, we investigated the effects of the purified cannabinoid Cannabigerol (CBG) on neutrophil-mediated immune responses in RA. Methods: We assessed the effects of CBG on human blood isolated neutrophil cytokine secretion, signal transduction and migration as ex vivo models. In addition, collagen antibody-induced arthritis (CAIA) was applied in C57BL/6 wt mice, and immune-cell recruitment and cytokine secretion were examined after CBG treatment. Results: Ex vivo experiments demonstrated that CBG hampered the secretion of pro-inflammatory cytokines from human neutrophils in a dose-dependent manner (TNF-α and IL-6 by 68% and 72%, respectively). Furthermore, CBG downregulated inflammatory signal transduction, such as P38-MAPK, ERK1/2 and Akt phosphorylationpost neutrophil activation by 41%, 54% and 78%, respectively. Importantly, 60% of the CBG downregulation of IL-6 was consistent with the CB2 receptor axis in a selective way. In addition, CBG attenuated neutrophil migration toward IL-8 by 67%. To further evaluate CBG therapeutic capacity, we used CAIA as an in vivo model. CBG treatment resulted in improving mice arthritis clinical scores and body weight in comparison to RA-diseased mice. Moreover, CBG reduced leukocyte recruitment to the inflamed joints by 48%, primarily through the inhibition of neutrophil and monocyte cells to 27% and 49%, respectively. Additionally, CBG showed its anti-inflammatory effect by decreasing inflammatory cytokines like IL-6 and IL-1β by 98% and 60% in the blood. Also, CBG reduced MCP-1 and IL-1β cytokines in the joints by 22% and 38%, respectively. Conclusions: These results show that CBG has anti-inflammatory capacity and therapeutic potential in regulating neutrophil-mediated immunity in RA. These findings are preclinical and require further validation before therapeutic positioning. Full article

Purpose: Whether medical cannabis reduces opioid use during early chemotherapy remains unclear. We examined cannabinoid and opioid prescribing among patients with GI cancers initiating chemotherapy. Methods: Patients with GI cancers initiating chemotherapy (2016–2025) were identified from the Epic COSMOS database. Cannabis exposure was defined as prescriptions for FDA-approved cannabinoids recorded in the EHR; non-prescription cannabis obtained through dispensaries were not captured. Patients with any cannabis or opioid use in the prior year or death within 90 days were excluded. Multivariable logistic regression evaluated factors associated with cannabinoid use. Results: Among 144,981 patients, 2.4% received cannabinoids within 90 days of chemotherapy initiation. Cannabinoid recipients were more likely to receive opioids than nonrecipients (60.6% vs. 31.1%, p < 0.01). In adjusted analyses, cannabinoid prescribing was more common among Black patients (aOR 1.45; 95%CI 1.30–1.61), women (aOR 1.11; 95%CI 1.03–1.19), and individuals with pancreatic cancer (aOR 3.26; 95%CI 2.97–3.58). Prescribing varied by region and declined over time, relative to 2017. Conclusions: Early cannabinoid prescribing was not associated with reduced opioid use. Use was more common among patients with pancreatic cancer and among Black patients, highlighting clinical and structural variation in supportive-care practices. Full article

Background: Several factors influence reasons for cannabis use in the U.S. This study examines reasons for cannabis use (recreational only, medical only, both) and their frequency of use in association with demographic variables, health-risk behaviors, legal status, and chronic disease. Methods: We performed a cross-sectional analysis of 466,355 adults (aged ≥18) in the 2018–2021 BRFSS surveys in areas that administered the cannabis module. The primary outcome variables were whether cannabis was used in the past 30 days and, if so, reasons for its use and the number of days of use. Regression techniques were used to assess these outcome measures according to selected variables. Results: Approximately 11.5% (SE = 0.1%) used cannabis in the past 30 days. The reasons for use were 36.7% (SE = 0.5%) recreation only, 36.4% (SE = 0.5%) medical and recreation, and 26.9% (SE = 0.4%) medical only. Cannabis use was significantly greater in areas where it was legal for medical and recreational use, but among those who used it, reasons for its use were not significantly associated with legal status. Among those who used cannabis in the past 30 days, using it for recreation only versus medical reasons only was significantly greater in the youngest age group, men, NH Blacks, never married, employed, students, college/technical school graduates, binge drinkers, never smokers, and non-obese and in the years 2020–2021 (vs. 2018–2021). Using it for both medical and recreational reasons versus medical reasons only tended to show similar results. Among those who used cannabis in the past 30 days, the mean number of days of cannabis use was 6.8 (SE = 0.3) days greater for those who used it for medical and recreational reasons vs. recreation only and 5.7 (SE = 0.3) days greater for those who used it for medical reasons only vs. recreation only, after adjusting for several potential confounders. Mean number of days of cannabis use varied significantly across the levels of several variables, including chronic disease status, in the adjusted model. Of those who used cannabis in the past 30 days and had arthritis, asthma, CHD, COPD, depression, diabetes, a heart attack, kidney disease, or cancer, less than half used it for medical purposes only. Conclusions: Cannabis use is more common in areas where it is legal for medical and recreational use, but legal status is not significantly associated with reasons for use. Those who use cannabis for medical purposes use it more often than those who use it for recreation only. Reasons for cannabis use vary by the levels of several variables, including chronic disease status. Less than half of those with a chronic disease use it solely for medical purposes. Full article

Marijuana use in the United States (U.S.) has diversified alongside expanding legalization, yet little is known about the psychosocial factors that distinguish medical from recreational use. This study examined whether psychological distress mediates the association between perceived social isolation (i.e., loneliness) and marijuana use type among U.S. adults. We analyzed cross-sectional, nationally representative data from the 2024 Health Information National Trends Survey (HINTS, cycle 7). Marijuana use was categorized as medical (including medical and both medical/recreational) versus recreational. Perceived social isolation was measured using the Patient-Reported Outcomes Measurement Information System (PROMIS) Social Isolation t-score, and psychological distress was assessed with the Personal Health Questionnaire (PHQ)-4. Survey-weighted descriptive analyses and a weighted structural equation mediation model accounting for the complex sampling design were conducted. Medical marijuana users reported significantly higher levels of psychological distress and perceived social isolation than recreational users. Greater social isolation was strongly associated with higher psychological distress, and higher distress was associated with a greater likelihood of medical (vs. recreational) marijuana use. The indirect effect of social isolation on marijuana use type through psychological distress was statistically significant, while the direct effect of social isolation was not significant after accounting for distress. Overall, greater perceived social isolation predicted medical marijuana use primarily through elevated psychological distress. These findings suggest that medical marijuana use among U.S. adults may reflect coping with psychological distress linked to social disconnection, underscoring the importance of integrating mental health and social context into clinical and public health approaches to cannabis use. Full article

Cannabis is the most-used psychoactive drug in Aotearoa—New Zealand (NZ); recreational use remains illegal, while medicinal use was legalized in 2020. Cannabis use is associated with increased risk of injury; however, there is little known on the causes and circumstances of cannabis-related fatal injuries. This retrospective population study utilized coronial case files to describe the contribution and circumstances of cannabis-related fatal injuries in NZ. Between 2012 and 2016, cannabis was reported in 273 of 3599 unintentional/assault injury deaths (1.32 deaths per 100,000 person-years, 95% CI 1.17, 1.49). High-risk groups included males aged 15–44 years, Indigenous Māori, and those in deprived areas, for whom higher rates of post mortem testing were conducted. Cannabis-related fatalities mainly resulted from road crashes and multi-drug poisonings with concomitant alcohol use common, especially in traffic crashes on public roads (49% of concomitant use). Cannabis use was mainly observed in the decedent (n = 256, 94%). One in five deaths involved a worker, either as a user or as a bystander to another’s use. Coronial files identified important opportunities for safety countermeasures targeting cannabis use among drivers and its concomitant use with alcohol. Improved coverage of post mortem testing could address data limitations, including biased testing patterns and missing medical use. Full article