Introduction: With the increasing use of medical cannabis (MC) worldwide, understanding potential sex-related differences in treatment patterns and outcomes has become increasingly important. The objective of this study was to characterize medical cannabis use in Israel, focusing on sex-related differences in usage patterns and adverse effects. Methods: We conducted a population-based, retrospective cohort study using data from the Israeli Medical Cannabis Agency registry (April 2018–March 2022). The dataset includes license holders’ demographics, indication for use, monthly dose, THC/CBD concentrations, and reported adverse effects. Sex-related differences were assessed using time-series analyses, Cox models, and relative risk estimates. Results: A total of 135,698 individuals (62% men) were issued a license to use MC in Israel during the study period. Men using MC were significantly younger than women (49 ± 18.3 vs. 55.3 ± 18.1). The leading indications among both sexes were chronic pain, symptoms related to oncological disease and chemotherapy treatment, and post-traumatic stress disorder. At initiation, men received higher monthly quantities than women (29.3 g vs. 26.1 g; p < 0.001), higher THC concentrations (14.3% vs. 11.9%; p < 0.001), and lower CBD concentrations (5.1% vs. 6.5%; p < 0.001). These differences remained significant over 2 years. Men had a lower discontinuation rate (HR 0.95, 95% CI: 0.93–0.97). Women were more likely than men to report at least one adverse effect (RR 1.51, 95% CI: 1.43–1.58). Conclusion: Sex-related differences in MC use likely reflect biological, behavioral, and systemic factors, influencing both outcomes and risk of misuse. These disparities highlight the need for sex-informed clinical approaches and further research to support equitable, evidence-based treatment.
Background: A pharmacologic approach for smoking cessation is enzyme inhibition. Cytochrome P450 2A6 (CYP2A6)–mediated nicotine metabolism is a key target, yet no safe or effective inhibitors are currently available. We examined associations between marijuana use and the nicotine metabolite ratio (NMR) in adults who smoke. Methods: We conducted a cross-sectional analysis of adults who currently smoke in the National Health and Nutrition Examination Survey (NHANES) 2013–2018. Marijuana use was assessed by two self-reported measures: marijuana use every month for 1 or more years and frequency of marijuana use. NMR was calculated as the ratio of serum trans -3′-hydroxycotinine (3-HCOT) to cotinine and categorized into quartiles based on weighted population cutoffs. Survey-weighted multinomial models adjusted for sociodemographic covariates were used. Results: Among 2984 adults who currently smoke, marijuana use every month for 1 or more years was associated with lower NMR. Compared with those who didn't use marijuana, participants who used marijuana every month for 1 or more years had reduced odds of being in NMR quartile 4 (adjusted odds ratio [aOR] = 0.59, 95% confidence interval [CI] = 0.41–0.85); no significant association was observed for quartile 2 or 3. When the frequency of marijuana use (DUQ230) was modeled categorically, weekly users had reduced odds of quartile 4 classification relative to never users (aOR = 0.53, 95% CI = 0.31–0.91). Monthly and daily use frequency showed a similar direction of association with reduced odds of quartile 4 classification (aOR = 0.73, 95% CI = 0.37–1.44; and aOR = 0.54, 95% CI = 0.28–1.04, respectively), though these did not reach statistical significance. Conclusions: People who smoke cigarettes and co-use marijuana had a lower NMR. Pharmacokinetic studies are needed to further determine whether cannabinoids affect nicotine metabolism. Impact: The nonpsychoactive forms of cannabinoids may be useful for the treatment of tobacco use disorder.
Introduction: Use of cannabinoid vape products during pregnancy is a major public health concern. Δ 9-tetrahydrocannabinol (THC), the main psychoactive constituent in cannabis, is rapidly absorbed after inhalation and transferred to the fetal brain. We developed a novel model of prenatal cannabinoid exposure (PCE) comprising THC vapor exposure across the human-equivalent full-term prenatal period in rats. This study examined gestational/parturitional outcomes and the distribution and metabolism of THC in maternal and filial blood and brains using this model. Materials and Methods: Pregnant female Sprague-Dawley rats were exposed to THC (200 mg/mL, n = 13) or vehicle (100% propylene glycol, n = 8) vapor daily during gestation until postnatal day (PD) 10 (i.e., human-equivalent full-term). Pups were exposed directly in the postnatal period. Gestational/parturitional assessments included dam food intake, dam and pup body weights, total gestation days, litter size, and sex ratio. Subsets of THC-exposed dams and pups were sampled immediately postvapor on gestational day (GD) 20 ( n = 4 dams, 24 pups) or PD 10 ( n = 2 dams, 33 pups) to quantify THC and its metabolites (11-hydroxy-Δ9-tetrahydrocannabinol [11-OH-THC], and 11-nor-9-carboxy-Δ9-tetrahydrocannabinol [THCCOOH]) concentrations in the brain (dams and pups) and plasma (dams). Results: THC decreased dam food intake and total gestation days compared to controls. THC concentrations in dam plasma and brain were 14.8 ± 47.8 ng/mL and 80.5 ± 38.6 ng/g on GD 20 and 68.9 ± 25.0 ng/mL and 125.0 ± 4.2 ng/g on PD 10. Birth weights were not different between THC-exposed offspring and controls, but postnatal weights were decreased. On GD 20, fetal brain THC, 11-OH-THC, and THCCOOH concentrations were 12 ± 5%, 118 ± 7%, and 75 ± 34% of maternal plasma. On PD 10, pup brain THC and 11-OH-THC concentrations were 29.6 ± 8.5 and 9.8 ± 2.1 ng/g. THCCOOH was not detected in PD 10 pup brain. Discussion: THC readily transferred from dams to pup brains during gestation in our full-term vapor exposure model. High THC and 11-OH-THC concentrations were detected in pup brains at both timepoints. This novel model is a valuable tool to investigate long-term effects of full-term PCE on offspring brain development and behavior.
Introduction: While recreational marijuana remains illegal under federal law in the United States, “hemp-derived” products that contain less than ≤ 0.3% Delta-9-tetrahydrocannabinol (THC) were legalized in 2018. New classes of intoxicating products have proliferated, such as Delta-8 products, with few regulatory restrictions. The current study sought to assess awareness and prevalence of use of Delta-8-THC products in the United States. Materials and Methods: Data are from 69,564 U.S. 16–65-year-old respondents to the 2021–2022 International Cannabis Policy Study (ICPS). Participants were asked about awareness, ever use, and past-month use of specific THC isomers. Logistic regression models examined correlates in the awareness and use of Delta-8-THC, including state cannabis laws. Results: In 2021, 14.5% of respondents reported ‘hearing’ about Delta-8 products, which increased to 21.8% in 2022 (AOR = 1.76, 95% CI = 1.59–1.95, p < 0.001). Ever use of Delta-8 was higher in states where ‘conventional’ Delta-9 cannabis was illegal (11.2%), compared with states where medical cannabis (8.5% vs. 11.2%, AOR = 0.68, 95% CI = 0.58–0.79, p < 0.001) and adult-use recreational cannabis is legal (6.5% vs. 11.2%, AOR = 0.44, 95% CI = 0.36–0.55, p < 0.001). Discussion: The cannabinoid market is rapidly diversifying with increased use of hemp-derived cannabinoid products, particularly in states where Delta-9-THC cannabis remains illegal. Conclusions: There is an urgent need for enhanced monitoring of the diversifying cannabinoid market. Education is warranted to inform consumers about the type and potential health risks of novel hemp-derived products.
BACKGROUND:Global expansion of medicinal and recreational cannabis markets has created an increasingly diverse range of products, intensifying demand for analytical methodologies that are accurate, high-throughput, environmentally sustainable, and adaptable to complex matrices. Cannabis poses unique analytical challenges owing to its chemically diverse phytochemical composition, thermolabile acidic cannabinoids, low-abundance minor constituents, and stringent regulatory requirements for potency determination and contaminant screening. Conventional extraction protocols often struggle to satisfy these evolving technical and operational needs, driving a transition toward miniaturized sample-preparation strategies integrated with advanced chromatographic platforms. AIM:This narrative review evaluates contemporary miniaturized extraction techniques for cannabis and cannabinoid analysis and their coupling with modern analytical instrumentation, focusing on analytical performance, matrix applicability, sustainability, automation potential, and regulatory relevance. RESULTS:Forty peer-reviewed studies published up to December 2025 were identified. Solid-phase microextraction (SPME), microextraction by packed sorbent (MEPS), dispersive liquid-liquid microextraction, fabric-phase sorptive extraction (FPSE), modified Quick, Easy, Cheap, Effective, Rugged and Safe (QuEChERS), and emerging sorbent-based approaches were identified as solutions to major analytical challenges, including preservation of acidic cannabinoids, lipid-rich matrices, trace-level detection, and high-throughput laboratory demands. MEPS and micro-solid-phase extraction (µSPE) showed suitability for biological fluids due to their enrichment capacity and automation compatibility, while SPME including headspace remained dominant for terpene and volatile profiling. When coupled to liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS) or ultra-high-performance liquid chromatography-high-resolution mass spectrometry (UHPLC-HRMS), miniaturized workflows achieved limits of detection comparable to or superior to conventional protocols and aligned closely with green sample preparation principles. Challenges included fiber durability, sorbent selectivity, microscale reproducibility, and the absence of harmonized regulatory standards. CONCLUSION:Miniaturized extraction integrated with advanced chromatographic platforms represents a major advance in cannabis analytics, enabling greener, faster, and regulatory-fit workflows. Techniques such as MEPS, µSPE, and modified QuEChERS appear particularly suitable for routine implementation. Broader validation across product classes and formal standardization within pharmacopeial and ISO frameworks are required to ensure widespread adoption and regulatory acceptance.
