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.
BACKGROUND:The chemical stability of cannabinoids in Cannabis sativa plant material and formulated products is a critical factor for quality control, therapeutic efficacy, and regulatory compliance. Cannabinoids such as THC are prone to degradation over time, which is heavily influenced by storage conditions and the product matrix. Despite its importance, comprehensive long-term stability data comparing different plant chemovars (high THC, high cannabidiol [CBD], and intermediate) alongside processed products like extracts and isolates remains limited. This study aims to evaluate the stability of cannabinoids in plant material, extracts, oil formulations, and isolates (CBD and Δ9-THC) under distinct environmental temperatures to optimize storage guidelines. METHODS:Cannabis plant material representing three distinct chemovars-high THC, high CBD, and intermediate (balanced THC/CBD), extracts, pure isolates (THC and CBD) and CBD extract as oil formulation were subjected to extended stability testing over a prolonged period under three controlled temperature environments: room temperature, refrigeration, and freezing. Quantitative analysis of cannabinoid content was performed at regular intervals using gas chromatography (GC/FID) to track degradation and potency over time. RESULTS:The stability profiles varied depending on the cannabinoid profile, temperature, and matrix type. For the majority of cannabis-derived products, exposure to room temperature accelerated the degradation of THC into cannabinol (CBN), whereas storage at -20°C preserved cannabinoid integrity over the extended timeline. Notably, a distinct divergence was observed between the compounds: CBD-only products demonstrated robust long-term stability even when maintained at room temperature. Conversely, THC-rich matrices were highly susceptible to ambient degradation but exhibited the highest stability when formulated as ethanolic solutions and stored in the freezer (-20°C). CONCLUSION:To maximize cannabinoid shelf-life and prevent degradation, storage temperatures must match product composition. While CBD-dominant products can tolerate room-temperature storage, THC-rich products require cold chain management, ideally stored in a freezer at -20°C for optimal long-term potency.
INTRODUCTION:Medical cannabis dosage for chronic low back pain (LBP) varies substantially between patients, yet clinicians lack validated tools to predict individual dosage requirements. We developed and internally validated the Cannabis Dosage Risk Score (CDRS), a practical bedside prognostic tool to identify patients likely to require high-dose (≥60 g/month) cannabis therapy. MATERIALS AND METHODS:We conducted a retrospective Target Trial Emulation analysis of a prospectively followed cohort of 225 patients with chronic LBP who consented to research participation and completed baseline assessments between January 1 and May 31, 2020, at an Israeli pain clinic. Patients were categorized by stabilized 5-year cannabis dosage as low dose (<40 g/month, n = 121), medium dose (40-59 g/month, n = 41), or high dose (≥60 g/month, n = 63). Primary analysis compared low-dose versus high-dose groups (n = 184); medium-dose patients were analyzed separately. Multivariable logistic regression identified independent predictors, which were converted to a weighted point-based scoring system. Model performance was assessed using bootstrap-validated area under the receiver operating characteristic curve (AUC-ROC), Hosmer-Lemeshow calibration, and decision curve analysis. RESULTS:The final CDRS incorporates 4 baseline clinical variables: disability status (odds ratio [OR] 5.10, 95% confidence interval [CI]: 2.42-10.76), absence of baseline opioid use (OR: 2.38, 95% CI: 1.06-5.26; equivalently, opioid-use OR: 0.42, p = 0.035), lower Patient-Reported Outcomes Measurement Information System (PROMIS) Sleep T-score (OR: 0.95 per point, 95% CI: 0.92-0.98), and lower Hospital Anxiety and Depression Scale (HADS) combined score (OR: 0.92 per point, 95% CI: 0.86-0.98). With an events-per-variable ratio of 15.8 and variance inflation factors <1.3, the model achieved AUC-ROC of 0.80 (optimism-corrected 0.78) with adequate calibration (Hosmer-Lemeshow p = 0.24). Ordinal logistic regression confirmed predictor validity across all three dose categories. Decision curve analysis demonstrated net clinical benefit across threshold probabilities of 10-70%. Risk stratification yielded: low risk (0-3 points, 17.2% high-dose rate), moderate risk (4-7 points, 24.7% high-dose rate), and high risk (≥8 points, 76.7% high-dose rate). At 5-year follow-up, all dose groups showed significant pain reduction (Brief Pain Inventory severity Δ: low -4.9, medium -4.7, high -6.2; analysis of variance p = 0.0005); high-dose patients had the greatest improvement, refuting the hypothesis of dose escalation by nonresponders. Among patients using baseline opioids, 93.1% (135/145) achieved opioid cessation at 5 years. CONCLUSIONS:The CDRS provides a practical, internally validated four-item bedside tool for predicting cannabis dosage requirements among patients with chronic LBP who initiate and continue medical cannabis therapy. Patients with disabilities who do not have baseline opioid use and who experience less sleep disturbance or psychological distress are most likely to require high-dose therapy. The 100% 5-year follow-up reflects the cohort's intake-based definition, its early-2020 (pandemic-onset) enrollment period, and structural features of the Israeli regulatory framework rather than post hoc selection of responders; retention in the same clinic's other cohorts was lower (82.5-92.9% at 5 years), and generalization to jurisdictions without comparable regulatory follow-up structures should be made cautiously. External validation in diverse populations is warranted.
INTRODUCTION:Fibromyalgia syndrome (FMS) involves central sensitization and possible endocannabinoid system dysfunction, with medicinal cannabis increasingly investigated as a treatment. We assessed whether chronic oral 1:1 THC:CBD alters plasma endocannabinoid-related N-acylethanolamines (NAEs)-palmitoylethanolamide (PEA), oleoylethanolamide (OEA), and stearoylethanolamide (SEA)-in FMS. MATERIALS AND METHODS:In a single-center, randomized, double-blind, placebo-controlled pilot trial, 24 women with FMS were allocated to cannabis oil (10 mg/mL THC and CBD) or placebo. Plasma samples were collected at five timepoints between enrollment and week 12 (over 16 weeks), ∼10-14 h after evening dosing, under fasting conditions. NAEs were quantified by ultra-high-performance liquid chromatography mass spectrometer. Repeated-measures analysis of variance tested main effects of time and group, and their interaction; Greenhouse-Geisser corrections were applied as required. Effect sizes were reported as partial eta squared. TRIAL REGISTRATION:ACTRN12623000345684. RESULTS:Twenty-two participants completed the trial (n = 11 per group). Plasma anandamide and 2-AG were below limits of detection and excluded from analyses. Mean plasma PEA, OEA, and SEA remained stable across all timepoints in both groups, with no significant effects of time, group, or time × group interaction (all p > 0.05). Effect sizes were minimal (partial η2 ≤ 0.06), indicating negligible influence of medicinal cannabis on peripheral NAEs. DISCUSSION:Despite clinical benefits observed with this treatment, peripheral NAEs were unchanged, suggesting they may have limited utility as biomarkers for monitoring therapeutic response to this formulation in FMS. These preliminary findings support investigation of alternative mechanisms, likely driven by central rather than peripheral processes.
BACKGROUND:Medical cannabis (MC) has emerged as a potential therapy for Parkinson's disease (PD), targeting motor and nonmotor symptoms (NMS), such as pain, sleep disturbance, and urinary dysfunction. Cannabinoid receptors in central and peripheral systems, including the bladder, provide a mechanistic basis for symptom modulation. This study evaluated the feasibility, safety, and preliminary clinical effects of MC on NMS in PD within a real-world, regulated framework. METHODS:In this single-center, open-label, prospective cohort, 68 patients with PD initiating MC were assessed at baseline and at 3 months using validated scales: the Non-Motor Symptoms Scale (NMSS), King's Parkinson's Disease Pain Scale (KPPS), PD Sleep Scale-2 (PDSS-2), PD Quality-of-Life Questionnaire-8 (PDQ-8), and International Prostate Symptom Score (IPSS), along with 2-day urinary diaries. Participants used either cannabis oil extract or inflorescence products with varying THC/CBD (Δ9-tetrahydrocannabinol/cannabidiol) ratios. Adverse events and withdrawals were recorded. Cannabinoid composition was analyzed via ultra-high-performance liquid chromatography and correlated with clinical outcomes. RESULTS:Fifty participants (mean age 65.6 ± 11.0 years; 68% male) completed follow-up. MC use was associated with improvements in NMSS total (Δ 14.5, p = 0.001), PDSS-2 (Δ 5.9, p < 0.001), KPPS (Δ 8.1, p = 0.004), PDQ-8 (Δ 1.5, p = 0.040), and the NMSS urinary domain (Δ 2.1, p = 0.050). Nighttime urinary frequency decreased (median Δ 0.5, p = 0.016), while daytime parameters were unchanged. No correlations were found between cannabinoid composition or THC/CBD enrichment type and clinical response. The dropout rate was 26.5%, mainly due to loss to follow-up. CONCLUSIONS:Short-term, self-titrated MC was feasible and appeared generally well tolerated in this open-label setting, suggesting potential benefits for pain, sleep, and nocturnal urinary frequency in PD. These exploratory findings warrant randomized controlled trials focused on these domains and incorporating standardized dosing, pharmacokinetic monitoring, and predefined cognitive safety assessments to determine efficacy, safety, and optimal dosing.
BACKGROUND:California legalized medical cannabis in 1996 and nonmedical adult use in 2016, with commercial recreational sales starting in 2018. The consequences of cannabis legalization and commercialization on medical cannabis utilization are not well understood. METHODS:We analyzed data from 178,832 adults (aged ≥18 years) in the California Health Interview Survey (2017-2024). Past-month cannabis use and doctor-recommended use were assessed each year. We fit survey-weighted logistic regression models with year as a categorical predictor, used omnibus Wald tests to assess whether prevalence differed across years, and estimated year-to-year differences with Tukey-adjusted contrasts. All analyses accounted for survey weights, strata, and primary sampling units. RESULTS:Between 2019 and 2024, about 1.6% of all respondents and 16.4% of past-month cannabis users reported doctor-recommended use. Among past-month users, doctor-recommended use fell from 18.5% (95% Confidence Interval [CI]: 16.6%-20.4%) in 2019 to 8.5% (95% CI: 7.3%-9.8%) in 2024 (p < 0.01). Overall past-month cannabis use held steady, at 16.5% (95% CI: 15.5%-17.6%) in 2019 and 15.4% (95% CI: 14.5%-16.2%) in 2024 (p = 0.22). Tukey-adjusted comparisons showed the decline was most apparent from 2021 onward. The pattern held across sex and most age and racial/ethnic groups, though differences did not reach statistical significance among young adults aged 18-25 (-7.6 percentage points; p = 0.09), Asian respondents (-2.9 percentage points; p = 0.62), or African American respondents (-8.8 percentage points; p = 0.47). DISCUSSION:After adult-use legalization and commercialization, doctor-recommended use decreased by more than half among past-month cannabis users, even as overall use remained stable. The decline in doctor-recommended use suggests that legalization and commercialization in California may have altered patterns of medical utilization without reducing population-level use. Together, these findings align with broader national trends in which recreational access may be displacing formal medical oversight. This reduction in physician oversight raises the concern that individuals with complex medical conditions may increasingly rely on the recreational marketplace without the benefit of clinician guidance.
INTRODUCTION:Cannabis sativa presents a highly complex phytochemical matrix, with numerous bioactive constituents, especially phytocannabinoids and terpenes, which justify the growing medicinal and industrial interest. As extraction strongly influences the chemical profile of the final product, this review synthesizes how extraction strategies and operating conditions affect the composition and quality of the extract. MATERIALS AND METHODS:This study is a narrative literature review of publications published between 2010 and 2025. Searches were conducted in major scientific databases, including PubMed, Scopus, Web of Science, MEDLINE, ScienceDirect, Google Scholar, and Cochrane Library, using descriptors related to C. sativa, cannabinoids, terpenes, extraction methods, and supercritical CO2. Eligible studies and reviews describing extraction approaches, process variables, and resulting chemical profiles were prioritized, with emphasis on more recent evidence when available. RESULTS:Extraction approaches were organized into solvent-free and solvent-based methods, and within solvent-based methods, into conventional and unconventional techniques. Solvent-free methods rely on mechanical separation and may favor the preservation of trichomes. Conventional solvent-based methods are simple and widely accessible but generally require longer processing times and greater solvent usage, with the potential for co-extraction of impurities. Unconventional solvent-based techniques can reduce extraction time and improve selectivity and may potentially align better with sustainable processing, depending on solvent choice and energy demand. DISCUSSION:The reviewed literature indicates that there is no universal extraction method suitable for all purposes. Instead, technique selection should be guided by the intended application and target profile (e.g., preservation of acidic cannabinoids, enrichment of neutral cannabinoids, terpene retention, and reduction of chlorophyll/other co-extractives). Key controllable variables, including solvent type, temperature, time, pressure, and solid:solvent ratio, govern mass transfer and chemical stability. Notably, higher temperatures may promote decarboxylation of acidic cannabinoids and contribute to terpene losses, potentially altering both chemical and organoleptic characteristics. Therefore, careful process design and parameter optimization are essential to obtain reproducible extracts with consistent composition and fit-for-purpose quality.
BACKGROUND:Cannabinoid type 1 receptor (CB1R) regulates glutamate release and plays a key role in neuroprotection and neuroinflammation. Since CB1R is implicated in HIV-associated neurocognitive disorders (HAND), it is important to determine how its expression changes with the neurotoxic human immunodeficiency virus type-1 (HIV-1) transactivator of transcription (Tat) protein. This study examined CB1R dynamics in an inducible HIV-1 Tat transgenic mouse model. METHODS:Tat expression was induced in Tat(+) mice using doxycycline (DOX). Longitudinal positron emission tomography (PET) with the CB1R-selective radiotracer [11C]-OMAR was performed at baseline, 2 weeks, and 3 months post-induction in Tat(-) and Tat(+) groups to track CB1R alterations across brain regions. Western blot analyses were conducted postmortem in the prefrontal cortex, striatum, hippocampus, cortex, cerebellum, and brainstem. RESULTS:In a longitudinal PET imaging study, we observed a significant upregulation of CB1R expression in the cortex and cerebellum after 2 weeks of DOX treatment in both Tat(-) and Tat(+) mice; however, this increase was not maintained at the 3-month timepoint. Western blot analysis revealed region-specific changes in CB1R levels for both genotypes with upregulation observed at 2 weeks post DOX treatment. Notably, a significant interaction between genotype × DOX in the hippocampus, cerebellum, and brainstem exhibited significant CB1R alteration by Tat expression, suggesting region-dependent regulatory mechanisms. CONCLUSION:DOX treatment and Tat expression appear to affect CB1R levels in a region-specific manner, underscoring the complexity of HAND. The differences between PET imaging and Western blot results suggest that [11C]-OMAR may lack the affinity and sensitivity to detect subtle CB1R changes at the 3-month timepoint. The low resolution of PET imaging may be another factor contributing to the detection limit. Lastly, these findings emphasize the importance of using multiple methodologies to capture nuanced molecular alterations in neuroinflammatory conditions.
BACKGROUND:Cannabis plants (Cannabis sativa) contain a diverse group of terpenophenolic compounds known as phytocannabinoids, with 131 cannabinoids identified to date. Rapid and low-cost analytical approaches capable of quantifying both major and minor cannabinoids are increasingly important for research, quality control, and regulatory applications. This study evaluates the patented Absorbance-Transmittance Excitation-Emission Matrix (A-TEEM™) spectroscopic technique as a fast and reliable alternative to conventional chromatographic methods. A-TEEM integrates ultraviolet-visible absorbance and fluorescence measurements while correcting for absorbance-dependent inner-filter effects, enabling linear relationships between fluorescence intensity and analyte concentration. The primary objective was to calibrate and validate machine learning models using A-TEEM data for cannabinoid quantification, benchmarked against a validated high-performance liquid chromatography-photodiode array (HPLC-PDA) reference method. MATERIALS AND METHODS:A total of 49 dry cannabis flower extracts were analyzed using the A-TEEM technique to quantify 14 cannabinoids. Spectral data generated by A-TEEM were directly compared with concentration data obtained from an established and validated HPLC-PDA method. Extreme gradient boosting regression models were developed using HPLC-PDA results as reference values to predict cannabinoid concentrations from A-TEEM spectral data and to evaluate quantitative performance. RESULTS:The A-TEEM method demonstrated rapid, robust, and sensitive quantification of all 14 target cannabinoids. Model performance metrics, including coefficients of determination (R2) and limits of detection (LOD) and limits of quantification (LOQ), are scaled proportionally with the maximum cannabinoid concentrations present in the samples. For major cannabinoids exceeding 0.35% concentration, the mean combined cross-validation and validation R2 reached 0.994 ± 0.005, with mean LOD and LOQ values of 0.0146% and 0.0442%, respectively. Cannabinoids present between 0.35% and 0.1% showed mean LOD/LOQ values of 0.00278% and 0.00842%, while minor cannabinoids below 0.1% exhibited even lower LOD/LOQ values of 0.0004% and 0.00128%, respectively. In addition, A-TEEM concentration profiles enabled clear qualitative and quantitative differentiation of three cannabis chemovars: tetrahydrocannabinol (THC)-dominant, cannabidiol (CBD)-dominant, and THC-CBD-intermediate hybrids. CONCLUSIONS:The A-TEEM technique provides a sensitive, rapid, and cost-effective approach for the qualitative and quantitative determination of both major and minor cannabinoids in solution. Its analytical performance is comparable to that of the reference HPLC-PDA method while offering substantial advantages in speed, simplicity, and suitability for high-throughput analysis.
INTRODUCTION:Graft versus host disease (GVHD) is a debilitating consequence of bone marrow (BM) transplantation for the treatment of hematological cancers and other conditions. Previous studies have demonstrated that mouse models of GVHD result in significant prefrontal cortical (PFC) neuroinflammation, which is mitigated by global and microglial-selective deletion of the type 2 cannabinoid receptor (CB2R). This study examined whether genetic deletion of CB2R similarly rescues the acute behavioral dysregulation produced by GVHD. MATERIALS AND METHODS:GVHD was initiated in C57BL/6 mice by irradiation followed by infusion of BM and splenocytes from major histocompatibility mismatched B10.BR donors. Fourteen-18 days after transplant, mice were exposed to a battery of behavioral tests. RESULTS:The primary behavioral effects of GVHD in wild-type mice were increased immobility in the open field and increased struggling in the forced swim. These effects of GVHD also occurred in global CB2R knockout mice and in mice with CB2R deletion in cells expressing CX3CR1, which includes microglia. GVHD did not affect social interactions, sucrose consumption, rotarod behavior, or time in the middle of the open field in any genotype. DISCUSSION:These data indicate that while CB2R deletion from the recipient mice protects against neuronal loss and inflammation in the brain, it does not protect against acute behavioral dysregulation.
INTRODUCTION:Edibles have become the second-most used cannabis product in legal U.S. states, wherein 64% of cannabis consumers reported using edibles within the past year. Among expansions to the legal cannabis industry are the newly marketed "fast-acting" edible compounds, which may address many of the issues associated with edible use related to overdose and dose management. The study hypotheses were that fast-acting edibles would reach peak concentration significantly faster than standard edibles and placebo edibles. MATERIALS AND METHODS:Twenty participants completed three arms within-subjects designed study to test hypotheses. The three arms were ingestion of a (1) fast-acting edible, (2) a standard edible, and (3) a Δ9-tetrahydrocannabinol (THC) terpene-derived placebo edible that was indistinguishable from the two THC-containing edibles. Blood plasma was analyzed for the presence of THC and THC analytes. The pharmacokinetic parameters tested were time to max concentration (Tmax), maximum concentration (Cmax), terminal half-life (t1/2), and area under the curve (AUC). RESULTS:Results supported study hypotheses in that Tmax was significantly faster for the fast-acting edible, observed 30 min post-ingestion and, on average, 30 min earlier than the Tmax for the standard edible. There were no significant differences between the fast-acting and standard edibles on Cmax, t1/2, and AUC; however, both the fast-acting and standard edibles were significantly different compared with the placebo across all pharmacokinetic parameters. DISCUSSION:The results indicate that the microencapsulation technology used to create the fast-acting edible enabled analyte concentrations to peak significantly faster compared to the standard and placebo edibles.
INTRODUCTION:Cannabis legalization and consumption in the United States have accelerated over the past decade, resulting in a rapidly diversifying marketplace of medical and adult-use products. As of 2025, medical cannabis is permitted in 47 states, while adult-use markets are authorized in 24 states and the District of Columbia. This expansion underscores the urgent need for robust and consistent safety testing to ensure consumer protection. Despite federal prohibition, states have independently developed their own regulatory frameworks for contaminant testing, leading to wide variability in allowable limits, analyte lists, and method validation requirements. METHOD:This review critically compares contaminant regulations across U.S. adult-use jurisdictions and evaluates analytical methodologies published between 2020 and 2025 for four major hazard categories: heavy metals, pesticides, mycotoxins, and residual solvents. Emphasis is placed on sample preparation strategies, analytical instrumentation, and method performance parameters relevant to complex cannabis matrices such as flower, concentrates, and infused products. RESULTS:Sample preparation approaches are tailored to matrix complexity and frequently utilize Quick, Easy, Cheap, Effective, Rugged, and Safe (QuEChERS) extraction followed by dispersive solid-phase extraction (dSPE). Cartridge SPE is commonly applied for enhanced cleanup, and immunoaffinity columns is used for selective isolation of aflatoxins and ochratoxin A. Instrumental analysis typically relies on Inductively Coupled Plasma-Mass Spectrometry (ICP-MS) for trace metals, liquid chromatography-tandem mass spectrometry and gas chromatography-tandem mass spectrometry (GC-MS/MS) for pesticide and mycotoxin detection, and headspace GC with flame ionization detection or GC-MS for residual solvent quantification. DISCUSSION:Although current methodologies provide sensitive and reliable detection, inconsistencies in regulatory oversight across jurisdictions limit data comparability and complicate interstate commerce. Establishing harmonized performance criteria, standardized reporting units, and national proficiency testing programs would improve method reliability and consumer confidence. Continued innovation in sample preparation and validated multi-residue methods will be critical as product diversity and testing demands continue to expand.
BACKGROUND:We explored whether self-reported current cannabis use is associated with inflammatory biomarkers among people with HIV (PWH), given high rates of cannabis use and chronic immune activation among PWH. METHODS:At seven Centers for AIDS Research Network of Integrated Clinical Systems (CNICS) cohort sites, which integrate data on participant characteristics including demographic and clinical information, and substance use behaviors, we used linear regression to estimate the average difference in biomarkers associated with cannabis use, adjusted for demographic characteristics and sampling weights. Cannabis use was considered as Never, Former, or Current (past 3-month) use. Thirteen plasma biomarkers were measured once on or after 2010 among a subset of PWH on antiretroviral therapy with HIV viral suppression within CNICS. Cannabis use was assessed within 1 year prior to biomarker collection. Biomarkers were log-transformed and scaled by standard deviation to standardize estimates. RESULTS:Among 532 PWH, the average age at biomarker collection date was 47 years, 84% were male, 61% non-White, 30% reported current cannabis use, 35% former use, and 35% never using cannabis. In adjusted linear regression, current cannabis use was associated with higher soluble CD14 (sCD14) levels (β = 0.35; 95% confidence interval [CI]: 0.09, 0.61). Former cannabis use was associated with lower C-reactive protein (CRP) (β = -0.25; 95% CI: -0.47, -0.04), although current use was not (β = -0.25; 95% CI: -0.51, 0.01) compared to never use. CONCLUSIONS:Cannabis use may be related to lower CRP and elevated markers of microbial translocation (e.g., sCD14), which could have implications in increasing the risk of vascular events and should be investigated in a longitudinal setting.
INTRODUCTION:Reliable case definitions (CDs) for cannabis use disorder (CUD) are essential for epidemiologic surveillance, health services research, and policy evaluation. As reliance on health administrative data increases, variation in diagnostic coding practices and limited validation of CDs may undermine the comparability and accuracy of CUD estimates. This systematic review aimed to identify, describe, and critically appraise how CUD has been operationalized within administrative health data sources, with particular attention to coding strategies and validation practices. METHODS:Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, we systematically searched PubMed, EMBASE, and related databases for studies using International Classification of Diseases (ICD) codes to define CUD in administrative health data. Two reviewers independently screened studies, extracted data on CD components and validation methods, and assessed methodological quality using the Newcastle-Ottawa Scale. RESULTS:A total of 56 studies met the inclusion criteria. Most relied on ICD-9 or ICD-10 diagnostic codes to identify CUD, typically using a one-or-more-code rule, although operational details varied by jurisdiction, coding framework, and observation window. No included study explicitly reported internal or external validation of its CD. Reported prevalence estimates ranged widely, from 0.06% in large administrative cohorts to 76.9% in highly selected clinical populations, reflecting differences in CD construction and study populations. CONCLUSIONS:CDs for CUD in administrative data vary substantially and lack empirical validation, limiting their reliability for surveillance and comparative research. The development and validation of standardized, transparent CDs are needed to strengthen cannabis epidemiology and to support reproducible research, health-system planning, and policy decision-making.
INTRODUCTION:People with long-term virologically suppressed HIV (PWH) experience chronic inflammation. Beneficial effects such as lower levels of inflammation were reported for cannabis-based medicine, but data on the safety of standardized low-dose full-spectrum cannabidiol (CBD) are limited. METHODS:This double-blind randomized placebo-controlled trial (NCT05306249) included 80 ART-treated PWH with undetectable viremia (median time on efficient ART 14 years, median age 54 years), encompassing 30% women. Participants received 1 mg/kg CBD oil twice daily (full-spectrum, tetrahydrocannabinol < 0.3%) or placebo for 12 weeks plus a 4-week follow-up. Primary trial end-point (autophagy gene expression) will be described elsewhere; here we evaluate the treatment impact on prespecified safety outcomes such as hemodynamic with electrocardiograms, HIV immunovirological parameters, and comprehensive assessments of liver and kidney functions, performed using standard blood tests. Mixed-effects models adjusted for baseline age, sex, body mass index, CD4 count and duration of viral suppression assessed longitudinal changes. RESULTS:Of 80 randomized participants, 35 PWH in CBD and 37 in placebo groups completed week 12. No clinically meaningful differences emerged in creatinine, aminotransferases (alanine aminotransferase, aspartate aminotransferase), or conjugated bilirubin. Total bilirubin decreased in the CBD arm vs placebo (mixed effect model considering time, group and time*group, adjusted for covariates, p = 0.046). In exploratory sex-stratified analysis, a significant difference starting at week 12 (-8.0 bpm [95% CI: -15.6; -0.4], p = 0.0425) and persisting at week 16 (-7.9 bpm [95% CI: -14.6; -1.3], p = 0.0191) evidences a lower heart rate in men belonging to the CBD group compared with the placebo group; no change in females. There was no change in plasma viral load, cell-associated HIV-DNA levels, and CD4/CD8 ratio. DISCUSSION:Low-dose full-spectrum GMP-certified CBD was well tolerated over 12 weeks in virally suppressed people with HIV. Observed reductions in total bilirubin and male heart rate are exploratory and warrant confirmation in adequately powered trials incorporating inflammatory biomarkers and pharmacokinetics.
BACKGROUND:Exogenous cannabinoids are considered promising therapeutic candidates for inflammatory bowel disease (IBD). However, robust pre-clinical evidence supporting its efficacy remains limited. This systematic review and meta-analysis aimed to evaluate the therapeutic effects of exogenous cannabinoids in animal models of IBD. METHODS:Controlled experimental studies involving animal models of IBD that evaluated the effects of exogenous cannabinoids compared to untreated models were included. Four databases (PubMed, Embase, Web of Science, and the Cochrane Library) were searched up to August 26, 2025. Two independent reviewers conducted study selection, data extraction, and the risk-of-bias assessment. The risk-of-bias assessment was performed using the Systematic Review Center for Laboratory Animal Experimentation tool. Meta-analyses were performed using standardized mean differences (SMDs) and random-effects models. The study was registered in INPLASY (INPLASY202540009). RESULTS:Twenty-seven pre-clinical studies involving 408 animals were included. Compared with controls, exogenous cannabinoids significantly reduced disease activity index (SMD = -3.43; 95% confidence interval [CI]: -4.98 to -1.89; I2 = 83%) and histopathological score (SMD = -4.46; 95% CI: -6.37 to -2.54; I2 = 84%). It also decreased levels of myeloperoxidase (MPO), TNF-α, IL-6, and IL-1β. However, substantial heterogeneity was noted across several outcomes. INTERPRETATION:Exogenous cannabinoids show beneficial effects in pre-clinical IBD models, likely through anti-inflammatory, antioxidant, and barrier-enhancing mechanisms. These findings provide a supportive foundation for future translational research. Nevertheless, the overall certainty of the evidence is limited by unclear randomization, lack of blinding, high heterogeneity, and small sample sizes. Although some clinical trials have already begun exploring its therapeutic potential, further rigorous and standardized animal studies are needed to clarify mechanisms, optimize dosing, and reinforce the translational pathway.
BACKGROUND:Cannabinoid hyperemesis syndrome (CHS) is increasingly being observed in emergency departments and is characterized by recurrent nausea and vomiting in some cannabis users. Despite its increasing prevalence, tools for early identification and intervention are lacking. This study aimed to improve our understanding of CHS by examining patterns of cannabis use and identifying symptom profiles of individuals suspected or diagnosed with CHS. By identifying the risk factors and initial warning signs, we can support earlier recognition, harm reduction, and intervention. MATERIALS AND METHODS:An anonymous survey was distributed via social media to gather detailed, self-reported information about cannabis consumption methods, frequency of use, product sourcing, and CHS-related symptoms. Participants were recruited online through organic outreach to CHS-focused social media communities in late 2024. RESULTS:A total of 1134 participants were included in the final analysis. Most respondents reported smoking cannabis flower or using vape cartridges, although the use of edibles and concentrates were also described. The overwhelming majority of respondents (96.5%) used cannabis products at least daily, with approximately half (45%) using them six or more times per day around the time they developed CHS symptoms. Most of the respondents (61.9%) sourced cannabis from licensed dispensaries. The duration of cannabis use prior to symptom onset varied widely among participants, with nearly two-thirds (65.4%) reportedly used for more than 3 years before symptom development. During the prodromal (early) phase, symptoms clustered in the morning (63.1%) and the predominant complaints were nausea and stomach pain. Women reported more frequent and prolonged symptoms than men. DISCUSSION:Our findings suggest that CHS is most associated with long-term, frequent use of inhaled delta-9-tetrahydrocannabinol (Δ9-THC) dominant cannabis. The acquisition source of cannabis products did not affect the syndrome presentation. Although many different cannabis consumption methods were represented, smoking and vape cartridges were the most commonly reported. The use of vape cartridges was associated with a shorter time to the development of CHS symptoms. Increased awareness of these patterns could improve the early recognition and management of CHS.
INTRODUCTION:The endocannabinoid system (ECS) is increasingly recognized as an important regulator of many physiological systems. People who use products derived from Cannabis sativa L. are exposed to exogenous cannabinoids. The influence of this exogenous exposure on the ECS is unclear. People who use cannabis have demonstrated lower basal levels of endocannabinoids, but the dynamic response of their ECS to a controlled stimulus is unknown. Our study purpose was to compare circulating concentrations of the endocannabinoid N-arachidonoylethanolamine (anandamide, AEA) and subjective experiences between people who use cannabis and those who do not, during and following a standardized exercise stimulus. MATERIALS AND METHODS:Twenty adults (n = 8 who regularly use cannabis [age: 21-32 years; 5/3 males/females] and n = 12 who do not use cannabis [age: 21-39 years; 7/5 males/females]) completed a 1-h treadmill run at an intensity equivalent to 65% of peak oxygen uptake. Arterialized-venous blood was collected prior to, during (including the last minute of exercise), and 15 min following exercise for determination of anandamide concentration. The subjective experiences of the participants during and after the run were assessed with responses to several questions assessed on a Likert scale. RESULTS:Compared with controls, the cannabis use group had lower AEA concentrations at end-exercise (0.47 ± 0.13 vs. 0.33 ± 0.10 ng/mL; p = 0.015) and 15-min post-exercise (0.57 ± 0.17 vs. 0.38 ± 0.18 ng/mL; p = 0.001). The cannabis use group also had worse mood (3.25 ± 1.03 vs. 2.29 ± 1.34; main effect of condition p = 0.05) and higher probability of feeling pain (p < 0.001). CONCLUSION:Habitual cannabis use was associated with diminished AEA response, worse mood, and more pain during/following exercise. These pilot data might have implications for clinical outcomes associated with cannabis use, including cannabis use disorder and withdrawal, as well as potentially for exercise adherence.
Cannabis rescheduling from Schedule I to Schedule III under the U.S. Controlled Substances Act would be the most significant federal cannabis policy shift in more than five decades, yet its legal and practical consequences are widely misunderstood. This policy analysis clarifies what Schedule III rescheduling would change-and what it would not-by synthesizing the U.S. Department of Health and Human Services' 2023 scientific and medical recommendation and its two-part inquiry into "currently accepted medical use," Congressional Research Service legal guidance on rescheduling consequences, administrative law scholarship on Drug Enforcement Administration rulemaking and deference to expert scientific findings, and interdisciplinary research on cannabis regulation, product development, and public health. We examine implications for federal-state conflict, criminal liability and collateral consequences, research access and scientific infrastructure, Food and Drug Administration (FDA) evidentiary standards for therapeutic claims, taxation and capital flows (including relief from Internal Revenue Code §280E), and uneven effects on regulated state markets and owner-operators. Drawing on scholarship documenting Schedule I research barriers, constrained access to representative research materials, and the growing role of real-world evidence alongside clinical trials, we argue that rescheduling may expand research capacity and strengthen incentives for FDA-compliant development without legalizing cannabis, approving dispensary products, authorizing interstate commerce, or resolving conflicts between federal and state law. We further assess equity implications, emphasizing that rescheduling does not expunge records, repair past harms, or ensure equitable participation and may accelerate consolidation absent protective safeguards. We conclude that Schedule III should be treated as a transitional status, with agencies prioritizing research access and public health surveillance while Congress addresses banking, interstate commerce, and durable criminal justice and equity reforms.
