搜索结果：Cannabis and cannabinoid research

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.

Simultaneous cannabis and alcohol use (co-use) is a public safety concern. Controlled data on the effects of co-ingestion of oral cannabis products (edibles) with alcohol are lacking, despite an increased prevalence of this behavior. To evaluate the individual and interactive effects of cannabis edibles and alcohol on simulated driving and subjective and objective impairment measures. This within-participant, double-blind, double-dummy crossover study of healthy adults included 7 outpatient sessions, separated by 1 week, at Johns Hopkins University School of Medicine from February 2022 to August 2025. Brownies containing 0 mg, 10 mg, or 25 mg Δ9-tetrahydrocannabinol (THC) combined with placebo drinks or alcohol-containing drinks, calculated to achieve breath alcohol concentrations (BrACs) of 0%, 0.05%, or 0.08%. Driving outcomes included the global drive score (GDS), a composite index of multiple driving measures, and the standard deviation of lateral position as the main outcomes. Other outcomes included cumulative impairment clues on standardized field sobriety tests (SFSTs), subjective drug effects, cognitive and psychomotor performance (using the DRUID [Driving Under the Influence of Drugs] application), and blood cannabinoid concentrations. Participants included 25 healthy adults (15 males [60%]; mean [SD] age, 25.6 [4.9] years) who reported recent binge drinking, prior cannabis and alcohol co-use, and fewer than 3 cannabis uses per week. Compared with placebo, all active drug conditions except 10 mg THC negatively impacted driving performance (ie, GDS). Driving impairment from alcohol alone at 0.08% BrAC was comparable with that of 0.05% BrAC and 10 mg THC (mean [SD] GDS, 1.6 [1.6] vs 1.6 [1.4]) and significantly lower than 0.05% BrAC and 25 mg THC (mean [SD] GDS, 2.5 [1.7]; P = .02). Driving impairment and subjective intoxication (eg, confidence to drive) were often greater under co-use conditions compared with cannabis or alcohol alone. Relative to placebo, SFST performance worsened at 0.08% BrAC (mean [SD] score, 2.2 [2.2] vs 0.2 [1.3]; P = .008) but not in several other conditions in which marked driving decrements were observed. THC and metabolite pharmacokinetics were not influenced by alcohol. In this crossover trial of healthy adults who co-used cannabis and alcohol, cannabis edibles combined with alcohol augmented driving impairment. The legal alcohol intoxication limit in most of the US (0.08% BrAC) may be too liberal if a driver has co-used cannabis and alcohol. In this era of expanding cannabis legalization, there is a pressing public health need for improved impairment detection strategies and consideration of cannabis and alcohol co-use in policies dictating access to these substances. ClinicalTrials.gov Identifier: NCT04931095.

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. 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. 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. 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.

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. 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. 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. 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.

On March 25, 2025, the University of California Office of the President, in partnership with the California Department of Cannabis Control, hosted the 2025 California Cannabis Research Workshop in Sacramento, CA. Building on prior gatherings in 2019, 2021, and 2023, the 2025 California Cannabis Research Workshop sought to strengthen collaboration between researchers and state policymakers during a time when the federal regulatory and scientific landscape is rapidly evolving. The event featured discussions on the role of state agencies supporting cannabis research, applications of cannabis research funding, strategies for accessing varied cannabis research products, innovations in agrarian research, and examples of state support for research. The 2025 workshop provided a platform for exploring how cannabis research can inform public policy and address emerging scientific and societal questions despite uncertainties arising from the federal landscape.

Cannabis sativa L. is an annual herbaceous plant with a long history of multipurpose use, including food, textile, and medicinal applications. The progressive legalization in several countries has significantly increased its large-scale cultivation, consequently generating a substantial amount of biomass waste. This scenario calls for innovative and sustainable strategies to valorize Cannabis residues, aiming at promoting the circular economy and technological innovation. An integrative review was conducted following Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Systematic searches were performed in SCOPUS, PubMed, and SciELO, complemented by specialized platforms such as CANNUSE and CONSENSUS. Peer-reviewed empirical studies were included if they addressed the utilization, reutilization, or recycling of C. sativa by-products or residues for the development of industrial products, processes, or inputs. The analysis considered thematic and commercial domains, geographic origin, and biomass type. A total of 262 studies were included, with 144 retrieved from indexed databases and 118 from alternative methods. The most commonly explored residues were stems (48.2%), seeds (21.0%), and postextraction residuum (9.7%). The majority of applications were related to technology and innovation (37.5%) and industrial sectors (36.9%). A total of 328 technologies were identified, highlighting applications such as textile fibers, bioplastics, biofuels, functional foods, adsorbents, and natural cosmetics. Italy, China, and the United States led in scientific production. Leaves (7.0%) and roots (0.9%) were significantly underexplored despite their bioactive potential. The findings demonstrate a growing global interest in the valorization of C. sativa residues, with promising applications in bioeconomy, regenerative agriculture, phytoremediation, and energy transition. The integration of traditional knowledge and green technologies is a key strategy to enhance sustainability and socioterritorial inclusion. Nonetheless, regulatory gaps and a lack of robust clinical and toxicological studies limit the use of by-products in food and feed chains. The residual biomass of C. sativa holds high technological, environmental, and economic value. Strategic valorization demands regulatory advancement, the development of green technologies, and the strengthening of multidisciplinary research. Industrial Cannabis emerges as a driver of ecological, social, and economic transformation toward sustainable circular production systems.

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. 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. Compared with controls, the cannabis use group had lower AEA concentrations at end-exercise (0.47 &#xb1; 0.13 vs. 0.33 &#xb1; 0.10 ng/mL; p = 0.015) and 15-min post-exercise (0.57 &#xb1; 0.17 vs. 0.38 &#xb1; 0.18 ng/mL; p = 0.001). The cannabis use group also had worse mood (3.25 &#xb1; 1.03 vs. 2.29 &#xb1; 1.34; main effect of condition p = 0.05) and higher probability of feeling pain (p < 0.001). 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.

Introduction: Hemp-derived semi-synthetic cannabinoids are marketed as legal alternatives to cannabis containing &#x2265;0.3% &#x394;9-tetrahydrocannabinol (THC) but remain unregulated at the federal and state levels. Their growing availability underscores the urgent need to investigate patterns of use and associated health risks. Methods: Data were collected via an online survey on self-reported patterns and associations of semi-synthetic cannabinoid use, as well as related factors and effects, from a sample of U.S. adults (&#x2265;18 years old) who reported past-year cannabis use. Results: In the sample (N = 229; 55.5% male, 63.8% White, 80.3% not Hispanic/Latino), nearly half (44.5%) reported using at least one semi-synthetic cannabinoid in the past year. Patterns of use varied by cannabinoid: &#x394;7-THC (10.0%), &#x394;8-THC (21.8%), &#x394;10-THC (14.0%), THC-O-acetate (5.2%), THC homologue tetrahydrocannabiphorol (24.4%), and hydrogenated derivative hexahydrocannabinol (3.5%). Older individuals had lower odds of reporting past-year semi-synthetic cannabinoid use (adjusted odds ratio [aOR] = 0.96, 95% confidence interval [CI] = 0.94, 0.99, p = 0.004); factors associated with higher odds of reporting semi-synthetic cannabinoid use included reporting 101-1,000 lifetime cannabis uses (vs. <100 times; aOR = 2.55, 95% CI = 1.02, 6.38, p = 0.046), reporting 1,001-10,000 lifetime cannabis uses (vs. <100 times; aOR = 4.40, 95% CI = 1.57, 12.33, p = 0.005), and reporting non-inhaled forms of cannabis as the most frequent route of administration in the past year (vs. smoking; aOR = 2.98, 95% CI = 1.18, 7.53, p = 0.021). Adverse effects were reported across all semi-synthetic cannabinoids. Discussion: Semi-synthetic cannabinoid use was prevalent among this sample, especially among younger individuals. Despite their popularity, adverse effects underscore the need for regulation and research to address these products' safety and public health implications.

Despite its long history of cultivation and diverse applications, Cannabis sativa remains underexplored at the genomic level, particularly in landrace populations that harbor untapped genetic diversity. In this study, we investigated the genetic architecture of 145 Iranian cannabis landrace accessions, including both male and female plants, using 233K common SNPs and genome-wide association studies. Our analysis revealed three genetically distinct subpopulations shaped by geography, climate, and traditional cultivation practices. We identified 91 significant genomic regions associated with 40 phenological, morphological, and phytochemical traits, including 15 key loci with pleiotropic effects linked to multiple traits, including flowering time, plant architecture, biomass accumulation, and cannabinoid biosynthesis. These findings highlight the complex interplay between developmental and metabolic pathways in cannabis. The high heritability of most traits and rapid linkage disequilibrium decay underscore the potential of these landraces for high-resolution mapping and genetic improvement. This work provides a valuable genomic resource for marker-assisted selection, supporting the development of improved cultivars with tailored cannabinoid profiles and agronomic traits. Cannabis has long been used for medicinal and industrial purposes, but little is known about the genetics of traditional landraces that possess valuable traits. Our study aimed to identify the genes associated with key characteristics in these plants using a genome&#x2010;wide association study. We connected specific genes to traits such as flowering time, plant shape, and production of compounds like cannabidiol (CBD) and tetrahydrocannabinol (THC). In total, we identified 91 genomic regions related to 40 traits, including genes that influence multiple features at once. This genetic map provides breeders with tools to develop improved cannabis varieties with higher yields, stress resistance, and tailored chemical profiles.

Light spectrum plays a crucial role in regulating the growth of hemp (Cannabis sativa L.) plants and the biosynthesis of secondary metabolites. Several studies have demonstrated that additional red-light exposure increases biomass accumulation, while supplementary UV-A light stimulates cannabinoid synthesis. Nevertheless, the potential of stage-specific supplementation of red and UV-A light remains underexplored in its capacity to optimize cannabinoid yield in indoor hemp cultivation. In the present study, the effect of red light in combination with UV-A light on hemp biomass and cannabinoid accumulation was investigated using a high-CBD strain. There were four treatments: (1) white light throughout the growth period (control; VWRW); (2) red light supplementation during the vegetative stage (VWRRW); (3) UV-A supplementation (VWRWUV) during the flowering stage; and (4) combined red and UV-A supplementation (VWRRWUV) during the vegetative and flowering stages. Results showed that VWRRW promoted the number of effective branches (increased by 18.0%) compared to the control (VWRW), resulting in an increase in inflorescence yield by 17.9%. VWRWUV increased CBG and CBD content by 52.7% and 12.1%, respectively, relative to the control. The effect of VWRRWUV on biomass and cannabinoid accumulation was the strongest among the treatments, with CBG and CBD yields reaching 0.53&#xa0;g and 4.62&#xa0;g per plant, representing significant increase of 91.8% (p&#x2009;<&#x2009;0.01) and 44.1% (p&#x2009;<&#x2009;0.01), respectively, compared to the control. However, there were no significant differences in CBD yield among the VWRRW, VWRWUV and VWRRWUV treatments, indicating that the combined supplementation of red and UV-A light did not have an additive effect on CBD accumulation. These findings highlight the potential of stage-specific spectral strategy to optimize both plant growth and phytochemical quantity.

Cannabis is among the most water-demanding crops, facing ongoing expansion and water use regulations. This study evaluated the effects of greenhouse sunlight plus increased LED supplemental lighting on flower yield, water use (WU), and efficiency (WUE), as well as flower partitioning, cannabinoids, terpenes, and leaf gas exchange in Cannabis sativa 'Suver Haze'. The supplemental lighting programs applied during the vegetative and flowering stages were: (1) Static LED levels (PPFD: 150, 300, 500, or 700 &#xb5;mol m-2 s-1 for 72 days) and (2) Dynamic LED levels (PPFD: 150, 300, or 500 for 28 days, followed by 700 &#xb5;mol m-2 s-1 for 44 days). Flower yield and crop WUE increased linearly with the increase of Dynamic and Static lighting. For instance, a 4.7-fold Static lighting increase caused a 4.1-fold increase in flower yield and reduced the evapotranspiration per gram of flower by 37%. Furthermore, plants in Dynamic lighting produced up to 10.4% more flowers and 24.8% higher WUE than plants in Static lighting at the same cumulative lighting. Higher leaf photosynthetic rate, WUE, and lower stomatal conductance due to higher light intensity supported the crop results. Cannabinoid and terpene changes were small and complex, with terpene concentration affected by the light program and light level. In conclusion, supplemental lighting substantially enhanced production and WUE, particularly when higher light was provided during flowering.

Cannabis and cannabis-derived products (CCDPs) have gained recognition for their therapeutic potential, driving legal and social shifts worldwide. In the United States, state-level medical cannabis programs exist alongside the federal drug development framework, which remains the gold standard for ensuring safety and efficacy. The Food and Drug Administration (FDA) botanical drug development guidance provides a structured approval pathway for plant-derived products, including CCDPs, accounting for their unique chemical complexity. Despite this guidance, significant gaps persist in preclinical and clinical data, particularly for minor cannabinoids. Development of botanical drugs from cannabis is further complicated by regulatory oversight from the Drug Enforcement Administration, which constrains the cultivation, handling, and distribution of cannabis and imposes logistical and security requirements during drug development. This article discusses the unique experience of drug developers navigating the scientific and regulatory challenges inherent in advancing CCDPs toward FDA drug approval. Collaborative efforts among federally compliant drug developers, regulatory bodies, healthcare providers, academic institutions, investors, and patients/patient advocacy groups are critical to generate rigorous, reproducible evidence to support the safe and effective use of CCDPs in medical conditions where they hold the greatest therapeutic potential. Such partnerships can advance studies that elucidate cannabinoid pharmacology, optimize dosing with rigorously characterized materials via clinically relevant routes, and identify clinical outcomes that are meaningful to patients. Advancing CCDPs through federally compliant drug development pathways will enable the translation of promising botanical therapies into safe, effective, and evidence-based treatments, ultimately informing clinical practice and benefiting patients.

Oxidative stress (OS) is widely recognized as a central promoter to the pathogenesis of neurodegenerative diseases, including Alzheimer's disease (AD), Parkinson's disease (PD), amyotrophic lateral sclerosis (ALS) and primary lateral sclerosis (PLS). Cannabis sativa L. synthesizes a complex array of bioactive compounds that extends well beyond the well-known cannabinoids to include a diverse suite of polyphenols, terpenes, fatty acids, tocopherols, and proteins. The non-cannabinoid polyphenolic fraction is composed primarily of flavonoids, stilbenoids, lignans, and lignanamides, which contribute substantially to the plant's antioxidant, anti-inflammatory, and neuroprotective properties. This study investigates the redox-modulating and cytoprotective properties of a polyphenolic fraction derived from Cannabis sativa L. in SH-SY5Y neuroblastoma cells. Neurons were treated with various concentrations of the aqueous polyphenolic cannabis extract and exposed to oxidative stress using hydrogen peroxide (100&#x202f;&#xb5;M). Protein and gene expression related to redox signalling were analyzed via Western blot and qPCR, and molecular docking studies were performed in silico. Furthermore, antioxidant enzymes activity was measured by spectrophotometry. Results revealed that the phenolic fraction significantly activated the Keap1/Nrf2 pathway, increased expression of PRDX1 and PRDX3, and enhanced endogenous antioxidant defences. Simultaneously, it reduced endoplasmic reticulum stress-induced apoptosis (via Bax/Bcl-2 modulation) and attenuated inflammatory markers, including NO, NF-&#x3ba;B2, IL-6, and IL-8. In silico docking studies identified Leu583 as a key residue in Nrf2-ligand interactions. These findings suggest that Cannabis sativa L. polyphenols are key bioactive compounds modulating redox homeostasis and inflammation, and offering neuroprotective benefits with potential relevance in diseases involving mitochondrial dysfunction and oxidative damage.

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. 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. 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. 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.

Since the 2018 Farm Bill, many new types of intoxicating cannabis products (ICPs) are widely sold throughout the United States. However, there is little information on popular brands, which is essential for understanding associated risks, marketing strategies, and major industry players who may oppose effective public health legislation. The current study identified popular ICP brands in vape shops across the U.S. In November-December 2023, telephone surveys were conducted for 520 vape shops across all 50 states, Washington, D.C., and Puerto Rico. Google Maps was used to locate 10 vape shops per state/territory. Shops were asked about the availability of THC products and popular brands. Responses were dual-coded, and descriptive statistics were used to describe popular ICP brands. Vape shops in 48 states/territories reported selling ICPs. Overall, 74% of shops surveyed sold ICPs. Among these, 62% (N&#x2009;=&#x2009;273) provided information about brands (N&#x2009;=&#x2009;188 unique brands; average 2.4 per shop). The top ten brands identified were Torch (12.7%), Mellow Fellow (9.7%), Cake (8.4%), Modus (8.0%), Delta Extrax (7.6%), Hidden Hills (7.6%), Looper (7.2%), Urb (7.2%), Ghost (6.3%), and Space Gods (6.3%). This is the first study to systematically document popular brands of ICPs sold in vape shops nationwide. Findings suggest substantial competition in the market including many popular brands. These brands provide a foundation for future research assessing the characteristics of products from these brands and use prevalence, the nature of the industries producing these products, and industry dynamics over time, all of which can help inform regulatory efforts.

The role of the cannabinoid system in human reproduction, and particularly in androgen biosynthesis, remains highly controversial. We recently observed significantly higher serum concentrations of testosterone and androstenedione in cannabis users than in the control group of a cohort of young Swiss men. To determine whether there is a direct causal relationship between cannabinoid exposure and androgen levels, we tested in vitro the effect of tetrahydrocannabinol (THC) and cannabidiol (CBD) on androgen biosynthesis in H295R cells. Modulation of steroidogenesis by phytocannabinoids and other agents was analysed in cell culture medium by liquid chromatography coupled to tandem mass spectrometry. Both THC and CBD significantly reduced in vitro DHEA, androstenedione and testosterone production by H295R cells in a concentration-dependent manner. The inhibitory action of cannabinoids was rapid and affected principally late steps of steroidogenesis. It was not prevented by rimonabant, a specific antagonist of the CB1 cannabinoid receptor. In addition, CBD (but not THC) appeared to affect the steroidogenic step involving the CYP17A1 enzyme. These results exclude a direct stimulation of steroidogenesis by phytocannabinoids in vivo as a putative mechanism for the positive association observed between cannabis use and blood androgen concentration in young men. Alternative explanations are discussed. Given that cannabis is frequently consumed by men of reproductive age, a better understanding of THC and CBD action on the reproductive system seems highly relevant in the context of the decline in male fertility observed in the general population.

Cannabis use is increasingly common, yet its effects on postoperative pain and opioid requirements remain unclear. While cannabinoids are used in chronic pain, their role in acute perioperative recovery is less defined. A systematic search of PubMed, CINAHL, and Embase identified studies published within the past ten years that examined preoperative cannabis use and its relationship with postoperative pain and opioid consumption. Forty-two studies met the inclusion criteria. Data were extracted and summarized using a narrative synthesis methodology. Exposure definitions, surgical specialties, and outcome metrics were heterogeneous, limiting cross-study comparability; therefore, effects were reported in their native form without pooling. Of the 42 included studies, 14 (33.3&#xa0;%) found that cannabis users reported higher postoperative pain, 10 (23.8&#xa0;%) reported no difference, 2 (4.8&#xa0;%) suggested reduced pain, and 16 (38.1&#xa0;%) did not report pain outcomes. Regarding opioids, 18 studies (42.9&#xa0;%) indicated greater postoperative requirements, 17 (40.5&#xa0;%) found no difference, 3 (7.1&#xa0;%) suggested reduced use, and 4 (9.5&#xa0;%) did not report opioid outcomes. Specialty-specific patterns emerged: mixed cohorts (90&#xa0;%) and spine populations (55&#xa0;%) more frequently reported increased opioid use, whereas arthroplasty studies more often reported no difference (62&#xa0;%). Limited, low-certainty evidence suggested that resuming cannabis after discharge was associated with lower persistent opioid use. Preoperative cannabis exposure is associated with increased postoperative pain and opioid requirements in some, but not all, surgical contexts. Outcomes vary by specialty, and residual confounding and nonstandardized exposure measurement constrain inference, underscoring the need for standardized exposure definitions, prospective designs, and individualized perioperative pain strategies.

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. 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). 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-&#x3b1;, IL-6, and IL-1&#x3b2;. However, substantial heterogeneity was noted across several outcomes. 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.

Cannabis sativa is a phytochemically rich plant producing over 500 compounds, with cannabinoids recognized as its most bioactive constituents. However, the natural exploration and exploitation of novel, pharmacologically active cannabinoids remain limited due to their trace abundance in the plant. To address this challenge, we employed an extract engineering strategy in which enriched fractions of major cannabinoids were chemically transformed through oxone/acetone oxidation under mild conditions. This approach enabled the purification of seven cannabinoid analogs, including rare and previously undescribed compounds, in appreciable quantities. The structures of these analogs were elucidated using high-resolution mass spectrometry combined with comprehensive 1D and 2D NMR spectroscopy. Antibacterial susceptibility assay revealed that out of seven compounds, Compound 1, 5, and 7 exerted significant inhibitory activity against both Staphylococcus aureus and methicillin-resistant S. aureus (MRSA) pathogens. A Checkerboard study revealed the synergistic interaction between active hits and Rifampin in both S. aureus and MRSA. The biofilm-based assay demonstrated the antibiofilm potential of the identified hits. The mechanistic exploration elucidated the cell membrane-based targeting of the potent hits, validated through scanning electron microscopy. Moreover, the Propidium iodide assay performed using flow cytometry and fluorescence microscopy revealed the membrane disruption effect of the identified hits. In addition, the ATP quantification study demonstrated a major decline in ATP levels along with an augmentation in ROS production in the MRSA pathogen. Thus, this work establishes extract engineering as a powerful strategy to unlock rare cannabinoid scaffolds and highlights their potential as leads for combating multidrug-resistant Staphylococcus infections.