Cannabidiol (CBD) exhibits multiple therapeutic properties, but its use in advanced cancer patients raises concerns about potential drug-drug interactions (DDIs) due to polypharmacy. This study aims to look for evidence of DDIs between concomitant medications and CBD oil in a randomized placebo-controlled trial of CBD oil for symptom control (MedCan-1 parent study). Surrogate measures were used to identify possible drug interactions: (1) the maximum mL of oil self-selected by patients in CBD or placebo groups in relation to opioids, specific drug groups, or individual agents; (2) the occurrence of any new or worse adverse effect in relation to the study arm and the concomitant medication classes/medications of interest. The dose of CBD self-selected by participants was not related to opioid use or medications, including benzodiazepines and antipsychotics. The likelihood of developing an adverse effect while on study or when taking specific medications was not increased by CBD. Participants on paracetamol tolerated a higher dose of CBD. Concerns regarding the development of clinically significant drug interactions when taking CBD in the context of anti-cancer and other concomitant medications at least in the short term may be unfounded.

The endocannabinoid system (ECS) is a widespread neurotransmitter system. A key characteristic of the ECS is that there are multiple endogenous ligands (endocannabinoids). Of these, the most extensively studied are arachidonoyl ethanolamide (AEA) and 2-arachidonoyl-glycerol (2-AG), both act as agonists at the cannabinoid CB receptor. In humans, three CB variants have been identified: hCB, considered the most abundant G protein-coupled receptor in the brain, alongside the less abundant and studied variants, hCB and hCB. CB exhibits a preference for coupling with inhibitory G proteins, although its interactions with specific members of the G family remain poorly characterized. This study aimed to compare the AEA and 2-AG-induced activation of various G protein subtypes at CB. Furthermore, we compared the response of human CB (hCB, hCB, hCB) and explored species differences by examining rodent receptors (mCB, rCB). Activation of individual G protein subtypes in HEK293 cells transiently expressing CB was measured with G protein dissociation assay utilizing TRUPATH biosensors. The performance of the TRUPATH biosensors was evaluated using Z-factor analysis. Pathway potencies and efficacies were analyzed using the operational analysis of bias to determine G protein subtype selectivity for AEA and 2-AG. Initial screening of TRUPATH biosensors performance revealed variable sensitivities within our system. Based on the biosensor performance, the G protein subtypes pursued for further characterization were G, G, G, G, G, G, and G. Across all pathways, AEA demonstrated partial agonism, whereas 2-AG exhibited full or high-efficacy agonism. Notably, we provide direct evidence that the hCB receptor couples to G and G proteins. Our findings do not indicate any evidence of G protein subtype selectivity. Similar observations were made across the human receptor variants (hCB, hCB, hCB), as well as at mCB and rCB. There was no evidence suggesting G protein subtype selectivity for AEA and 2-AG at CB, and this finding remained consistent across human receptor variants and different species.

Florida's medical cannabis (marijuana) program is among the largest in the United States. Smokable cannabis forms were not legally available in this program until 2019, and five years after other forms of cannabis were available. This study assessed changes in Δ-9 tetrahydrocannabinol (THC) dispensed per patient following legalization of smokable cannabis in Florida. This quasi-experimental study used data from the Florida Department of Health Office of Medical Marijuana Use Reports on THC dispensing from April 6, 2018, through March 13, 2020. Certified medical cannabis user during the study period was included. The exposure was the dispensed amount of THC from legalized smokable forms of medical cannabis (statute identified as SB182), effective as of March 2019. Changes in level and trend of average milligram (mg) of dispensed THC per certified patient with 95% confidence intervals (CIs), before and after SB182, were calculated by fitting a generalized least squares linear model and allowing a 17-week phase-in period. The number of certified patients increased by 24.8% from 197,107 (March 22, 2019) to 246,079 (July 19, 2019) and to 325,868 by March 13, 2020. Assuming that a 20% THC concentration in smokable products, there was a significant level increase in the mean weekly dispensed THC amount per certified patient of 138.45 mg (95% CI: 102.69-174.20), translating to a 42.18% increase (95% CI: 33.14-50.28), from the pre-policy period. We noted a continuous increase of 5.62 mg per certified patient per week (95% CI: 4.35-6.89) throughout the 35 weeks following the policy, when compared with the period before. Assuming 10% THC concentration in smokable products, we observed a significant level increase of 35.10 mg (95% CI: 5.31-64.88), corresponding to an increase of 10.70% (95% CI: 1.70-18.89), and a trend increase of 2.23 mg per certified patient per week (95% CI: 1.18-3.29). The expansion of the Florida medical cannabis program to include smokable cannabis forms was associated with a significant increase in the mean amount of weekly dispensed THC per certified patient. Findings suggest that the dispensed amount of THC after legalization of smokable medical cannabis far exceeds the maximum recommended daily dose, based on extrapolation from oral cannabis product dosing recommendations from one expert consensus statement, raising questions about the safety, and need for consumer education.

Although cannabinoid type 2 (CB2) receptor activity is known to promote diverse biological functions in the kidney, published data regarding CB2 receptor protein levels and cellular distribution within the kidney is inconsistent. The goal of the present study was to investigate the changes of CB2 in the kidney obtained from mice exposed to various forms of kidney injury using a genetic mouse model expressing green fluorescent protein (GFP) driven by the endogenous cannabinoid receptor 2 (Cnr2) promoter. Kidney injury was established in a genetic mouse model expressing green fluorescent protein (GFP) driven by the endogenous Cnr2 promoter. Kidney injury was initiated by either treatment with different chemicals [cisplatin or lipopolysaccharide (LPS)] or by unilateral ureteral obstruction (UUO). Changes in the detection of GFP were used as a proxy for CB2 levels and localization. Histological changes due to the injury stimuli were observed by time-related, morphological changes in kidney cytoarchitecture and blood parameters, such as serum creatinine levels. Cnr2 mRNA levels were detected by reverse transcription coupled to polymerase chain reaction (RT-PCR) while protein changes in the tissue lysates were measured by Western blot analysis. Cellular localization of GFP was detected by fluorescent microscopy. Our data demonstrated that there was no band or a minimally detectable band for GFP using kidney lysates from vehicle- or cisplatin-treated mice. A similar lack of GFP was detected in the UUO kidney versus the contralateral control kidney. This is consistent with the low, albeit detectable levels of Cnr2 mRNA in the kidney samples from control or cisplatin treatment. In frozen kidney sections from vehicle and cisplatin-treated mice, GFP fluorescence was not detectable in tubular epithelia, glomeruli or blood vessels in the cortex. Instead, GFP was detected in rare cells within the interstitial space. A second chemical injury model using LPS found a similar lack of GFP protein levels and an absence of legitimate GFP fluorescence in the main cell types within the kidney. These findings suggest that Cnr2 promoter activity is minimally active in normal or injured kidneys, and that pharmacological manipulation of CB2 receptors may be associated with receptors being expressed in cells recruited to the kidney.

The conscientious prescribing of antiemetics by chemotherapy-induced nausea and vomiting (CINV) risk was highlighted in the American Society of Clinical Oncology (ASCO) "Choosing Wisely" recommendations. The pharmacologic properties of medical marijuana (MMJ) may allow for decreased incidence of CINV; however, little is known about the effects of MMJ on the use of antiemetics. This study aimed to determine if MMJ cardholder status, which enables access to MMJ, is associated with antiemetic overuse among patients with cancer. This population-based secondary data analysis examined a retrospective cohort derived from the linked Arkansas All Payers Claims Database (2013-2020) and MMJ cardholder registry (2013-2019). The cohort consisted of 20,558 patients with cancer aged 18 and older with a chemotherapy claim in an outpatient setting within 12 months of a cancer diagnosis. Exposure was a registration to receive an MMJ card that permitted access to MMJ. The primary outcome of interest was antiemetic overuse, as characterized by the ASCO recommendation. Antiemetic use associated with chemotherapy was identified through filled prescriptions and medical claims. Multivariable logistic regression, adjusted for baseline demographic and prescription characteristics, was used to calculate the adjusted odds ratios (aOR) of antiemetic overuse among MMJ cardholders compared with non-MMJ cardholders. Among 20,558 eligible patients, 436 (2.1%) had an MMJ card at some point in the study period. Antiemetic overuse was identified in 7.5% of chemotherapy cycles. Compared with non-MMJ cardholders, MMJ cardholders were less likely to experience antiemetics overuse (aOR: 0.76, < 0.001). Patients with fewer chemotherapy cycles and younger in age had higher odds of antiemetic overuse compared with those with more chemotherapy cycles. The risk of antiemetic overuse did not differ based on gender and rurality of residency. Route of chemotherapy administration, CINV risk category, and type of cancer also impacted the odds of antiemetic overuse. The findings indicate that MMJ cardholders are significantly less likely to experience antiemetic overuse than non-MMJ cardholders. Further investigation into the use, effectiveness, and safety of cannabis for CINV mitigation is needed to inform patient and provider decision-making.

Cannabidiol (CBD), a phytocannabinoid of increasing interest for its purported therapeutic effects, is primarily consumed ingestion and inhalation. While the toxicology of orally administered CBD has been reported, little is known about the effects of CBD inhalation. Doses selected for the present analysis allowed for evaluation of dose-response at concentrations >100-fold higher than typical human consumption levels. CBD (98.89% pure) was formulated in propylene glycol (PG) and aerosolized by nebulization to evaluate biological response after nose-only inhalation. Sprague Dawley rats ( = 35 males, 30 females) were exposed to 1.0 and 1.3 mg/L nominal concentrations of CBD and PG, respectively, for 12-180 min. Resulting average daily presented dose ranges were 8.9-138.5 mg/kg CBD and 11.3-176.0 mg/kg PG. Aerosols of 1.4 µm median diameter were achieved. Biological response indicators included clinical signs, clinical chemistry, hematology, body/organ weights, and pulmonary/systemic histopathology. Inflammatory and necrotic responses were observed in the nose at the highest doses of CBD. Limited findings in the larynx and lung were mainly observed at higher doses. There were no histological findings in extrapulmonary organs. Dosimetry modeling differentiated the no observable adverse effect level between the nasal region and lungs to be 2.8 and 10.6 mg/kg CBD, respectively. Dose-depending findings of histological changes in the respiratory tract are observed at high doses. At lower doses consistent with typical over-the-counter vape products there appears to be substantial safety margin in the present study (93- and 353-fold lower for nose and lung, respectively).

Cannabis use is highly prevalent in people with psychotic disorders and is associated with adverse outcomes. We updated our 2020 systematic review related to the efficacy of technology-based psychological interventions (TBPIs) to decrease cannabis use in individuals with psychosis, the design of TBPIs, and their acceptability. We searched Medline, PubMed, Embase, CINAHL, PsycINFO, and EMB Reviews for references indexed between November 27, 2019, and July 27, 2023, and used the PRISMA guidelines to report the results. We screened 5083 unique records and retained three studies for the narrative synthesis. Two quantitative studies showed promising results of internet or virtual reality-based psychological interventions that incorporate cognitive behavioral therapy, motivational interviewing, and psychoeducation principles on the frequency and quantity of cannabis use. A qualitative exploratory study provided an integrative synthesis of patient and clinician opinions pertaining to the use of psychological approaches and technology to tackle cannabis misuse in individuals with psychosis. In contradiction with the rapidly expanding mobile-health solutions in the field of mental health, there is a dearth of research related to the use of internet and app-based psychological interventions for cannabis use in individuals with psychosis. The use of qualitative research is pivotal in the development of TBPIs. Our initial review and its update show that only 11 peer-reviewed journal articles that met our inclusion criteria have been published so far.

Although the majority of cannabinoid research has focused on delta-9-tetrahydrocannabinol (Δ-THC) and cannabidiol (CBD), there is increasing interest in the therapeutic effects of other phytocannabinoid compounds (i.e., minor cannabinoids), as there is little known about their effects or interaction with CBD. The current study objective was to determine the concentrations of 15 minor cannabinoids in unregulated, over-the-counter CBD products. A cross-section sample of 80 local and national brands of hemp-derived oil products was purchased both online and in local retail outlets in central Kentucky. Epidiolex® was included as a regulated control. Samples from each product were extracted by solvent extraction and quantified by liquid-chromatography tandem mass-spectrometry. The targeted cannabinoids were: cannabidiolic acid (CBDA), cannabidivarin (CBDV), cannabidivarinic acid, Δ-tetrahydrocannabivarin, Δ-tetrahydrocannabivarinic acid, Δ-tetrahydrocannabinolic acid-A, Δ-tetrahydrocannabinol (Δ-THC), cannabigerol (CBG), cannabigerolic acid, cannabinol (CBN), cannabinolic acid, cannabicyclol (CBL), cannabicyclolic acid, cannabichromene (CBC) and cannabichromenic acid. Among the unregulated products included in this analysis, the most frequently detected minor cannabinoids were CBDV (100% of samples tested), CBG (77%), CBC (72%), CBN (67%), CBL (67%), and CBDA (51%). Δ-THC was not detected in any of the products tested. Concentrations of these cannabinoids varied widely from trace concentrations to several mg/mL (e.g., CBDA: 0.006-12.258 mg/mL). These data indicate CBD products often contain minor cannabinoids, although the array and concentrations of these cannabinoids vary widely across products. The concentrations of these minor cannabinoids are largely absent from product labels, leaving consumers uninformed about product contents.

Following the introduction of metabolic dysfunction-associated steatotic liver disease (MASLD) as a replacement term for nonalcoholic fatty liver disease, the relationship between MASLD and cannabis use has yet to be established. With the global rise in cannabis consumption, understanding its impact on MASLD is critical for clinical guidance. Our study investigated the association between cannabis use, MASLD, and clinically significant fibrosis (CSF) among U.S. adults. Data were collected from the National Health and Nutrition Examination Survey for the period 2017 to 2018 to conduct a cross-sectional analysis. The diagnosis of hepatic steatosis and CSF was based on median values of the controlled attenuation parameter and liver stiffness measurement, with thresholds of 285 dB/m and 8.6 kPa, respectively. Information on cannabis use was obtained through self-report questionnaires. Multinomial logistic regression models and subgroup analyses were used to investigate the association between cannabis use and MASLD with CSF. Our study assessed data from 2,756 U.S. adults (51.1% female; 32.2% white; mean age 39.41 ± 11.83 years), who had complete information on liver stiffness measurements through transient elastography alongside reported cannabis use. Results indicated that cannabis use overall was not associated with liver stiffness in patients with MASLD. However, among females, cannabis use was associated with MASLD accompanied by CSF, with an adjusted odds ratio (OR) of 0.47 (95% confidence interval [CI]: 0.24-0.91). Heavy cannabis use (9 to 30 times per month) was associated with MASLD accompanied by CSF among female participants, with an adjusted OR of 0.12 (95% CI: 0.02-0.88). In our study, cannabis use did not show a significant association with liver stiffness in patients diagnosed with MASLD. However, heavy cannabis consumption in women was associated with MASLD accompanied by CSF. These findings suggest that the effects of cannabis on liver health may differ based on gender and frequency of cannabis use, emphasizing the need for further research in this area.

Anandamide (AEA) and 2-arachidonoylglycerol are endogenous agonists of the cannabinoid receptors and regulate and control many cellular functions. Their activities are governed by enzymes and proteins that regulate their synthesis, receptor binding, transport, and degradation, which are known as the endocannabinoid system (ECS). The aim of this study was to investigate the regulation of endocannabinoid activity in the endometrium by studying the RNA and protein expression of the ECS within endometrial cell types and during different menstrual cycle stages and the impact of endometriosis. The RNA expression of 70 ECS genes was assessed using RNA sequencing of isolated endometrial epithelial and stromal cells. Subsequent immunofluorescence-stained endometrial samples on ECS components of interest were objectively analyzed an agnostic and automated image analysis pipeline to extract quantitative information. Differential gene and protein expression was investigated between the two cell types, menstrual cycle phases, and endometriosis cases and controls. Sufficient RNA expression was detected for 45 genes, and 17 (38%) genes were significantly different between epithelial and stromal cells. RNA was significantly higher in epithelial cells compared with stromal cells. Protein expression analysis of the main synthesizing (NAPE-PLD) and catabolizing (FAAH and NAAA) enzymes of AEA revealed a significantly stronger epithelial expression compared to stromal cells. The RNA and protein expression of CB1 receptors was very low with no significant difference between epithelial and stromal cells. Eleven ECS genes were regulated across the menstrual cycle, and there was no gene with significant difference between endometriosis cases and controls in epithelial cells. Differential expression of ECS genes supports a cell type-specific endocannabinoid activity in the endometrium. As endocannabinoids are short-lived signaling molecules, higher RNA and protein expression of FAAH in the epithelial cells suggests an active regulation of endocannabinoid activity in epithelial cells within the endometrium.

This investigation examined the association of pancreatitis and pancreatitis-related pain with serum levels of two endocannabinoid molecules such as anandamide (AEA) and 2-arachidonoylglycerol (2-AG) and two paracannabinoid molecules such as oleoylethanolamide (OEA) and palmitoylethanolamide (PEA). A case-control study was conducted within the Prospective Evaluation of Chronic Pancreatitis for Epidemiological and Translational Studies, including participants with no pancreas disease ( = 56), chronic abdominal pain of suspected pancreatic origin or indeterminate chronic pancreatitis (CP) ( = 22), acute pancreatitis ( = 33), recurrent acute pancreatitis ( = 57), and definite CP ( = 63). Circulating AEA concentrations were higher in women than in men ( = 0.0499), and PEA concentrations were higher in obese participants than those who were underweight/normal or overweight ( = 0.003). Asymptomatic controls with no pancreatic disease had significantly ( = 0.03) lower concentrations of AEA compared with all disease groups combined. The highest concentrations of AEA were observed in participants with acute pancreatitis, followed by those with recurrent acute pancreatitis, chronic abdominal pain/indeterminant CP, and definite CP. Participants with pancreatitis reporting abdominal pain in the past year had significantly ( = 0.04) higher concentrations of AEA compared with asymptomatic controls. Levels of 2-AG were significantly lower ( = 0.02) among participants reporting abdominal pain in the past week, and pain intensity was inversely associated with concentrations of 2-AG and OEA. Endocannabinoid levels may be associated with stage of pancreatitis, perhaps through activation of the CB1 receptor. Validation of our findings would support the investigation of novel therapeutics, including cannabinoid receptor-1 antagonists, in this patient population.

The use of medical cannabis (MC) to treat a host of conditions has expanded considerably in the United States; however, precise quantitative assessments of purchasing characteristics are unknown. This study sought to characterize the trends in MC purchases, US dollars spent, and type and amount purchased by demographic and clinical characteristics. This descriptive exploratory association study examined statewide MC registry data in Arkansas linked at the person level with statewide transaction data documenting each MC purchase. MC transaction data (May 11, 2019-August 31, 2022) were assessed to identify persons who could be linked to the registry data and made at least one purchase. Individual demographic characteristics and MC qualifying conditions (QCs) were ascertained. Product types were classified into plant cannabis, cannabis extract for inhalation (vape), edibles, and others. The average daily total delta-9-tetrahydrocannabinol (THC) purchased was calculated based on the concentration and quantity purchased. Purchasing characteristics are described and demographic and clinical factors associated with THC purchased per day and dollars spent per year were estimated by ordinary least square regression and general linear models with a gamma distribution. On average, 89,057 MC purchasers spent $3343 (interquartile range [IQR], $907-$4802), had 33.34 (IQR, 8.32-46.03) transaction days per year, and purchased 162.32 mg (IQR, 30.51-237.69) of THC per day. Most persons predominantly purchased plant cannabis (68.27%), followed by edibles (14.92%) and vape (11.96%). Individuals younger than 18 years of age (β=-78.23; 95% confidence interval [CI], -116.599 to -39.863), persons 70 and older (β = -122.30; 95% CI, -128.18 to -116.422), and women (β=-33.70; 95% CI, -35.95 to -31.446) purchased less THC per day than their counterparts after multivariate adjustment. The most common QCs were pain and post-traumatic stress disorder (PTSD), and compared to those with cancer, persons with pain (β = 26.30; 95% CI, 18.636-33.96) and PTSD (β = 38.34; 95% CI, 30.467-46.222) purchased more THC per day. The average THC purchased per person per day exceeds typically recommended daily doses for therapeutic uses, and further research is warranted to assess the safety and benefits of MC across these conditions.

Mounting evidence suggests that the phytocannabinoid cannabidiol (CBD) holds promise as an antidepressant agent in conditions underlined by inflammation. Full-spectrum CBD extracts might provide greater behavioral efficacy than CBD-only isolates and might require lower doses to achieve the same outcomes due to the presence of other cannabinoids, terpenes, and flavonoids. However, investigations in this area remain limited. We evaluated the behavioral response to the administration for 7 days of 15 and 30 mg/kg of a CBD isolate and a full-spectrum CBD product in a rat model of subchronic lipopolysaccharide (LPS, 0.5 mg/kg/day/7 days, intraperitoneal)-induced depressive-like and sickness behavior. The forced swim test was used to assess depressive-like behavior, the open field test (OFT) to assess locomotion, and the elevated plus maze to assess anxiety-like behavior. The full-spectrum CBD extract at both doses, but not the CBD isolate, reversed the LPS-induced depressive-like behavior in the forced swim test. Moreover, the full-spectrum CBD extract at the higher dose but not the CBD isolate restored the subchronic LPS-induced hypolocomotion in the OFT. Repeated administration of both formulations elicited an anxiogenic-like trend in the elevated plus maze. Full-spectrum CBD products might have greater therapeutic efficacy in resolving inflammation-induced depressive and sickness behavior compared to a CBD-only isolate.

Early life is a sensitive period for brain development. Perinatal exposure to cannabis is increasingly linked to disruption of neurodevelopment; however, research on the effects of cannabidiol (CBD) on the developing brain is scarce. In this study, we aim to study the developmental effects of neonatal CBD exposure on behavior and dendritic architecture in young adult rats. Male and female neonatal Sprague Dawley rats were treated with CBD (50 mg/kg) intraperitoneally on postnatal day (PND) 1, 3, and 5 and evaluated for behavioral and neuronal morphological changes during early adulthood. Rats were subjected to a series of behavioral tasks to evaluate long-term effects of neonatal CBD exposure, including the Barnes maze, open field, and elevated plus maze paradigms to assess spatial memory and anxiety-like behavior. Following behavioral evaluation, animals were sacrificed, and neuronal morphology of the cortex and hippocampus was assessed using Golgi-Cox (GC) staining. Rats treated with CBD displayed a sexually dimorphic response in spatial memory, with CBD-treated females developing a deficit but not males. CBD did not elicit alterations in anxiety-like behavior in either sex. Neonatal CBD caused an overall decrease in dendritic length and spine density (apical and basal) in cortical and hippocampal neurons in both sexes. Sholl analysis also revealed a decrease in dendritic intersections in the cortex and hippocampus, indicating reduced dendritic arborization. This study provides evidence that neonatal CBD exposure perturbs normal brain development and leads to lasting alterations in spatial memory and neuronal dendrite morphology in early adulthood, with sex-dependent sensitivity.

This research investigated the impact of Cannabistilbene I on Angiotensin II (Ang II)-induced cardiac hypertrophy and its potential role in cytochrome P450 (CYP) enzymes and arachidonic acid (AA) metabolic pathways. Cardiac hypertrophy, a response to increased stress on the heart, can lead to severe cardiovascular diseases if not managed effectively. CYP enzymes and AA metabolites play critical roles in cardiac function and hypertrophy, making them important targets for therapeutic intervention. Adult human ventricular cardiomyocyte cell line (AC16) was cultured and treated with Cannabistilbene I in the presence and absence of Ang II. The effects on mRNA expression related to cardiac hypertrophic markers and CYP were analyzed using real-time polymerase chain reaction, while CYP protein levels were measured by Western blot analysis. AA metabolites were quantified using liquid chromatography-tandem mass spectrometry (LC-MS/MS). Results showed that Ang II triggered hypertrophy, as evidenced by the increase in hypertrophic marker expression, and enlarged the cell surface area, effects that were alleviated by Cannabistilbene I. Gene expression analysis indicated that Cannabistilbene I upregulated CYP1A1, leading to increased enzymatic activity, as evidenced by 7-ethoxyresorufin-O-deethylase assay. Furthermore, LC-MS/MS analysis of AA metabolites revealed that Ang II elevated midchain (R/S)-hydroxyeicosatetraenoic acid (HETE) concentrations, which were reduced by Cannabistilbene I. Notably, Cannabistilbene I selectively increased 19(S)-HETE concentration and reversed the Ang II-induced decline in 19(S)-HETE, suggesting a unique protective role. This study provides new insights into the potential of Cannabistilbene I in modulating AA metabolites and reducing Ang II-induced cardiac hypertrophy, revealing a new candidate as a therapeutic agent for cardiac hypertrophy.

Research has linked marijuana use with lower body mass index (BMI). The current study explores the correlation between marijuana use on BMI in the general U.S. population. It reports the prevalence of marijuana in adults in relation to BMI, overall and across the levels of important variables. This study used a probability sample of U.S. adults 18 years of age and older from the 2016 through 2022 Behavioral Risk Factor Surveillance System, a telephone-administered survey. The survey collects data from a representative sample regarding health-related risk behaviors, chronic health conditions, and use of preventive services. The primary outcome variables are current (at least once in the last 30 days) and daily (at least 20 of the last 30 days) marijuana use. The study sample consists of 735,921 participants in the surveys that completed the optional module on marijuana use. Prevalence of marijuana use in adults doubled during the study period (7.48% to 14.91%). The increase directly corresponds with a shift toward legalization of medical and recreational marijuana. On average, the prevalence of use is 9% higher when medical marijuana is legal and 81% higher when recreational marijuana is legal (vs. not legal). For obese individuals, prevalence of current marijuana use is 35% lower than for nonobese individuals on average. Lower prevalence of marijuana use in obese individuals is consistently observed across the levels of certain demographic variables, employment status, tobacco smoking history, marijuana legalization status, and certain medical conditions (asthma, arthritis, and depression). In 2022, the adjusted odds of current or daily marijuana use are significantly lower and similar among obese (vs. non-obese) (0.68, 0.69, respectively), such that reduced obesity does not require daily use. Similarly, the adjusted odds of current marijuana use decrease in similar fashion to daily marijuana use with higher BMI weight classification. Marijuana use is correlated with lower BMI. As legalization and prevalence of the drug in the U.S. increases, the prevalence of obesity may decline. However, clinicians should view this outcome along with the known health risks associated with marijuana use.

extract has been used as an herbal medicine since ancient times. It is one of the most researched extracts, especially among supportive treatments against cancer. Prostate cancer is one of the most frequently diagnosed cancer types in men worldwide and an estimated 288,300 new cases were diagnosed in 2023. Today, many advanced therapeutic approaches are used for prostate cancer, such as immunotherapy and chemotherapy, but acquired drug resistance, long-term drug usage and differentiation of cancer cells mostly restricted the efficiency of therapies. Therefore, it is thought that the use of natural products to overcome these limitations and improve the effectiveness of existing therapies may offer promising approaches. The present study focused on the investigation of the possible enhancer role of cannabidiol (CBD), which is a potent ingredient compound of Cannabis, on the chemotherapeutic agent etoposide in prostate cancer cells. Herein, we tested the potentiator role of CBD on etoposide in prostate cancer cells by testing the cytotoxic effect, morphological alterations, apoptotic effects, autophagy, unfolded protein response (UPR) signaling, endoplasmic reticulum-associated degradation mechanism (ERAD), angiogenic and androgenic factors, and epithelial-mesenchymal transition (EMT). In addition, we examined the combined treatment of CBD and etoposide on colonial growth, migrative, invasive capability, 3D tumor formation, and cellular senescence. Our findings demonstrated that cotreatment of etoposide with CBD importantly suppressed autophagic flux and induced ERAD and UPR signaling in LNCaP cells. Also, CBD strongly enhanced the etoposide-mediated suppression of androgenic signaling, angiogenic factor VEGF-A, protooncogene c-Myc, EMT, and also induced apoptosis through activation caspase-3 and PARP-1. Moreover, coadministration markedly decreased tumorigenic properties, such as proliferative capacity, colonial growth, migration, and 3D tumor formation and also induced senescence. Altogether, our data revealed that CBD has a potent enhancer effect on etoposide-associated anticancer activities. The present study suggests that the use of CBD as a supportive therapy in existing chemotherapeutic approaches may be a promising option, but this effectiveness needs to be investigated on a large scale.

The chronic effects of cannabidiol (CBD) supplementation on factors that could impact the quality of life (anxiety, sleeping quality, memory, etc.) are poorly explored. Hence, the aim of this study was to establish whether chronic CBD supplementation will improve self-reported outcomes related to quality of life. In this randomized crossover trial, 64 patients with primary hypertension were assigned to receive CBD (225-450 mg) for 5 weeks followed by 5 weeks of placebo or vice versa, with a 2-week washout in-between the two. Self-reported outcomes were assessed using short form-36 (SF-36), Pittsburgh sleep quality index (PSQI), Epworth sleepiness scale (ESS), memory complaint questionnaire (MAC-Q), and state-trait anxiety inventory (STAI). Five-week administration of CBD, but not of placebo, resulted in improvement of ESS score (F = 6.738, = 0.011), as well as fatigue/vitality (Δ = 5.0, < 0.001) and psychological well-being dimensions of SF-36 (Δ = 7.4, = 0.039). No overall benefit of CBD on quality of life was noted ( = 0.674). No changes were seen in total scores of MAC-Q, PSQI, or STAI ( = 0.151, = 0.862, = 0.702, respectively). No significant correlations were found between plasma CBD concentrations and any of the scores. Chronic CBD administration reduced excessive daytime sleepiness, despite the fact that no change was observed in self-reported quality of sleep. Furthermore, self-reported fatigue and psychological well-being dimensions of quality of life also improved following chronic CBD use.

Animal studies suggest that adolescent exposure to Δ-tetrahydrocannabinol (Δ-THC), the intoxicating constituent of cannabis, causes lasting functional alterations in brain and other organs. Those studies often neglect the impact that age- and sex-dependent differences in the distribution and metabolism of the drug might exert on its pharmacological effects. Here, we provide a comparative analysis of Δ-THC pharmacokinetics in adolescent and adult female mice, which identify significant dissimilarities in distribution and metabolism of Δ-THC between females of these age groups. We administered Δ-THC (5 mg/kg, intraperitoneal) to adolescent (37-day old) and young adult (70-day old) female mice and quantified Δ-THC and its first-pass metabolites-11-hydroxy-Δ-THC (11-OH-THC) and 11-nor-9-carboxy-Δ-THC (11-COOH-THC)-in plasma and brain tissue using liquid chromatography/tandem mass spectrometry. Maximal plasma concentrations of Δ-THC were 8 times higher in adolescent than adult female mice. Conversely, brain concentrations and brain-to-plasma ratios were 25-50% higher in adults than adolescents. Concentrations of Δ-THC metabolites were higher in plasma but lower in brain of adolescent compared to adult female mice. The results identify multiple age-dependent differences in the pharmacokinetic properties of Δ-THC in female mice, which might influence the pharmacological response to the drug.

Cannabis use is becoming increasingly prevalent worldwide, yet the full spectrum of its effects largely remain unknown. Although cannabis have immunomodulatory properties, there remains a significant gap in our understanding of the potential impact of marijuana use on COVID-19 outcomes. The purpose of this study is to evaluate the effect of chronic cannabis use on severe COVID-19. National Inpatient Sample Database was used to sample individuals admitted with the diagnosis of COVID-19. Patients were divided into two groups based on cannabis use. Baseline demographics and comorbidities were collected using ICD-10 codes. Patients with missing data or age under 18 were excluded. Propensity matching using R was performed to match cannabis users to non-cannabis users 1:1 on age, race, gender, and 17 other comorbidities. The primary outcome was severe COVID-19 infection, defined as a composite of acute respiratory failure, intubation, acute respiratory distress syndrome (ARDS), or severe sepsis with multiorgan failure. Out of 322,214 patients included in the study, 2,603 were cannabis users. Cannabis users were younger and had higher prevalence of tobacco use. On initial analysis, cannabis users had significantly lower rates of severe COVID-19 infection, intubation, ARDS, acute respiratory failure, severe sepsis with multiorgan failure, mortality, and shorter length of hospital stay. After 1:1 matching, cannabis use was associated with lower rates of severe COVID-19 infection, intubation, ARDS, acute respiratory failure, severe sepsis with multiorgan failure, mortality, and shorter length of hospital stay. Cannabis users had better outcomes and mortality compared with non-users. The beneficial effect of cannabis use may be attributed to its immunomodulatory effects.