The legalization of cannabis in several states across the United States has increased the need to better understand its effects on the body, brain, and behavior, particularly in different populations. Previous rodent studies have revealed age and sex differences in response to injected Δ-tetrahydrocannabinol (THC). However, the pharmacokinetic and pharmacodynamic properties of THC administered through more translationally relevant routes of administration are less well known. Here, we addressed this gap by investigating age and sex differences in pharmacokinetics and the acute behavioral effects of vaporized cannabis e-liquid in mice. Adolescent (postnatal day [P] 35-50) and adult (≥P70) mice of both sexes received noncontingent exposure to vehicle vapor, 150 mg/mL (CAN150), or 300 mg/mL (CAN300) vaporized cannabis extract diluted in either 80% propylene glycol/20% vegetable glycerin (PG/VG) or 100% polyethylene glycol 400 (PEG). Immediately after exposure, body temperature, hot plate withdrawal latency, and locomotion were assessed. Blood was collected at 0, 30, and 60 min after vapor exposure, and plasma THC, 11-hydroxy-THC, and 11-nor-9-carboxy-THC were analyzed. THC concentrations were higher in both the plasma of vapor-exposed mice and the cannabis extract solutions when PEG was the carrier oil compared with PG/VG. Vaporized cannabis (mixed with PEG) at the highest dose tested induced hypothermic, antinociceptive, and locomotor-suppressing effects in all groups of mice. We found a dose-dependent age difference in locomotion, indicating that adolescents were less sensitive to the locomotor-suppressing effects of vaporized cannabis, which may be related to differences in circulating THC levels. Although we found no sex differences in the acute behavioral effects of vaporized cannabis, there were sex differences in plasma THC metabolites, suggesting that female mice may metabolize vaporized cannabis more slowly than male mice. Taken together, these findings add to a growing literature implementing vaporized cannabinoid delivery approaches by revealing PEG as a more effective carrier oil than PG/VG for studies involving cannabis extract.

Cannabinoid formulations have been increasingly proposed as therapeutic potential options for anxiety disorders (ADs). Several countries have expanded regulatory frameworks facilitating access to these compounds due to their alleged therapeutic benefits, including their application in ADs. Given its public health significance, we evaluated existing evidence regarding the efficacy of different medical cannabinoids as interventions for ADs and related mental conditions. A comprehensive search was conducted in PubMed, Embase, PsycInfo, Web of Science, Scielo, and Lilacs databases. We included randomized controlled trials (RTCs) assessing the effects of various cannabinoid formulations on patients with ADs and related conditions. Distinct meta-analyses were performed for cannabinoid subtypes. Analyses were conducted using Jamovi software, relying on standardized mean difference (SMD) calculations of pre/post-intervention score changes for both intervention and control groups. We incorporated 21 placebo-controlled RCTs, examining cannabinoid interventions in social anxiety disorder (SAD = 5), generalized anxiety disorder (GAD = 1), post-traumatic stress disorder (PTSD = 7), obsessive-compulsive disorder (OCD = 1), and Tourette syndrome (TS = 7). Data extraction indicated considerable heterogeneity across outcomes, including clinical symptoms, neuroimaging findings, well-being, psychosocial functioning, safety, and tolerability. In studies utilizing pure or enriched CBD, the meta-analytic measure indicated a nonsignificant difference (SMD = -0.40; 95% CI: -0.84/0.03). However, a subgroup analysis of pure CBD compounds yielded a moderate, statistically significant effect size (SMD: -0.61, 95% CI: -1.15/-0.07). For studies investigating pure or enriched delta-9-tetrahydrocannabinol (Δ9-THC), the meta-analytic measure was -0.65 (95% CI: -1.06/-0.24), suggesting a moderate, significant effect favoring Δ9-THC-dominant compounds. In meta-analyses of studies with Δ9-THC and cannabidiol (CBD) mixtures, the effects were not significant (SMD = -0.73, 95% CI: -2.00/0.55). Although suggesting a potential superior efficacy of pharmaceutically pure formulations of Δ9-THC and CBD over alternative versions, these results must be interpreted with caution due to heterogeneous study designs and small sample sizes. The current evidence is limited. Low-quality evidence suggests that pharmaceutical-grade CBD may have limited efficacy for SAD and GAD. In addition, low-quality evidence supports Δ9-THC's efficacy for the reduction of nightmares in PTSD and tic severity in TS. Further double-blind, randomized, placebo-controlled trials with larger and heterogeneous samples are required to investigate the clinical outcomes of pharmaceutical-grade cannabinoids and standardized cannabis extracts in the treatment of ADs.

Tolerance and dependence are known to occur with prolonged cannabis use. Few animal experiments on spontaneous withdrawal from delta-9-tetrahydrocannabinol (THC), the primary psychoactive compound in cannabis, have been conducted. The experiments that have been conducted use extremely high doses and report relatively mild symptoms. The objective of the present experiment was to determine the magnitude and duration of spontaneous THC withdrawal in male and female rats using voluntary home cage wheel running as a sensitive, objective, and continuous measure of withdrawal. Male and female Sprague-Dawley rats were injected with THC (3 mg/kg, s.c.) or vehicle twice daily for 7 days to induce tolerance and dependence. Spontaneous withdrawal was assessed for 5 days beginning 24 h after the day 8 tolerance test in which all rats received a THC injection. On day 1, THC profoundly decreased wheel running in male and female rats compared to vehicle-treated rats. On day 8, THC given to vehicle-treated rats produced a significantly greater decrease in running than in rats previously treated with THC, indicating tolerance development. There was no sex difference in the magnitude of the decrease in wheel running caused by THC injections or in the development of tolerance. There were no significant changes in wheel running associated with spontaneous THC withdrawal. These data suggest that spontaneous THC withdrawal in male and female rats is mild at best despite profound locomotor suppression and tolerance to repeated injections. The lack of spontaneous THC withdrawal contrasts sharply with the pronounced changes in wheel running produced by opioid withdrawal.

HYPER-H21-4 trial, a randomized, placebo-controlled, crossover trial, showed that chronic cannabidiol (CBD) supplementation reduces blood pressure (BP) in patients with primary hypertension. Given the association between the endocannabinoid (EC) system and hypertension, we aimed to determine whether changes in circulating ECs, signaling molecules of the EC system, could explain CBD-mediated cardiovascular effects. For this purpose, anandamide (AEA) and 2-arachidonoylglycerol (2-AG) were measured in 66 patients with hypertension. Patients were assigned to receive CBD for 5 weeks (225-300 mg/day for the first 2.5 weeks, increasing to 375-450 mg/day for the subsequent 2.5 weeks), followed by 5 weeks of placebo, or 5 weeks of placebo followed by 5 weeks of CBD. Administration of the CBD formulation for 5 weeks resulted in a significant increase in plasma AEA levels, whereas no such increase was observed during the placebo period (Placebo: 37.0 ± 18.0 ng/mL vs. 38.9 ± 20.8 ng/mL, CBD: 36.7 ± 18.0 ng/mL vs. 47.9 ± 24.6 ng/mL, = 3.592, = 0.042; ΔAEA 11.1 ± 3.7 ng/mL, = 0.025). Change in AEA levels following CBD administration (ΔAEA) did not correlate with change in systolic BP following CBD administration (ΔSBP) ( = -0.106, = 0.428). Multivariate analysis showed that body mass index, current antihypertensive treatment, and fasting plasma glucose at baseline emerged as significant predictors of AEA increase, while BP reduction did not demonstrate a significant association. No significant association was found between chronic CBD administration and 2-AG plasma concentrations (placebo: 28.8 ± 4.3 ng/mL vs. 38.9 ± 20.8 ng/mL; CBD: 36.7 ± 18.0 ng/mL vs. 47.9 ± 24.6 ng/mL; = 0.513, = 0.478). Collectively, these findings suggest that although chronic CBD administration appears to increase AEA, but not 2-AG plasma levels, this study provides no conclusive evidence that such alterations explain CBD-mediated BP reduction.

Prenatal alcohol exposure (PAE) is a leading cause of birth defects and developmental impairments, resulting in a spectrum of disorders ranging from mild to severe, which are termed fetal alcohol spectrum disorders (FASD). Globally, there is a high prevalence of FASD, and currently, there is no known available cure. PAE most severely impacts the developing brain, causing long-term structural and functional impairments. Cerebral blood circulation plays a critical role in neuronal and overall brain development. Previous studies have shown that PAE leads to a decrease in fetal brain blood flow velocity via fetal cerebral artery dilation, but the specific targets underlying this effect remain largely unknown. A previous study indicated that a mixture of cannabinoid blockers ablated alcohol-induced vasodilation, but the exact mechanism(s) involved have not been fully elucidated. Here, we investigated the concentration-dependent effects of alcohol on fetal cerebral arteries (anterior, middle, posterior, and basilar) in baboons ( sp.) using toxicologically relevant alcohol concentrations. We observed effects best described by polynomial fittings in both male and female fetuses, with low alcohol concentrations (5-30 mM) causing vasodilation. However, the alcohol concentrations that caused maximal dilation varied among cerebral arteries. Quantitative PCR analysis confirmed the presence of cannabinoid receptor 1 (CB1 receptor) but not cannabinoid receptor 2 (CB2 receptor) transcripts in fetal cerebral arteries. Probing of pressurized cerebral arteries with a selective CB1 receptor antagonist (AM251) before alcohol exposure at the maximal vasodilating concentration resulted in decreased alcohol effect in the basilar arteries of female fetuses and in the middle cerebral arteries of male fetuses. In addition, liquid chromatography-mass spectrometry revealed no significant changes in endocannabinoid levels (anandamide and 2-arachydoniylglycerol). Our findings suggest that alcohol may activate CB1 receptors independently of endocannabinoid production to trigger vasodilation. In summary, alcohol induces fetal cerebral artery dilation via the CB1 receptor, with regional and sex-specific differences. Our work provides new insights into the role of the fetal cerebrovascular CB1 receptor in the effect of PAE on cerebral circulation.

Hemp-derived semi-synthetic cannabinoids are marketed as legal alternatives to cannabis containing ≥0.3% Δ-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. Data were collected 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 (≥18 years old) who reported past-year cannabis use. In the sample ( = 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: Δ-THC (10.0%), Δ-THC (21.8%), Δ-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, = 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, = 0.046), reporting 1,001-10,000 lifetime cannabis uses (vs. <100 times; aOR = 4.40, 95% CI = 1.57, 12.33, = 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, = 0.021). Adverse effects were reported across all semi-synthetic cannabinoids. 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.

The prevalence of prenatal cannabis use has nearly doubled in the United States. Cannabinoid 2 receptors are predominately expressed in cells of the human immune system, and delta-9 tetrahydrocannabinol (THC), the primary active component of cannabis, has been shown to suppress immune responses. Despite these findings, there is very little evidence on the impact of cannabis use on maternal immune system. Here, we evaluate the association between urine-verified cannabis use and the levels of T helper cytokines in the maternal circulation. This was an ancillary study of a prospective cohort of pregnant women who participated in the Michigan Archive for Research on Child Health study. Pregnant women (age ≥18 years) were recruited from 22 prenatal clinics in Michigan and matched on age, race, and tobacco smoking ( = 144). The urinary metabolite of delta-9 THC, 11-nor-9-carboxy-delta-9-THC (THC-COOH), was used to define cannabis use status. A bead-based assay was used for the simultaneous detection of maternal cytokines associated with cannabis use and pregnancy outcomes in previous studies. Repeated-measures linear mixed models indicated that urine-verified cannabis use was associated with the suppression of maternal pro-inflammatory cytokines including interferon gamma (β = -0.5; 95% confidence interval [CI] = -0.8, -0.1) and interleukin (IL)-12 (β = -0.3; 95% CI = -0.6, -0.05), as well as the anti-inflammatory IL-4 (β = -0.7; 95% CI = -1.3, -0.2) and IL-10 (β = -0.4; 95% CI = -0.7, -0.03). Similar results were observed when heavy cannabis use was defined using the top tertile of urinary THC-COOH at each trimester. Urine-verified cannabis use was associated with the suppression of pro- and anti-inflammatory T helper cytokines in a cohort of pregnant women, suggesting that cannabis use can lead to modest dysregulation of the maternal immune system. Additional studies are needed to investigate the role of maternal immune responses in explaining birth outcomes linked to cannabis use.

Cannabis consumption among adults, including pregnant and breastfeeding women, continues to rise. However, the long-term effects of early-life exposure to cannabinoids on brain development remain unclear. Δ9-tetrahydrocannabinol (THC) is the main psychoactive cannabinoid in cannabis and is an agonist of cannabinoid type 1 receptor, a critical component of the endocannabinoid system (ECS) that functions in normal pre- and postnatal brain development. We hypothesized that perinatal exposure to THC perturbs ECS-regulated neurodevelopment and leads to lasting cognitive effects in later life. Male and female Sprague Dawley rat pups received a single intraperitoneal injection of THC (5 mg/kg) or vehicle (sesame oil) at postnatal day 3. At postnatal weeks 6-8, animals were assessed for spatial memory and anxiety-like behavior using the Barnes maze, open field, and elevated plus maze. Following behavioral testing, brains were processed using Golgi-Cox staining to examine dendritic morphology and spine density in the frontal cortex and hippocampus. THC exposure during the neonatal period induced a spatial memory deficit later in young adult female, but not male, rats. Anxiety-like behavior was not altered in either sex. THC-exposed animals of both sexes exhibited decreased spine density reductions, as well as decreases in dendritic length, branching, and complexity in cortical and hippocampal (cornu ammonis 1 [CA1], CA3, dentate gyrus) neurons. These findings demonstrate that a single neonatal THC exposure induces long-lasting, sex-dependent cognitive impairment and structural alterations in cortical and hippocampal neurons in rats. Our results underscore the vulnerability of the developing brain to cannabinoid exposure.

Epidemiological data indicate that regular users of cannabis products may be protected from type 2 diabetes, although the mechanism is not understood. Observations from animal studies suggest that the cannabinoid, cannabidiol (CBD) may protect/improve glucose tolerance; an effect that may be partially mediated by favorable modifications to the gut microbiome. The aims of the current pilot project were to gain initial insight into the influence of short-term CBD ingestion on oral glucose tolerance, the gut microbiome, and inflammation in sedentary adults with overweight or obesity and free from diabetes. Using a randomized, double-blind, repeated measures, parallel design, oral glucose tolerance was determined in 16 adults (6 males, 10 females) prior to and following 4 weeks of daily ingestion of either placebo or CBD (30 mg every 12 h). Fecal samples were collected at baseline and post-intervention. Compared with placebo, CBD did not influence glucose tolerance (Matsuda Index: placebo-pre 7.6 [5.5], placebo-post 10.1 [5.5], . CBD-pre 11.7 [7.9], and hCBD-post 10.1 [10.2]; median [interquartile range]; > 0.05). Characteristics of the gut microbiome or inflammation were not appreciably modified by CBD or placebo. Short-term daily ingestion of low-dose CBD did not appear to favorably modify glucose tolerance in sedentary adults with overweight or obesity. It is possible that CBD may not account for the previously reported protection from type 2 diabetes bestowed to regular users of cannabis products.

Human studies indicate a relationship between delta-9-tetrahydrocannabinol (THC) and alcohol use, yet research on their codependency remains limited. Rodent models have shown that cannabinoids can enhance the incentive salience and hedonic value of sucrose and alcohol. However, results seem to vary by the functions of THC dose and route of administration. The present study addresses these discrepancies by using a translational model of THC consumption, using lower oral doses of synthetic THC (Dronabinol). Male Long-Evans ( = 24) rats consumed a vehicle or THC-containing cookie (0.05 mg/kg or 0.5 mg/kg) before testing the palatability of rewarding and aversive substances in the taste reactivity paradigm. Separate, linear, mixed-effect models revealed that THC dose-dependently increased hedonic reactions to both sucrose (0.1 M and 0.5 M) and alcohol (10% and 40% ETOH) compared with control. Comparatively, THC reduced aversion to alcohol (10% and 40%) and quinine compared with vehicle. Western blot data analyzed one-way Analysis of Variance (ANOVA) followed by Tukey's analysis revealed that repeated oral THC consumption dose-dependently downregulated cannabinoid receptor 1 receptor expression in the dorsal hippocampus, while no significant changes were observed in the nucleus accumbens or amygdala.  These findings suggest that oral THC enhances the hedonic value of rewarding and aversive substances and provide insights into the neurobiological mechanisms that may contribute to the bidirectional use of cannabis and alcohol.

The endocannabinoid system regulates numerous physiological functions, including the stress response, and is frequently implicated in stress-related disorders. Understanding how this system is altered during stress is therefore critical for both diagnostic and therapeutic applications. The primary ligands of the endocannabinoid system, N-arachidonoylethanolamine (AEA) and 2-arachidonoyl glycerol (2-AG), are measurable in circulation and are commonly used to assess endocannabinoid function under various conditions in humans. More recently, endocannabinoids have also been detected in saliva; however, the physiological relevance of their salivary responses remains poorly understood. The present study, therefore, aims to compare stress-induced changes in endocannabinoid and related molecule levels in saliva and plasma, with the goal of advancing understanding of stress-related alterations in salivary endocannabinoids. The Maastricht Acute Stress Test was used to induce acute stress in 59 participants, with plasma and saliva samples collected at baseline, immediately after stress, and 25-min post-stress. Stress-induced changes in AEA, 2-AG, N-palmitoylethanolamine, N-oleoylethanolamine, arachidonic acid, cortisol, cortisone, and dehydroepiandrosterone sulfate (DHEA-S) were measured using liquid chromatography-tandem mass spectrometry. Norepinephrine was also analyzed in plasma using an enzyme-linked immunosorbent assay. Changes over time and associations among these analytes in response to stress were then examined. Salivary endocannabinoid concentrations were independently stress-responsive of those in plasma, suggesting they reflect distinct physiological functions. Although changes in salivary endocannabinoid concentrations were not associated with changes in plasma norepinephrine, post-stress changes in salivary 2-AG correlated with changes in DHEA-S and subjective stress ratings. The findings from this study provide new evidence that salivary endocannabinoids offer a novel approach to examining the endocannabinoid system during the stress response and may reflect its crosstalk with other physiological systems.

Cannabis use among older persons has been increasing relative to younger populations, and persons over 50 years old are more likely to use cannabis for age-related therapeutic purposes. We suspected that spouses, adult children, and other older informal care partners (ICPs) of older adults are using cannabis as a form of self-care to address physical and/or mental health needs. We described ICPs over 50 years old who used cannabis in the past year, contrasted them with those who did not, and determined if cannabis use was associated with health care service use. We obtained 2019 California Health Interview Survey (CHIS) public use files and linked base survey responses with caregiving and cannabis questions answered by 9,984 Californians aged 50 and over. We used survey data to measure background characteristics, health behaviors, physical health status, psychological status, caregiving characteristics, and cannabis use. We differentiated among older ICPs using logistic and multivariate regression models. We identified a total of 2,802 (28.1%) CHIS respondents over 50 who provided care to an older adult. ICPs were more likely to have used cannabis in the past year compared with noncaregivers (odds ratio [OR] 1.4; confidence interval [CI]: 1.2, 1.7). When compared with those ICPs who did not use, we did not observe differences in self-reported physical distress but found cannabis users were more likely to report being diagnosed with asthma (OR 2.0; CI: 1.2, 3.2) and diabetes (OR 1.80; CI: 1.1, 3.0). ICPs who used cannabis also were more likely to report feeling nervous (OR 2.1; CI: 1.3, 3.8). ICPs who provided care to someone with Alzheimer's disease or a related dementia (ADRD) were more likely to use cannabis (OR 1.50; CI: 1.1, 2.0). Nearly one out of every three older Californians including those who serve as ICPs used cannabis in the past year. We found older ICPs were more likely to use than non-ICPs, especially if they were providing care to someone with ADRD. Given the demand currently placed on spouses and adult children over 50 years old to assume care for an older adult in need, further research should determine if cannabis serves as a benefit or harm.

In recent years, the impact of recreational cannabis legalization (RCL) on road safety and motor vehicle accidents (MVAs) has become a growing area of research, given increasing cannabis legalization and the impact of cannabis on motor control and attention. In 2023, Connecticut legalized recreational cannabis, and this study explored changes in MVAs both in a statewide analysis and in the local vicinity of recreational cannabis dispensaries. We conducted an ecological study to assess the impact of recreational cannabis dispensaries on MVAs in Connecticut after legalization on January 10, 2023. Using crash data from Connecticut and Maryland (as a control) for two 24-week periods before and after legalization, we performed a difference-in-differences analysis with negative binomial regression, controlling confounders. At the dispensary level, we compared MVAs within an 800-m radius 8 weeks before and after opening, employing interrupted time series analysis with negative binomial mixed-effects regression models. In the statewide analysis comparing Connecticut with Maryland over two 24-week periods before and after RCL in Connecticut, no significant effect on MVAs was found after adjusting for autocorrelation and seasonal variations (interaction term coefficient = -0.0391, = 0.0696). In the local analysis, examining accident rates within an 800-m radius of 13 dispensaries over 8 weeks before and after their openings, the negative binomial mixed-effects model showed no significant change (incidence rate ratio = 1.10, 95% confidence interval: 0.74-1.64, = 0.63). These findings suggest that cannabis legalization and dispensary openings did not significantly impact motor vehicle accident rates during the study period.

The effect of cannabis use on health is likely to depend on individual differences. In particular, there is a growing need to understand the impact of cannabis and delta-9-tetrahydrocannabinol (THC) on brain and behavioral health across the lifespan. We conducted a narrative review summarizing the effects of cannabis and THC across three stages of life: , adolescence, and late adulthood. We also provide an up-to-date report on past 30-day cannabis use and risk perceptions from the National Survey on Drug Use and Health (NSDUH; 2002-2023) during pregnancy, adolescence, and late adulthood. We note that NSDUH data collected during 2020 and since 2021 are not directly comparable to earlier years due to shifts in data collection methods. Recent epidemiological data indicate a potential reversal of both the escalating rates of cannabis use and low perceptions of risk among pregnant women and adolescents. Findings across preclinical and clinical studies support high perceptions of risk for individuals and adolescence, when alterations in brain development indicate potential for susceptibility to neuropsychiatric disorders. The escalating rates of cannabis use and associated low perceptions of risk have shifted to the late adulthood population, which may face unique health risks associated with cannabis use. Our findings emphasize the necessity for clinical and policy recommendations to mitigate the risks associated with cannabis use and to enhance public understanding of its implications on neurodevelopmental and psychiatric disorders. Continued research and educational strategies are essential to address these evolving trends and reduce harm.

Cannabinoid-based medicines (CBMs) have garnered attention due to their anti-inflammatory potential in people with HIV (PWH), whose comorbidities are driven by chronic inflammation. The expanded endocannabinoid system (or endocannabinoidome, eCBome) is an important target of cannabinoids that cross talks with gut microbiota and regulates many homeostatic processes and inflammation. In a prospective, pilot clinical trial, PWH on antiretroviral therapy (ART) were randomly assigned to receive cannabidiol (CBD) ± Δ9-tetrahydrocannabinol (THC) capsules for 12 weeks, titrating doses as tolerated, to examine the impact of cannabinoids on plasma eCBome mediators and gut microbiota. Ten individuals were randomized, five to the CBD+THC arm and five to the CBD-only arm. Eight individuals completed the study. Plasma was collected at each visit and measured in batches by liquid chromatography (LC)-mass spectrophotometry (MS). The eCBome mediators were measured at each visit by LC-MS-MS, whereby fecal microbiota composition was assessed by 16S rDNA sequencing at the initiation and end of treatment. Plasma concentrations of THC and CBD metabolites varied throughout the course of the study. Capsule administration resulted in a significant decrease in monoacylglycerols 2-eicosapentaenoylglycerol (2-EPG) and 2-oleoylglycerol (2-OG) after treatment. No changes were observed in the levels of other mediators measured. PWH in the distinct treatment arms had different fecal bacterial taxa at baseline. These differences persisted through the course of the study and were not altered by cannabinoid administration. However, and UCG001 relative abundance was lower, while was higher, in the THC/CBD compared with the CBD arm. 2-EPG and 2-OG were both reduced following cannabinoid administration. No changes in fecal bacterial taxa were observed following 12 weeks of treatment. Larger studies are needed to understand if these changes reflect adaptation of the eCBome to the beneficial effects of CBM in PWH. ClinicalTrials.gov Identifier NCT0355035.

More adults can legally purchase cannabis in the United States than ever before. However, there is limited understanding as to how cannabis consumers make decisions about what products to purchase. Further insight is needed to guide policies that balance public health with profitable business strategies. Respondents were cannabis consumers participating in the legal adult-use market in Washington State. They were recruited through flyers posted in cannabis retail stores. Both the online survey and flyer were created by the Washington State Liquor and Cannabis Board and the Department of Health. Respondents answered questions on demographics, cannabis use patterns, and cannabis retail store employment status. Respondents also rated the importance of 10 different attributes when making a cannabis purchase: company/brand name, strain/cultivar name, production method, cost, tetrahydrocannabinol (THC), cannabidiol or terpene profile, perceived positive effects, perceived negative effects, flavor, and appearance/look. Linear regressions were conducted to predict the importance of each attribute by gender, age, cannabis use patterns, and cannabis retail employee status. There were 437 survey respondents. All respondents were legal adult cannabis users and 137 reported they were employed at a cannabis retail store. Several group differences emerged. For example, cannabis retail employees rated THC concentration as less important ( = -1.67, < 0.001) but brand name ( = 1.30, < 0.001) and product appearance ( = 0.81, = 0.001) as more important than nonretail employees. More frequent users rated cultivar/strain name ( = 0.50, < 0.001), production method ( = 0.43, < 0.001), price ( = 0.26 = 0.01), and product appearance ( = 0.49, < 0.001) as more important than less frequent users. Differences in purchasing decisions by subgroups have important public health, economic, and policy implications. For example, results showed that retail employees place less emphasis on THC relative to their nonemployee counterparts. If retail employees were to emphasize to customers about the attributes they focus on when purchasing cannabis (e.g., product appearance), this could help redirect market demand away from higher-THC products.

Cannabis is the most used federally controlled substance in the United States. Given the increasingly widespread use of cannabis, further examination of its health implications is needed. We evaluated the association of cannabis use and longitudinal kidney outcomes among a cohort of adults living in Baltimore, MD. We used data from healthy aging in neighborhoods of diversity across the life span study. Baseline cannabis use (obtained between 2004 and 2009) was categorized as never tried, tried, never used regularly (irregular use), regular use >6 months prior (former regular use), and regular use within the past 6 months (current regular use). The primary outcome was incident chronic kidney disease (CKD), defined as an estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m at follow-up (2013-2017). Risk of rapid kidney function decline (decline in eGFR of >3 mL/min per 1.73 m per year) and incident albuminuria (albumin-to-creatinine ratio [ACR] ≥ 30 mg/g) were also assessed. Multivariable logistic regression was used to evaluate the association of cannabis use with kidney outcomes. Among 1,521 participants, the mean age was 48 years, 58% were female, and 58% were of Black race. Participants with current regular cannabis use were more likely to be younger, male, Black, and to concurrently use cigarettes, opiates, and/or cocaine. Compared with those with no history of cannabis use, participants with current regular cannabis use were not at higher risk of incident CKD (OR: 0.79 [95% CI: 0.37-1.68]), rapid kidney function decline (OR: 0.80 [95% CI: 0.43-1.49), or incident albuminuria (OR: 0.84 [95% CI: 0.38-1.87]) after adjustment for sociodemographics, health factors, and concurrent use of cigarette, opiate, or cocaine. In this Baltimore-based cohort of adults without CKD, there was no independent association between cannabis use and adverse kidney outcomes over time.

Cannabis use disorder (CUD) is one of the most common substance use disorders (SUDs) worldwide and is frequently associated with high rates of polysubstance use; however, despite rising rates of polysubstance use disorders (PUD), the characteristics of individuals with both CUD and PUD remain unclear. This study, therefore, aims to examine social and clinical characteristics of adults diagnosed with CUD and comorbid PUD. It also aims to assess whether psychiatric disorders are linked to higher odds of PUD among individuals with CUD. Using a nationally representative U.S. dataset, we assessed 972 individuals with past-year DSM-5 CUD, grouped as CUD only, CUD individuals with one additional SUD (CUD + 1), and CUD individuals with two or more SUDs (CUD + 2). Descriptive statistics summarized social and clinical presentations; multivariate logistic regression examined factors contributing to PUD, controlling for clinical diagnoses and childhood maltreatment. Among CUD individuals, 89.3% ( = 868) used at least one other substance in the past year, with 34.2% ( = 332) using two or more. Both the CUD + 1 and CUD + 2 groups experienced significantly more severe childhood maltreatment than CUD only. After adjusting for controls, personality disorders were associated with membership in the CUD + 1 group (odds ratio [OR]: 1.88, = 0.01); mood disorders were associated with a higher likelihood of being in the CUD + 1 group (OR: 1.50, = 0.049) and CUD + 2 group (OR: 2.58, = 0.005). Mood and personality disorders were highly prevalent and linked with PUD in CUD cases. We recommend screening for these disorders in complex CUD cases.