Cannabis and Cannabinoid Research最新文献

Introduction: Taxane-induced peripheral neuropathy (TIPN) is experienced by most patients with breast cancer, and there is no efficacious treatment. In pre-clinical studies, co-administration of two constituents of cannabis, Δ⁹-tetrahydrocannabinol (THC) and cannabidiol (CBD), synergistically reduces TIPN. Materials and Methods: The goal of this 8-week, double-blind, randomized pilot study, conducted from 2019 to 2021, was to test the feasibility and tolerability of oral cannabis (100 mg CBD: 5 mg THC, TID) relative to placebo on pain resulting from TIPN. Participants with painful TIPN completed daily questionnaires online about their pain, sleep, and medication use, and weekly questionnaires on neuropathy. Results: All participants (12 women; 51 ± 6 years) randomized to placebo (n = 6) or active (n = 6) cannabis capsules completed the trial. Participants in both medication groups requested dose reductions (mean ± SEM capsules/day: placebo: 2.4 ± 0.4; active: 2.0 ± 0.4). In a preliminary evaluation of efficacy, measures of pain, pain interference, sleep, and functional well-being significantly improved over time (p < 0.03), but participants receiving cannabis had significantly higher ratings of neuropathy at each week (p < 0.035) and lower ratings of functional well-being in the last 3 weeks of treatment compared with participants receiving placebo (p < 0.02). Similarly, cannabis significantly worsened ratings of sleep and pain interference relative to placebo (p < 0.05). Discussion: This study demonstrates that: (1) double-blind, placebo-controlled testing of cannabis capsules in this dose range is feasible and well tolerated in women with TIPN and (2) ratings of pain, neuropathy, and well-being significantly improved over 8 weeks, but cannabis significantly worsened several endpoints relative to placebo. These findings highlight the necessity of placebo control when assessing the therapeutic utility of cannabis. Although there was no signal of efficacy herein, a fully powered study testing a range of cannabis doses for TIPN is warranted, given its impact on most patients with breast cancer, promising pre-clinical data, and the widespread use of cannabis among patients with cancer.

Background: Epilepsy is a neurological chronic disorder that affects about 70 million people worldwide. Status epilepticus (SE) are neural disturbances that cause intense glutamatergic excitatory discharges that modulate changes in normal brain physiological activity. Cannabidiol (CBD) is the main nonpsychomimetic compound present in Cannabis sativa and exhibits a wide spectrum of neuroprotective properties. The use of zebrafish (Danio rerio) is regarded as an important alternative animal model for studies on seizures, as it has neuronal mechanisms similar to humans. Objective: This study aims to evaluate the effects of CBD on SE induced by kainic acid (KA) in zebrafish. Methods: Animals received CBD (5, 10, or 40 mg·L^-1 tank water) for 24 h followed by KA administration (5 mg/kg intraperitoneally). The convulsive pattern of alterations was then assessed. After 12 h, cerebral glutamate transport and oxidative stress were also verified. Results: CBD at 5 and 40 mg·L^-1 induced a significant decrease in the seizure intensity (26.1% and 29.9%) and an increase in the latency to reach SE (from 10.71 min to 17.5 and 25 min), respectively. In addition, CBD administration (40 mg·L^-1) attenuated the decrease in cerebral glutamate transport following 12 h KA-induced seizure. The KA-induced seizure was also able to alter the oxidative stress parameters 2',7'-dichlorofluorescin, and catalase activity. However, CBD (40 mg·L^-1) did not influence these markers. The present study indicates that CBD promotes a neuroprotective response against the epileptic profile in zebrafish. These findings contribute to the understanding of the influence of CBD on the modulation of excitatory/inhibitory disruption on zebrafish seizure.

Background: Several countries have legalized cannabis (Cannabis sativa) and kratom (Mitragyna speciosa), increasing accessibility to these psychotropic plants for medicinal and recreational purposes. Cooking is a popular method to utilize cannabis and kratom at the household level. The aim of this research was to study the effect of cooking conditions on psychoactive compounds, namely cannabidiol (CBD) and tetrahydrocannabinol (THC) derivatives (△8, △9THC, and tetrahydrocannabinolic) in cannabis and mitragynine in kratom. Methods: Quantitative analysis of these substances was performed using LC/MS/MS. Cannabis and kratom were subjected to different cooking conditions based on popular cooking methods, including steaming, boiling, deep-frying, stir-frying, and products. Results: The results indicate that boiling and steaming retain the highest content of THC in cannabis. For mitragynine in kratom, there was a varied degree of mitragynine reduction by different cooking methods, which ranged from 20% to 50%. The total phenolic content of all treated samples was lower than the fresh samples. Conclusion: Various cooking methods and product formulation affect THC and CBD quantity, so it is important to assess the retention of those phytocannabinoids in the finished product. However, the adverse effects of THC are unlikely as they are present in low quantities.

Introduction: This study explores whether the cannabis edibles industry uses brand names that might impact consumer appeal and harm perceptions. Materials and Methods: An exploratory thematic text analysis of brand names for 1344 cannabis edible products from 250 brands advertised online between June and November 2022 was performed. Brands marketing only delta-9-tetrahydrocannabinol (THC) products (n = 80), THC and cannabidiol (CBD) products (n = 130), and only CBD products (n = 40) were compared. Results: Five core themes emerged: cannabis culture (42% of brands, n = 106), product characteristics (30%, n = 76), medicine and health (23%, n = 58), environment and nature (20%, n = 51), and identity and culture (14%, n = 34), with 15 subthemes. Brands only marketing CBD products more often had names with medicine and health (45%, n = 18) themes with subthemes of health and wellness (30%, n = 12) and expected effects (18%, n = 7) in contrast to brands marketing THC products (18%, n = 14; 2%, n = 2; 11%, n = 9 THC-only; 20%, n = 26; 5%, n = 6; 13%, n = 17 THC and CBD). Brands marketing THC products more often had names with cannabis (12%, n = 10 THC-only; 18%, n = 23 THC and CBD; 8%, n = 3 CBD-only) and spiritual/mystical (9%, n = 7 THC-only; 9%, n = 12, THC and CBD; 0%, CBD-only) subthemes. Food type subthemes were also more common among brands marketing THC products (19%, n = 15 THC-only; 21%, n = 27 THC and CBD; 8%, n = 3 CBD-only). Unconventionality (6%, n = 5 THC-only; 2%, n = 2 THC and CBD; 0% CBD-only) and names and places (16%, n = 13 THC-only; 5%, n = 8 THC & CBD; 5%, n = 2 CBD-only) were subthemes more common among brands only marketing THC products. Conclusions: This study identified distinct cannabis edibles brand name marketing strategies for THC versus CBD products that may affect consumer appeal and perceptions of harm, underscoring the need to monitor and potentially regulate cannabis edibles marketing to ensure that it does not mislead consumers or downplay potential risks.

Introduction: With the changing legal landscape, the acceptance and availability of cannabis products have increased. Cannabis products are generally considered "natural" and relatively safe by consumers. However, growing empirical evidence from humans and other animals indicates that cannabis negatively affects human health. In contrast to the well-known teratogenic effects of alcohol and tobacco products, the safety of cannabis product use during pregnancy has not yet been established. The goal of this systematic review was to determine the patterns that exist in human and rodent literature on the effects of prenatal exposure to cannabis products and delta-9-tetrahydrocannabinol (THC) on birth outcomes. Methods: A systematic review of rodent and human studies was conducted using PRISMA guidelines. Rodent search strategy used PubMed and Scopus with terms "prenatal OR perinatal OR in utero OR maternal exposure AND cannabis OR THC or cannabinoids AND exposure NOT review NOT Human." Human search strategy used PubMed, CINAHL, and Scopus with terms "cannabinoids OR cannabis OR THC OR marijuana" AND "pregnancy OR pregnant OR prenatal AND "infant outcome OR infant health." After deleting duplicates and studies that did not fit the inclusion criteria, 21 rodent and 36 human studies were selected for review. Rodent studies focused on birth weight, litter size, mortality, and gestation length. Human studies have focused on birth weight, gestational age, and infant health at delivery. Results: In both human and rodent studies, prenatal exposure to cannabis was significantly associated with lower birth weight; however, it was not significantly associated with gestational age in rodents or humans. In most rodent studies, prenatal exposure to cannabis did not affect mortality or litter size. In human studies, there was a tendency for infants exposed to cannabis during pregnancy to have worse health at delivery. Findings indicate that cannabis exposure in utero may be associated with worse birth outcomes; however, the results are mixed and vary by species and outcome. Discussion: Methodological differences and scant existing research may have contributed to this inconsistency. Given the legalization of cannabis product use for recreational and medicinal purposes is growing, additional research is necessary to determine its influence on fetal and infant health outcomes.

Introduction: As opioid-related drug overdoses remain a public health crisis, there is a critical need for innovative approaches to developing safer analgesics with improved safety profiles. BDH-001 is a fixed-dose combination of low-dose buprenorphine (BUP) and cannabidiol (CBD) being developed as a safer analgesic than currently available opioids. The purpose of this study was to examine the analgesic and opioid-sparing effects of BDH-001 and to complete an in vivo safety assessment in rats. Methods: Analgesic effect of BDH-001 was assessed using the chronic constriction injury model of chronic neuropathic pain with pain threshold assessed via Von Frey testing. Drug-drug interaction effects on pharmacokinetic (PK) parameters were assessed in a single dose PK study in rodents. The effects on respiratory depression were also assessed and confirmed in two separate rodent studies performing blood gas analysis and measuring O₂ saturation. Results: BDH-001 (combination of subanalgesic BUP dose and CBD) resulted in statistically significant increases in pain threshold compared to saline (p < 0.001), CBD alone (p < 0.01), and BUP alone (p < 0.05). The half-life of BUP was significantly shorter in the presence of CBD compared to BUP alone (p = 0.008), with no significant changes in any other BUP pharmacokinetic parameter assessed. CBD was found to attenuate BUP-induced respiratory depression in rats when assessing blood gases (p < 0.05) and O₂ saturation (p < 0.05) over several time bins. Conclusions: Data obtained in the present study indicate the addition of CBD to BUP was opioid-sparing and attenuated BUP- but not morphine-induced respiratory depression. There was no evidence these findings were the result of a PK interaction. Results support the hypothesis that BDH-001, a fixed-dose combination of BUP and CBD, may provide effective analgesia with a more favorable safety profile.

Background: 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. Objectives: 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. Research Design and Methods: 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. Results: 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). Discussion: 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.

Background: 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. Methods: 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. Results: 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, Coprobacillus and Lachnospiraceae UCG001 relative abundance was lower, while Collinsella was higher, in the THC/CBD compared with the CBD arm. Conclusion: 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. Trial Registration: ClinicalTrials.gov Identifier NCT0355035.

Introduction: 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. Materials and Methods: We conducted a narrative review summarizing the effects of cannabis and THC across three stages of life: in utero, 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. Results: 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 in utero 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. Conclusions: 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.