Cannabis and Cannabinoid Research最新文献

Introduction: 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. Methods: 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: 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. Conclusion: 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.

Introduction: Ultra-endurance exercise events result in central fatigue, impacting on mental alertness and decision making. Endocannabinoids are typically elevated during endurance exercise and have been implicated in central processes such as learning and memory, but their role in central fatigue has never been studied. Materials and Methods: Twenty-four recreational male ultrarunners participated in a 100-km trail run, and 18 of them completed at least 60 km and were included in the analyses. A cognitive test battery to assess median reaction time (MRT) and median movement time during a reaction time task and median response latency during a rapid visual information processing task was completed prior to and immediately after the trail. Blood serum samples pre- and postexercise were analyzed for endocannabinoids and related lipids (anadamide: AEA; 2-arachidonoylglycerol: 2-AG; palmitoylethanolamide: PEA; oleoylethanolamide: OEA; stearoylethanolamine: SEA) via liquid chromatography-mass spectrometry. Results: Ultra-endurance exercise worsened all cognitive parameters and increased abundance of AEA, PEA, OEA, and SEA but not 2-AG. Interestingly, the exercise-induced change in MRT showed moderate, positive correlations with the change in different endocannabinoids, that is, AEA (r = 0.5164, p = 0.0338), PEA (r = 0.5466, p = 0.0251), and OEA (r = 0.5442, p = 0.0239). Conclusion: These results indicate a potential role of endocannabinoids on mental alertness following ultra-endurance exercise.

Background: Activation of cannabinoid receptor 1 (CB1R) in the nervous system modulates the processing of acute and chronic pain. CB1R activity is regulated by desensitization and internalization. SH3-containing GRB2-like protein 3-interacting protein 1 (SGIP1) inhibits the internalization of CB1R. This causes increased and prolonged association of the desensitized receptor with G protein-coupled receptor kinase 3 (GRK3) and beta-arrestin on the cell membrane and results in decreased activation of extracellular signal-regulated kinase 1/2 (ERK1/2) pathway. Genetic deletion of SGIP1 in mice leads to altered CB1R-related functions, such as decreased anxiety-like behaviors, modified cannabinoid tetrad behaviors, reduced acute nociception, and increased sensitivity to analgesics. In this work, we asked if deletion of SGIP1 affects chronic nociception and analgesic effect of Δ⁹-tetrahydrocannabinol (THC) and WIN 55,212-2 (WIN) in mice. Methods: We measured tactile responses of hind paws to increasing pressure in wild-type and SGIP1 knock-out mice. Inflammation in the paw was induced by local injection of carrageenan. To determine the mechanical sensitivity, the paw withdrawal threshold (PWT) was measured using an electronic von Frey instrument with the progression of the applied force. Results: The responses to mechanical stimuli varied depending on the sex, genotype, and treatment. SGIP1 knock-out male mice exhibited lower PWT than wild-type males. On the contrary, the female mice exhibited comparable PWT. Following THC or WIN treatment in male mice, SGIP1 knock-out males exhibited PWT lower than wild-type males. THC treatment in SGIP1 knock-out females resulted in PWT higher than after THC treatment of wild-type females. However, SGIP1 knock-out and wild-type female mice exhibited similar PWT after WIN treatment. Conclusions: We provide evidence that SGIP1, possibly by interacting with CB1R, is involved in processing the responses to chronic pain. The absence of SGIP1 results in enhanced sensitivity to mechanical stimuli in males, but not females. The antinociceptive effect of THC is superior to that of WIN in SGIP1 knock-out mice in the carrageenan-induced model of chronic pain.

Objectives: Cannabidiol (CBD) is rising in popularity, including as a potential medicinal product. Yet data on use of commercial CBD for medicinal or health reasons in adolescents are lacking. In this study we aim to detail characteristics of adolescents given commercial CBD for health reasons (health CBD [hCBD]) and to investigate predictors of use. Materials and Methods: The Adolescent Brain Cognitive Development (ABCD) Study is a population-based cohort study following U.S. healthy, community-based adolescents annually, with data from 2018 to 2022 (11- to 15-year-olds; N=11,189). Participants and caregivers completed questionnaires, including whether adolescents were given CBD with parent or doctor's permission. Participants reported past-month pain, attention problems, externalizing symptoms, internalizing symptoms, and total mental health problems. Caregivers reported youth sociodemographics, sleep problems, whether the youth had mental health treatment or sought medical treatment, and rules about recreational cannabis use. We describe youth given hCBD, and run generalized estimating equations predicting odd ratios (ORs) and 95% confidence intervals of adolescents given hCBD by mental health, physical health, or sociodemographics of factors. Results: Of the 11,189 participants across up to three waves of data, 48% were female. Mean age across waves was 12.8 years old (SD=1). In total, 307 (2.8%) were given hCBD. Common administration methods were oil (42%), topical (31%), and edibles (29%). Increased hCBD odds were associated with being older (OR=1.32 [1.17-1.49]), White (relative to Black, OR=05.97 [2.81-12.65] or Hispanic, OR=1.82 [1.17-2.82]), parents with some college (relative to no high school diploma, OR=3.55 [1.09-11.6]), internalizing symptoms (OR=1.81 [1.13-2.91]), mental health treatment (OR=1.76 [1.3-2.38]), pain (OR=1.38 [1.09-1.76]), medical treatment (OR=1.39 [1.08-1.79]), and sleep problems (OR=1.69 [1.27-2.25]). Rules against recreational cannabis decreased odds of hCBD (OR=1.75 [1.30-2.36]). Conclusions: Findings indicate some healthy adolescents are given hCBD, and predictors of use include mental and physical health concerns, being White, older, and parents with some college education. Providers should ask if their youth patients are being given CBD medicinally, and transparently discuss potential benefits, consequences, and unknowns of CBD.

Background: In 2020, the Lebanese parliament legalized cannabis for medical and industrial use, sparking diverse reactions among health care professionals (HCP). Few studies have been conducted to reflect the position of HCP on the topic, and no previous studies targeted all physicians with relevant specialties or had a large sample size. The current study aimed to assess the knowledge, attitude, and practice of the Lebanese medical community toward medicinal cannabis (MC). Methods: A cross-sectional study was conducted targeting HCP from different backgrounds and specialties. The survey questionnaire was disseminated through different scientific societies in the Lebanese Order of Physicians and other professional bodies. An online survey was shared with oncologists, rheumatologists, psychiatrists, neurologists, pharmacists, and psychotherapists across different geographic regions. It covered questions about sociodemographic details, knowledge, attitude, and practice related to MC. Descriptive and bivariate analyses were performed. A total of 202 HCP responded to the survey, yielding a response rate of 34%. Results: Eighteen percent of the participants described their level of knowledge about the indications of MC as good. Twenty-five percent of the respondents are willing to prescribe, and 30% "may consider" it. Among those willing to prescribe, the majority may consider MC to treat chronic pain, palliative care, post-traumatic stress disorder, epilepsy, and anxiety. Respondents' knowledge about the side effects of MC is as follows: driving difficulties (82%), addiction (69%), drug interactions (65%), and weight gain (43%). Willingness to prescribe varies by medical specialty, previous clinical experience with MC, and gender. The majority of the participants expressed concerns about the potential harm of using MC and indicated that legalization would negatively impact society. Sixty-nine percent of the respondents reported not receiving any formal education about MC and agreed on the need to expand knowledge about its indications and side effects. The majority agreed that MC should be dispensed based on a prescription from a physician with special training and recognized the importance of establishing a national registry for patients undergoing MC treatment, as well as the necessity of guidelines for approval. Conclusion: The current data indicate that attitudes toward prescribing MC vary by medical specialty, gender, and clinical experience. Implementation of effective educational strategies in Lebanon to enhance HCP knowledge about MC and promote its proper use is crucial.

Introduction: Chronic neuropathic pain is as a severe detriment to overall quality of life for millions of Americans. Current pharmacological treatment options for chronic neuropathic pain are generally limited in efficacy and may pose serious adverse effects such as risk of abuse, nausea, dizziness, and cardiovascular events. Therefore, many individuals have resorted to methods of pharmacological self-treatment. This narrative review summarizes the existing literature on the utilization of two novel approaches for the treatment of chronic pain, cannabinoid constituents of Cannabis sativa and alkaloid constituents of Mitragyna speciosa (kratom), and speculates on the potential therapeutic benefits of co-administration of these two classes of compounds. Methods: We conducted a narrative review summarizing the primary motivations for use of both kratom and cannabis products based on epidemiological data and summarize the pre-clinical evidence supporting the application of both kratom alkaloids and cannabinoids for the treatment of chronic pain. Data collection was performed using the PubMed electronic database. The following word combinations were used: kratom and cannabis, kratom and pain, cannabis and pain, kratom and chronic pain, and cannabis and chronic pain. Results: Epidemiological evidence reports that the self-treatment of pain is a primary motivator for use of both kratom and cannabinoid products among adult Americans. Further evidence shows that use of cannabinoid products may precede kratom use, and that a subset of individuals concurrently uses both kratom and cannabinoid products. Despite its growing popularity as a form of self-treatment of pain, there remains an immense gap in knowledge of the therapeutic efficacy of kratom alkaloids for chronic pain in comparison to that of cannabis-based products, with only three pre-clinical studies having been conducted to date. Conclusion: There is sufficient epidemiological evidence to suggest that both kratom and cannabis products are used to self-treat pain, and that some individuals actively use both drugs, which may produce potential additive or synergistic therapeutic benefits that have not yet been characterized. Given the lack of pre-clinical investigation into the potential therapeutic benefits of kratom alkaloids against forms of chronic pain, further research is warranted to better understand its application as a treatment alternative.

Background: Cannabidiol (CBD) has been proposed to have a therapeutic potential over a wide range of neuropsychiatric disorders, including substance use disorders. Pre-clinical evidence suggests that CBD can increase anandamide (AEA) plasma concentration, possibly mediating some of its therapeutic properties. Whether CBD exerts such an effect on AEA in individuals with cocaine use disorder (CUD) remains unknown. Aims: To explore the sustained effects of daily CBD administration on AEA plasma concentrations compared with placebo in CUD. Methods: We used data from a randomized, double-blind, placebo-controlled trial evaluating CBD's efficacy in CUD. Seventy-eight individuals were randomized to receive a daily oral dose of 800 mg CBD (n = 40) or a placebo (n = 38). Participants stayed in an inpatient detoxification setting for 10 days, after which they were followed in an outpatient setting for 12 weeks. AEA plasma concentration was measured at baseline and at 23-h post CBD ingestion on day 8 and week 4. A generalized estimating equation model was used to assess CBD's effects on AEA, and sensitivity analyses were computed using Bayesian linear regressions. Results: Sixty-four participants were included in the analysis. Similar mean AEA plasma concentrations in both treatment groups (p = 0.357) were observed. At day 8, mean AEA plasma concentrations (± standard deviation) were 0.26 (± 0.07) ng/mL in the CBD group and 0.29 (± 0.08) ng/mL in the placebo group (p = 0.832; Bayes factor [BF] = 0.190). At week 4, they were 0.27 (± 0.09) ng/mL in the CBD group and 0.30 (± 0.09) ng/mL in the placebo group (p = 0.181; BF = 0.194). Conclusion: While not excluding any potential acute and short-term effect, daily CBD administration did not exert a sustained impact on AEA plasma concentrations in individuals with CUD compared with placebo. Registration: clinicaltrials.gov (NCT02559167).

Introduction: 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. Materials and Methods: 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. Results: 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). Discussion: 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.

Introduction: Cannabis use has been associated with reduced physical activity and increased sedentary behavior in adolescents. In adults, however, there is no conclusive evidence of such an association, and existing studies have primarily relied on self-reported activity measures. As cannabis use increases globally, a deeper understanding of its relationship with activity levels may inform clinical counseling and guidelines. This study investigated the association between recent cannabis use and accelerometer-measured activity. Methods: Data were obtained from the National Health and Nutrition Examination Survey (NHANES) from 2011 to 2014. We included adults in the United States who responded to a cannabis questionnaire and had at least 4 days of activity data from an ActiGraph GT3X+ accelerometer, which comprised participants from 18 to 59 years. The primary exposure was any self-reported cannabis use in the past 30 days. The primary outcome was daily sedentary time and secondary outcomes were daily light physical activity (LPA) and moderate-to-vigorous physical activity (MVPA). Analyses were performed with multivariable quasi-Poisson regression models. Results: Of 4666 included adults, 658 (14.1%) reported recent cannabis use. After covariate adjustment, recent cannabis use was not associated with daily sedentary time (adjusted incidence rate ratio [aIRR] 0.99, 95% confidence interval [CI]: 0.98-1.01) or daily MVPA time (aIRR 1.01, 95% CI: 0.98-1.04). Daily LPA time was 4% greater with recent cannabis use (aIRR 1.04, 95% CI: 1.01-1.06). Conclusion: Recent cannabis use in young to midlife adults was not associated with accelerometer-measured sedentary or MVPA time, but it was associated with a marginal increase in LPA time of unclear clinical significance. Our findings provide evidence against existing concerns that cannabis use independently promotes sedentary behavior and decreases physical activity. Future prospective studies are needed to determine if these findings generalize to specific populations using cannabis including chronic pain patients.