Cannabis and Cannabinoid Research最新文献

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.

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.

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.

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.

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).

Background: 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. Methods: 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. Results: 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. Conclusion: Full-spectrum CBD products might have greater therapeutic efficacy in resolving inflammation-induced depressive and sickness behavior compared to a CBD-only isolate.

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.

Background: Cannabis is one of the world's most commonly used substances; however, many questions remain unanswered as to how cannabis impacts the body. Recently, there has been a resurgence of research into the effects of plant-derived cannabinoids on mitochondrial health. In particular, a number of studies implicate mitochondrial-Δ9-tetrahydrocannabinol (Δ9-THC) interactions with altered memory, metabolism, and catalepsy in mice. Although the research in this field is expanding rapidly, there is little known about the effects of cannabis on mitochondria health in human subjects either in acute or chronic term use. Methods: Blood samples were obtained from a double-blind, placebo-controlled, parallel-group randomized clinical trial in which adults who regularly use cannabis (1-4 days/week) aged 19-25 years were randomized 2:1 to receive either an active (12.5% Δ9-THC) cigarette or placebo (<0.01% Δ9-THC) cigarette containing 750 mg of cannabis before driving simulator testing. DNA was extracted from whole blood using commercial spin columns, followed by measurement of mt-ND1, mt-ND4, and β2M using quantitative polymerase chain reaction. One-way repeated measures analysis of variance (ANOVA) followed by Dunnett's multiple comparisons test was used to observe changes in mitochondrial DNA (mtDNA) copy number over time. A two-tailed Pearsons R test was used to assess correlations between mtDNA copy number and cannabinoid levels (Δ9-THC and metabolites) in blood. Results: We found that exposure to active cannabis containing Δ9-THC, as opposed to placebo, was associated with an acute reduction in mitochondrial DNA copy number in whole blood at 15 min and 1 h after smoking. The observed decrease in mtDNA copy number negatively correlated with blood concentrations of 11-hydroxy-Δ9-tetrahydrocannabinol (11-OH-THC) and 11-Nor-9-carboxy-Δ9-tetrahydrocannabinol (THC-COOH), the two primary metabolites of Δ9-THC, but not Δ9-THC itself. Further, the negative correlation between 11-OH THC and THC-COOH concentrations and mtDNA copy number was found in only a subgroup of participants who use cannabis infrequently, suggesting a tolerance effect. Conclusions: These results illuminate mitochondrial alterations attributed to Δ9-THC consumption, which may be mediated by metabolites. These results appear to suggest stronger effects in individuals who consume cannabis less frequently, suggesting some form of tolerance to the effects of Δ9-THC and its metabolites on mtDNA content in whole blood. Keywords: Mitochondria; mtDNA; cannabis; THC; THC metabolites; blood; THC-COOH; 11-OH-THC.

Introduction: Food and beverage products containing cannabidiol (CBD) is a growing industry, but some CBD products contain Δ⁹-tetrahydrocannabinol (Δ⁹-THC), despite being labeled as "THC-free". As CBD can convert to Δ⁹-THC under acidic conditions, a potential cause is the formation of Δ⁹-THC during storage of acidic CBD products. In this study, we investigated if acidic products (pH ≤ 4) fortified with CBD would facilitate conversion to THC over a 2-15-month time period. Materials and Methods: Six products, three beverages (lemonade, cola, and sports drink) and three condiments (ketchup, mustard, and hot sauce), were purchased from a local grocery store and fortified with a nano-emulsified CBD isolate (verified as THC-free by testing). The concentrations of CBD and Δ⁹-THC were measured by Gas Chromatography Flame Ionization Detector (GC-FID) and Liquid Chromatography with tandem mass spectrometry (LC-MS/MS), respectively, for up to 15 months at room temperature. Results: Coefficients of variation (CVs) of initial CBD concentrations by GC-FID were <10% for all products except ketchup (18%), showing homogeneity in the fortification. Formation of THC was variable, with the largest amount observed after 15 months in fortified lemonade #2 (3.09 mg Δ⁹-THC/serving) and sports drink #2 (1.18 mg Δ⁹-THC/serving). Both beverages contain citric acid, while cola containing phosphoric acid produced 0.10 mg Δ⁹-THC/serving after 4 months. The importance of the acid type was verified using acid solutions in water. No more than 0.01 mg Δ⁹-THC/serving was observed with the condiments after 4 months. Discussion: Conversion of CBD to THC can occur in some acidic food products when those products are stored at room temperature. Therefore, despite purchasing beverages manufactured with a THC-free nano-emulsified form of CBD, consumers might be at some risk of unknowingly ingesting small amounts of THC. The results indicate that up to 3 mg Δ⁹-THC from conversion can be present in a serving of CBD-lemonade. Based on the previous studies, 3 mg Δ⁹-THC might produce a positive urine sample (≥15 ng/mL THC carboxylic acid) in some individuals. Conclusion: Consumers must exert caution when consuming products with an acidic pH (≤4) that suggests that they are "THC-Free," because consumption might lead to positive drug tests or, in the case of multiple doses, intoxication.