Cannabis and Cannabinoid Research最新文献

Background: Glycosylphosphatidylinositol-anchored protein deficiencies (GPI-ADs) are commonly associated with drug-resistant epilepsy (DRE). Cannabidiol (CBD) is approved for the adjunctive treatment of seizures in Dravet/Lennox-Gastaut Syndromes and Tuberous Sclerosis Complex. We report on the efficacy and safety of CBD for the treatment of DRE in patients with genetically proven GPI-AD. Patients and Methods: Patients received add-on treatment with purified GW-pharma CBD (Epidyolex^®). Efficacy endpoints were the percentage of patients with ≥50% (responders) or >25<50% (partial responders) reduction in monthly seizures from baseline and at 12 (M12) months of follow-up. Safety was evaluated through adverse events (AEs) monitoring. Results: Six patients (5 males) were enrolled. The median age at seizures onset was 5 months and the syndromic diagnosis was early infantile developmental and epileptic encephalopathy in 4 patients and focal non-lesional epilepsy or GEFS+ in one patient each. Five out of six (83%) patients were responders at M12, while one was a partial responder. No severe AEs were reported. Mean prescribed CBD dose was 17.85 mg/kg/day and median treatment duration is currently 27 months. Conclusions: In summary, off-label treatment with CBD was effective and safe in patients with DRE due to GPI-ADs.

Background: The literature supports the benefits of medical cannabis for core and comorbid symptoms in autistic individuals and anxiety-related symptoms in individuals without autism. However, no study has specifically investigated how cannabidiol (CBD)-rich cannabis affects anxiety subtypes in autistic children or its relationship with restricted and repetitive behaviors and interests (RRBI). Understanding the effects of CBD-rich cannabis treatment on anxiety subtypes and RRBI could offer more precise treatment approaches to managing anxiety symptoms and reducing RRBI frequency in autistic children. Objectives: To examine (1) the impact of CBD-rich cannabis treatment on autistic children's (1a) anxiety levels and subtypes and (1 b) RRBI and subtypes and (2) whether changes in anxiety explain changes in RRBI following cannabis treatment. Method: In this open-label study, we analyzed data from 65 autistic children (5-12 years) who had participated in research on the effects of CBD-rich cannabis on children with autism. Their parents completed the Repetitive Behavior Scale-revised to assess the frequency and severity of six subgroups of their children's recurrent behaviors and the Screen for Child Anxiety-Related Emotional Disorders for symptoms related to five types of anxiety disorders. They completed these assessments at three time points: (T1) before treatment, (T2) after 3 months, and (T3) after 6 months of treatment. Results: The results indicated reduced RRBI and symptoms related to various anxiety subtypes in autistic children following 6 months of CBD-rich cannabis treatment. Specifically, we observed significant differences in the autistic children's overall anxiety and in some anxiety subtypes (i.e., general, social, panic, and separation anxieties). Significant improvements were observed in RRBI, including the total score, and specifically in compulsive, ritualistic, and sameness behaviors. Our findings revealed that reduced anxiety, particularly within the panic- and separation-related subtypes, predicted a subsequent decrease in RRBI, specifically sameness behaviors, following cannabis treatment. Conclusions: The findings of the cannabis treatment's potential benefits for alleviating anxiety symptoms, leading to reduced RRBI, may provide evidence for the meaningful relationship between these variables and for the potential benefits of cannabis treatment for autistic children. We strongly recommend further double-blind, placebo-controlled studies using standardized assessments to validate these findings.

Aim: To evaluate the label accuracy and content of various hemp-derived cannabidiol (CBD) products (cannabinoid products with ≤0.3% Δ⁹-tetrahydrocannabinol [THC]), as well as evaluate advertised claims on product labels. Methods: Hemp haircare, cosmetics, and food/drink products that were advertised to contain CBD were purchased from retail stores in the Baltimore, Maryland area (purchased in July 2020) and online (purchased in August 2020). Cannabinoid concentrations were measured using gas chromatography-mass spectrometry. Percent deviations between labeled and actual CBD concentrations were determined. Label information such as references to the Food and Drug Administration (FDA), external testing claims, and other claims (i.e., cosmetic or beauty, therapeutic, health halo effect, or "other") were quantified. Results: Ninety-seven products were purchased (35 in-store, 62 online). Of the 71 products with a specific total CBD amount on the label, 35 (49%) were underlabeled (>10% more CBD than advertised), 27 (38%) were overlabeled (>10% less CBD than advertised), and 9 (12.7%) were accurately labeled (within ±10% of labeled CBD). The median (range) percentage deviations were -53% (-100%-76%) for haircare products, +18% (-100%-1076%) for cosmetics, and -1% (-100%-4468%) for food/drinks. CBD label accuracy did not differ significantly between products with external testing claims versus those without (t₄₀ = 0.23, p = 0.82). Overall, 24% of the 97 (total) products made a cosmetic or beauty claim (e.g., "skin looks more youthful"), 40% made a therapeutic claim (e.g., "pain relief"), and 86% made a health halo effect claim (e.g., "paraben-free," "dye-free," etc.). Most products (63%) did not include a disclaimer that claims had not been evaluated by the FDA. Conclusions: Most of the products included in this sample were inaccurately labeled for CBD content, including those claiming to have been tested by third party laboratories. A notable finding was that 10 products did not contain any CBD. Many products made therapeutic claims or used marketing tactics to seemingly convey they were safe/healthy, but only about one-third included disclaimers that these statements had not been evaluated by the FDA. These findings highlight the need for proper regulatory oversight of cannabinoid-containing products to ensure quality assurance and deter misleading or unfounded health claims in product marketing.

Purpose: Inflammatory bowel disease (IBD) has two main variants, ulcerative colitis (UC) and Crohn's disease (CD), which are characterized by a cycle of remission and relapse. The aim of this scoping review is to understand the landscape of unprescribed and prescribed cannabis use among patients with IBD and investigate objective clinical benefits. Methodology: A literature search was performed across Medline, Embase via Ovid, Scopus, and Cochrane Library databases. We included 40 studies (14 abstracts/letters, 7 randomized controlled trials [RCTs], 6 cohort studies [2 case-matched], 10 cross-sectional surveys, and 3 meta-analyses) in the review. Results: Between 11% and 17.6% of surveyed patients used cannabis for symptom control with a lifetime prevalence of 39.8-78.2%. Patients reported reduced abdominal pain, emotional distress, stool frequency, and anorexia. There was a higher rate of depression, tobacco, and alcohol use among patients with IBD who used cannabis. Individual studies showed patients who were prescribed cannabis were more likely to have had surgery for IBD (14.5% vs. 4.7%, p = 0.0008), require future abdominal surgery (odds ratio = 5.03), report a lower quality of life (p = 0.0001), currently be on corticosteroids (18.1% vs. 10.4%, p = 0.04) and opioids (27.7% vs. 6.4%, p = 0.0001). RCTs of cannabinoids reported mild reductions in disease activity and variable endoscopic inflammation improvement. Conclusions: Patients who use cannabis for IBD are a cohort with refractory disease and lower quality of life who report improvements in symptom management. However, the ability to reduce underlying disease activity appears very modest. Further trials using refined cannabinoid formulations may define a use in IBD.

Background: Patients have been known to use cannabinoids for treating established chemotherapy-induced peripheral neuropathy (CIPN) based on anecdotal information and retrospective reports suggesting that such might be beneficial. In response, a double-blinded, placebo-controlled, randomized, pilot clinical trial was developed to evaluate whether resultant data would support a phase III trial for testing whether a cannabidiol (CBD) cream might improve CIPN. Methods: Forty patients with established CIPN were randomized, in a double-blinded manner, to topical CBD or a placebo cream. The study product was applied for 2 weeks, followed by a crossover for 2 weeks. Neuropathy was evaluated using the European Organization of Research and Treatment of Cancer (EORTC)-CIPN20, the Chemotherapy-Induced Peripheral Neuropathy Assessment Tool, and the Global Impression of Change instruments. Side effects were recorded by symptom diaries. Results: The EORTC-CIPN20 scores were similar in the patients receiving CBD versus the placebo. Likewise, the toxicity scores were similar in patients who received the CBD versus the placebo. Conclusions: This pilot trial did not support that the studied CBD isolate cream improved painful established CIPN. It was well tolerated overall. Clinical Trial Registration Number: NCT05388058.

Tetrahydrocannabivarin (THCV) is a phytocannabinoid that is becoming popular across the North American cannabis market. THCV has been reported to reduce blood sugar and act as an appetite suppressant in several independent pre-clinical studies, which has earned it the popular nickname of "diet weed," despite few human studies of these effects. Additionally, THCV is usually and incorrectly categorized as an intoxicating analogue of tetrahydrocannabinol (THC), which causes confusion among both consumers and regulators. In this article, we examine what is known pre-clinically and clinically about THCV, as well as highlight mechanisms of action, in order to clarify the scientific differences between THCV and THC. THCV, although structurally similar to THC, has distinct pharmacological activity and physiological effects at the doses currently reported in the literature. We highlight areas of opportunity for further THCV research in order to determine the full and appropriate potential for unique health, wellness, and therapeutic applications of this compound.

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.

Purpose: The purpose of this pilot study was to investigate cannabidiol (CBD) cream's effects on muscle soreness and performance after exercise. Materials and Methods: This double-blinded, placebo-controlled experiment included 15 men and 13 women (n = 28; mean ± standard deviation age: 23.29 ± 2.54 years) untrained in lower-body resistance training. Participants were randomized into control (NG, n = 9), CBD (CG, n = 9), or placebo (PG, n = 10) groups. Participants completed a lower-body fatigue protocol (FP) consisting of unilateral maximal concentric and eccentric isokinetic muscle actions of the quadriceps and hamstrings (5 sets, 10 repetitions, both legs). CG and PG participants applied ∼100 mg CBD or placebo cream, respectively, matched for weight and appearance to the quadriceps on three separate days. NG participants engaged in a sitting rest period matched in duration to cream application processes. Questionnaires, pressure-pain threshold (PPT), peak torque test (PTT), and countermovement jump (CMJ) were assessed. Mixed-model analysis of variance was conducted to assess main effects and interactions (group × muscle × time; group × time). Results: There were no significant interactions or main effects for group for PPT, CMJ, or PTT. There were main effects for time (p < 0.05) for all soreness questions, PPT, CMJ, and PTT. There was one significant interaction (group × time; p = 0.045) for cream/rest effect questions, in which PG participants perceived the effect of cream to be greater than the effect of rest for NG participants. There were main effects for group (p ≤ 0.031) for all soreness questions, in which PG participants perceived enhanced recovery. Conclusions: The present pilot study did not discover any significant impacts of CBD cream use for muscle recovery. For individuals seeking to attenuate muscle soreness and improve performance, the current dose of this topical CBD product may not be an effective treatment.

Background: The endocannabinoid system (ECS) is active in brain regions involved in stress, food intake, and emotional regulation. The CB1 receptor and the fatty acid amide hydrolase (FAAH) enzyme regulate the ECS. Genetic variants in the FAAH gene (rs324420) and in the CNR1 gene (rs1049353) have been involved in both chronic stress and obesity. As a maladaptive strategy to evade the stress, three dysfunctional eating patterns may appear: cognitive restriction, disinhibition, and emotional eating. Aim: To evaluate the association of variants rs324420 in the FAAH gene and rs1049353 in the CNR1 gene with perceived stress, dysfunctional eating patterns, and anthropometric and body composition variables. Methods: This cross-sectional study included 189 participants from western Mexico. The Spanish version of the Three-Factor Eating Questionnaire and the Perceived Stress Scale were applied. Genotyping was performed with TaqMan^® probes. Results: It was found that subjects with CA/AA genotypes in FAAH had a higher risk of presenting high scores in stress perception than CC genotype carriers (odds ratio [OR] 1.85, 95% confidence interval [CI] 1.007-3.339; p = 0.048); in addition, the CC genotype of this genetic variant was related to higher body weight and body fat, but no association was found with dysfunctional eating patterns. As for the CNR1 single-nucleotide polymorphism, this variant showed no significant association with stress perception scores, but subjects with GA/AA genotypes in CNR1 had a lower risk of presenting high scores of restriction in food intake compared with GG genotype carriers (OR 0.11, 95% CI 0.046-0.322; p < 0.001). Therefore, this study suggests a differential role of the ECS genes FAAH and CNR1 in perceived stress and dysfunctional eating patterns, respectively. Further studies in other populations are required.