Medical Cannabis and Cannabinoids最新文献

Introduction: Cannabidiol (CBD), a non-psychoactive phytocannabinoid, attributed to its therapeutic benefits and positive safety profile is being studied for its potential to treat various medical conditions. The low oral bioavailability and significant first-pass metabolism present pharmacokinetic (PK) challenges. The present study aimed to evaluate the PK profile of a novel nanodispersible CBD oral solution (150 mg/mL) under fasting and fed conditions in healthy male subjects.

Methods: In this randomized, single-dose, two-arm (fasting and fed), open-label trial, 18 subjects (9 fasting and 9 fed) received 300 mg of CBD (2 mL of 150 mg/mL). Plasma concentrations of CBD and its major metabolites, specifically 7-hydroxy-cannabidiol (7-OH-CBD) and 7-carboxy-cannabidiol (7-COOH-CBD) were quantified and the PK parameters including C_max, time to reach maximum concentration (T_max), AUC_0-∞, and t½ were analyzed using non-compartmental modeling methods.

Results: The fed state significantly increased the area under the curve (AUC_0-∞) for CBD by 3.0-fold (p < 0.0001) and prolonged the T_max. C_max was moderately higher in the fed state (1.3-fold). The 7-COOH-CBD metabolite reached the highest plasma concentration, followed by the parent CBD and 7-OH-CBD. The administration of nanodispersible CBD oral solution was well tolerated, with no major adverse events.

Conclusions: The nanodispersible CBD oral solution showed enhanced bioavailability under fed conditions and was well tolerated in healthy subjects. Food intake increased CBD's C_max and AUC and delayed T_max. Further studies are required to confirm the therapeutic efficacy in patient populations.

Introduction: This decentralized, randomized, triple-blind, placebo-controlled study evaluated efficacy and safety of oral cannabigerol (CBG) in Veterans with sleep issues.

Methods: After a 2-week run-in phase, participants received CBG (25 mg daily for 2 weeks, then 50 mg daily for a further 2 weeks) or placebo. The primary endpoint was change in sleep quality via the Medical Outcomes Study Sleep Problems Index II questionnaire (MOS-SS SPI-II). Additional endpoints included change in quality of life measured via the World Health Organization Disability Assessment Schedule, version 2.0 instrument (WHODAS-2.0-12), post-traumatic stress disorder (PTSD) symptoms evaluated via the PTSD Checklist for the Diagnostic and Statistical Manual of Mental Disorders-Fifth Edition (PCL-5 (PCL-5), and sleep actigraphy data via Fitbit.

Results: A total of 63 participants were randomized to receive CBG (n = 33) or placebo (n = 30). A total of 35 participants completed the study without major protocol deviations (CBG [n = 18]; placebo [n = 17]). MOS-SS SPI-II scores indicated improved sleep with no statistically significant difference between the CBG and placebo groups. Similar patterns were observed for WHODAS-2.0-12 and PCL-5 scores. CBG was well tolerated.

Conclusion: While no firm conclusion on the efficacy of CBG in improving sleep can be made, the favorable safety profile supports future studies with CBG. ClinicalTrials.gov ID: NCT05088018.

Introduction: Multiple sclerosis (MS) is a neurodegenerative disease presenting with a wide range of motor, sensory, and psychiatric symptoms. Although nabiximols is licensed for MS-induced spasticity, cannabis-based medicinal products (CBMPs) have also displayed promising therapeutic potential for managing pain, sleep, and anxiety. Therefore, further evaluation of CBMP treatment for MS is warranted. This study aimed to assess the efficacy and tolerability of CBMP treatment in patients with MS by investigating changes in MS-specific and general health-related patient-reported outcome measures and adverse events.

Methods: This was a prospective case series including patients with MS enrolled on the UK Medical Cannabis Registry. Changes in MS Quality of Life-54 (MSQOL-54), Generalised Anxiety Disorder-7 (GAD-7), Single-Item Sleep Quality Scale (SQS), and EQ-5D-5L scores were assessed from baseline up to 24 months. The prevalence and severity of all adverse events were also assessed.

Results: This study included 203 patients, of whom 47.29% (n = 96) were female and 80.79% (n = 164) had prior cannabis exposure. Improvements in the MSQOL-54 subscales: change in health, energy, health distress, pain, physical function, and physical role limitations, along with improvements in SQS and EQ-5D-5L scores, were seen at all follow-up times compared to baseline (p < 0.050). A total of 278 adverse events were reported by 26 patients (12.81%). Most adverse events were mild (n = 91, 32.73%) or moderate (n = 138, 49.64%) in severity, with fatigue (n = 27, 13.30%) and spasticity (n = 17, 8.37%) being the most common.

Conclusion: CBMP treatment over 24 months was associated with improvements in health-related quality of life and was well tolerated in patients with MS. Future randomised controlled trials with more representative study populations are needed to establish causal relationships.

Background: At least 60% of individuals with anxiety disorders report sleep disturbances, which might be explained by shared physiological mechanisms, including cortisol dysregulation and executive function skills disruption. The scientific literature regarding medical cannabis as a potential therapeutic candidate for these conditions increased about 15 times in the last 10 years. However, assessments of cannabinoid exposure, anxiety, and sleep are inconsistent across studies, and the quality of the evidence is not often assessed.

Summary: We conducted a scoping review to examine the current knowledge on cannabinoid use for anxiety and sleep disturbances. We applied our search strategy to PubMed, EMBASE, Cochrane Database of Systematic Reviews, Cochrane Central Register of Controlled Trials, CINAHL, LILACS, and PsycINFO. Papers were selected by duplicate using PRISMA guidelines. Quality assessment was conducted for included studies, and data extraction was performed according to our predefined protocol. Of 1,132 retrieved documents, 29 studies met the inclusion criteria, encompassing randomized clinical trials, observational studies, and case series. Cannabinoids, particularly cannabidiol (CBD), showed potential efficacy in improving anxiety symptoms and sleep disturbances. However, substantial heterogeneity in study design, cannabinoid types, and dosing regimens limited generalizability. Approximately 45% of studies reported positive effects on both outcomes, yet few provided standardized dosing protocols or effect sizes.

Key messages: Cannabinoids, especially CBD, may improve anxiety and sleep disturbances, but methodological limitations and the lack of standardized dosing hinder definitive conclusions. Future research should prioritize dose-response relationships and standardized methodologies to better inform clinical practice.

Introduction: Chronic pain is the most common qualifying condition found in states with legal (certified) access to medical cannabis (MC). We assessed the geographic distribution of MC certifications for severe chronic or intractable pain in Pennsylvania (PA) between 2018 and 2024, identifying relationships between community variables with the percentage of adults with an MC certification for pain.

Methods: Using data from the PA Department of Health (PDOH) from 2018 to 2024 (N = 44,645 to 165,740 certifications for pain/year), we mapped zip codes associated with MC certifications for pain to counties and zip code tabulation areas (ZCTAs), geographic areas that approximate a standardized representation of zip codes for statistical purposes. The difference between the highest and lowest counties was determined. A linear regression evaluated correlations between community variables and the percentage of adults in geographical areas with an MC certification for pain in 2024.

Results: There was almost a four-fold difference in the percent of adults with an MC certification for pain in the highest (Perry = 2.3%) versus lowest (Tioga = 0.6%) counties in 2024. Bradford and Tioga County had a significantly (p < 0.05) lower percentage certified relative to the county-wide average. There was a significantly higher proportion of certifications for pain in counties with larger population densities of adults (1.76 ± 0.12%) than counties with smaller population densities (1.38% ± 0.14%) of adults (t(65) = 4.66, p < 0.001, d = 1.14). At the county level, higher median household income (r(65) = +0.335, p < 0.01), lower median age (r(65) = -0.241, p = 0.0499), and higher rural-urban continuum code (r(65) = +0.644, p < 0.001) were associated with a greater percentage of adults with an MC certification for pain using simple linear regression. Using a multiple regression model, only rural-urban continuum code was significantly associated with the percent of adults with an MC certification for pain (p < 0.001). At the ZCTA level, the proportion of non-white individuals, including Hispanics, showed a significant inverse association with the percent of adults with an MC certification for pain (r(1,722) = -0.07, p < 0.01).

Conclusions: This study identified four-fold county-level disparities in MC certifications for pain. The association between median household income and MC pain certifications may indicate differences in accessibility of MC based on financial status. Further research may be warranted pending any changes to the legal status or demand for MC.

Introduction: The endocannabinoid system plays a role in sleep-wake regulation. In clinical practice, people with central disorders of hypersomnolence (CDH) frequently report use of cannabis.

Methods: We compared lifetime and current use of cannabis of people with CDH to the Dutch general population. Additionally, we assessed cannabis use in relation to hypersomnolence symptoms.

Results: In total, 76 (out of 88) patients completed the online questionnaire. Lifetime cannabis use (42% vs. 23%, p < 0.001) and current use (18% vs. 4%, p < 0.001) were higher in people with CDH compared to the Dutch general population. For 57% of patients currently using cannabis, improvements of at least one CDH symptom were the motivation for use. Additionally, 79% of current cannabis users reported cannabis-related effects on a symptom, which were mostly positive (43%), some negative (7%), or mixed effects (29%). Patients that stopped using mostly started using cannabis before symptom onset and for recreational purposes. The most reported reasons to stop using were disadvantages of using or changes in the social environment.

Conclusion: This study provides a rationale for future research on the potential benefits of cannabis in CDH.

Background: Despite significant gaps in the research literature, the integration of cannabidiols into chewing gum as a drug delivery system is a novel and promising approach for various cannabinoid therapeutic applications. Chewing gum offers a unique delivery mechanism that may promote both local and systemic effects through the oral mucosa, enhancing the bioavailability and efficacy of cannabinoid medications.

Summary: This commentary explores and delves into the potential of cannabinoid-infused chewing gum, highlighting its putative benefits for managing an array of conditions, including oral health, anxiety, and pain. The therapeutic potential of cannabinoids is explored in the context of their anti-inflammatory, antimicrobial, analgesic, and anxiolytic properties that may be especially impactful in the oral cavity and at the oral-pharyngeal mucosa. Additionally, we reviewed the advantages of using chewing gum for discrete self-medication and rapid onset of salutary effects.

Key messages: Despite a long-standing widespread history of chewing gum use in general, there is sparse experience and even less clinical research on the effects and possible clinical value of incorporating cannabidiol or any other cannabinoid in a chewing gum product. Despite promising reports, research gaps remain, particularly in understanding the absorption mechanisms, dosing precision, and long-term safety of cannabinoid-based chewing gum. Addressing these challenges will position cannabinoid-infused chewing gum as a versatile and effective drug delivery system for a range of health conditions.

Introduction: Cannabis contains hundreds of chemical constituents beyond delta-9-tetrahydrocannabinol (Δ9-THC), which is thought to be the primary driver of most of its acute pharmacodynamic effects. The entourage effect theory asserts that the pharmacological and therapeutic effects of cannabis are not solely attributable to Δ9-THC but are influenced by other constituents, such as minor cannabinoids and terpenes, through distinct pharmacological action. However, empirical studies that have systematically evaluated this theory in humans remain limited. This study tested the hypothesis that the terpene α-pinene can attenuate the acute memory-impairing effects of inhaled Δ9-THC in humans.

Methods: Participants (N = 19; last cannabis use 39 days, on average, prior to first test session [SD = 84; range = 2-365]) completed six double-blind outpatient drug administration sessions during which they inhaled, using a Mighty Medic hand-held vaporizer, α-pinene alone (15 mg), Δ9-THC alone (30 mg), Δ9-THC and α-pinene together (30 mg Δ9-THC + 0.5 mg α-pinene; 30 mg Δ9-THC + 5 mg α-pinene; 30 mg Δ9-THC + 15 mg α-pinene), or placebo (ambient air) in a randomized order. Outcomes, which were collected up to 6 h post-drug exposure, included subjective drug effects, cognitive/psychomotor performance, and vital signs.

Results: Administration of 15 mg α-pinene alone produced no significant pharmacodynamic effects compared to placebo. Administration of 30 mg Δ9-THC alone elicited subjective, cognitive, and physiological effects consistent with acute Δ9-THC-dominant cannabis exposure, including impairment of cognitive performance and working memory ability compared to placebo. The co-administration of α-pinene with Δ9-THC did not mitigate Δ9-THC-induced memory impairment or significantly alter other acute subjective, cognitive, or physiological effects.

Conclusions: Inhaled α-pinene, at doses at and above those naturally found in cannabis flowers, did not mitigate Δ9-THC-induced cognitive impairments as hypothesized or influence other common acute effects of Δ9-THC in this sample of healthy adults. This result is inconsistent with some cannabis industry claims and speculation by some cannabis researchers. By systematically varying both Δ9-THC and terpene exposure and assessing their interaction across multiple pharmacodynamic domains, this work provides a model for future investigations into Δ9-THC-terpene interactions. As cannabis use continues to expand for both medicinal and non-medicinal purposes, more research is needed to better understand the acute effects of lesser studied chemical constituents of the plant and how they interact with predominant phytocannabinoids like Δ9-THC. This can inform cannabinoid drug development and product regulations.