Cannabis and Cannabinoid Research最新文献

Introduction: In recent years, the production and consumption of cannabinoids have increased significantly. Researchers are particularly interested in cannabidiol (CBD), Δ⁸-tetrahydrocannabinol (Δ⁸-THC), and Δ⁹-tetrahydrocannabinol (Δ⁹-THC). Despite the growing prevalence of these molecules in everyday life, research shows that cannabinoid products are often mislabeled. In this study, we quantified and compared the label accuracy of CBD in full- and broad-spectrum tinctures to evaluate whether there is a public health concern related to CBD, Δ⁸-THC, and Δ⁹-THC. Materials and Methods: A total of 18 samples from different brands sold online in the United States were obtained for the study. Reverse-phase high-performance liquid chromatography with ultraviolet/visible light detection (RP-HPLC-UV) was employed to detect and quantify the concentration of CBD and THC isomers within the samples. Labels were deemed inaccurate if the actual concentration of CBD deviated by more than 10% from the labeled amount. Results: Our findings showed that 12 out of 18 samples had inaccurately labeled CBD concentrations. Notably, a significant difference in CBD label accuracy was observed between broad- and full-spectrum tinctures (p = 0.0282). No significant correlation was found between the cost of the tinctures and the label accuracy for CBD (p = 0.2117). While none of the broad-spectrum tinctures contained Δ⁸-THC, two contained Δ⁹-THC. All full-spectrum tinctures contained both Δ⁸-THC and Δ⁹-THC at levels below the federal limit for hemp of 0.3% on a dry weight basis. Discussion: Accurate labeling of CBD and THC in tincture products is a crucial public health concern, both locally in Texas and across the United States. There is a need for the U.S. Food and Drug Administration to promulgate regulations for labeling products that contain CBD and THC.

Introduction: Cannabis was legalized in California for recreational use through the passage of Proposition 64: The Adult Use Marijuana Act of 2016. This analysis from the Impact 64 study describes the cannabis use patterns of adults 21 years and older in California since the passage of Proposition 64. Methods: An online questionnaire addressing use of tetrahydrocannabinol-containing cannabis (including frequency, product(s), length, source, and purpose) was administered from December 2022 to February 2023. Of the initial 15,309 census-weighted participants, a subset of participants completed a detailed cannabis use questionnaire, including 4,020 people who currently use cannabis. Cannabis users were grouped by use frequency, and chi-squared analysis was utilized for descriptive analysis. Multinomial logistic regression was applied to assess significant variables associated with specific use patterns. Results: Of the initial sample of 15,208, 37% reported current cannabis use (with use in the past 3 months), 30% formerly used cannabis, and 33% were nonusers. Among current users, 38% reported very frequent use (multiple times a day), 33% frequent use (four times per week to daily), and 30% occasional use (three times per week or less). Compared with occasional users, very frequent users were more likely to be male (65%, odds ratio [OR] = 1.8, p < 0.001), less educated (OR = 1.7, p < 0.001), and have lower incomes (under 50K vs 100K, OR = 2.3, p < 0.001). Most users reported multiple cannabis products, mainly flower inhalation (80%), vaping (66%), and edibles (61%), primarily sourced from dispensaries (77%), which the majority (94%) perceived as licensed. Of all current users, most used cannabis at home (93%) or for entertainment (75%), with many reporting use during creative activities (45%), with alcohol (36%) and/or with cigarettes (24%). Positive impacts were reported in mental (82%), emotional (81%), and physical (62%) health. The internet (51%) and friends/family (50%) were the main sources of information. Most current users felt comfortable discussing cannabis with their primary doctor (78%), although only 66% of primary doctors knew about recreational use. Discussion: There is a high prevalence of daily cannabis use among adult Californians, with most users obtaining products from perceived licensed dispensaries or delivery services. While most users feel comfortable discussing cannabis use with physicians, they primarily obtain information from other sources, highlighting the need to bridge this information gap.

Background: In 2023, Japan's Cannabis Control Act underwent its first major revision since its establishment in 1948. The legal framework surrounding cannabis had long remained rigid, with limited scope for medical or industrial applications. Methods: This review examines the content and implications of the 2023 legal amendments based on governmental documents, legislative records, and secondary analyses of regulatory shifts. The assessment focuses on three key domains: medical application, industrial use, and drug control. Results: Under the revised law, cannabis-derived products intended for medical use were brought under the same regulatory framework as opioid analgesics, theoretically enabling physicians to prescribe them. Simultaneously, the longstanding restriction limiting industrial use to mature stalks and seeds was lifted. However, this liberalization was counterbalanced by the introduction of a stringent THC threshold. On the criminal side, cannabis continues to be regulated as an illicit substance, and new penalties for use have been introduced. The revised law came into effect on December 12, 2024. Conclusion: The 2023 amendment represents a significant shift in Japan's cannabis policy, aiming to balance expanded medical and industrial opportunities with continued drug control. Its practical implications remain to be seen and warrant close monitoring in the coming years.

Introduction: Despite prohibitions against youth-appealing packages, deceptive "copycat" cannabis edible packages have been commonly seen in U.S. states that legalized recreational cannabis. Copycat packages mimic the branding features of popular food products, posing a high risk for accidental ingestion, particularly for the younger population. Materials and Methods: An online experiment was conducted among a representative sample of young adults aged 18-29 (N = 2,523). Participants were asked in timed trials to identify whether each package in a series of images contained cannabis content. Regression analysis was conducted to analyze the association between package type and correct identification and the association between correct identification and appeal ratings. Results: Copycat cannabis packages were associated with lower odds of correct identification of cannabis content (odds ratio = 0.35, 95% CI = [0.31, 0.40]) compared with the non-copycat branded cannabis package. Correct identification of cannabis content was associated with lower appeal ratings (odds ratio = 0.75, 95% CI = [0.69, 0.81]). Discussion: Copycat cannabis packages were associated with elevated risk of misidentification of cannabis content, making them a public health risk for accidental ingestion. Package features that make a package easily identifiable were less appealing, underscoring the need of requiring salient features to indicate cannabis content on cannabis packages.

Introduction: Cannabis cultivars were usually categorized based on their genetic profile as sativa, indica, or hybrid types. However, these three criteria do not allow sufficient differentiation between the numerous varieties of cannabis strains. Furthermore, this classification is based on morphological and bio-geographical properties of the plants and does not represent the chemical composition of different cultivars. The concentration of cannabinoids and terpenes are crucial for the pharmacological effect, not only because of the known entourage effect, and therefore needs to be considered by categorization. Materials and Methods: A total of 140 medicinal cannabis flowers available on the German market were analyzed regarding their individual terpene profile using GC-MS analysis. Statistical evaluation was performed to investigate correlations and data relations as well as for clustering. Results: Multivariate analysis showed correlations between individual terpenes. However, there was no statistical correlation between terpene profiles and their respective genetic profile. Terpene profiles of sativa, indica, and hybrid strains are quite heterogenous and clearly showed that there is no relation between terpenes and the estimated pharmacological effect. As a result, we suggest a new classification system based on individual terpene profiles to faster a comprehensive understanding of the expected medical effect. Discussion: Considering main terpenes, we established a concept of six clusters with various terpene profiles being attributed to different medicinal applications. We excluded tetrahydrocannabinol (THC) and cannabidiol (CBD) content from clustering as most of the strains were THC dominant and therefore distort the results. Our pattern of strains with similar terpene profiles might refine the existing classes of chemotypes with different THC:CBD content. Conclusion: The categorization of cannabis strains based on their terpene profiles allows a clearer, finer and, above all, more meaningful classification than the existing sativa/indica classification. Due to the entourage effect and the interactions between cannabinoids and terpenes, this group of substances is also given the necessary consideration when selecting the right medicine for the individual. Within the next steps, further studies are needed with the aim of mapping clinical validated effects to our chemovars. If it is possible to correlate therapy of symptoms to specific chemical profiles personalized cannabinoid therapy will be possible.

Background: Chronic noncancer pain (CNCP) affects one in five adults and is commonly managed with long-term opioid therapy. Concerns regarding rare but catastrophic harms associated with opioids, including overdose and death, have generated interest in alternatives including cannabis; however, the comparative cost-effectiveness of these management options is uncertain. Methods: We used findings from a network meta-analysis of 90 randomized trials to develop a 1-year microsimulation model to compare costs and quality-adjusted life years (QALY) between oral medical cannabis and opioids for CNCP. We used a publicly funded health care payer perspective for our analyses and obtained cost and utility data from publicly available sources. All costs are reported in 2023 Canadian dollars. All analyses were probabilistic, and we conducted sensitivity and scenario analyses to assess robustness. Results: Total mean annual cost per patient was $1,980 for oral medical cannabis and $1,851 for opioids, a difference of $129 (95% confidence interval [CI]: -$723 to $525). Mean QALYs were 0.582 for both oral medical cannabis and opioids (95% CI: -0.007 to 0.015). Cost-effectiveness acceptability curves showed that oral medical cannabis was cost-effective in 31% of iterations at willingness-to-pay thresholds up to $50,000/QALY gained. Use of opioids is associated with nonfatal and fatal overdose, whereas medical cannabis is not. Discussion: Our findings suggest that medical cannabis as an alternative to opioids for chronic pain may confer similar, but modest, benefits to patients, and reduce the risk of opioid overdose without substantially increasing costs.

Introduction: Following the spread of recreational cannabis legalization and commercialization, cannabis has become increasingly available at lower prices. As policies regulating prices are common tools to control the demand for commercialized drugs, it is crucial to understand how cannabis use responds to price changes. In this study, we assessed the association between wholesale prices for legal cannabis flower and adults' self-reported current cannabis use in ten states with recreational cannabis commercialization in the U.S. Materials and Methods: We conducted a secondary data analysis using individual-level data on cannabis use from the longitudinal Population Assessment of Tobacco and Health Study, during 2015 and 2021. Our analysis included 19,812 U.S. adults from ten states that legalized recreational cannabis sales during the study period. We first conducted logistic regressions to estimate the association between state-level cannabis prices and individual current cannabis use. To address potential endogeneity of cannabis prices, we then employed generalized method of moment (GMM) estimator, using cannabis taxes as an instrumental variable (IV). Results: IV-based GMM regressions suggested that cannabis taxes were a significant predictor of cannabis prices. However, the association between legal cannabis flower prices and adults' current cannabis use was negative but statistically insignificant (coefficient = -0.18, p = 0.086). Price elasticity estimates for current cannabis use ranged from -0.66 to -0.59 across different model specifications. Conclusion: In the initial years of recreational cannabis commercialization in the U.S., the price elasticity of cannabis use among adults was negative but statistically insignificant. Given the rapid progression of commercialization, further research utilizing longer-term data is needed.

Objective: Cannabidiol (CBD), a phytocannabinoid of increasing interest for its purported therapeutic effects, is primarily consumed via ingestion and inhalation. While the toxicology of orally administered CBD has been reported, little is known about the effects of CBD inhalation. Doses selected for the present analysis allowed for evaluation of dose-response at concentrations >100-fold higher than typical human consumption levels. Materials and Methods: CBD (98.89% pure) was formulated in propylene glycol (PG) and aerosolized by nebulization to evaluate biological response after nose-only inhalation. Sprague Dawley rats (n = 35 males, 30 females) were exposed to 1.0 and 1.3 mg/L nominal concentrations of CBD and PG, respectively, for 12-180 min. Resulting average daily presented dose ranges were 8.9-138.5 mg/kg CBD and 11.3-176.0 mg/kg PG. Aerosols of 1.4 µm median diameter were achieved. Biological response indicators included clinical signs, clinical chemistry, hematology, body/organ weights, and pulmonary/systemic histopathology. Results: Inflammatory and necrotic responses were observed in the nose at the highest doses of CBD. Limited findings in the larynx and lung were mainly observed at higher doses. There were no histological findings in extrapulmonary organs. Dosimetry modeling differentiated the no observable adverse effect level between the nasal region and lungs to be 2.8 and 10.6 mg/kg CBD, respectively. Conclusions: Dose-depending findings of histological changes in the respiratory tract are observed at high doses. At lower doses consistent with typical over-the-counter vape products there appears to be substantial safety margin in the present study (93- and 353-fold lower for nose and lung, respectively).

Introduction: Although cannabinoid type 2 (CB2) receptor activity is known to promote diverse biological functions in the kidney, published data regarding CB2 receptor protein levels and cellular distribution within the kidney is inconsistent. The goal of the present study was to investigate the changes of CB2 in the kidney obtained from mice exposed to various forms of kidney injury using a genetic mouse model expressing green fluorescent protein (GFP) driven by the endogenous cannabinoid receptor 2 (Cnr2) promoter. Materials and Methods: Kidney injury was established in a genetic mouse model expressing green fluorescent protein (GFP) driven by the endogenous Cnr2 promoter. Kidney injury was initiated by either treatment with different chemicals [cisplatin or lipopolysaccharide (LPS)] or by unilateral ureteral obstruction (UUO). Changes in the detection of GFP were used as a proxy for CB2 levels and localization. Histological changes due to the injury stimuli were observed by time-related, morphological changes in kidney cytoarchitecture and blood parameters, such as serum creatinine levels. Cnr2 mRNA levels were detected by reverse transcription coupled to polymerase chain reaction (RT-PCR) while protein changes in the tissue lysates were measured by Western blot analysis. Cellular localization of GFP was detected by fluorescent microscopy. Results: Our data demonstrated that there was no band or a minimally detectable band for GFP using kidney lysates from vehicle- or cisplatin-treated mice. A similar lack of GFP was detected in the UUO kidney versus the contralateral control kidney. This is consistent with the low, albeit detectable levels of Cnr2 mRNA in the kidney samples from control or cisplatin treatment. In frozen kidney sections from vehicle and cisplatin-treated mice, GFP fluorescence was not detectable in tubular epithelia, glomeruli or blood vessels in the cortex. Instead, GFP was detected in rare cells within the interstitial space. A second chemical injury model using LPS found a similar lack of GFP protein levels and an absence of legitimate GFP fluorescence in the main cell types within the kidney. Conclusion: These findings suggest that Cnr2 promoter activity is minimally active in normal or injured kidneys, and that pharmacological manipulation of CB2 receptors may be associated with receptors being expressed in cells recruited to the kidney.

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.