Cannabis and Cannabinoid Research最新文献

Background: The increase in cannabinoid use among adolescents has become a public health concern in North America, with more than one-third of 12th graders in the United States reporting consumption of some form of cannabis within the past year (2023).^1,2 The use of cannabinoids during adolescence, a vulnerable stage for brain development, may alter the neuroplasticity dependent on brain-derived neurotrophic factor (BDNF),³ an essential protein for brain development. BDNF is found either as its precursor, pro-BDNF, involved in synaptic pruning and apoptosis, or its mature form (m-BDNF), which stimulates dendritic growth and cell survival. The synthetic cannabinoid Win55,212-2 (WIN) acts as a dual agonist for the endocannabinoid CB1 and CB2 receptors (eCBRs), emulating the psychotropic activity of Δ9-tetrahydrocannabinol. This study investigates the impact of WIN administration on levels of pro and m-BDNF in the adolescent brain (medial prefrontal cortex [mPFC], hippocampus, and cerebellar vermis[CbVr]) of adolescent male rats.

Methods: Male adolescent Sprague-Dawley rats received two intraperitoneal injections, either WIN (0.8 mg/kg) or saline solution (0.9% NaCl) every 48 h, from postnatal day (PND) 30 to 37. On the final day (PND 38), a single injection of either WIN or saline was administered. The rat's whole brain tissue was collected an hour after the last injection.

Results: Chronic WIN administration during adolescence caused a significant increase in pro-BDNF levels in the brain's CbVr and m-BDNF in the mPFC.

Conclusion: Our findings suggest that chronic WIN administration can alter the baseline levels of pro and m-BDNF in the brains of male adolescent rats, which may have implications for synaptic plasticity and neurodevelopment.

Introduction: Although classified in the United States as Schedule I drugs, medical and recreational cannabis and Δ⁹-tetrahydrocannabinol (THC) are becoming increasingly consumed by pregnant women. Determining the potential adverse effects following exposure during early development is essential for risk communication. Materials and Methods: Following exposure to 0.08, 0.4, or 1 µM THC for 6-96 h post fertilization (hpf) in wild-type zebrafish, latent behavioral effects caused by THC were evaluated at 3 weeks post fertilization (wpf) (juvenile), 11 wpf (onset of sexual maturity), and 24 wpf (adult) and in F1 offspring. Bioenergetics were measured in F0 adult brain mitochondria. Results: Open field tests conducted at 3 wpf and 11 wpf indicated concentration-dependent hyperactivity (increased velocity) and increased thigmotaxis (anxiety-like wall-hugging) at the two highest THC concentrations. The 5D F1 generation of zebrafish (exposed to THC as germ cells) also demonstrated significant dark-phase hyperactivity at 120 hpf in the larval photomotor response. Brain mitochondrial bioenergetics in adults developmentally exposed to THC showed that oxygen consumption rate was significantly increased at the two highest THC concentrations for females and the highest concentration for males. Discussion: Collectively, these results show that exposure to THC during a critical period of development caused behavioral and mitochondrial alterations that persisted into adulthood and across generations.

This article examines the effects of biotic and abiotic influences on trichome development in cannabis and how these influences may shape the ultimate cannabinoid and terpene profiles in cannabis cultivars. As cannabis agriculture focuses primarily on either high tetrahydrocannabinol or cannabidiol production, the result has been an attenuation of genetic and chemical diversity observed in contemporary cannabis cultivars. Techniques for modulating trichome development remain an active area of commercial importance. The clinically therapeutic role of varied cannabis metabolite profiles, which include the wider range of cannabinoids and terpenes, also ultimately tied to trichome development. This review will analyze how different stressors can modify phytochemical ratios and alter trichome development.

Introduction: The availability of recreational cannabis in the United States has increased dramatically. Neighborhood cannabis dispensary availability may increase problematic use. State and local studies suggest that cannabis dispensary availability may be correlated with neighborhood sociodemographic characteristics. We provide a national-level examination of census tract (CT) sociodemographic characteristic correlates with the availability of cannabis dispensaries in 18 U.S. states that have legalized adult recreational cannabis use. Methods: We downloaded the locations of cannabis dispensaries (N = 3,167) from Weedmaps in November 2021. We downloaded ethnic, racial, and socioeconomic estimates from the U.S. Census and categorized CTs into quintiles (Q), where Q1 represents the CTs with the lowest percentage of a variable and Q5 represents CTs with the highest. We fit unadjusted generalized linear mixed models to examine associations between quintiles of each sociodemographic characteristic and the presence of at least one dispensary (vs. none). Results: CTs with a greater percentage of Black residents had a higher odds of having at least one cannabis dispensary (vs. none) across all quintiles. For example, compared to CTs with the lowest percentage of Black residents (Q1), CTs with the greatest percentage of Black residents (Q5) had 2.07 (95% CI: 1.70-2.52) times the odds of having at least one dispensary versus none. We observed a similar pattern of a greater likelihood of a CT having a dispensary (vs. none) as the percentage of Hispanic/Latine residents and percentage of individuals living below the federal poverty line increased across all quintiles. In contrast, as the percentage of homeowner-occupied housing increased across all quintiles, there were lower odds of having at least one dispensary (vs. none). For example, CTs with the highest percentage of homeowner-occupied housing (vs. lowest) had 0.21 (95% CI: 0.17-0.26) times the odds of having at least one dispensary vs. none. Discussion/Conclusions: Differences in cannabis dispensary availability exist by neighborhood sociodemographic composition. The growing acceptance of cannabis, concern about public health and safety, and the proliferation of adult recreational use laws offer local and state policymakers an opportunity to engage local communities in shared decision-making about the location of dispensaries.

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.

Introduction: Cannabinoid formulations have been increasingly proposed as therapeutic potential options for anxiety disorders (ADs). Several countries have expanded regulatory frameworks facilitating access to these compounds due to their alleged therapeutic benefits, including their application in ADs. Given its public health significance, we evaluated existing evidence regarding the efficacy of different medical cannabinoids as interventions for ADs and related mental conditions. Methods: A comprehensive search was conducted in PubMed, Embase, PsycInfo, Web of Science, Scielo, and Lilacs databases. We included randomized controlled trials (RTCs) assessing the effects of various cannabinoid formulations on patients with ADs and related conditions. Distinct meta-analyses were performed for cannabinoid subtypes. Analyses were conducted using Jamovi software, relying on standardized mean difference (SMD) calculations of pre/post-intervention score changes for both intervention and control groups. Results: We incorporated 21 placebo-controlled RCTs, examining cannabinoid interventions in social anxiety disorder (SAD = 5), generalized anxiety disorder (GAD = 1), post-traumatic stress disorder (PTSD = 7), obsessive-compulsive disorder (OCD = 1), and Tourette syndrome (TS = 7). Data extraction indicated considerable heterogeneity across outcomes, including clinical symptoms, neuroimaging findings, well-being, psychosocial functioning, safety, and tolerability. In studies utilizing pure or enriched CBD, the meta-analytic measure indicated a nonsignificant difference (SMD = -0.40; 95% CI: -0.84/0.03). However, a subgroup analysis of pure CBD compounds yielded a moderate, statistically significant effect size (SMD: -0.61, 95% CI: -1.15/-0.07). For studies investigating pure or enriched delta-9-tetrahydrocannabinol (Δ9-THC), the meta-analytic measure was -0.65 (95% CI: -1.06/-0.24), suggesting a moderate, significant effect favoring Δ9-THC-dominant compounds. In meta-analyses of studies with Δ9-THC and cannabidiol (CBD) mixtures, the effects were not significant (SMD = -0.73, 95% CI: -2.00/0.55). Although suggesting a potential superior efficacy of pharmaceutically pure formulations of Δ9-THC and CBD over alternative versions, these results must be interpreted with caution due to heterogeneous study designs and small sample sizes. Discussion: The current evidence is limited. Low-quality evidence suggests that pharmaceutical-grade CBD may have limited efficacy for SAD and GAD. In addition, low-quality evidence supports Δ9-THC's efficacy for the reduction of nightmares in PTSD and tic severity in TS. Further double-blind, randomized, placebo-controlled trials with larger and heterogeneous samples are required to investigate the clinical outcomes of pharmaceutical-grade cannabinoids and standardized cannabis extracts in the treatment of ADs.

Introduction: Veterans use cannabis as a chronic pain treatment due to a combination of the easing of restrictions and dissatisfaction with care standards. The segregation of medical cannabis from conventional health systems may translate to opportunities and disadvantages that are not well defined. Our study aimed to characterize how Veterans with chronic pain approach using cannabis for symptom management, including product access, developing a treatment plan, and its integration into daily life. Materials and Methods: We used an interpretive description design and conducted semi-structured interviews with U.S. Veterans in Michigan who had chronic pain; were aged 21 years or older; and (a) used cannabis, (b) were planning to use cannabis, or (c) interested in learning about how cannabis could help with pain. We analyzed deidentified interview transcripts to develop themes that focused on how Veterans approached new and continued use of cannabis for chronic pain management. Results: Participants were Veterans with chronic pain, median age = 50 years (n = 32). Participants described how factors at the individual, relationship, community, and societal levels influenced their interest in and use of cannabis for chronic pain. We identified five main themes: (1) cannabis supports holistic wellness, but there are also undesired effects; (2) medical cannabis requires a personalized treatment approach; (3) Veterans seek expanded access to medical cannabis and more assurance regarding product safety and efficacy; (4) sociopolitical attitudes and advocacy shape medical cannabis acceptability; and (5) the interest in research to inform treatment approaches and facilitate access. Discussion: This article illustrates how Veterans approached using cannabis for chronic pain management. Findings illuminate the potential value of cannabis for Veterans with chronic pain while also highlighting numerous obstacles and limitations related to its use. There are opportunities for health care providers to support Veterans who are interested in cannabis while research regarding efficacy and safety continues. Future efforts should engage Veterans to collectively work toward a better understanding of cannabis as a pain treatment option.

Introduction: The administration of cannabinoids for disease and symptom management such as pain continues to elicit significant interest, albeit limited information that is available regarding their pharmacokinetics and pharmacodynamics to guide clinical practice. Cannabis-based medicines contain a wide variety of chemical compounds, of which the most common include the cannabinoids delta-9-tetrahydrocannabinol (Δ9THC), and the nonpsychomimetic cannabidiol (CBD). The pharmacokinetics of cannabis-based medicines and the effects observed depend on the formulation and route of administration. THC and CBD are subject to extensive first-pass hepatic metabolism and pharmacokinetic drug interactions, the latter via inhibition or induction of enzymes and transporters. This study was conducted to describe the pharmacokinetics of CBD, THC, and its metabolites following orobuccal administration, providing pivotal information to guide the clinical development program of a self-assembled micellized nanoparticle formulation containing 1:1 Δ9THC and CBD. Methods: Pharmacokinetic data was obtained from a phase 1, two-stage study in patients with advanced cancer, and modelled using a population pharmacokinetic approach. To provide an indication of predicted exposure with multiple dosing, the final population pharmacokinetic models were used to simulate concentration-time profiles for each of the active compounds. Results: The developed population pharmacokinetic models provided important information on the bioavailability of CBD and THC, with estimated values of 10% and 27%, respectively. These values were approximately two-fold greater than that which has been previously described for oromucosal formulations. Discussion: This enhanced bioavailability can most likely be attributed to the NanoCelle® technology. This technology provides evidence to support the application of this innovative drug delivery platform to overcome limitations associated with cannabinoid administration for therapeutic use.

Introduction: Medicinal cannabis (MC) has potential therapeutic effects in Tourette Syndrome (TS), however there has been limited research in adolescent patients. This pilot study aimed to investigate the feasibility of conducting a randomized placebo-controlled crossover trial of MC in adolescents with TS. Method: This was a phase I/II double-blind, cross-over pilot study comparing MC with matched placebo in adolescents aged 12-18 years with TS. The active medication was Δ9-tetrahydrocannabinol (THC) 10 mg/mL and CBD 15 mg/mL in peppermint-flavored medium-chain triglyceride oil. The dose titration schedule was stratified into two participant weight bands: below 50 kg (max THC 10 mg/day) or ≥50 kg (max THC 20 mg/day). Each treatment phase lasted 10 weeks, with a 4-week washout period. Results: Ten adolescents were randomized (mean age 14.8 years, 50% male) and seven completed the full study protocol. Two adolescents discontinued due to adverse events (one on MC, one placebo) and one was lost to follow-up. The most common adverse event was dizziness (67%). There were no serious adverse events. Among actively enrolled participants, protocol adherence was excellent: study visits 100%, blood test completions 100%, and online questionnaire completion 97.6%. Medication adherence was acceptable in 63.6%. Parents reported a high degree of study design acceptability. On the Clinical Global Impression-Improvement scale, three participants were rated as much improved on MC compared with one on placebo at 10 weeks. Discussion: The findings suggest that the study protocol is feasible and acceptable to patients with TS and their families. A fully powered study is needed to evaluate the efficacy of MC in adolescent TS.

Background: Hemp and cannabidiol (CBD) products are now widely available for purchase in the United States and in many international jurisdictions. However, these products are largely unregulated (with very few exceptions) and are widely available without restriction. This has created a market in which low-quality and contaminated products are commonplace. The aim of the current study was to analyze the cannabinoid content of 56 selected CBD gummy products. Methods: Gummy-based CBD products from national brands, available for purchase online, were obtained. Liquid chromatography-tandem mass spectrometry (LC-MS/MS) was used for cannabinoid analysis. Key outcome measures included: (1) concentration of CBD in each product, (2) accuracy of the product labeling regarding CBD concentration, and (3) concentration of Δ⁹-tetrahydrocannabinol (Δ⁹-THC) and other cannabinoids of interest (e.g., cannabidivarin and cannabinol) in each product. An exploratory analysis assessed within-product consistency of CBD and THC concentrations (e.g., variation in cannabinoid content from gummy to gummy within a single bottle). Results: The products contained a mean of 21.38 (±11.16) mg CBD per gummy (range: 5.70 - 59.99 mg). In total, 70% of the gummies contained CBD in a concentration that differed by >10% of the dose listed on the packaging. In total, 39% of the products contained Δ⁹-THC and concentrations were highly variable (range: 0.019-0.88 mg Δ⁹-THC/gummy); 9 products (16% of products tested) contained >0.4 mg Δ⁹-THC per gummy. Within-product analysis (n = 10 products) revealed high variability across gummies (coefficient of variation for CBD: 2.1 - 27.1%; Δ⁹-THC: 3.1 - 23.5%). Conclusions: As several studies have demonstrated, unregulated CBD product packaging is not an accurate indication of the product constituents. This study further confirms that CBD products do not have reliable CBD concentrations-both relative to the dose listed on the label and among individual gummies within the same bottle. These products also frequently contain Δ⁹-THC (and occasionally Δ⁸-THC), often unbeknownst to the consumer. The results of this study support the growing body of literature suggesting the necessity of CBD product regulation to ensure customer health and safety.