Journal of cannabis research最新文献

Cannabis sativa yields a wide range of bioactive compounds, including terpenes, flavonoids, and cannabinoids. Tetrahydrocannabinolic acid (THCA), cannabidiolic acid (CBDA), cannabigerolic acid (CBGA), and cannabichromenic acid (CBCA) are the acidic biosynthetic precursors of the neutral cannabinoids Δ9-tetrahydrocannabinol (THC) and cannabidiol (CBD), which have been the subject of much research. This review examines the biosynthesis, decarboxylation, molecular pharmacology, and therapeutic significance of acidic cannabinoids, intending to address a significant knowledge gap. Peer-reviewed literature from major scientific databases was used in a systematic narrative review with an emphasis on investigations of acidic cannabinoid chemistry, pharmacology, pharmacokinetics, and disease-specific applications. According to the reviewed data, acidic cannabinoids exhibit unique biological activities that distinguish them from their neutral counterparts. These include neuroprotective, anti-inflammatory, anticonvulsant, and anti-proliferative actions, which are mediated by molecular targets such as serotonin 5-HT1A receptors, cyclooxygenase-2 (COX-2), transient receptor potential (TRP) channels, and peroxisome proliferator-activated receptor-γ (PPARγ). Acidic cannabinoids are more appealing for therapeutic usage in children and the elderly, considering that they are not intoxicating like THC; however, this distinction applies primarily to non‑heated consumption. Chemical instability, low bioavailability, and a dearth of controlled human trials impede clinical translation despite their potential. According to the findings, acidic cannabinoids are an underutilized yet potentially valuable class of precision medicines. In this study, we outline existing understanding on acidic cannabinoids, discuss their production and transformation, and identify research needs that could influence cannabis science research.

Background: Synthetic cannabinoids (SC) are created as alternatives to delta-9-tetrahydrocannabinol (∆⁹-THC) and can cause serious side effects like hallucinations and death. The DEA has identified eleven concerning synthetic cannabinoids: ADB-BUTINACA, ADB-HEXINACA, ADB-4en-PINACA, ADB-FUBIATA, 4F-MDMB-BICA, 4F-ABUTINACA, FUB-144, FUB-AKB-48, 5F-EMB-PICA, 5Cl-AKB-48, and MDA-19. These compounds were tested in rodent models to evaluate their effects on locomotion, discrimination, and potency relative to ∆⁹-THC.

Methods: The eleven SC were tested for locomotor activity in Swiss-Webster mice and drug discrimination (DD) in Sprague-Dawley rats trained to discriminate ∆⁹ THC.

Results: In tests for locomotor depression, all the test compounds were more potent than ∆⁹-THC (ED₅₀ = 3.3 mg/kg) except for FUB-144, 5Cl-AKB-48, and ADB-FUBIATA (ED₅₀ > 6.1 mg/kg), which produced weak locomotor depressant effects. Similarly, in the DD assay, most compounds substituted fully with greater potency t than ∆⁹ -THC (ED₅₀ = 0.55 mg/kg) except for FUB-144 (ED₅₀ = 1.44 mg/kg), and 5Cl-AKB-48 (ED₅₀ = 3.21 mg/kg). ADB-FUBIATA and MDA-19 tested in doses up to 100 mg/kg, failed to fully substitute for the discriminative stimulus of ∆⁹-THC.

Conclusion: In summary, slight structural differences led to shifts in behavioral pharmacology outcomes in rodent models, which helped predict their potency relative to ∆⁹-THC. Therefore, future research on emerging SCs, along with structure-activity relationships at the receptor level, should include behavioral pharmacology testing of SCs to better predict their abuse potential and toxicity.

Support: Supported by NIDA contract N01DA-18-8936; N01DA-23-8936.

Background: Cannabidiol (CBD), a phytocannabinoid produced by Cannabis sativa, is widely consumed and interacts with components of the endocannabinoid system, including enzymes and receptors, through indirect and complex mechanisms. However, how CBD influences endogenous cannabinoids such as anandamide (AEA), and related N-acylethanolamines like N-palmitoylethanolamine (PEA) and N-oleoylethanolamine (OEA), remains poorly understood. This study investigates the acute impact of marketed CBD doses on the plasmatic levels of these signaling lipids in occasional cannabis users, addressing a critical gap in understanding the biological effects of low-dose CBD in non-therapeutic contexts.

Methods: In a triple-blind, placebo-controlled, randomized crossover trial, 70 healthy volunteers received ten sequences of four oral CBD doses (20, 50, 100, 200 mg) and placebo. Blood was sampled at baseline and five timepoints post-dose. Plasma AEA, PEA, and OEA were quantified by LC-MS, and dose-response assessed with linear mixed-effects models on plasma concentrations (model 1) and Area Under the Curve to increase (AUCi, model 2), including participant ID (nested in sequence) as random effect, and visit, sequence, sex, and baseline levels as fixed effects.

Results: Model 2 revealed a significant effect of CBD dose on AUCi of PEA and OEA, but not AEA. Pairwise comparisons showed that placebo was associated with significantly higher AUCi values than the 50 mg dose (p < 0.05; moderate effect sizes), and trended higher than the 200 mg dose (p < 0.10; small-to-moderate effect sizes). No differences were observed for other dose contrasts. Importantly, sex emerged as a significant factor: sub-group analyses indicated that these reductions in AUCi were driven by female participants, with lower PEA and OEA exposure confirmed at both 50 mg and 200 mg (only PEA) compared to placebo. No corresponding effects were observed in males. All plasma levels decreased overall throughout each visit, at every dose of CBD and placebo.

Conclusions: This study revealed that among healthy adults who consume cannabis occasionally, low-dose oral CBD formulations were able to significantly decrease the cumulative plasma levels of PEA and OEA in a female-specific fashion, confirming the importance of sex-differences in cannabinoid response, and emphasizing the relevance of a personalized approach to cannabis consumption and its effects, as well as public health messaging.

Trial registration: (ClinicalTrials.gov, registration: NCT05407285, Registration date: 2022-06-02).

Background: Cannabis supply methods vary depending on the country, legislation, availability, and population characteristics. In many countries, cannabis consumption remains illegal and poses a major public health concern. Therefore, it is essential to study the factors associated with cannabis supply.

Methods: Data were obtained from the 2017 French ESCAPAD and Health Barometer surveys (HBS). ESCAPAD is a national cross-sectional survey representative of 17-year-olds, while the HBS is a national cross-sectional telephone survey representative of French individuals aged 18-64. To ensure representativeness, data were weighted, and missing data were imputed. Three cannabis supply methods used in the past year were available in both databases and were analyzed using multivariate multinomial logistic regressions: (a) obtained for free; (b) bought from friends, relatives, or dealers; (c) home cultivation.

Results: The study included 2,943 17-years-old and 1,221 adults who reported using at least one of the analyzed methods to obtain cannabis. The majority had purchased cannabis (60% in ESCAPAD and 68% in HBS), while 33% and 24%, respectively, obtained it free, and only 5% and 8% had cultivated it. Among both 17-year-olds and adults, compared with obtaining cannabis for free, being male and experiencing problematic cannabis use were associated with buying or cultivating cannabis. Among 17-year-olds, being an apprentice was associated with a higher likelihood of cultivation, while earning money in the past 30 days and experiencing depression were associated with buying cannabis. Early experimentation with cannabis was associated with both supply methods among adolescents. Among adults, the 26-34 age group was associated with both buying and cultivating, while having less than a high school diploma was associated only with purchasing.

Conclusion: Cannabis supply methods are similar between minors and adults, with buying from friends, relatives, or dealers being the most common source. This study identifies vulnerable people who use cannabis and their acquisition practices, providing valuable insights for public policies.

Background: Cannabinoids have proven to useful for attenuating adverse effects of HIV. People living with HIV use cannabis at higher rates, with evidence suggesting it alleviates physiological symptoms such as nausea, loss of appetite, etc.. Cannabis can alter physiology as well as essential behavioral functions such as motivation. This study investigated the effect of delta-9-tetrahydrocannabinol (THC), the main psychoactive component of cannabis, on physiological responses and motivation in HIV-1 transgenic (tg) rats and their controls.

Methods: In Experiment 1, adult female and male HIV-1tg (n = 46) rats and their controls (wildtype littermates [WT] and Fischer344 [F344] rats; n = 87) were tested for acute THC-induced (0, 0.3, 3 mg/kg) physiological effects using the cannabinoid tetrad assay: 1) nociception, 2) body temperature, and 3) locomotor and exploratory behavior. In Experiment 2, adult female and male HIV-1tg (n = 58) rats and controls (n = 84) were tested in the Progressive Ratio Breakpoint Task (PRBT) to assess effortful motivation at baseline, after acute THC, then chronic (16 days) THC treatment (0, 0.3, 3 mg/kg). Data collected was analyzed using separate univariate ANOVA test with group (HIV-1tg, WT, F344), drug (0, 0.3, 3 mg/kg THC) and sex (female and male) as fixed factors. Bonferroni adjustments were used to correct for multiple comparisons.

Results: THC (3 mg/kg) reduced nociception, temperature, and locomotor and exploratory activity across genotypes with some sex-dependent effects. Further, HIV-1tg and WT rats showed reduced motivation compared to F344 controls across PRBT testing timepoints. Acute 3 mg/kg THC reduced breakpoints but with no effects after chronic treatment.

Conclusion: Hence, THC produces consistent physiological and motivational across HIV-1tg rats and their controls. Additionally, the HIV-1tg rat exhibited motivational deficits only when compared to the F344 but not WT controls, suggesting careful selections of control groups in future studies.

Background: Depression, anxiety, and cannabis use are growing, interconnected primary care concerns, but remain understudied due few health systems conducting systematic cannabis use screening. This study examines cannabis use and risk of cannabis use disorder (CUD) among primary care patients, comparing outcomes by depression and anxiety diagnoses and psychotropic prescriptions.

Methods: We assessed past three-month cannabis use, reasons for use, and risk of CUD among 170,032 adult primary care patients at a large health system in Los Angeles, CA under a routine screening protocol using the validated, self-administered ASSIST survey. This survey was embedded in the electronic health record (EHR), where data on ICD-10 diagnostic codes for depressive and anxiety disorders, psychotropic prescriptions, and demographics were collected. Logistic regression analysis assessed the association of depression and anxiety diagnoses on risk of CUD.

Results: Median age was 48 years (IQR 35-61), 57.8% were female, and 17.5% reported cannabis use. 24.0% had anxiety diagnoses and 9.0% had depression diagnoses. Cannabis use was higher among patients diagnosed with depression or anxiety than other patients (21.7%-27.4% vs. 15.5%, p < 0.001). Most patients who reported cannabis use and had depression or anxiety diagnoses reported using cannabis to manage emotional symptoms (62.5%-71.3%); notably, 47.3% of these patients had current antidepressant or anxiolytic prescriptions. Moderate-to-high risk of CUD was elevated among patients who reported cannabis use diagnosed with depression (9.8%), anxiety (8.0%), and particularly depression and anxiety (12.9%) (other patients = 4.9%; p < 0.001). After adjusting for age, sex, race and ethnicity, sexuality (LGB + versus heterosexual), employment, and Charlson Comorbidity Index, depression and anxiety diagnoses were associated with elevated risk of CUD [aOR 1.99 (95% CI 1.78-2.23); aOR 1.6 (95% CI 1.51-1.69), respectively], with the highest association among patients with both diagnoses [aOR 2.58 (95% CI 2.34-2.83)].

Conclusions: Clinical depression and anxiety diagnoses were associated with elevated cannabis use prevalence and risk of CUD. Many primary care patients reported using cannabis to manage mental health-related symptoms, even when prescribed psychotropic medications. These findings highlight the need for providers to assess and address cannabis use and potential CUD among primary care patients, especially those diagnosed with depression or anxiety.

Trial registration: Clinical trial number: not applicable.