Journal of cannabis research最新文献

Background: Poor sleep quality is a commonly reported reason for medical cannabis (MC) use, yet evidence regarding its long-term impact on sleep remains limited. This study evaluated changes in subjective sleep quality over a 12-month period among adults initiating MC treatment in Pennsylvania and explored whether preferred route of administration and referring condition were associated with observed changes.

Methods: A total of 137 adults newly referred for MC in PA completed the Pittsburgh Sleep Quality Index (PSQI) at baseline and at 3, 6, 9, and 12 months. Linear mixed effects models assessed changes in PSQI global and subscale scores over time. Additional models evaluated whether preferred administration route (oral vs. other) and referring condition (chronic pain, anxiety, PTSD) were associated with differences in observed outcomes.

Results: Global sleep quality scores, where higher values indicate poorer sleep quality, were significantly higher at baseline than at each follow-up point (p < .0001), with no significant differences among follow-up assessments, suggesting early and sustained improvements in self-reported sleep quality. Improvements were observed across all PSQI subscales. No significant relationships were found between sleep quality scores and either administration route or referring condition.

Conclusions: These findings suggest that MC may be associated with improvements in subjective sleep quality, though its impact did not vary as a function of administration route or primary referring condition. Additional research using objective sleep measures and controlled designs is needed to clarify MC's role in sleep quality.

Background: Cannabis use is on the rise yet the systematic molecular impact of key cannabinoid components on various tissues in diverse organisms remains incompletely understood. We aim to systematically elucidate the molecular pathways and networks affected by delta-9-tetrahydrocannabinol (THC) and cannabidiol (CBD) across species and tissue types.

Methods: We curated 105 THC- and CBD-related RNA sequencing (RNAseq) and microarray datasets from Gene Expression Omnibus (NCBI GEO) with a focus on mammalian species (human, non-human primate rhesus macaque, mouse, rat). Differentially expressed genes (DEGs) were identified using limma for microarrays and DESeq2 for RNAseq data, followed by a meta analysis to identify meta-DEGs. DEGs were analyzed for pathway enrichment using EnrichR, network regulation using Mergeomics key driver analysis, and disease associations using Mergeomics Marker Set Enrichment Analysis. Comparative analyses were conducted across compounds, datasets, species, and tissues.

Results: CBD datasets demonstrated more DEGs and enriched pathways across species and experimental conditions compared to THC. CBD datasets clustered more tightly by route of administration and species and were more frequently enriched for pathways related to zinc homeostasis, inflammation suppression, and cell cycle regulation. In contrast, THC signatures were more heterogeneous and did not exhibit consistent clustering, although consistently altered genes associated with antioxidant activity, neuronal myelination, synaptic signaling, and transcriptional regulation were identified across datasets. THC altered endocannabinoid signaling genes more often in brain tissues, while CBD affected this pathway more heavily in both central and peripheral tissues. Disease enrichment analyses revealed significant associations of CBD DEGs with lipid metabolism and body composition traits, while DEGs of both compounds showed links to neuropsychiatric disorders and type 2 diabetes.

Conclusions: THC and CBD demonstrated distinct and largely non-overlapping transcriptomic responses, with CBD showing more coherent molecular effects across datasets. Our results underscore the potential therapeutic relevance of CBD to metabolic and psychiatric regulation, highlight the context-dependency of THC's molecular actions, and offer molecular insights into the therapeutic and side effects of cannabinoids.

Background: Cannabidiol (CBD) is a non-psychoactive cannabinoid with potential therapeutic applications, including anti-inflammatory, analgesic, and anticancer effects. However, experts raised concerns about its potential to induce DNA damage and chromosomal aberrations at low concentrations. Notably, these studies used liver cell lines, which may not fully reflect the metabolic processing of CBD, potentially limiting the generalizability of their findings. This study investigated the short time effects of CBD on DNA double-strand breaks (DSBs) and proliferation in the human liver-derived cell line HepG2.

Methods: HepG2 cells were treated with CBD (5 - 50 [Formula: see text], 3 - 72h incubation). To investigate potential imbalances in the expression of cannabinoid receptors 1 and 2 (CB1 / CB2) within HepG2 cells, we examined their expression using Western blot analysis. We hypothesized that such an imbalance could be associated with pathogenic processes. Double-strand breaks were then detected (5 [Formula: see text] Etoposide (ETP) served as positive control) via indirect immunofluorescence analysis using γ H2AX and 53BP1 antibodies, followed by quantification of DSB foci.

Results: Expression of CB2 but not CB1 was downregulated by 30 % in HepG2 cells after exposure to 5 [Formula: see text] CBD (24h incubation; [Formula: see text]0.05) and 70 % downregulated after exposure to 50 [Formula: see text] CBD (24h incubation; [Formula: see text]0.01). This effect was dose-dependent. Whilst ETP induced dose dependent DSBs, we could not confirm findings by others that CBD significantly increases the number of γ H2AX and 53BP1 foci between 5 [Formula: see text] and 50 [Formula: see text] (3h incubation; [Formula: see text]0.05).

Conclusion: In our model, CBD stimulated the cells, as confirmed by modulation of CB2 expression as well as changes in intracellular cAMP. Our results show that CBD in ranges between 5 [Formula: see text] to 50 [Formula: see text] does not significantly increase the amount of DNA double strand breaks in HepG2 cells compared to the control. However, we did observe a significant reduction in cell proliferation and a significant increase in intracellular cAMP levels following CBD treatment.

Cannabis sativa L. containing < 0.3% delta-9 tetrahydrocannabinol (THC) is currently defined as hemp. Many different legal products in the United States now contain hemp and are marketed for their cannabinoid effects, as an alternative to tobacco products, or even as an aid for tobacco smoking cessation. The hemp cigarettes analyzed have similar designs to tobacco cigarettes with a filter and filler wrapped in paper. Cannabis sativa, like tobacco (Nicotiana tabacum), is a hyperaccumulator of metals. Currently, no publications have reported analyses of metals in these cigarette-like products. Hemp and cannabidiol (CBD) products are increasing in popularity. Thus, reporting the metal concentrations from a variety of hemp cigarette brands can help assess the potential for harmful exposures. We analyzed the hemp filler in 14 commercial brands for beryllium (Be), chromium (Cr), manganese (Mn), cobalt (Co), nickel (Ni), arsenic (As), cadmium (Cd), lead (Pb), and uranium (U) content.The hemp cigarette filler metals concentrations are compared to previously published metals levels in tobacco cigarette and little cigar filler. NIST Reference Material (RM) 8210 Hemp Plant was also analyzed to assess and confirm analytical accuracy. Of note, all hemp cigarette filler cadmium concentrations were below our lowest reportable level, and statistically lower than our previously published U.S. tobacco cigarettes and little cigars filler. The other metal concentration ranges were similar to previous tobacco cigarettes and little cigars results, although mean concentrations were statistically different in many cases. Different states have testing requirements with action limits for selected metals concentrations in Cannabis sativa L. Several hemp cigarette brands had chromium, nickel, arsenic, and lead concentrations that were above some state action limits.

Background: Harm reduction strategies encourage people who use cannabis to adopt lower-risk behaviors, such as refraining from daily or intensive use or limiting simultaneous use with other psychoactive substances. However, little is known about the characteristics of people who use cannabis but are at lower risk of cannabis use disorder (CUD). This study identified sociodemographic, lifestyle, and mental health factors associated with lower-risk cannabis use among adults in their mid-thirties.

Methods: Cross-sectional data from 731 adults in the Nicotine Dependence in Teens study were analyzed from the 2022-2023 data collection. Risk of CUD was assessed with the Cannabis Abuse Screening Test (CAST). Sociodemographic, mental health, lifestyle factors, and patterns of cannabis use were compared across participants who did not use cannabis, those with lower-risk cannabis use, and those at higher risk of CUD using cross-tabulations. Among participants who used cannabis, log-binomial regression models adjusted for age, sex, and education were fitted to identify factors associated with lower-risk cannabis use.

Results: Of 731 participants (mean [SD] age = 35.3 [0.6] years; 58% female), 44% reported past-year cannabis use, including 63% classified as lower risk and 37% at higher risk of CUD. Compared with other participants, those at higher risk of CUD were more often male and had lower levels of education. Several mental health indicators were less favorable among participants at higher risk of CUD, who also reported a higher prevalence of cigarette smoking. In multivariable models, being female and simultaneous cannabis and alcohol use were associated with a higher prevalence of lower-risk cannabis use, whereas higher frequency of cannabis use, simultaneous cannabis and tobacco use, cigarette smoking, and GAD-7 scores > 10 were associated with a lower prevalence.

Conclusion: Participants with lower-risk cannabis use resemble participants who do not use cannabis more than participants at higher risk of CUD. While use frequency is key, other factors, such as cigarette smoking, distinguish higher CUD risk from lower-risk cannabis use. Findings underscore the importance of harm reduction strategies and evidence-based education for cannabis-related policies.

Background: Since the passage of the 2018 US Farm Bill there has been a market for cannabinoid products derived from Cannabis sativa L. that contain < 0.3% delta-9 tetrahydrocannabinol (THC). Understanding the characteristics and motivations of cannabinoid product users is crucial for appropriate regulation of these products.

Methods: We conducted a cross-sectional survey of 1,523 adults 18 years or older using the probability-based Ipsos KnowledgePanel, representative of 97% of US households. We assessed lifetime use of cannabidiol (CBD), delta-8 THC, cannabinol (CBN), cannabigerol (CBG), and hexahydrocannabinol (HHC), as well as self-reported reasons for using these products (i.e., medical vs. recreational). Using multivariable logistic regression models, we investigated associations of demographic and health behavior characteristics with product use. Lastly, we used the Medical Dictionary for Regulatory Activities to code medical reasons for cannabinoid product use into system organ class and preferred term categories.

Results: Lifetime use of CBD was 35.2% (95% CI 32.7-37.9), compared with 7.7% (95% CI 6.5-9.1) for delta-8 THC, 4.5% (95% CI 3.7-5.6) for CBN, 1.3% (95% CI 0.9-1.9) for CBG, and 1.5% (95% CI 1.0-2.1) for HHC. More adults used CBD for medical purposes (71.9%, 95% CI 68.9-74.7) than recreation (47.1%, 95% CI 43.9-50.3), which was also the case for CBN, CBG and HHC. Conversely, more adults used delta-8 THC for recreation (76.1% 95% CI 67.0-83.3) than for medical reasons (50.9; 95% CI 42.6-59.2). The most cited preferred terms for CBD use were anxiety (14.7%, 95% CI 13.0-16.6), pain (13.1%, 95% CI 11.5-15.0) and arthralgia (11.2%, 95% CI 9.5-13.2), for delta-8 THC use they were anxiety (18.6%, 95% CI 13.3-25.3), pain (15.2%, 95% CI 11.1-20.5) and insomnia (10.7%, 95% CI 7.4-15.3), and for CBN use they were insomnia (15.4%, 95% CI 9.6-23.9), pain (11.1%, 95% CI 6.4-18.7) and anxiety (10.9%, 95% CI 6.0-19.0).

Conclusions: Use of cannabinoid products is appreciable, particularly CBD and delta-8 THC. Most adults use CBD, CBN, CBG, and HHC for medical reasons, but delta-8 THC for recreation. Pain, anxiety, insomnia and arthralgia were common medical reasons for use across the different cannabinoids assessed.

Background: Cannabidiol (CBD), a non-psychoactive cannabinoid increasingly used during pregnancy, has been proposed to modulate inflammatory processes. However, its effects on human placental immune functions remain poorly characterized. This study investigates the impact of CBD on lipopolysaccharide (LPS)-induced inflammation in human placenta explants and primary trophoblast cells, focusing on cytokine expression, receptor involvement, and underlying mechanisms.

Methods: Term placental explants and syncytiotrophoblast cells were exposed to LPS with or without CBD. Inflammatory cytokine levels were quantified by ELISA and RT-qPCR. Receptor involvement was assessed using selective antagonists for cannabinoid receptors type 1 and 2 (CB1 and CB2), and transient receptor potential cation channel subfamily V member 1 (TRPV1). NF-κB activation was evaluated by immunofluorescence, and caspase-1 activity was measured to explore inflammasome-related pathways.

Results: CBD significantly attenuated LPS-induced interleukin-1β (IL-1β), tumor necrosis factor alpha (TNF-α), interleukin 6 (IL-6), and interleukin 18 (IL-18) expression in a concentration-dependent manner, without inducing cytotoxicity. These effects were not reversed by CB1, CB2, or TRPV1 antagonists, indicating that other pathways are likely involved. CBD was associated with reduced NF-κB p65 nuclear translocation yet did not affect caspase-1 activity or transcript levels, indicating inflammasome-independent suppression.

Conclusion: CBD exerts anti-inflammatory effects in human placenta and trophoblasts, associated with reduced NF-κB p65 nuclear translocation and independent of CB1, CB2, and TRPV1 signaling, without evidence of canonical inflammasome activation. Given the placenta's role in fetal programming, these findings underscore the importance of evaluating CBD's developmental impact in the context of its growing perinatal use.