“Cannabidiol (CBD) has shown therapeutic potential for post-traumatic stress disorder (PTSD) by reducing spontaneous recovery (SR), yet the underlying mechanisms remain unclear.
We examined the effects of CBD on SR in male and female mice and found greater behavioral efficacy in males. To uncover the molecular basis of these effects, we performed transcriptomic profiling of the prelimbic (PL) and infralimbic (IL) subregions of the medial prefrontal cortex (mPFC).
We identified distinct and overlapping SR-associated gene sets in each subregion, and CBD shifted the expression of a significant subset of these genes toward non-stressed control levels, including genes involved in retrograde endocannabinoid signaling. Cross-species comparisons with human PTSD transcriptomic datasets revealed conserved gene alterations within each subregion, suggesting shared molecular signatures between mouse SR and human PTSD.
These findings highlight region-specific and conserved pathways through which CBD may exert therapeutic effects and provide mechanistic insight to advance CBD-based interventions for PTSD-associated spontaneous recovery.”
“Triple-negative breast cancer (TNBC) remains a major clinical challenge due to its aggressive nature and limited treatment options, while therapeutic resistance in estrogen receptor-positive (ER+) breast cancer continues to limit treatment efficacy.
Although olaparib is primarily effective in BRCA-mutated cancers, its activity in BRCA-wild type (BRCA-wt) tumors is limited. Therefore, this study aimed to investigate whether cannabidiol (CBD) can enhance the response of BRCA-wt breast cancer cells to PARP inhibition.
The effects of olaparib (OLAP) and CBD, alone and in combination, were evaluated in MDA-MB-231 (TNBC) and MCF-7 (ER+) cell lines using comprehensive two-dimensional (2D) mechanistic analyses and three-dimensional (3D) spheroid models, including HCC-70 cells to extend TNBC validation.
The results demonstrate that combined OLAP and CBD treatment enhanced cytotoxic effects compared to single treatments, with more pronounced responses observed in 3D spheroid models, particularly in TNBC models. Flow cytometry and caspase 3/7 assays indicated increased apoptosis and G2/M phase arrest following combination treatment. Gene expression analysis revealed downregulation of key DNA damage response and cell cycle-related genes (ATM, ATR, BRCA1/2, RAD51, and CDK1/2/4/6), supporting a role for cell cycle arrest and DNA damage modulation in mediating these effects. Functional assays showed reduced colony formation and migratory capacity, although these effects may reflect both cytotoxic and cytostatic responses under the selected experimental conditions.
Overall, these findings suggest that CBD may enhance the efficacy of olaparib in BRCA-wt breast cancer models and highlight its potential as a combinational therapeutic strategy in breast cancer treatment.”
“Cannabinoids have been reported to enhance the effects of conventional cancer treatments, including chemotherapy and radiotherapy, thereby improving therapeutic efficacy while potentially reducing treatment-related toxicity.”
“CBD, in particular, has shown promising antitumor activity in triple-negative breast cancer (TNBC) by inducing apoptosis, autophagy, and oxidative stress through modulation of signaling pathways such as AKT/mTOR.”
“Hypertension (HTN) results from intricate molecular mechanisms, making clinical remission difficult to achieve. This study explores the molecular pathways through which cannabidiol (CBD) may influence HTN.
Methods
Several RNA sequencing datasets related to HTN were retrieved from the GEO database and divided into training and validation sets. Candidate genes potentially associated with HTN were screened through differential expression analysis and weighted gene co-expression network analysis. The interactions and binding potential between CBD and key target proteins were then systematically investigated using bioinformatics, machine learning, immune cell infiltration analysis, and molecular dynamics simulation.
Result
Seventy genes were identified as potential targets for CBD intervention in HTN. Machine learning analysis refined this list to five core genes: pyruvate kinase PKM (PKM), thyroid hormone receptor beta (THRB), aldo–keto reductase family 1 member B1 (AKR1B1), TGF-beta receptor type-1 (TGFBR1), and proto-oncogene tyrosine-protein kinase Src (SRC). Among these, PKM, THRB, AKR1B1, and SRC were significantly upregulated in HTN, while TGFBR1 was downregulated (P < 0.05). These genes formed a regulatory network, showing direct or indirect interactions, and were associated with infiltration levels of neutrophils and resting mast cells. Molecular dynamics simulation revealed that CBD exhibits strong binding specificity to these target proteins.
Conclusion
This integrated analysis prioritized PKM, THRB, AKR1B1, TGFBR1, and SRC as candidate genes potentially associated with HTN progression. Molecular dynamics simulation suggested a favorable binding potential between CBD and these targets. These findings may provide supportive evidence for future studies exploring the potential mechanisms by which CBD may act in HTN.”
“Background: No studies have examined the differential and combined effects of prenatal alcohol and cannabis exposure (PAE/PCE) on longitudinal trajectories of adolescent cognitive development. Further, previous alcohol research is mixed, with some evidence for negative PAE effects on cognition and other studies reporting null or positive associations. This study examined associations between PAE, PCE, and growth trajectories of adolescent cognition in a large, diverse sample.
Methods: N = 11,029 adolescents from the Adolescent Brain Cognitive Development℠ Study completed the NIH Toolbox cognitive battery at baseline (Mage = 9.95), two-year follow-up (Mage = 11.95), and four-year follow-up (Mage = 14.07). Retrospective parent report of PAE and PCE was assessed at baseline. Univariate growth trajectories were estimated for cognitive measures: Pattern Comparison, Picture Sequence Memory, Oral Reading, Flanker Task, and Picture Vocabulary. Cross-product terms for PAE and PCE tested combined use.
Results: Most mothers reported no prenatal alcohol (n = 8257; 74%) or cannabis (n = 10,812; 94%) use. Overall, use was low: across pregnancy, women reporting any alcohol use averaged 33.31 drinks, and those reporting any cannabis use averaged 33.00 use occasions. Before including covariates, there were negative main effects of PCE and positive main effects of PAE on intercepts for all five cognitive domains. There was little evidence for PCE/PAE effects on slopes for cognition. After adding covariates, no negative effects of PCE remained. Small positive PAE effects on intercepts for multiple domains persisted. Cross-product terms for combined exposure were not significant.
Conclusions: Little evidence emerged for negative effects of low PAE, PCE, or combined exposure on adolescents’ cognitive development after accounting for sociodemographic factors. Light drinking in families with social features positively associated with cognitive ability may result in few negative consequences. This study is the first to demonstrate weak evidence for adverse differential and combined low-level PAE and PCE effects on the development of adolescent cognition.”
“Little evidence emerged for negative effects of low level prenatal alcohol, cannabis, or combined exposure on adolescents’ cognitive development after accounting for sociodemographic factors.”
“Avian infectious bronchitis virus (IBV), a gamma coronavirus, remains the predominant pathogen affecting poultry worldwide, posing a significant threat to the poultry industry.
Cannabidiol (CBD), the primary non-psychoactive constituent of Cannabis sativa, has demonstrated diverse pharmacological properties.
This study investigated the inhibitory effects of CBD against IBV infection both in vitro and in vivo. Chicken embryo kidney (CEK) cells infected with IBV were treated with CBD at various concentrations (2–20 µM).
Our results demonstrated that CBD significantly suppressed IBV replication in a dose-dependent manner without affecting cell viability. Furthermore, in SPF chickens, CBD treatment markedly alleviated clinical symptoms, reduced tracheal and renal histopathological lesions, and significantly decreased viral loads in tissues. Transcriptomic analysis of tracheal tissue suggested that CBD may inhibit IBV infection through modulation of immune-related signaling pathways, particularly the JAK-STAT pathway and interferon-stimulated gene expression.
These findings indicate that CBD represents a promising candidate for therapeutic intervention against IBV infection.”
“This review explores the molecular and cellular pathways of soft tissue wound healing and the potential therapeutic use of the non-psychotropic cannabinoid cannabidiol (CBD), integrating findings from in vitro and in vivo preclinical studies as well as completed and ongoing clinical trials.
It provides a comprehensive summary of the next steps in new CBD-based product development by analyzing current trends in dosage optimization, treatment guidance, delivery systems, ranging from liposomes, microemulsions to hydrogels. Additionally, the review examines clinical trials related to CBD formulations, delivery routes, and participant outcomes, offering a deeper understanding of the mechanisms guiding the activity beyond binding to cannabinoid 1 (CB1) and CB2 receptors. Furthermore, it highlights challenges and future perspectives in CBD formulation studies, presenting both currently studied approaches and emerging possibilities for innovation.
Therapeutic potential of CBD has proved itself in the recent years and only regulatory issues and clarity in treatment and delivery routes will limit its widespread use in soft tissue healing.”
“The therapeutic properties of Cannabis sativa have been recognized for over five millennia, with it use as a medical substance dating back to the Christian era in Central and Northeast Asia, particularly in India. However, despite its potential, this plant has undergone limited scientific exploration of its chemical and biological properties, and its medical use has remained restricted, particularly following its classification as a substance with no medical value under the United Nations Single Convention on Narcotic Drugs.”
“The historical use of cannabinoids in ancient medicine, coupled with modern preclinical investigations into their various components, unveils a broad spectrum of its potential clinical applications for soft tissue regeneration.”
“The unique therapeutic properties of CBD hold great promise for the treatment of different diseases and disorders, including alleviating pain associated with various soft tissue injuries or conditions, fibrosis, inflammation, and addressing muscle disorders.”
“Anxiety commonly co-occurs with childhood epilepsy, yet treatments targeting both are limited.
Epidiolex (cannabidiol, CBD) is an FDA-approved treatment for seizures associated with rare pediatric epilepsies and may have anxiolytic effects. We evaluated its effects on seizures and anxiety in pediatric patients with refractory epilepsy, representing diverse seizure etiologies and circulating endocannabinoids and related biomarkers.
Twelve participants (12.17 ± 5.17 years; 6 female) initiated Epidiolex for 4-6 weeks. Caregivers completed pre- and post-treatment seizure diaries; validated anxiety and quality-of-life assessments; and plasma endocannabinoids, related lipids, and CBD metabolites-including 7-hydroxycannabidiol (7-OH-CBD)-were measured.
Post-treatment, 73% of caregivers reported improvements in anxiety and seizure frequency with minimal side effects and improved sleep. Plasma 2-arachidonoylglycerol increased from baseline to study end, with greater elevations in those with lower baseline concentrations. Plasma 7-OH-CBD increased from baseline to study end, confirming systemic CBD exposure.
Epidiolex may provide anxiolytic benefits across pediatric epilepsy, potentially involving endocannabinoids.”
“HIV-1 transmission depends on the structure and immune cell composition of mucosal epithelia. Transmission mechanisms involve direct infection of CD4+ T-cells or macrophages, and indirect viral transfer to CD4+ T-cells from Langerhans cells (LCs) or dendritic cells (DCs). LCs-mediated HIV-1 transfer is inhibited by the neuropeptide calcitonin gene-related peptide (CGRP), due to upstream activation in LCs of the transient receptor potential vanilloid 1 (TRPV1) ion channel.
Herein, we investigated the potential anti-HIV-1roles of cannabidiol (CBD), the non-psychoactive compound in marijuana, which has well-described immunosuppressive functions and principally activates TRPV1 over its cognate CB1 and CB2 receptors.
We found that via TRPV1 activation, CBDinhibitsin-vitroinfection of mucosal HIV-1 cellular targets. Specifically, CBD inhibits macrophages HIV-1 direct infection, and CD4+ T-cells HIV-1 direct infection or upon viral transfer from LCsand DCs. Moreover, inhibition of macrophages infection and LCs-mediated HIV-1 transfer involves secreted CGRP.Importantly,
CBD also blocks early events of HIV-1 transmission ex-vivo in human inner foreskin tissues, namely formation of epidermal LC-T-cell conjugates and resulting CD4+ T-cells infection.
Altogether, CBD inhibits infection of all HIV-1 cellular targets, and commercial CBD products might be repositioned as novel HIV-1 pre-exposure prophylaxis, namely ‘CBD PrEP’.”
“Bases on our results, we propose an alternative that we coin as ‘CBD PrEP’. This would consist of the repositioning of commercially available CBD-containing products as novel microbicides for the purpose of clinical HIV-1 prevention.”
“People with HIV (PWH) are at an increased risk of venous thromboembolism (VTE), and cannabis use is common in this population. However, evidence of cannabis impact on VTE risk has been conflicting and not well evaluated in PWH.
Using data from five Centers for AIDS Research Network of Integrated Clinical Systems sites (2009-2020), we assessed the association between cannabis use and VTE risk.
Among 13,646 PWH, 30% reported current cannabis use. In adjusted Cox models, neither former (adjusted hazard ratio [aHR] 0.78, 95% confidence interval (CI) 0.57-1.07) nor current (aHR 0.74, 95% CI 0.51-1.06) cannabis use showed a significant increase in VTE incidence compared with never use. Additionally, no dose-dependent relationship was observed between cannabis use frequency and VTE.
Among PWH, cannabis use does not appear to be associated with an elevated risk of VTE.
Further research is needed to elucidate the relationship between cannabis and VTE risk in this population.”
“Background: Against the background of widely inconsistent data from randomized controlled trials (RCT), the use of cannabis-based medicines (CBM) from the perspective of patients with chronic non-cancer pain (CNCP) was described.
Methods: Based on a purposive/convenient sampling, patients were recruited from the Pain Clinic of Hannover Medical School who had been using CBM prescribed by a doctor for at least 6 months. The patients discussed their experiences with CBM in semi-structured individual interviews. The interview transcripts were coded and analyzed using a modified grounded theory approach with the help of MAXQDA®. In addition, the Treatment Satisfaction Questionnaire with Medication (TSQM) was used.
Results: Theoretical saturation was reached after 32 interviews. Open and selective coding revealed the overarching phenomenon of “subjective pain experience under CBM therapy”, with one of the main themes being the “effect of CBM”. This revealed the categories “effect on pain” and “psychological” and “somatic effect”. The most important concepts were “pain intensity”, “pain management”, “stress management”, “musculoskeletal system”, and “sleep quality.” Constructing a theoretical framework 4 groups of responses to CBM treatment were identified. The focus is either on (I) pain reduction, (II) pain coping, (III) reduced stress or (IV) multidimensional aspects. When this classification was applied to topic of quality of life (QOL), the greatest effectiveness and highest overall satisfaction were found in group (IV). Mixed methods showed a continuous increase in the perceived effectiveness of CBM on pain-centered complaints from group (I) to (IV).
Conclusions: In line with the biopsychosocial understanding of chronic pain, it appears that those CNCP patients who benefit most from CBM are those who show the most far-reaching effects on both a physical and psychological level. The pleiotropic effects of CBM may be responsible for this. Based on these results, interdisciplinary prospective research appears sensible and necessary to further and systematically investigate this clinically relevant topic.”
