Monthly Archives: October 2025

Antiviral and Anti-inflammatory Effects of Cannabidiol in HIV/SIV Infection

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“Persistent reservoirs and chronic immune activation are hallmarks of HIV, despite the effectiveness of antiretroviral therapy (ART) in suppressing viral replication. Here, we use rhesus macaques and primary and induced pluripotent stem cell (iPSC)-derived human immune cells to evaluate the virologic and immunologic consequences of cannabidiol (CBD) exposure during HIV/SIV infection.

We show that CBD, in the absence of ART, suppresses viral replication and establishment of the viral reservoir to levels comparable with first-line therapies during acute SIV infection of rhesus macaques.

This antiviral effect of CBD extended to in vitro HIV infection of human macrophages, T cells, and microglia. Immunologically, we observe CBD slowed CD4+ T cell decline and polarization, decreased CD14+CD16+ monocyte expansion, and reduced interferon-inducible cytokine release in rhesus macaques. We identify comparable effects on cytokine production with in vitro CBD treatment of human macrophages, T cells, and microglia.

Importantly, we find CBD inhibits cytokines only when an immune response is elicited by HIV, suggesting it is not broadly immunosuppressive. Finally, we determine CBD regulates endocannabinoid receptors, modulators, and transporters and inhibits NF-κb and STAT1 activation when mediating its antiviral and anti-inflammatory effects.

These findings show beneficial effects of CBD in laboratory models of untreated HIV, thus placebo-controlled clinical trials to evaluate the safety and effectiveness of adjunctive CBD use with ART is warranted.”

https://pubmed.ncbi.nlm.nih.gov/41040324/

https://www.biorxiv.org/content/10.1101/2025.09.25.678534v1

Optimal Cannabinoid-Terpene Combination Ratios Suppress Mutagenicity of Gastric Reflux in Normal and Metaplastic Esophageal Cells

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“Background: Esophageal adenocarcinoma (EAC) frequently arises from chronic exposure to acid and bile reflux, with secondary bile acids, such as deoxycholic acid (DCA), contributing to its pathogenesis through mechanisms involving reactive oxygen species (ROS), oxidative DNA damage, and resistance to apoptosis. The human endocannabinoid system (ECS) regulates diverse anti-inflammatory, antioxidant, and analgesic pathways implicated in disease modulation. Despite its therapeutic promise, effective pharmacological activation of the ECS remains challenging.

Objectives: This study aimed to evaluate whether specific cannabinoid-terpene combinations targeting the ECS could attenuate the mutagenic and cytotoxic effects of bile acid-induced stress in esophageal cell models. Additionally, we assessed the clinical significance of ECS-related protein receptors in the progression of EAC.

Design: In vitro experimental models combined with clinical samples analyses.

Methods: We utilized in vitro models, including human esophageal epithelial cell lines exposed to DCA and a Barrett’s esophagus gastroesophageal reflux (GER) model subjected to low pH and a bile acid cocktail. Patient-derived samples were analyzed to investigate the clinical association of ECS pathway markers with EAC progression. Experimental models were treated with varying ratios of phyto-cannabinoids and terpenes. Endpoints included assessment of DNA damage, mitochondrial membrane potential, and ROS production to identify optimal compound combinations. Expression of ECS-related protein receptors was evaluated in clinical samples to elucidate their role in EAC development.

Results: A 1:5 ratio of cannabigerol (CBG) to Phytol (Phy) was found to significantly reduce DCA-induced DNA damage, preserve mitochondrial membrane potential, and decrease ROS levels. This combination also enhanced apoptosis in damaged cells and diminished mutagenicity. Analysis of patient samples revealed that the expression of the ECS-associated receptor protein CB1 correlated with EAC progression, suggesting a broader clinical role for ECS modulation in cancer prevention.

Conclusion: Modulation of the ECS through carefully selected cannabinoid-terpene ratios can mitigate bile acid-induced esophageal damage and may reduce carcinogenic progression. These findings support further in vivo investigations and raise the possibility of expanding cannabinoid-terpene therapeutics to other conditions involving similar pathogenic processes.”

https://pubmed.ncbi.nlm.nih.gov/41040236/

https://www.biorxiv.org/content/10.1101/2025.09.23.678062v1

No differences in neural responses or performance during cannabis cue-specific inhibitory control tasks between recreational cannabis users and non-users: Insights from fNIRS

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“Background: Impaired inhibitory control has been observed in regular cannabis users. Theories suggest that regular cannabis use is maintained by reward-driven behaviour, which may be underpinned by adaptations in neural reward and inhibitory control systems, thus increasing vulnerability to dependency.

Aims: This study investigated neural correlates of cannabis cue-specific inhibitory control in regular cannabis users and non-users using functional near-infrared spectroscopy (fNIRS).

Methods: Thirty regular cannabis users and thirty non-user controls completed two inhibitory control tasks (Go/No/Go and Stop-Signal Task), and a measure of attentional bias (Cannabis Stroop task). fNIRS recorded prefrontal and orbitofrontal haemodynamic responses (oxygenated haemoglobin and deoxygenated haemoglobin). Group comparisons and exploratory regressions examined cannabis use characteristics as predictors of behavioural and neural outcomes.

Results: No significant group differences were found in behavioural performance or haemodynamic activity across tasks. Exploratory regressions showed no significant associations between cannabis use characteristics and behavioural or neural outcomes after adjusting for covariates.

Conclusions: No evidence of impaired inhibitory control, attentional bias, or differences in prefrontal function were found in non-dependent cannabis users. Future studies should investigate whether such deficits emerge with heavier or dependent use.”

https://pubmed.ncbi.nlm.nih.gov/41037310/

“In summary, this study found no significant differences in behavioural performance or neural activation between regular cannabis users and non-user controls during cue-specific inhibitory control tasks.”

https://journals.sagepub.com/doi/10.1177/02698811251358814

Can cannabinoids alleviate behavioral symptoms in older adults with dementia? A systematic review

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“Background: Behavioral and psychological symptoms of dementia (BPSD) affect patients’ and caregivers’ well-being. Cannabinoids may offer a promising therapeutic option for managing BPSD.

Aims: This systematic review aims to explore the strengths of using this class of substances in the context of dementia care.

Methods: We conducted a comprehensive search across Embase Ovid, PubMed, Cochrane Library, APA PsycInfo, and Web of Science, identifying 1839 studies, with 14 selected for full review. Quality was assessed using the Newcastle-Ottawa and the modified Jadad Scales.

Results/outcomes: Ten studies (278 participants) were finally included. They showed cannabinoids helped reduce agitation and nocturnal disturbances.

Conclusions/interpretation: In conclusion, cannabinoids show promise in managing BPSD in dementia, with good tolerability and safety. Further studies could solidify these findings.”

https://pubmed.ncbi.nlm.nih.gov/41035223/

https://journals.sagepub.com/doi/10.1177/02698811251375895

New insights into the crosstalk between endocannabinoids and sphingosine-1-phosphate

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“This review aims at highlighting the interplay between the endocannabinoids (eCBs) anandamide and 2-arachidonoylglycerol, and sphingosine-1-phosphate (S1P) signaling. The eCBs and S1P are bioactive compounds that exemplify a paradigm of crosstalk among lipid signals, with profound implications for physiological processes and disease pathogenesis.

Cross-communication between eCBs and S1P occurs through multiple mechanisms: (i) receptor heterodimerization and co-regulation, (ii) mutual metabolic modulation, and (iii) integrated regulation of downstream effectors. The latter emerged as a key mechanism underlying the bidirectional interactions between eCBs and S1P, with functional overlaps that regulate several processes including inflammation, vascular function, and neuronal activity.

In addition, cannabis-derived compounds (such as cannabidiol) can influence eCBs and S1P signaling, calling for further research into their therapeutic exploitation.

Overall, the dynamic interplay between endogenous eCBs and S1P – as well as with exogenous cannabidiol – described here offers a compelling example of the complexity of interactions among bioactive lipids. A deeper mechanistic understanding of these relationships could pave the way to novel strategies in drug design and development, emphasizing the importance of integrated approaches in the study of bioactive lipid biochemistry.”

https://pubmed.ncbi.nlm.nih.gov/41033556/

“In conclusion, it seems apparent that eCB and S1P signaling pathways operate through interconnected networks of remarkable complexity. As yet, the biochemical crosstalk between these bioactive lipids remains incompletely understood, potentially limiting the therapeutic exploitation of these signals. Future strategies targeting the spatiotemporal dynamics of lipid transport – from intracellular trafficking to extracellular distribution – combined with selective receptor engagement, may unlock novel therapeutic opportunities that current approaches have not fully realized.”

https://www.jbc.org/article/S0021-9258(25)02633-X/fulltext

Preclinical assessment of pharmacokinetics and anticonvulsant activity of CBDTech, a novel orally administered cannabidiol (CBD) formulation for seizure and epilepsy

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“Oral cannabidiol (CBD) product use is increasing despite suboptimal pharmacokinetics (PK) of currently available formulations. This study aimed to investigate the PK of CBD formulated using the drug delivery technology DehydraTECH™, which is hypothesized to increase absorption by bypassing first-pass liver metabolism due to enhanced lipophilic composition.

Anticonvulsant activity of the leading formulation was investigated in the maximal electroshock seizure (MES) model. For the PK studies, Sprague Dawley rats were orally administered 25 mg/kg CBD in MCT oil or test formulations incorporating DehydraTECH™ (n = 10 per group). Plasma, brain tissue and urine and feces samples were collected to determine comparative absorption, distribution, and excretion by liquid chromatography with tandem mass spectrometry (LC-MS/MS). For the efficacy studies, a series of experiments was conducted using the lead formulation (CBDtech) from the PK trial. Effective dose (ED) of CBDtech in comparison to Epidiolex® (50-100 mg/kg), time of peak efficacy (TPE), and median ED (ED50) were assessed in the acute MES model. Clinical observations, presence/absence of hind limb extension (HLE), and maximum seizure severity (MSS) were recorded. No abnormal clinical signs were observed following dosing in any study. Area under the curve from dosing to the last measurable concentration (AUClast) was 391 to 2708% improved following treatment with DehydraTECH™ formulations as compared with the MCT control (all p < 0.01). CBD was detected in brain, urine, and feces samples following all DehydraTECH™ treatments.

Treatment with the ED of CBDtech (75 mg/kg) resulted in full protection (absence of HLE) in 66.6% of test subjects following MES test compared to 50% in the Epidiolex® group. The one-hour timepoint was determined to be the TPE for CBDtech; HLE was absent in 75% of animals and partial in 12.5% of animals. In comparison, in the Epidiolex® group HLE was absent in 50% of animals and partial in 12.5% of animals. The calculated ED50 was 75 mg/kg.

Formulation of CBD with DehydraTECH™ resulted in improved bioavailability and efficacy in an acute seizure model. These findings contribute to a deeper understanding of CBD PK and will aid in the design of more effective CBD-based therapeutic interventions.”

https://pubmed.ncbi.nlm.nih.gov/41029806/

“In summary, these data demonstrate the improved bioavailability and anticonvulsant activity of CBD using advanced formulations employing DehydraTECH™. These findings support the further investigation of novel CBD formulations, to improve the efficacy of lipophilic drug candidates, including CBD.”

https://jcannabisresearch.biomedcentral.com/articles/10.1186/s42238-025-00322-7

VER-01 Shows Enhanced Gastrointestinal Tolerability, Superior Pain Relief, and Improved Sleep Quality Compared to Opioids in Treating Chronic Low Back Pain: A Randomized Phase 3 Clinical Trial

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“Introduction: Chronic low back pain (CLBP) affects over half a billion people worldwide. Current pharmacologic treatments, comprising mainly non-steroidal anti-inflammatory drugs and opioids, offer limited efficacy and pose significant risks, warranting the development of tolerable, safe and effective alternatives.

Methods: This randomized controlled trial on adults with CLBP was designed to confirm the superior efficacy and gastrointestinal tolerability of VER-01, a novel, standardized full-spectrum extract from Cannabis sativa DKJ127 L., over opioids. Subjects were randomized (1:1) to receive VER-01 or a range of commercially available opioids. After a 3-week titration, subjects underwent 24 weeks of treatment, followed by 2 weeks of wash-out. The primary endpoint was the relative risk of constipation occurrence after 27 weeks treatment. Secondary endpoints included changes in pain and sleep scores, determined using an 11-point numeric rating scale (NRS), with key secondary endpoints defined for week 27.

Results: A total of 384 individuals were randomized to receive VER-01 (n = 192) or opioids (n = 192). Subjects receiving VER-01 were fourfold less likely to develop constipation than those receiving opioids (relative risk [RR] VER-01/opioids 0.25; 95% confidence interval [CI] 0.09-0.69; p = 0.007) and threefold less likely to use laxatives (RR 0.34; 95% CI 0.18-0.65; p < 0.001). Longitudinal analysis revealed that VER-01 was superior to opioids in terms of pain reduction over 6 months of treatment, although differences in secondary endpoints limited to week 27 alone were not significant. Throughout the 6 months of treatment, mean pain reduction was 2.50 NRS points with VER-01 versus 2.16 with opioids (mean difference [MD] 0.34; 95% CI 0.00-0.67; p = 0.048), and sleep improved by 2.52 points with VER-01 versus 2.07 with opioids (MD 0.45; 95% CI 0.11-0.79; p = 0.009). These benefits were particularly pronounced in participants with severe pain, with greater pain reduction (MD 0.58; 95% CI 0.01-1.15) and sleep improvement (MD 0.66, 95% CI 0.05-1.27) compared to opioids.

Conclusions: VER-01 demonstrated superiority over opioids in treating CLBP, both in terms of efficacy and gastrointestinal tolerability.”

https://pubmed.ncbi.nlm.nih.gov/41028525/

“In summary, this study provides robust evidence that VER-01 offers better tolerability, as well as superior pain relief and sleep quality compared to opioids in patients with CLBP. These findings highlight its potential as a promising new pharmacological option within a multimodal treatment approach that could fundamentally shift the paradigm in the treatment of chronic pain.”

https://link.springer.com/article/10.1007/s40122-025-00773-z