Monthly Archives: April 2026

Elucidating the putative role of cannabigerol: a hypothesis-generating review of neuroinflammatory and neuroprotective mechanisms with implications for drug-resistant epilepsy

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“Drug-resistant epilepsy (DRE) affects approximately 30% of individuals with epilepsy and remains a major clinical challenge despite the availability of multiple antiseizure medications (ASMs). Beyond recurrent seizures, accumulating evidence implicates chronic neuroinflammation, blood-brain barrier (BBB) dysfunction, excitotoxic injury, and progressive neurodegeneration as processes associated with epileptogenesis and disease progression.

While cannabidiol (CBD) has demonstrated clinical efficacy in specific DRE syndromes, increasing recognition of these mechanisms has motivated interest in exploratory, mechanism-oriented approaches that extend beyond direct seizure suppression.

Cannabigerol (CBG) is a non-psychoactive phytocannabinoid with a pleiotropic pharmacological profile, interacting with cannabinoid receptors, transient receptor potential (TRP) channels, nuclear receptors such as peroxisome proliferator-activated receptor gamma (PPARγ), and additional neuromodulatory targets.

Preclinical studies indicate that CBG can modulate inflammatory, oxidative, and cell-survival pathways across diverse experimental models of neuroinflammatory and neurodegenerative injury. Importantly, most available evidence derives from non-epilepsy paradigms or in vitro systems, and direct support for antiseizure efficacy or disease modification in epilepsy remains limited.

This review synthesizes current preclinical evidence on the molecular targets and mechanistic actions of CBG, with particular emphasis on neuroimmune modulation and neuronal vulnerability, while critically addressing the limitations and translational gaps of the existing literature. Rather than providing confirmatory evidence, this work is intended as a hypothesis-generating framework to inform future epilepsy-focused studies evaluating whether modulation of neuroinflammatory and neurodegenerative pathways by CBG may hold relevance within disease-modifying research strategies for DRE.”

https://pubmed.ncbi.nlm.nih.gov/41919226

“Recent preclinical research has highlighted CBG as a multi-target phytocannabinoid capable of modulating neuroinflammatory, oxidative, and cell-survival pathways across diverse experimental systems.”

https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2026.1755956/full

Cannabidiol and pBDNF Cotreatment Attenuates Pathological Symptoms and Improves Cognition in 3 month-Old 5XFAD Mice

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“The marginal efficiency observed with the existing therapies in Alzheimer’s Disease (AD) can be attributed to the timing of the treatment. The beneficiaries of symptomatic or disease-modifying therapy for AD are mild-cognitive-impairment (MCI) or late-stage dementia patients. At this stage, the pathological features are already advanced and irreversible, as the shift in biomarker levels starts in a continuum 15-20 years prior. Early intervention, therefore, is a plausible solution to this issue. Consequently, we selected 3 month-old 5XFAD AD mice as an early intervention model.

We administered cannabidiol (CBD) and plasmid brain-derived neurotrophic factor (BDNF) encapsulated in liposome nanoparticles, functionalized with penetratin and mannose for brain-targeting, as a therapy.

Neuroinflammation is emerging as a key driver of AD progression by its interaction with amyloid plaques and phosphorylated tau. Therefore, CBD, which is anti-inflammatory and neuroprotective, was used.

BDNF, a synaptic modulation and cognitive maintenance agent, is declined and, thus, aggravates pathology and cognition in AD. BDNF expressed from the liposome nanoparticles supplements the reduced BDNF and aids in ameliorating AD pathology.

We found four weekly doses of our formulation reduced the amyloid burden by 3.04-fold (p-value < 0.0001), declined pro-inflammatory cytokines TNF-α by 2.51-fold (p-value < 0.0001), IL-1β by 2.34-fold (p-value < 0.0001) and microglial activation by 2.15-fold (p-value < 0.0001) than saline controls. In addition, it increased the synaptic markers level and promoted adult hippocampal neurogenesis, eventually improving cognitive functions.

These findings suggest the use of CBD and pBDNF has a potential therapeutic combination for AD management if intervened early.”

https://pubmed.ncbi.nlm.nih.gov/41924980

https://pubs.acs.org/doi/10.1021/acschemneuro.5c01009

Cannabidiol as a Modulator of the Gut-Liver Axis: Clinical and Pharmacological Insights into Hepatic and Metabolic Disorder Therapies

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“A non-intoxicating substance produced from Cannabis sativa, cannabidiol (CBD) has shown promise as a treatment for metabolic and hepatic diseases, primarily due to its capacity to alter the gut-liver axis.

A vital bidirectional communication pathway, the gut-liver axis is where substances produced from the liver affect gut homeostasis and gut-derived microbial products and metabolites influence liver health. Conditions including alcoholic liver disease (ALD), metabolic syndrome, and non-alcoholic fatty liver disease (NAFLD) are mostly caused by dysregulation of this axis.

According to preclinical research, CBD has hepatopro-tective benefits via improving the integrity of the gut barrier, decreasing intestinal permea-bility, altering the gut microbiota, and suppressing inflammatory signaling pathways such NF-κB and NLRP3 inflammasome activation. Furthermore, CBD improves insulin sensitivi-ty and lowers hepatic steatosis via modifying lipid and glucose metabolism via the PPARγ and CB1/CB2 receptor pathways. Its antioxidant qualities also help to lessen cellular dam-age and oxidative stress in hepatic tissues.

Despite these encouraging results, there is still inconsistency in the clinical data because of variations in dosage, formulation, administra-tion method, and patient-specific variables including liver function and microbiota makeup. Furthermore, broad therapeutic usage is restricted by issues with hepatic metabolism, pos-sible drug-drug interactions, and regulatory obstacles.

This review highlights information gaps, critically assesses the available preclinical and clinical evidence, and investigates the mechanisms underlying CBD’s impact on the gut-liver axis. Additionally, it identifies po-tential avenues for future optimization of CBD-based therapies targeting liver and metabol-ic illnesses through personalized medicine, sophisticated delivery methods, and standard-ized clinical trial procedures.”

https://pubmed.ncbi.nlm.nih.gov/41935387

https://www.eurekaselect.com/article/154488


Safety and Tolerability of Low-Dose Full-Spectrum Cannabidiol in Long-Term Virally Suppressed Adults with HIV: A Randomized Double-Blind Placebo-Controlled Trial

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“Introduction: People with long-term virologically suppressed HIV (PWH) experience chronic inflammation. Beneficial effects such as lower levels of inflammation were reported for cannabis-based medicine, but data on the safety of standardized low-dose full-spectrum cannabidiol (CBD) are limited.

Methods: This double-blind randomized placebo-controlled trial (NCT05306249) included 80 ART-treated PWH with undetectable viremia (median time on efficient ART 14 years, median age 54 years), encompassing 30% women. Participants received 1 mg/kg CBD oil twice daily (full-spectrum, tetrahydrocannabinol < 0.3%) or placebo for 12 weeks plus a 4-week follow-up. Primary trial end-point (autophagy gene expression) will be described elsewhere; here we evaluate the treatment impact on prespecified safety outcomes such as hemodynamic with electrocardiograms, HIV immunovirological parameters, and comprehensive assessments of liver and kidney functions, performed using standard blood tests. Mixed-effects models adjusted for baseline age, sex, body mass index, CD4 count and duration of viral suppression assessed longitudinal changes.

Results: Of 80 randomized participants, 35 PWH in CBD and 37 in placebo groups completed week 12. No clinically meaningful differences emerged in creatinine, aminotransferases (alanine aminotransferase, aspartate aminotransferase), or conjugated bilirubin. Total bilirubin decreased in the CBD arm vs placebo (mixed effect model considering time, group and time*group, adjusted for covariates, p = 0.046). In exploratory sex-stratified analysis, a significant difference starting at week 12 (-8.0 bpm [95% CI: -15.6; -0.4], p = 0.0425) and persisting at week 16 (-7.9 bpm [95% CI: -14.6; -1.3], p = 0.0191) evidences a lower heart rate in men belonging to the CBD group compared with the placebo group; no change in females. There was no change in plasma viral load, cell-associated HIV-DNA levels, and CD4/CD8 ratio.

Discussion: Low-dose full-spectrum GMP-certified CBD was well tolerated over 12 weeks in virally suppressed people with HIV. Observed reductions in total bilirubin and male heart rate are exploratory and warrant confirmation in adequately powered trials incorporating inflammatory biomarkers and pharmacokinetics.”

https://pubmed.ncbi.nlm.nih.gov/41934259

https://journals.sagepub.com/doi/10.1177/25785125261439014