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Protective Role of CBD Against Nicotine Pouch-Induced Seizure Aggravation and Alterations in Brain Glymphatic Biomarkers

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“Introduction: Nicotine pouches are rapidly increasing in popularity, yet their long-term neurological consequences remain poorly understood. Emerging evidence suggests nicotine may influence seizure susceptibility and neuroimmune signaling, while cannabidiol (CBD) has demonstrated neuroprotective and anti-inflammatory effects. This study investigated the time-dependent impact of acute versus chronic oral nicotine exposure on seizure vulnerability, neuroinflammation, and glymphatic function, and evaluated whether inhaled CBD can reverse these pathological changes.

Methods: Mice were exposed to acute or 7-day chronic nicotine pouch prior to kainic acid-induced seizures. Seizure severity was scored using the Racine scale. Neuroinflammatory markers (IL-6, HMGB1), neuronal activation markers (BDNF, c-FOS), and AQP4 expression were quantified via flow cytometry, immunofluorescence, and Western blotting. Glymphatic function was assessed using cisterna magna injection of rhodamine dextran tracers. An ex vivo IL-6 modulation assay evaluated nicotine-induced cytokine production and CBD-mediated suppression, with or without IL-6 receptor blockade.

Results: Acute nicotine transiently reduced seizure severity, whereas chronic exposure significantly exacerbated seizures, elevated IL-6, HMGB1, BDNF, and c-FOS, and markedly downregulated AQP4. CSF tracer studies confirmed impaired glymphatic influx following chronic nicotine exposure. CBD inhalation effectively reversed seizure severity restored AQP4 expression, normalized IL-6 and HMGB1 levels, and reduced c-FOS protein expression. The IL-6R blockade assay showed that nicotine induces IL-6 production in brain-derived immune cells, while CBD suppresses this response upstream of IL-6 signaling.

Conclusions: Chronic nicotine pouch exposure promotes seizure susceptibility through converging neuroimmune and glymphatic disruptions. Inhaled CBD counteracts these effects, supporting its potential as a targeted therapeutic strategy for nicotine-associated neurological risk.”

https://pubmed.ncbi.nlm.nih.gov/41384771

https://academic.oup.com/ntr/advance-article-abstract/doi/10.1093/ntr/ntaf253/8377968?redirectedFrom=fulltext&login=false

Cannabis Use and Nicotine Vaping Cessation Outcomes: A Secondary Analysis of a Randomized Clinical Trial

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“Importance: Cannabis use is prevalent among adolescents and young adults who vape nicotine. It is not known if cannabis use affects nicotine vaping cessation success.

Objective: To assess whether baseline frequency of cannabis use or cannabis use disorder (CUD) symptom severity was associated with nicotine vaping cessation in a randomized clinical trial.

Design, setting, and participants: This secondary analysis of a randomized clinical trial with youth who vaped nicotine recruited at a single site in Massachusetts from June 2022 to May 2024. The trial included 3 groups receiving 12 weeks of varenicline treatment and placebo (both double-masked, paired with counseling), as well as single-masked referral to texting-app-based nicotine vaping cessation support (enhanced usual care [EUC]). Eligible participants were aged 16 to 25 years who reported vaping nicotine regularly and did not smoke tobacco.

Exposure: Baseline cannabis use was assessed via self-reported number of days of cannabis use per week and with Cannabis Use Disorder Identification Test (CUDIT) scores.

Main outcomes and measures: Biochemically verified 7-day point prevalence nicotine vaping abstinence at week 12. Logistic regression models estimated associations between baseline cannabis use and vaping abstinence. Interaction terms were evaluated to examine whether cannabis use moderated the effect of varenicline on nicotine abstinence.

Results: Among the 261 participants randomized to nicotine vaping cessation treatment (mean [SD] age, 21.5 [2.0] years; 139 female [53%]), 28% (73 participants) reported no past-month cannabis use, 38% (100 participants) reported using cannabis more than 0 and less than 4 d/wk, and 30% (78 participants) reported using cannabis 4 to 7 d/wk. Cannabis use frequency was not significantly associated with nicotine vaping cessation (eg, 4 to 7 d/wk use vs no use: adjusted odds ratio [aOR], 1.14; 95% CI, 0.51-2.57; overall P = .20). Nor did cannabis frequency modify the effect of varenicline (eg, abstinence varenicline vs placebo or EUC among those with 4 to 7 d/wk use: aOR, 8.47; 95% CI, 2.78-28.25; vs among those with no use: aOR, 5.60; 95% CI, 1.97-17.06; overall interaction P = .32). Findings were similar for CUD symptom severity.

Conclusions and relevance: Among adolescents and young adults attempting to reduce or stop nicotine vaping, baseline cannabis use was not associated with nicotine vaping abstinence. Varenicline proved helpful for nicotine vaping cessation regardless of cannabis use, indicating that co-use of cannabis may not represent a barrier to successful nicotine vaping cessation treatment.”

https://pubmed.ncbi.nlm.nih.gov/41385228

“Findings indicate that regular cannabis or alcohol use is not expected to diminish the effectiveness of offering varenicline for nicotine vaping cessation in youth.”

https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2842688

Design and Semisynthesis of Aminocannabinoids as Neurological Magic Shotguns

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“The design of neurological “magic shotguns” represents a modern approach toward the treatment of complex central nervous system disorders, and many natural products like cannabidiol possess distinct potential due to their unique polypharmacological profiles toward central nervous system targets.

Herein, we describe the computational design, semisynthesis, and preliminary biological screening of aminergic cannabidiol derivatives as neurological magic shotguns.

A small library of 22 aminergic cannabidiol derivatives were synthesized and evaluated through radioligand binding assays, revealing that these derivatives generally exhibit higher affinity toward serotonin, dopamine and sigma receptors than the parent compound.

Notably, compounds 8d and 8e displayed significantly improved affinity toward sigma-1 receptors (Ki = 4.8 nM and 8.3 nM, respectively). We then established the functional behavior of compound 8e in mouse primary hippocampal neurons through whole-cell patch clamp assays: exposure to compound 8e potentiates N-methyl-d-aspartate receptors, an effect that may be reversed in the presence of a selective sigma-1 receptor antagonist.

These results suggest that compound 8e behaves as an agonist of sigma-1 receptors, thereby promoting downstream potentiation of N-methyl-d-aspartate receptors.

Altogether, these findings provide preliminary evidence that aminergic cannabinoids, and potentially other derivatives of promiscuous natural products, may hold utility as neurological magic shotguns.”

https://pubmed.ncbi.nlm.nih.gov/41378694

https://pubs.acs.org/doi/10.1021/acs.jnatprod.5c01236

Spectroscopy-Based Evaluation of the Antioxidant Capacity of Hemp (Cannabis sativa)

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“In the present study, a comprehensive evaluation of the antioxidant properties of various parts of the hemp plant, specifically its leaves and flowers, in a new feminized variety of Cannabis sativa with an admixture of Cannabis ruderalis was investigated.

Methods such as Electron Paramagnetic Resonance (EPR) and UV-visible (UV-vis) spectroscopy were used to assess trolox equivalent antioxidant capacity (TEAC) and total polyphenol content (TPC). TEAC values of the analyzed samples ranged from 29.5 μmol TE/g DW to 150.2 μmol TE/g DW, while TPC varied between 5.4 mg GAE/g DW and 20.3 mg GAE/g DW.

The findings indicate that hemp exhibits significant antioxidant properties, especially in its leaves. This is attributed to a diverse range of antioxidants, including cannabinoids, flavonoids, and phenolic compounds, which offer notable health benefits.

Furthermore, the method of drying hemp has been shown to influence its antioxidant properties significantly. Research indicates that freeze-dried and air-dried hemp retains higher levels of antioxidant compounds compared to other drying methods. This suggests that selecting an appropriate drying technique is essential for preserving the bioactive compounds responsible for hemp’s antioxidant activity.”

https://pubmed.ncbi.nlm.nih.gov/41373841

“Cannabis plants, in general, owe their antioxidant capabilities to compounds like polyphenols, terpenes, and cannabinoids. Among these, delta-9-tetrahydrocannabinol (THC) and the nonpsychoactive cannabidiol (CBD) are the most recognized. Both THC and CBD exhibit antioxidant activities comparable to vitamins E and C, effectively scavenging free radicals, reducing metal ions, and counteracting oxidative stress.”

“The hemp plant, C. sativa, has emerged as a promising source of natural antioxidants, with various parts of the plant exhibiting diverse levels of antioxidant activity.”

“As global interest in hemp rises, a deeper understanding of its health benefits, particularly its antioxidant properties, will be essential for fully capitalizing on this plant. Research into its bioactive compounds could pave the way for innovative natural remedies and contribute to developing new products that support well-being.”

https://www.mdpi.com/1422-0067/26/23/11696

The Endocannabinoid System: Scientific Insight and Biblical Reflection

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“The endocannabinoid system (ECS) is typically associated with using cannabis or cannabinoids. However, the ECS is a complex regulatory network within the human body that plays a vital role in maintaining physiological homeostasis. The ECS can become dysregulated through various mechanisms.

This article describes the physiology of the ECS using a biblical worldview. Nurses who understand the causes of ECS dysfunction can help lead patients toward lifestyle habits that reflect God’s design for balance, resilience, and wholeness.”

https://pubmed.ncbi.nlm.nih.gov/41359460

“The endocannabinoid system (ECS) is a crucial regulatory network in the human body, often linked to cannabis use but primarily responsible for maintaining physiological balance. This article explores the ECS from a biblical perspective, emphasizing its role in health and homeostasis.

Dysregulation of the ECS can occur through various mechanisms, and nurses who grasp these causes can guide patients towards lifestyle choices that align with a holistic approach to health, reflecting a divine design for balance and resilience.

Understanding the ECS can empower healthcare professionals to support patients in achieving overall well-being.”

https://journals.lww.com/journalofchristiannursing/abstract/2026/01000/the_endocannabinoid_system__scientific_insight_and.11.aspx

“Natural and synthetic cannabinoids finely regulate the endogenous cannabinoid system.”

https://www.sciencedirect.com/science/article/pii/S1043661825004475

The History and Use of Medical Cannabis

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“Archaeological and historical evidence indicate that cannabis has been used for medicinal purposes for almost 5,000 years. Although cannabis once was valued for its therapeutic properties, shifting social norms and political influences led to its criminalization and widespread stigma. This article explores the historical trajectory of medical cannabis from early therapeutic uses to integration into Western medicine, subsequent prohibition, and cautious resurgence. Implications for Christian healthcare providers are discussed. Key historical milestones are noted along with a comprehensive view of cannabis’ evolving role in health and healing across cultures and centuries.”

https://pubmed.ncbi.nlm.nih.gov/41359459

“Cannabis has been used medicinally for nearly 5,000 years, but its acceptance has fluctuated due to changing social norms and political pressures. Initially valued for its therapeutic benefits, cannabis faced criminalization and stigma, impacting its use in Western medicine. This article traces the history of medical cannabis, highlighting key milestones from its early use to its prohibition and recent cautious re-emergence. It also examines the implications for Christian healthcare providers, offering a broad perspective on cannabis’ role in health and healing across different cultures and eras.”

https://journals.lww.com/journalofchristiannursing/abstract/2026/01000/the_history_and_use_of_medical_cannabis.10.aspx

Bioreactor-Based Suspension Cultures of Cannabis sativa for Enhanced Production of Anti-Inflammatory Cannabinoid Derivatives

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“Cannabis sativa synthesizes diverse cannabinoids with significant pharmacological value, but existing suspension cultures show low metabolite yields and limited scalability.

This study establishes bioreactor-based cell suspension system to enhance cannabinoid biosynthesis in C. sativa. Petiole explants cultured on MS medium with 4 mg/L BAP and 0.01 mg/L NAA produced 95.83 ± 0.74% friable callus. Suspension cultures accumulated 352.29 ± 3.90 g/L fresh biomass in 28 days, showing 22.4-fold increase upon scale-up in stirred-tank bioreactor.

Methanolic extracts (60 °C) showed strong anti-inflammatory activity, reducing TNF-α and IL-6 by 88.40 ± 0.87 and 92.03 ± 1.55% at 30 μg mL-1 without cytotoxicity. Metabolomic profiling identified putative cannabinoid derivatives, with THCA-C1 (0.05%) exhibiting highest binding affinity (-8.4 kcal/mol) to inflammatory targets based on docking and dynamics analyses.

Overall, these results provide the first evidence for scalable cannabinoid biosynthesis in bioreactor-grown C. sativa cell suspensions, underscoring their potential for sustainable production of anti-inflammatory therapeutics.”

https://pubmed.ncbi.nlm.nih.gov/41359809

https://pubs.acs.org/doi/10.1021/acs.jafc.5c10683


Evaluation of long-term safety profile of an EU-GMP certified Cannabis sativa L. strain in a naturally aging preclinical model

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“Aging is characterized in part by chronic, low-grade inflammation, a major driver of cognitive decline, metabolic imbalance and organ dysfunction. Despite its central role in age-related morbidity, pharmacological strategies with well-defined long-term safety profiles remain limited.

Phytocannabinoids have been proposed as modulators of neuroinflammatory and metabolic pathways, but their chronic safety during natural aging is poorly characterized.

Our team has previously reported the acute and 28-day repeated-dose toxicity profile of an EU-GMP certified Cannabis sativa L. strain (Cannabixir® Medium Flos). Here, we extend this work by assessing its long-term safety in a naturally aging preclinical model. Mature to older mice received chronic, intermittent administration of Cannabixir® Medium Flos (2.5, 5, and 10 mg/kg), defined as daily weekday dosing for 3 or 6 months. Clinical and histopathological evaluations were conducted with a focus on systemic and central nervous system safety.

Chronic administration was well tolerated across all doses and durations.

Body weight remained stable despite increased food intake. Respiratory quotient values were preserved and close to 1 across all groups. Histological analyses confirmed preserved neuronal and glial architecture with no evidence of central nervous system injury or other organ-level toxicity. Long-term, intermittent Cannabixir® Medium Flos administration was well tolerated in naturally aged mice, with no adverse effects on systemic physiology or central nervous system integrity.

Together with prior acute and sub-chronic toxicity data, these findings provide robust evidence supporting the long-term safety of EU-GMP certified Cannabis sativa L. strain in the context of aging.”

https://pubmed.ncbi.nlm.nih.gov/41357885

“Importantly, the endocannabinoid system itself undergoes profound remodeling with aging, including reduced endocannabinoid tone, altered receptor expression and impaired signaling efficiency, changes that correlate with increased vulnerability to inflammation, metabolic imbalance, and neurodegeneration. These age-related alterations highlight the importance of evaluating the long-term safety of cannabinoid-based interventions in naturally aging bodies.”

“These findings suggest the potential for phytocannabinoid-mediated neuroprotection via modulation of the endocannabinoid system, although the precise molecular pathways remain to be elucidated.”

https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2025.1716366/full

Evaluation of two different Cannabis sativa L. extracts as antioxidant and neuroprotective agents

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“Cannabis sativa L. is a plant that contains numerous chemically active compounds including cannabinoids such as trans-Δ-9-tetrahydrocannabinol (Δ9-THC) and cannabidiol (CBD), and flavone derivatives, such as luteolin-7-O-glucuronide and apigenin glucuronide.”

“These extracts could be a source of compounds with potential benefit on human health, especially related to neurodegenerative disorders.”

https://pubmed.ncbi.nlm.nih.gov/36176449

“In conclusion, this study provided new insights into the biological activities of two different extracts of C. sativa. It was revealed that these extracts constitute a valuable and interesting natural source of bioactive molecules with great antioxidant properties, potentially capable of preventing neurodegenerative diseases.”

https://www.frontiersin.org/articles/10.3389/fphar.2022.1009868/full

 

Characterization and antifungal properties against Botrytis cinerea of bacteria isolated from hemp seed oil

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“Botrytis cinerea is a pathogen infecting Cannabis sativa L. plants, causing economic losses, and can develop resistance to chemical fungicides, the use of which is restricted in cannabis production. Thus, developing biocontrol methods is imperative.

Seven bacterial strains were isolated from hemp seed oil, characterized, and examined for the potential to control a B. cinerea isolate from cannabis.

Three isolates, Bacillus mojavensis HOB3, Paenibacillus sp. HOB6 and Bacillus subtilis HOB7 exhibited significant inhibition of B. cinerea. These isolates were further evaluated for their biosurfactant activity using two liquid media, Lysogeny Broth (LB) and hydrocarbon-amended Bushnell and Haas (BH). The oil-spreading and drop-collapse assays revealed growth-medium-dependent variation in surface activity associated with biosurfactant presence. The BH cell-free extract (BH-CFE) of B. subtilis HOB7 showed the highest estimated biosurfactant presence and antifungal activity against B. cinerea, but both activities were absent when using the LB cell-free extract (LB-CFE) of B. subtilis HOB7.

Thus, a potential relationship between antifungal activity and biosurfactant production was suggested. Genome mining of the strains identified gene clusters encoding compounds with antifungal activity, including the biosurfactants polymyxin B, fusaricidin B, fengycin, and surfactin.

To our knowledge, this is the first report of the isolation of hemp seed oil bacteria with potential biocontrol properties against fungal phytopathogens.”

https://pubmed.ncbi.nlm.nih.gov/41349011

https://cdnsciencepub.com/doi/10.1139/cjm-2025-0241

“Polymyxin B, fusaricidin B, fengycin, and surfactin are all natural lipopeptides (or cyclic non-ribosomal peptides) produced by bacteria of the Paenibacillus and Bacillus genera. They act as biosurfactants and have various antimicrobial properties, particularly as antibiotics and fungicides.”