Author Archives: David Worrell

Potential Antimicrobial Use of Cannabidiol in Dentistry: A Scoping Review

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“Background/Objectives: The use of cannabidiol (CBD) as an antimicrobial and antifungal agent has gained interest in medicine, with studies suggesting potential against various microorganisms. However, its effectiveness against oral pathogens remains underexplored in dental research, highlighting the need for further studies. This scoping review summarizes current evidence on the antimicrobial properties of CBD in dental and oral health. 

Methods: A systematic search was conducted across seven databases (PubMed, the Cochrane Library, Scopus, Embase, Web of Science, SciELO, and LILACS) up to January 2025. The inclusion criteria encompassed studies that explored the effects of CBD on oral microbiology (in vitro and in vivo in animal models), regardless of language or year of publication. The gray literature was evaluated in the Google Scholar database. 

Results: A total of 1284 articles were identified, of which 10 met the inclusion criteria for this scoping review. These studies, published between 2019 and 2025, primarily focused on bacterial and fungal cultures. The most commonly used methods were the minimum inhibitory concentration test and counting colony-forming units. The contact methods between CBD and bacterial/fungal cell cultures were either dilution or direct contact. 

Conclusions: CBD shows promising antimicrobial properties against a range of oral bacteria and fungi, suggesting its potential application in managing oral health conditions.”

https://pubmed.ncbi.nlm.nih.gov/41294500

“The current knowledge regarding the microbiological properties of CBD indicates its antimicrobial potential against oral microorganisms such as P. gingivalis, S. mutans, and C. albicans. Several studies have evaluated CBD antimicrobial effects through assays such as the MIC test and bacterial growth assays, with varying concentrations and formulations. These studies suggest that CBD can inhibit microbial growth, though its effectiveness varies according to CBD concentration, microbial strain, and the delivery system.”

https://www.mdpi.com/2304-6767/13/11/519

CBD Disrupts Malme-3M Cell Metabolism via Glycolytic Shift and Redox Imbalance

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“Background: Accumulating evidence suggests that cannabidiol (CBD) exerts variable effects on cancer cells that influence cellular activity, including growth. While anecdotal evidence abounds, mechanistic studies have lagged.

Methods: Malme-3M cells derived from melanoma and less-aggressive BJ fibroblast cells were incubated with CBD. CE-MS mass spectroscopy was used to measure metabolite changes resulting from CBD treatment.

Results: Data indicate a differential response between malignant Malme-3M cells and BJ fibroblasts with respect to metabolites critical for primary metabolic function. A significant reduction in TCA metabolites is seen with a corresponding increase in glycolytic output in the Malme-3M cell line. A similar reduction in TCA activity in BJ fibroblasts appears to differentially activate fatty acid oxidation. ATP is significantly reduced in the Malme-3M cells with a corresponding decrease in metabolites associated with redox maintenance.

Conclusions: This is the first metabolomics analyses of malignant Malme-3M cells and less-aggressive BJ fibroblasts after pre-treatment with CBD. The data suggest that the CBD-induced metabolic perturbation could reprogram cellular metabolism and affect ATP production and redox maintenance of the more-aggressive Malme-3M cells.”

https://pubmed.ncbi.nlm.nih.gov/41296432

“For the first time, an analysis of metabolomics of both less-aggressive BJ fibroblasts and malignant Malme-3M cells after pre-treatment with CBD has been made. As a result of CBD treatment, there is reprogramming of key metabolic processes including the TCA cycle, redox maintenance, and fatty acid oxidation. While more studies are needed to fully elucidate the mechanistic effects of CBD treatment, there is a clear and differential cellular metabolic consequence of CBD treatment between these cell types.”

https://www.mdpi.com/1467-3045/47/11/928

“This title means that the compound cannabidiol (CBD) disrupts the metabolism of Malme-3M cancer cells by forcing them to switch from their normal energy-producing processes to a more primitive, less efficient one called glycolysis, and by throwing off their cellular “redox” balance (a state of chemical reactions that are key to maintaining cell health). This metabolic disruption is a mechanism through which CBD may have anti-cancer effects.”

Tetrahydrocannabinols: potential cannabimimetic agents for cancer therapy

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“Tetrahydrocannabinols (THCs) antagonize the CB1 and CB2 cannabinoid receptors, whose signaling to the endocannabinoid system is essential for controlling cell survival and proliferation as well as psychoactive effects.

Most tumor cells express a much higher level of CB1 and CB2; THCs have been investigated as potential cancer therapeutic due to their cannabimimetic properties. To date, THCs have been prescribed as palliative medicine to cancer patients but not as an anticancer modality.

Growing evidence of preclinical research demonstrates that THCs reduce tumor progression by stimulating apoptosis and autophagy and inhibiting two significant hallmarks of cancer pathogenesis: metastasis and angiogenesis. However, the degree of their anticancer effects depends on the origin of the tumor site, the expression of cannabinoid receptors on tumor cells, and the dosages and types of THC.

This review summarizes the current state of knowledge on the molecular processes that THCs target for their anticancer effects. It also emphasizes the substantial knowledge gaps that should be of concern in future studies. We also discuss the therapeutic effects of THCs and the problems that will need to be addressed in the future. Clarifying unanswered queries is a prerequisite to translating the THCs into an effective anticancer regime.”

https://pubmed.ncbi.nlm.nih.gov/36696005/

https://link.springer.com/article/10.1007/s10555-023-10078-2

Analysis of Anti-Cancer and Anti-Inflammatory Properties of 25 High-THC Cannabis Extracts

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“Cannabis sativa is one of the oldest cultivated plants. Many of the medicinal properties of cannabis are known, although very few cannabis-based formulations became prescribed drugs. Previous research demonstrated that cannabis varieties are very different in their medicinal properties, likely due to the entourage effect-the synergistic or antagonistic effect of various cannabinoids and terpenes.

In this work, we analyzed 25 cannabis extracts containing high levels of delta-9-tetrahydrocannabinol (THC). We used HCC1806 squamous cell carcinoma and demonstrated various degrees of efficiency of the tested extracts, from 66% to 92% of growth inhibition of cancer cells.

Inflammation was tested by induction of inflammation with TNF-α/IFN-γ in WI38 human lung fibroblasts. The efficiency of the extracts was tested by analyzing the expression of COX2 and IL6; while some extracts aggravated inflammation by increasing the expression of COX2/IL6 by 2-fold, other extracts decreased inflammation, reducing expression of cytokines by over 5-fold.

We next analyzed the level of THC, CBD, CBG and CBN and twenty major terpenes and performed clustering and association analysis between the chemical composition of the extracts and their efficiency in inhibiting cancer growth and curbing inflammation.

A positive correlation was found between the presence of terpinene (pval = 0.002) and anti-cancer property; eucalyptol came second, with pval of 0.094. p-cymene and β-myrcene positively correlated with the inhibition of IL6 expression, while camphor correlated negatively. No significant correlation was found for COX2. We then performed a correlation analysis between cannabinoids and terpenes and found a positive correlation for the following pairs: α-pinene vs. CBD, p-cymene vs. CBGA, terpenolene vs. CBGA and isopulegol vs. CBGA.

Our work, thus, showed that most of high-THC extracts demonstrate anti-cancer activity, while only certain selected extracts showed anti-inflammatory activity. Presence of certain terpenes, such as terpinene, eucalyptol, cymene, myrcene and camphor, appear to have modulating effects on the activity of cannabinoids.”

https://pubmed.ncbi.nlm.nih.gov/36144796

“Cannabis sativa is a plant with a long history of consumption as food and medicine. Delta-9-tetrahydrocannabinol (THC) is one of the main cannabinoids in cannabis; it has many properties, including anti-cancer, anti-inflammatory, analgetic and others.”

https://www.mdpi.com/1420-3049/27/18/6057/htm

Administration of Δ9-Tetrahydrocannabinol Following Controlled Cortical Impact Restores Hippocampal-Dependent Working Memory and Locomotor Function

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“Hypothesis: Administration of the phytocannabinoid Δ9-tetrahydrocannabinol (Δ9-THC) will enhance brain repair and improve short-term spatial working memory in mice following controlled cortical impact (CCI) by upregulating granulocyte colony-stimulating factor (G-CSF) and other neurotrophic factors (brain-derived neurotrophic factor [BDNF], glial-derived neurotrophic factor [GDNF]) in hippocampus (HP), cerebral cortex, and striatum. 

Materials and Methods: C57BL/6J mice underwent CCI and were treated for 3 days with Δ9-THC 3 mg/kg intraperitoneally (i.p.). Short-term working memory was determined using the spontaneous alternations test during exploratory behavior in a Y-maze. Locomotor function was measured as latency to fall from a rotating drum (rotometry). These behaviors were recorded at baseline and 3, 7, and 14 days after CCI. Groups of mice were euthanized at 7 and 14 days. Extent of microgliosis, astrocytosis, and G-CSF, BDNF, and GDNF expression were measured at 7 and 14 days in cerebral cortex, striatum, and HP on the side of the trauma. Levels of the most abundant endocannabinoid (2-arachidonoyl-glycerol [2-AG]) was also measured at these times. 

Results: Δ9-THC-treated mice exhibited marked improvement in performance on the Y-maze indicating that treatment with the phytocannabinoid could reverse the deficit in working memory caused by the CCI. Δ9-THC-treated mice ran on the rotarod longer than vehicle-treated mice and recovered to normal rotarod performance levels at 2 weeks. Δ9-THC-treated mice, compared with vehicle-treated animals, exhibited significant upregulation of G-CSF as well as BDNF and GDNF in the cerebral cortex, striatum, and HP. Levels of 2-AG were also increased in the Δ9-THC-treated mice. 

Conclusion: Administration of the phytocannabinoid Δ9-THC promotes significant functional recovery from traumatic brain injury (TBI) in the realms of working memory and locomotor function. This beneficial effect is associated with upregulation of brain 2-AG, G-CSF, BDNF, and GDNF. The latter three neurotrophic factors have been previously shown to mediate brain self-repair following TBI and stroke.”

https://pubmed.ncbi.nlm.nih.gov/34747647

https://www.liebertpub.com/doi/10.1089/can.2021.0053

Impact of Hemp Flour on the Nutritional, Sensory and Functional Characteristics of Wheat and Whole Wheat Muffins

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“The growing consumer demand for plant-based, protein- and fiber-enriched foods has encouraged the incorporation of novel functional ingredients into bakery products.

Hemp flour (HF), obtained from cold-pressed hemp seeds, represents a sustainable ingredient rich in proteins, dietary fibers, lipids, and bioactive compounds, making it suitable for nutritional fortification.

This study investigated the impact of HF addition (5-40%) on the quality of muffins prepared with wheat flour (WF) and whole wheat flour (WWF).

An initial hedonic sensory evaluation identified 5-20% HF as the most acceptable substitution range, which was then subjected to detailed physicochemical, sensory, textural, colorimetric, and microbiological analyses.

Incorporation of HF significantly increased protein (up to +44%), fiber (up to +172%), and ash (up to +76%) contents, while decreasing moisture (-39%). Both WF and WWF muffins darkened with HF incorporation, with a greater lightness reduction in WF. Texture changes (increased firmness and gumminess) were more pronounced in WF muffins. Sensory analysis revealed that WF muffins were best accepted at 10-15% HF, whereas WWF muffins maintained good acceptability up to 20% HF, indicating better integration of HF in the whole grain matrix. All samples complied with microbiological safety requirements.

Overall, the optimal substitution level was 10-15% HF in WF muffins and 20% HF in WWF muffins, demonstrating that HF can enhance the nutritional profile of muffins while maintaining acceptable technological and sensory properties in a matrix-dependent manner.”

https://pubmed.ncbi.nlm.nih.gov/41154114

“In conclusion, HF offers clear advantages as a sustainable, plant-based ingredient for functional food development. It improves the protein, fiber, and mineral content of muffins, while the type of base flour plays a decisive role in determining texture, sensory quality, and overall acceptability. Future research should focus on optimizing formulations to achieve a balance between nutritional enhancement and sensory appeal, with particular attention paid to moisture retention and improving the palatability of higher HF levels in WF-based products.”

https://www.mdpi.com/2304-8158/14/20/3578


Peptide profiling and antioxidant characterization of the simulated gastrointestinal digest of hemp seed proteins

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“Hemp seeds have a long history as a foodstuff and are traditionally associated with longevity in China.

In this study, the simulated digestion of hemp seed protein (HSP) was investigated to evaluate its health benefits.

After digestion, a higher degree of hydrolysis, elevated DPPH and ABTS radical-scavenging activities, and enhanced FRAP reducing power were observed, reflecting the digestibility and antioxidant potential of HSP. Moreover, the HSP digest improved HepG2 cell viability under H2O2-induced oxidative stress.

Peptidomic analysis identified 1101 peptides (75 % < 1 kDa), among which 89 were predicted to be bioactive. From these, 27 water-soluble, non-toxic peptides were further examined. Molecular docking showed that most peptides had stronger binding affinities to ABTS, DPPH, and Keap1 than glutathione.

A 100-ns molecular dynamics simulation further confirmed the antioxidant potential of the peptides, highlighting HSP digest as a promising source of antioxidant peptides with direct radical-scavenging activity and potential Nrf2-pathway activation.”

https://pubmed.ncbi.nlm.nih.gov/41075652

“This study demonstrated that simulated gastrointestinal digestion of HSP yields a peptide-rich hydrolysate with potent antioxidant effects. The HSP digest showed significantly improved free-radical scavenging capacity and protection against oxidative stress in cells.”

https://www.sciencedirect.com/science/article/abs/pii/S030881462503910X?via%3Dihub

The association between marijuana use and oral cancer risk: a systematic review and meta-analysis of case-control studies

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“The relationship between marijuana use and oral cancer risk remains controversial, with conflicting evidence from epidemiological studies. This systematic review and meta-analysis aimed to synthesize available evidence on the association between marijuana consumption and oral cancer incidence.

Following PRISMA guidelines, we conducted comprehensive searches across Scopus, PubMed, Web of Science, and Embase databases up to August 2025. We included only case-control studies reporting quantitative risk estimates for marijuana use and histologically confirmed oral cancer (ICD-10 codes C00-C06). Data extraction followed standardized protocols, and study quality was assessed using the Joanna Briggs Institute checklist. Statistical analyses were performed using Comprehensive Meta-Analysis software with random-effects models. Heterogeneity was evaluated using I2 statistics, and publication bias was assessed through funnel plots and Egger’s regression test. Six case-control studies involving 4,686 cases and 10,370 controls were included.

The pooled odds ratio demonstrated a statistically significant inverse association between marijuana use and oral cancer risk (OR = 0.659, 95% CI: 0.500-0.869, p = 0.003, I2 = 47.35).

Subgroup analyses were performed based on the duration of use, gender, and age at initiation of marijuana use; however, no clear dose-response relationship was observed. Sensitivity analyses confirmed robustness of findings, with ORs ranging from 0.599 to 0.708 across iterations. No significant publication bias was detected (Egger’s test p = 0.532). Three individual studies showed statistically significant protective effects, while three others were non-significant.

This meta-analysis suggests marijuana use is associated with reduced oral cancer risk.

However, given methodological limitations, heterogeneity in exposure assessment, and conflicting recent evidence, these findings require cautious interpretation. Future large-scale prospective cohort studies with standardized exposure measurements are essential for definitive conclusions.”


https://pubmed.ncbi.nlm.nih.gov/41236922/

https://www.tandfonline.com/doi/full/10.1080/15332640.2025.2581692

Durable complete response of advanced hepatocellular carcinoma using cannabis oil: a report of two cases

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“Hepatocellular carcinoma (HCC) is a leading cause of cancer-related mortality worldwide with a grim prognosis. Current treatment options for advanced HCC are limited, and a large proportion of patients is not amenable to any form of treatment, with best supportive care as the only remaining option.

Meanwhile, the use of cannabis-derived products is rising in oncological patients who are seeking symptom relief. Cannabinoids, similar to endogenous endocannabinoids, have shown promise in recent preclinical cancer research due to their ability to interact with various signaling pathways and molecular mechanisms of interest.

Case presentation

In this report, we present two patients (A aged 82 and B 77, respectively) with advanced HCC with a high tumor burden who demonstrated durable and complete regression after use of cannabis oil (A 10% delta-9-tetrahydrocannabinol (THC) and 5% cannabidiol (CBD), two droplets sublingually three times daily and B 15% THC and 2% CBD, 5 droplets sublingually two times daily) for symptom relief. The observations in this report build on previous (pre)clinical research highlighting the potential anti-tumor qualities of cannabinoids and stress the need for clinical trials investigating the anti-tumor effects of cannabinoids in cancer patients.

Conclusion

Based on the two cases presented here, we call for further research into the potential beneficial effect of cannabinoids in patients with advanced HCC.”

“The authors present two cases of durable and complete remission in two patients with advanced hepatocellular carcinoma using cannabinoids, thus stressing the call for further research into the anti-tumor effects of cannabinoids in this patient population with limited therapeutic options. These findings are hypothesis-generating and underscore the urgent need for controlled clinical trials.”

https://link.springer.com/article/10.1186/s42238-025-00353-0

https://pubmed.ncbi.nlm.nih.gov/41287047

A Preliminary Investigation of Brain Cannabinoid Receptor Type 1 (CB1R) Availability in Men with Opioid Use Disorder

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“The endocannabinoid (eCB) system has been proposed as a potential target for developing new medications for opioid use disorder (OUD). However, the status of the eCB system, specifically brain cannabinoid receptor type 1 (CB1R) in OUD, is unknown.

In this study, CB1R availability was measured in males with OUD on stable opioid agonist treatment (OAT) (n = 10) versus healthy controls (HC) (n = 18), using High-Resolution Research Tomography (HRRT) and the CB1R-specific radiotracer, [ 11 C]OMAR. The average volume of distribution ( V T ) across 13 regions was compared between the OUD and HC groups. Average V T was 15% lower in OUD vs. HC subjects (p = 0.04). Lower V T in OUD compared to HC was also observed in several corticolimbic areas.

Within OUD no effects on CB1R availability were observed for treatment medication (methadone vs. buprenorphine), current stress levels, or antidepressant medication. No associations between the average V T and duration of OAT treatment or time since the last illicit opioid use were observed.

This preliminary study suggests lower CB1R availability in men with OUD. Larger studies are necessary to replicate these findings. Future research should also draw from a more heterogeneous population, particularly by incorporating females, to better assess the potential confounding and moderating clinical factors. If confirmed, the observed alterations in CB1R availability in OUD may provide a rationale for targeting the eCB system in the treatment of OUD.”

https://pubmed.ncbi.nlm.nih.gov/41282260

https://www.researchsquare.com/article/rs-7715611/v1