Author Archives: David Worrell

Quality by Design-Driven Formulation Development of Cannabidiol Orally Disintegrating Tablets

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Orally disintegrating tablets may offer a more convenient way to deliver cannabidiol, particularly for people who have difficulty swallowing conventional pills. In this study, researchers used a Quality by Design approach to optimize a CBD tablet formulation for rapid disintegration, dose consistency, and reliable pharmaceutical performance.

“The development of cannabidiol (CBD) orally disintegrating tablets (ODTs) is effective in treating anxiety in a patient-friendly manner. The application of Quality by Design (QbD) enhances the efficiency and robustness of the pharmaceutical development of CBD ODTs.

The objective of this work was to develop a formulation for CBD ODTs using a QbD-driven approach. Quality target product profile, critical quality attributes, and an initial risk assessment were identified and evaluated. Subsequently, a Box-Behnken design was employed to analyze the effects of varied compression force, the quantity of microcrystalline cellulose, and the quantity of croscarmellose sodium to create a design space and control space.

Results indicated that the design and control spaces produced tablets with hardness ranging from 4 to 6 kg-force, a disintegration time (DT) ≤ 30 s, and a friability ≤ 1%. All formulations contained 4% CBD (or 10 mg per tablet). The optimal formulation consisted of 35% microcrystalline cellulose and 1% croscarmellose sodium and was compressed at 1400 pounds per square inch.

This formulation exhibited a hardness of approximately 5 kg-force, a DT of 13-15 s, and a friability of approximately 0.3%. Verification data confirmed the accuracy of the predictions made by computer software. The content uniformity and assay determined using validated high-performance liquid chromatography ranged between 90% and 100%. CBD was released from the CBD ODT in 1% sodium lauryl sulfate solution, with approximately 76% dissolved within 3 h in the dissolution study.

In conclusion, the QbD-driven approach successfully facilitated the formulation development of CBD ODTs with the desired properties for the treatment of anxiety in a patient-friendly manner.”

https://pubmed.ncbi.nlm.nih.gov/42662497

“The present study demonstrates the successful development of CBD ODTs using the QbD approach, which has proven effective in enhancing both the efficiency and robustness of the formulation process.

Overall, this study demonstrates the successful implementation of a QbD-driven strategy for laboratory-scale formulation development and optimization of CBD ODTs.

The findings contribute to pharmaceutical development efforts involving cannabinoid-based formulations and may provide useful guidance for future studies related to scale-up, stability evaluation, and in vivo performance.

https://onlinelibrary.wiley.com/doi/10.1155/sci5/3553253


Differential Effects of Cannabidiol and Cannabigerol on Cognition, Neuroinflammation, and Blood-Brain Barrier Integrity in a Rat Model of Iron Overload

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Researchers comparing cannabidiol (CBD) and cannabigerol (CBG) found that both cannabinoids reversed recognition-memory impairment and restored a protein important to blood-brain barrier integrity in rats exposed to excessive iron early in life.

Both CBD and CBG reduced the inflammatory marker IL-1β, although their broader effects on inflammation differed. The findings suggest that the two phytocannabinoids may protect cognitive function through distinct but complementary mechanisms involving neuroinflammation and the blood-brain barrier.

“Iron is an essential micronutrient for brain development, participating in mitochondrial respiration, myelination, and neurotransmitter synthesis. However, previous studies have demonstrated that excessive iron during early postnatal life induces oxidative reactions, leading to mitochondrial dysfunction and synaptic failure. These alterations compromise energy metabolism and neuronal integrity, contributing to long-lasting cognitive dysfunction and increased brain vulnerability later in life.

This study evaluated the effects of cannabidiol (CBD) and cannabigerol (CBG) on behavioral, neuroinflammatory, and blood-brain barrier (BBB) outcomes in rats exposed to early-life iron overload.

Male Wistar rats received iron carbonyl (30 mg/kg, intragastrically) from postnatal day 12 to 14. At three months of age, they were treated intraperitoneally with CBD, CBG (both at 10 mg/kg), or vehicle for 21 days. Cognitive performance was assessed in the open field and object recognition tasks. We examined hippocampal levels of interleukin-1 beta (IL-1β), interleukin-6 (IL-6), tumor necrosis factor alpha (TNF-α), as proinflammatory markers, and occludin, a protein known to regulate BBB permeability.

Iron-exposed animals showed impaired recognition memory, with elevated TNF-α and IL-1β, while CBD reversed memory deficits and reduced IL-1β in iron-treated animals, without affecting TNF-α.

CBG restored memory, decreased IL-1β in both iron-treated and controls, and increased TNF-α in controls. Also, iron overload reduced occludin expression in vehicle-treated rats which was reversed by both CBD and CBG.

These findings highlight inflammation and BBB disruption as mediators of iron-induced cognitive dysfunction and show that both phytocannabinoids act through distinct but complementary mechanisms, supporting their therapeutic potential in neuroinflammation linked to iron overload.”

https://pubmed.ncbi.nlm.nih.gov/42663810

https://link.springer.com/article/10.1007/s12640-026-00826-x


A comparative network analysis to explore cancer patient experiences with cannabis

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This study examined how people with cancer described the benefits and barriers they encountered when using CBD-only products compared with products containing both CBD and THC.

The findings point to a meaningful difference in patient experience: pain relief was especially prominent among those using CBD+THC products, while participants across the study also reported benefits including improved sleep, physical relaxation, emotional regulation, and reduced use of other medications.

“Introduction: Approximately 20% of cancer patients report cannabis use, yet only 30% of oncologists feel sufficiently informed to make recommendations on its use. This study aimed to visualize the network of themes that arise within cancer patients’ reported experiences with cannabis.

Materials and methods: Data was collected via an online survey of 65 patients who self-reported the use of cannabis in their treatment for cancer, details about the cannabis product(s) being used, their perceived benefits and problems associated with cannabis use, their reasons for starting cannabis use, and any reasons for stopping cannabis use. Epistemic Network Analysis (ENA) was used to compare two groups of cancer patients: 1) those who only used CBD-dominant products (CBD-only group) versus 2) those who used cannabidiol (CBD)- and delta-9-tetrahydrocannabinol (THC)-containing products (either CBD-dominant and THC-dominant cannabis products or cannabis products containing a balanced ratio of both CBD and THC; CBD+THC group).

Results: Cannabis use conferred therapeutic benefits for several health issues commonly encountered by cancer patients. Common benefits reported across the cohort of patients included pain relief, improved sleep, physical relaxation, emotional regulation, and reduction of concomitant medication. The most frequently reported barriers to cannabis use were the stigma associated with THC use and the high cost of CBD-dominant and THC-dominant products. Pain relief emerged as the most prominent, interconnected theme reported by the CBD+THC group, whereas emotional regulation was the most prominent theme for the CBD-only group.

Conclusion: Symptom relief differed based on the cannabinoid composition of the cannabis products. The following trends emerged, which must be confirmed with larger samples: pain relief was more prominent in responses from users of CBD+THC, whereas emotional regulation was more prominent in only the users of CBD-only products. These findings are a step toward assisting cancer patients and providers with clinical decision-making on cannabis use. This study highlights the continued perception of stigma associated with THC use and the need for insurance coverage of medicinal cannabis to reduce the financial burden for this patient population. Finally, this study exemplifies the value of ENA in studying the therapeutic utility of cannabis with qualitative data.”

https://pubmed.ncbi.nlm.nih.gov/42666469

“Pain relief is more frequently reported among users of CBD+THC products.”

“Emotional regulation is more frequently reported among users of only CBD.”

“Overall, pain relief was the most frequently discussed benefit and was associated with other benefits: emotional regulation, sleep or physical relaxation, and medication reduction. Primary patient concerns were stigma and cost.”

https://www.frontiersin.org/journals/psychiatry/articles/10.3389/fpsyt.2026.1737119/full

Cannabidiol Suppresses Glioma Growth and Limits Invasion Partly Through an LOXL2-Associated EMT-Like Program

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A new study found that cannabidiol (CBD) suppressed glioma growth and reduced tumor-cell migration and invasion in laboratory and animal models. The researchers linked part of this effect to reduced LOXL2 activity, suggesting CBD may interfere with molecular programs that help glioma cells spread into surrounding brain tissue.

The study adds new mechanistic evidence to the growing body of research examining CBD as a potential therapeutic compound in glioma and glioblastoma.

“Background: Gliomas, particularly glioblastoma, remain difficult to control because diffuse infiltration into surrounding brain tissue limits complete resection and contributes to recurrence. Cannabidiol (CBD), a nonpsychoactive cannabinoid capable of entering the central nervous system, has shown antitumor activity in glioma models, but the mechanisms underlying its anti-invasive effects remain unclear. Lysyl oxidase-like 2 (LOXL2) regulates extracellular-matrix remodeling and mesenchymal phenotypes in several cancers. We therefore tested the hypothesis that CBD limits glioma growth and invasion partly by suppressing an LOXL2-associated extracellular-matrix and EMT-like program.

Methods: Human U87 and murine GL261 glioma cells were used to examine CBD effects on tetrazolium-based cell viability, clonogenic growth, cell-cycle progression, apoptosis, migration, and invasion. The two cell lines provided complementary human and murine models, and the immunocompetent intracranial GL261 model enabled syngeneic in vivo validation. RNA sequencing and public glioma datasets were used to identify and contextualize CBD-responsive molecules. Mechanistic involvement was tested by determining whether LOXL2 knockdown phenocopied and LOXL2 overexpression attenuated the anti-invasive effects of CBD.

Results: CBD reduced glioma-cell viability and clonogenicity, induced G1-phase arrest and apoptosis, and suppressed migration and invasion. C CCK-8-derived IC50 values (mean ± SD, n = 3) at 24, 48, and 72 h were 36.5 ± 0.3, 26.7 ± 0.3, and 21.4 ± 0.3 μM in U87 cells and 33.3 ± 0.2, 29.3 ± 0.2, and 25.5 ± 0.4 μM in GL261 cells, respectively. CBD treatment was accompanied by reduced MMP2 and MMP9 expression and increased TIMP3 expression. Transcriptomic profiling identified LOXL2 as a prominent CBD-downregulated molecule, and public datasets associated higher LOXL2 expression with aggressive molecular features and shorter overall survival. LOXL2 silencing reproduced the antimigratory and anti-invasive phenotype, whereas LOXL2 overexpression enhanced cell motility and partially attenuated the effects of CBD. The partial rescue involved vimentin, MMP9/TIMP3, EMT-related transcription factors, and F-actin-rich protrusions. In vivo, CBD reduced intracranial tumor burden and produced tissue changes consistent with lower proliferation, enhanced apoptosis, and suppression of the LOXL2-associated mesenchymal program.

Conclusions: CBD suppresses glioma growth and limits invasion, at least in part, by attenuating an LOXL2-associated EMT-like and extracellular-matrix-remodeling program. Because LOXL2 overexpression produced only a partial rescue and direct target engagement was not tested, LOXL2 should be interpreted as a functional mediator rather than the sole or direct molecular target of CBD. These findings support further validation in patient-derived and pharmacokinetically informed glioma models.”

https://pubmed.ncbi.nlm.nih.gov/42661582

https://onlinelibrary.wiley.com/doi/10.1155/bmri/6385332

Chronic THC exposure modulates behavioral outcomes and endocannabinoid signaling in HIV-1 Tg26 mice in a sex-dependent manner

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Researchers examined how chronic THC exposure affects behavior and endocannabinoid signaling in an HIV-1 mouse model.

Chronic THC helped attenuate the decline in motor coordination and was associated with increased CB1 receptor expression in the cerebellum. The study also found major sex-dependent differences, with female and male mice showing different patterns of motor impairment and endocannabinoid signaling.

THC did not produce detectable pain-relieving effects in this model, but the findings suggest that chronic THC can influence HIV-related neurological changes through the endocannabinoid system.

Overall, the study highlights the complex relationship between THC, HIV-associated neurological dysfunction, and biological sex.

“While combined antiretroviral therapy (cART) has transitioned HIV-1 into a manageable chronic condition, it fails to eradicate latent viral reservoirs in the central nervous system (CNS) that drive persistent neuroinflammation and synaptodendritic injury. Consequently, people living with human immunodeficiency virus type-1 (HIV-1) often utilize cannabis to manage neurological symptoms, yet the long-term impact of exogenous cannabinoids on the HIV-1-burdened brain remains poorly understood.

In this study, we utilized the HIV-1 Tg26 mouse model to evaluate how chronic Δ9-tetrahydrocannabinol (THC, 3mg/kg) exposure influences motor coordination, thermal nociception, and endocannabinoid (eCB) signaling in the context of constitutive viral protein expression.

Our results demonstrate that HIV-1 viral protein expression was associated with impaired acquisition of cerebellum-dependent motor learning in a sex-dependent manner. This deficit was primarily driven by females and coincided with altered markers of eCB plasticity, characterized by elevated monoacylglycerol lipase (MAGL) expression and a depletion of 2-arachidonoylglycerol (2-AG). Conversely, males exhibit increased cerebellar CB1R and CB2R expression, which paralleled preserved rotarod performance. In the spinal cord, viral protein expression was associated with thermal hyposensitivity and a reduction in 2-AG and cannabinoid receptor levels, a pattern consistent with HIV-1-associated alterations in sensory processing circuits.

While chronic THC failed to produce detectable antinociceptive effects, consistent with spinal CB1R downregulation, it successfully attenuated the temporal decline of motor coordination with upregulating cerebellar CB1R. Data from a separate acute THC cohort demonstrated detectable THC and metabolite concentrations in plasma and cortex, while also revealing sex- and genotype-dependent differences in these measures.

Together, these findings identify sex-specific eCB signaling as a critical factor associated with the neurobiological response to HIV-1 proteins and provide a biological framework for understanding sex-dependent variability in cannabinoid efficacy.”

https://pubmed.ncbi.nlm.nih.gov/42660238

“Collectively, these results provide a biological framework for understanding sex-dependent variability in cannabinoid responses and support the inclusion of sex as a key factor in the development of cannabinoid-based adjunct therapies for chronic neuroinflammatory conditions.”

https://www.sciencedirect.com/science/article/pii/S0361923026003862?via%3Dihub

Cannabis laws and health-related workplace absenteeism in the United States

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A new U.S. study examining more than three decades of employment data found that medical cannabis decriminalization was associated with fewer health-related work absences, with some of the strongest effects appearing in physically demanding occupations and industries where chronic pain is common.

The findings suggest that access to medical cannabis may have implications not only for individual patients, but also for workforce participation and productivity.

“This study evaluated the impact of medical and recreational cannabis laws in the United States on health-related workplace absenteeism across different demographics, occupations, and industries.

Using state-level variation in the timing of cannabis decriminalization and the onset of regulated sales, we applied a flexible difference-in-differences approach to monthly data from the Current Population Survey, covering the period from January 1990 to March 2025.

The findings indicate that medical cannabis decriminalization reduced the likelihood of health-related work absences by about 6.9%, with decriminalization having a larger quantitative effect and greater statistical significance than the commencement of regulated sales.

We found no significant effect of recreational cannabis legalization on health-related workplace absenteeism. The absenteeism-reducing effects of medical cannabis decriminalization were notable in occupations (e.g., manual laborers, machine operators) and industries (e.g., manufacturing, agriculture, construction) where conditions more predisposed to cannabis treatment (e.g., chronic pain associated with physical work) are prevalent.”

https://www.tandfonline.com/doi/full/10.1080/15555240.2026.2680016#abstract

“University of Georgia study links legal marijuana use to fewer sick days”

https://www.livenowfox.com/news/university-georgia-study-links-legal-marijuana-use-fewer-sick-days

Lower Rates of Hepatocellular Carcinoma Observed Among Cannabis Users: A Population-Based Study

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Hepatocellular carcinoma (HCC) is the most common form of primary liver cancer and remains a major cause of cancer death worldwide.

In a population-based study involving more than 101 million U.S. hospital patients, researchers found a striking association between cannabis use and HCC: after adjusting for multiple potential confounding factors, patients with documented cannabis use were 55% less likely to have hepatocellular carcinoma than patients without documented cannabis use.

The study adds large-scale human observational evidence to earlier preclinical research examining cannabinoids and liver cancer.

“Background: Hepatocellular carcinoma (HCC) is one of the most common malignancies worldwide and the fourth leading cause of cancer deaths in the world. The association between HCC and cannabis has been identified in mice; however, to our knowledge has not been identified in humans. Therefore, we aim to investigate the relation between HCC and cannabis use in humans.

Methods: Using data from the National Inpatient Sample (NIS) database between 2002 and 2014, we identified the patients with HCC and cannabis use diagnosis using the International Classification of Disease 9th version codes (ICD-9). Then, we identified patients without cannabis use as the control group. We adjusted for multiple potential confounders and performed multivariable logistic regression analysis to determine the association between cannabis abuse and HCC.

Results: A total of 101,231,036 patients were included in the study. Out of the total, 996,290 patients (1%) had the diagnosis of cannabis abuse versus 100,234,746 patients (99%) in the control group without cannabis abuse. We noticed that patients with cannabis abuse were younger (34 vs 48 years), had more males (61.7% vs 41.4%) and more African Americans (29.9% vs 14.2%) compared with the control group (P<0.001 for all). Besides, patients with cannabis use had more hepatitis B, hepatitis C, liver cirrhosis, and smoking, but had less obesity and gallstones, (P<0.001 for all). Using multivariable logistic regression, and after adjusting for potential confounders, patients with cannabis abuse were 55% less likely to have HCC (adjusted Odds Ratio {aOR}, 0.45, 95% Confidence Interval {CI}, 0.42-0.49, P<0.001) compared with patients without cannabis abuse.

Conclusion: Based on our large database analysis, we found that cannabis use patients were 55% less likely to have HCC compared to patients without cannabis use. Further prospective studies are needed to assess the role of cannabis use on HCC.”

https://pubmed.ncbi.nlm.nih.gov/35651376

“Our analysis revealed that cannabis users were 55% less likely to have HCC compared to non-cannabis users.” 

https://www.cureus.com/articles/90568-lower-rates-of-hepatocellular-carcinoma-observed-among-cannabis-users-a-population-based-study#!

Essential Oils from Seed-Depleted Infructescences of Industrial Hemp: Chemical Diversity and Biological Potential

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Industrial hemp is increasingly being studied not only for cannabinoids, fiber and seed products, but also for valuable compounds that can be recovered from plant material often treated as agricultural waste.

In this study, researchers examined essential oils obtained from seed-depleted hemp infructescences and found substantial chemical diversity along with antioxidant and antimicrobial activity. The results suggest that this underused post-harvest material may have potential value in pharmaceutical, cosmetic and oral healthcare applications.

The findings also highlight another way hemp biomass could be more fully utilized rather than discarded.

“Industrial hemp is a chemically rich plant increasingly explored within sustainable production systems aimed at the full utilization of all plant fractions. While hemp inflorescences have been extensively investigated, the biological potential of seed-depleted infructescences remains largely underexplored.

This study compared essential oils (EOs) distilled from inflorescences and seed-depleted infructescences of hemp (Cannabis sativa L. cv. Futura 75).

Their chemical composition was determined by gas chromatography-mass spectrometry (GC-MS), and their cytotoxicity, hemocompatibility, effects on blood coagulation, and antibacterial activity against a panel of 11 Gram-positive, Gram-negative, and microaerophilic bacterial strains were evaluated.

The major EO constituents included α-Pinene, (E)-Caryophyllene, Myrcene, α-Humulene, Caryophyllene oxide, and Cannabidiol.

EOs obtained from seed-depleted infructescences exhibited distinct chemical profiles, low cytotoxicity toward BJ human skin fibroblasts, minimal haemolytic activity, no significant effects on blood coagulation, and, in most cases, stronger antibacterial activity than inflorescence-derived EOs. Particularly high activity was observed against skin- and oral-associated bacteria, including Cutibacterium acnes and Streptococcus species.

These findings demonstrate that seed-depleted infructescences represent underutilized post-harvest biomass and a valuable and sustainable source of biologically active EOs, supporting their further investigation for potential pharmaceutical, cosmetic, and oral healthcare applications.”

https://pubmed.ncbi.nlm.nih.gov/42653967

https://link.springer.com/article/10.1007/s13365-026-01338-2


Impact of cannabis use on white matter hyperintensities in adults with and without chronic HIV disease

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People living with HIV can develop changes in the brain’s white matter even when the virus is well controlled with antiretroviral therapy, raising questions about whether cannabis use adds to that neurological burden.

In this study of 296 adults with and without HIV and cannabis use, researchers used MRI imaging to examine white matter hyperintensities and their relationship to neurocognitive function.

The findings help clarify whether cannabis use independently contributes to these brain changes or meaningfully alters their impact in people living with chronic HIV.

“White matter hyperintensities (WMH) are prevalent among people living with HIV (PLWH), even with sustained viral suppression on antiretroviral therapy. This study investigated whether cannabis use contributes to additional WMH load among PLWH and its association to neurocognitive function.

A total of 296 adult participants, stratified by HIV and cannabis status (74 control, 73 cannabis-only, 76 HIV-only and 73 HIV+cannabis) were enrolled. High resolution anatomical MRI and fluid-attenuated inversion recovery (FLAIR) images were collected, along with a battery of neuropsychological tests. Periventricular (pvWMH) and deep (dWMH) WMH loads were quantified using an automated pipeline. Statistical tests were employed to examine the main and interaction effects of HIV and cannabis use on WMH, and to explore the association of WMH loads with neuropsychological performance. The cohort had a mean age of 39.84 years, and all PLWH had sustained viral suppression.

pvWMH loads were higher in the cannabis-only and HIV-only groups compared to controls. A significant interaction effect of HIV by cannabis was found for pvWMH load, such that participants with co-occurring HIV and cannabis use had similar pvWMH load compared to controls. In addition, increased pvWMH load significantly correlated with lower cognitive performance.

Our findings suggest that cannabis use does not contribute additively to WMH burden in PLWH and may potentially be associated with a reduced WMH burden. However, future work is warranted to substantiate this finding, particularly with respect to type and levels of circulating cannabinoid metabolites.”

https://pubmed.ncbi.nlm.nih.gov/42658415

https://link.springer.com/article/10.1007/s13365-026-01338-2


Therapeutic Potential of Cannabidiol in Dysbiosis-Related Oral Biofilm Diseases: Antibiofilm, Antivirulence and Host Response Evidence

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Dental caries and periodontal disease are driven in part by harmful shifts in the microbial communities that form oral biofilms, making new approaches to controlling those biofilms an important area of research.

In this review, researchers examined the therapeutic potential of cannabidiol (CBD) and found evidence that it may inhibit biofilm formation, reduce microbial virulence, modulate periodontal inflammation and support tissue-protective responses.

The findings highlight CBD as a potential future adjunct for oral health, particularly in conditions linked to microbial dysbiosis such as tooth decay and periodontal disease.

“Dysbiosis-related oral biofilm diseases, particularly dental caries and periodontal diseases, pose major global health challenges because ecological shifts within oral microbial communities enhance biofilm virulence, resilience, and host inflammatory responses.

Cannabidiol (CBD), a non-psychoactive phytocannabinoid with antimicrobial, antibiofilm, immunomodulatory, and antioxidant properties, has attracted increasing interest as an investigational, ecology-oriented adjunct for oral health applications.

This narrative review evaluates current antibiofilm, antivirulence, and host response evidence for CBD in dysbiosis-related oral biofilm diseases, with emphasis on dental caries and periodontal diseases and selected supportive evidence from other oral biofilm-associated conditions.

Current evidence suggests that CBD can inhibit biofilm formation, attenuate cariogenic and fungal virulence traits, modulate periodontal inflammation and immunity, and support tissue-protective responses. However, most evidence remains preclinical and model-dependent, particularly in caries research, and CBD’s hydrophobicity, limited stability, uncertain dose windows, and incomplete microbiome-level evidence remain major barriers to translation.

Future studies should clarify CBD’s ecological effects on oral microbial communities, define clinically relevant dosing and exposure timing, and develop oral-retentive delivery systems.”

“Cannabidiol (CBD), a non-psychoactive phytocannabinoid with multi-target pharmacological properties, including rebalancing gut microbial homeostasis, anti-inflammatory, immunoregulatory, and antioxidant effects, has garnered attention in dentistry, particularly regarding dysbiosis-related oral biofilm diseases.”

“Accumulating evidence supports further investigation of CBD in dysbiosis-related oral biofilm diseases, particularly dental caries and periodontal diseases.”

https://www.mdpi.com/1424-8247/19/8/1221