Author Archives: David Worrell

Dual-Function Plant-Derived Nanovesicles From Regenerated Cannabis sativa Roots for Immunotherapy and Vaccine Delivery

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“Cannabis sativa is a medicinal plant that produces a diverse array of pharmacologically active metabolites, making it a valuable resource for pharmaceutical applications.

In this study, an adventitious root (AR) culture system was established from C. sativa using two representative plant growth regulators-naphthaleneacetic acid (NAA; hereafter referred to as N-ARs) and indole-3-butyric acid (IBA; hereafter referred to as I-ARs) -from which plant-derived nanovesicles (PDNVs) were subsequently isolated (hereafter N-PDNVs and I-PDNVs, respectively).

The resulting N-PDNVs and I-PDNVs exhibited average diameters of 128 ± 2 and 124 ± 4 nm, respectively, with zeta potentials of -12.9 and -15.7 mV. Both PDNV types maintained structural integrity and colloidal stability under diverse external stress conditions, underscoring their physicochemical robustness. Metabolite profiling of PDNVs revealed 25 distinct metabolites. Functionally, I-PDNVs markedly enhanced dendritic cell maturation through Toll-like receptor 2 (TLR2)- and TLR4-dependent pathways, promoted T cell proliferation and activation (notably IFN-γ- and IL-17A-producing subsets), and increased natural killer (NK) cell activity compared with N-PDNVs.

In immunosuppressed and tumour-bearing mouse models, I-PDNVs further augmented NK cell, Th1 and cytotoxic T lymphocyte (CTL) responses, thereby confirming their superior potential as immunotherapeutic agents. Moreover, in immunized mouse models, OVA257-264-encapsulated I-PDNVs demonstrated a clear advantage as a vaccine delivery platform by eliciting a potent OVA257-264-specific CTL response.

When applied as a prophylactic cancer vaccine, they not only delayed tumour growth but also reshaped the antitumour immune landscape, characterized by enhanced CTL responses, reduced regulatory T cell frequencies and diminished exhausted CD8⁺ T cell populations.

Collectively, these findings highlight the potential of I-PDNVs as dual-function PDNVs, serving both as immunotherapeutic agents and as vaccine delivery platforms for applications requiring reinforced Th1, CTL and NK cell responses.”

https://pubmed.ncbi.nlm.nih.gov/41316982

“Nanovesicles, commonly referred to as extracellular vesicles (EVs) are secreted by various organisms or are artificially isolated under various conditions, with their sizes ranging from 30 nm to 10 µm. Owing to their functional properties, such as immunity promotion, inflammation control and antioxidant activities, nanovesicles have attracted attention as promising candidates for drug delivery systems (DDS) and for treating various immune-related diseases, including cancers, infectious diseases and autoimmune disorders.”

“Our study is the first to report the differences in the metabolic properties and immunoenhancing efficacy between I-PDNVs and N-PDNVs isolated from C. sativa AR induced by two distinct plant hormones, IBA and NAA. I-PDNVs strongly promoted a Th1-biased immune response by inducing both innate and adaptive immune activation, demonstrating their superior potential as an immunotherapeutic agent for immunosuppression and cancer treatment. Furthermore, the multifunctionality of I-PDNVs is highlighted by validating their potential as an integrated adjuvant and DDS in a cancer vaccine model.

Our findings suggest that I-PDNVs are promising immunotherapeutic candidates not only for cancer treatment, but also for intracellular infectious diseases and chronic viral infections, emphasizing their role as a multifunctional nanomaterial capable of integrating adjuvant and vaccine delivery functions for next-generation vaccine development.”

https://isevjournals.onlinelibrary.wiley.com/doi/10.1002/jev2.70206

Evaluating cannabis substitution for alcohol within the context of a canadian managed alcohol program

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“Introduction: Managed Alcohol Programs (MAPs) provide beverage alcohol alongside housing and social supports to mitigate alcohol-related harms among individuals experiencing severe alcohol use disorder (AUD) and unstable housing. MAPs have been shown to stabilize alcohol use, reduce alcohol-related harms, improve quality of life, and decrease emergency service utilization. However, concerns about the long-term health risks associated with high levels of alcohol use have driven interest in cannabis substitution as an additional harm reduction strategy. Given the lower harm profile of cannabis, its integration into MAPs offers a promising avenue for further reducing alcohol-related harms. This study evaluates a novel cannabis substitution program within a Canadian MAP, leveraging the unique context of cannabis legalization and harm reduction programming.

Methods: Beginning in January 2023, participants (N = 35) were offered the choice of a pre-rolled cannabis joint or their prescribed alcohol dose multiple times per day. Data were drawn from five waves of quantitative surveys (January 2023 to February 2024; n = 20), two years of program records (January 2022 to February 2024; N = 35), and qualitative interviews (n = 14). Hierarchical mixed-effects models were used to predict alcohol use by cannabis use and time. Qualitative data were analyzed using interpretive description methodology.

Results: The final model found evidence of a substitution effect: participants who used more cannabis on average also consumed less alcohol overall. Specifically, each additional 0.4-gram joint consumed (approximately 15.2 standard THC units or 76 mg THC) was associated with an estimated 2.43 fewer mean daily standard drinks. Within-person cannabis use was not a significant predictor, indicating that short-term fluctuations in cannabis use were not associated with concurrent changes in alcohol consumption. Alcohol use also declined over time. Qualitative findings provide insights into the dynamic factors shaping drinking and cannabis use patterns.

Conclusion: This study highlights the potential for cannabis substitution to meaningfully reduce alcohol-related harms. Implications for program development and future research evaluating changes in health, wellbeing, and harm outcomes are discussed.”

https://pubmed.ncbi.nlm.nih.gov/41313909

“Emerging evidence suggests that cannabis substitution for alcohol may offer a promising approach to mitigating alcohol-related harms. Cannabis is associated with lower toxicity, fewer long-term health risks, and a lower likelihood of overdose compared to alcohol.”

https://www.sciencedirect.com/science/article/pii/S0955395925003792?via%3Dihub

Cannabidiol alleviates methamphetamine-induced autophagy and oxidative stress by suppressing sigma 1 receptor expression

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“Methamphetamine (METH) is currently considered one of the most notorious drugs globally. Chronic long-term METH abuse results in severe neurotoxicity, wherein oxidative stress and autophagy are key pathological phenomena and toxic phenotypes. However, the molecular mechanism by which METH induces oxidative stress and autophagy remains elusive.

In this study, METH-induced autophagy and oxidative stress were replicated in both HT22 cells and C57BL/6 J mice. Notably, METH up-regulated the expression of chaperon protein sigma 1 receptor (S1R). However, METH-induced autophagy and oxidative stress were alleviated after targeted intervention with S1R using the chemical inhibitor, gene knockdown, or knockout techniques.

More importantly, cannabidiol (CBD), a non-psychoactive natural cannabinoid derived from cannabis, exhibited therapeutic efficacy by down-regulating the high expression of S1R, autophagy, and oxidative stress following METH exposure both in vivo and in vitro.

Overall, these results suggest that METH mediates autophagy and oxidative stress by up-regulating S1R expression, whereas CBD alleviates METH-induced autophagy and oxidative stress by suppressing S1R expression.

This study expands our understanding of METH-induced neurotoxicity, identifying S1R as a potential therapeutic target against aberrant autophagy and oxidative stress, and further validates the medical value of CBD for the treatment of METH use disorder.”

https://pubmed.ncbi.nlm.nih.gov/41314517

“Cannabidiol (CBD), a non-psychoactive natural cannabinoid derived from cannabis, exerts distinct pharmacological effects, such as antioxidant, anti-inflammatory, and neuroprotective effects, demonstrating therapeutic potential in several neurological diseases.”

“CBD alleviated METH-induced autophagy and oxidative stress by suppressing S1R expression.”

https://www.sciencedirect.com/science/article/abs/pii/S0898656825006953?via%3Dihub

Use of Cannabidiol and Cannabigerol in the Treatment of Trigeminal Neuralgia and Postherpetic Pain

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“The use of cannabidiol (CBD) as an adjuvant in the treatment of trigeminal neuralgia (TN) and postherpetic neuropathy has shown beneficial effects in patients refractory to conventional treatments.

This case study describes a 57-year-old patient diagnosed with TN in 2019, initially treated with low-power laser therapy and oxcarbazepine. In 2021, she developed vesicular-bullous lesions on the right side of the supraorbital region, accompanied by severe pain confirmed by positive serology for shingles. Following the diagnosis of postherpetic neuropathy, the drug dose was adjusted and combined with laser therapy. However, the pain remained significant and reduced quality of life.

In 2023, treatment was started with CannaMeds CBD Full Spectrum – 3000 mg/30 ml + CannaMeds CBG Isolate 1500 mg/30 ml. After 15 days, the patient appeared pain-free, allowing the laser to be discontinued and the drug dose to be reduced.

CBD is a treatment option for patients who do not respond to conventional treatments.”

https://pubmed.ncbi.nlm.nih.gov/41281696

“It is difficult to find an effective treatment for these conditions, because over time patients no longer respond to treatment. Therefore, the use of CBD and cannabigerol could be an adjuvant treatment option for patients who do not respond to conventional treatment for neuropathic pain.”

https://journals.lww.com/cocd/fulltext/2025/07000/use_of_cannabidiol_and_cannabigerol_in_the.10.aspx

Cannabis Laws and Opioid Use Among Commercially Insured Patients With Cancer Diagnoses

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“Importance: Pain is a prevalent cancer-related symptom, but limited research investigates whether cannabis is an effective analgesic for cancer pain.

Objective: To examine the association of medical and recreational cannabis dispensary availability on prescription opioid dispensing among commercially insured patients with cancer.

Design, setting, and participants: This cross-sectional study used synthetic control to investigate the association of cannabis dispensary openings with pain medication dispensing among patients with cancer. Data were extracted from Optum’s deidentified Clinformatics Data Mart database from January 1, 2007, to December 31, 2020. The study population included patients aged 18 to 64 years with a cancer diagnosis and at least 6 months of continuous enrollment. Associations were estimated by age, race and ethnicity, and sex. Data were analyzed between December 2024 and February 2025.

Exposures: Exposures included indicators for whether a medical or recreational cannabis dispensary was open in each state-quarter.

Main outcomes and measures: The outcome measures for opioids prescriptions were (1) the rate of patients with a prescription per 10 000 patients, (2) the quarterly mean days’ supply per prescription, and (3) the quarterly mean number of prescriptions per patient.

Results: The study included a mean (SD) of 3.05 (0.86) million patients annually across the US (mean [SD] age, 43.7 [9.6] years; mean [SD] 59.0% [0.32%] female). Medical cannabis dispensary openings were associated with significant reductions in all opioid outcomes. The rate of patients with cancer with opioid prescriptions changed by -41.07 per 10 000 (95% CI, -54.78 to -27.36 per 10 000; P < .001), the quarterly mean days’ supply by -2.54 days (95% CI, -3.16 to -1.92 days; P < .001), and the mean number of prescriptions per patient by -0.099 (95% CI, -0.121 to -0.077; P < .001). Recreational dispensary openings were also associated with reductions in opioid outcomes, though estimated treatment effects were smaller. The rate of prescriptions changed by -20.63 per 10 000 (95% CI, -35.35 to -5.91 per 10 000; P = .049), the mean daily supply by -1.09 days supplied per prescription (95% CI, -1.72 to -0.46 days; P = .04), and the mean number of prescriptions per patient by -0.097 (95% CI, -0.134 to -0.060; P = .01).

Conclusions and relevance: This study’s findings indicate cannabis may be a substitute for opioids in the management of cancer-related pain. However, further research directly observing cannabis use is needed to evaluate the efficacy of cannabis as a treatment for cancer-related pain.”

https://pubmed.ncbi.nlm.nih.gov/41105418

“Results of this study suggest that cannabis may serve as a substitute for opioids in managing cancer-related pain, underscoring the potential of cannabis policies to impact opioid use.”

https://jamanetwork.com/journals/jama-health-forum/fullarticle/2840030

Motor-Related Neural Dynamics are Modulated by Regular Cannabis Use Among People with HIV

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“Recent work has shown that people with HIV (PWH) exhibit deficits in cognitive control and altered brain responses in the underlying cortical networks, and that regular cannabis use has a normalizing effect on these neural responses.

However, the impact of regular cannabis use on the neural oscillatory dynamics underlying motor control deficits in PWH remains less understood. Herein, 102 control cannabis users, control nonusers, PWH who regularly use cannabis, and PWH who do not use cannabis performed a motor control task with and without interference during high-density magnetoencephalography.

The resulting neural dynamics were examined using whole-brain, voxel-wise statistical analyses that examined the impact of HIV status, cannabis use, and their interaction on the neural oscillations serving motor control, spontaneous activity during the baseline period, and neurobehavioral relationships.

Our key findings revealed cannabis-by-HIV group interactions in oscillatory gamma within the prefrontal cortices, higher-order motor areas, and other regions, with the non-using PWH typically exhibiting the strongest gamma interference responses. Cannabis-by-HIV interactions were also found for oscillatory beta in the dorsal premotor cortex. Spontaneous gamma during the baseline was elevated in PWH and suppressed in cannabis users in all regions exhibiting interaction effects and the left primary motor cortex, with spontaneous levels being correlated with behavioral performance.

These findings suggest that regular cannabis use has a normalizing effect on the neural oscillations serving motor control and the abnormally elevated spontaneous gamma activity that has been widely replicated in PWH, which may suggest that cannabis has at least some therapeutic utility in PWH.”

https://pubmed.ncbi.nlm.nih.gov/40473990

“The current study found evidence of multiple novel interactions between cannabis use and HIV status in beta and gamma interference responses across a broad network of brain regions. Further, these findings corroborate multiple recent studies showing elevated spontaneous gamma activity in PWH, and that regular cannabis use is associated with a marked suppression in such spontaneous activity.”

https://link.springer.com/article/10.1007/s11481-025-10219-0

Cannabidiol in Gliomas: Therapeutic Potential and Nanocarrier Strategies, with an Emphasis on Vesicular Delivery Systems

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“Cannabidiol (CBD), a nonpsychoactive phytocannabinoid extracted from Cannabis sativa, has emerged as a compound of considerable therapeutic interest across numerous medical disciplines, including pain management, anti-inflammatory therapy, and oncology.

This review critically examines the potential of CBD in the treatment of glioblastoma multiforme (GBM), one of the most aggressive and treatment-resistant primary brain tumors.

Particular emphasis is placed on the molecular mechanisms underlying CBD’s antitumor activity, including the modulation of key signaling pathways, inhibition of tumor proliferation, and enhancement of chemosensitivity. Furthermore, the review highlights the increasing role of nanotechnology in overcoming the intrinsic pharmacokinetic limitations of CBD, particularly its low oral bioavailability, which presents a significant challenge to its clinical application. Advanced nanocarrier platforms, including nanoemulsions, nanoparticles, nanoparticle-based transdermal systems, nanocapsules, and liposomes, have shown promise in optimizing CBD delivery to the central nervous system (CNS).

Notably, the integration of CBD into lipid-based drug delivery systems (LBDDS) is highlighted as a particularly promising strategy to potentiate its therapeutic efficacy. This approach enhances bioavailability and may amplify synergistic effects when combined with conventional chemotherapeutics or targeted agents.

Overall, the synergistic use of nanotechnological approaches and CBD-based therapies may open new avenues for research, offering the potential to significantly advance treatment efficacy in glioblastoma and other diseases.”

https://pubmed.ncbi.nlm.nih.gov/41288593

https://pubs.acs.org/doi/10.1021/acs.molpharmaceut.5c00853


Cannabinomics in the flower of Cannabis sativa: a systematic review of extraction, analytical identification, and micro/nanoencapsulation methods for bioactive metabolites

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“Introduction: The use of Cannabis sativa has evolved from textile applications in ancient times to a growing interest in its therapeutic and nutraceutical properties. Its regulation varies worldwide, with restrictions on ∆9-THC concentrations depending on the country. Cultivation factors, such as temperature, humidity and photoperiod, affect the concentration of their bioactive metabolites, among which phytocannabinoids have demonstrated impact on the biological regulation of the human organism. Their application in the pharmaceutical, cosmetic and food industries has prompted research into the optimization of their production and extraction.

Objective: The purpose of this systematic review is to identify methodologies for the extraction, analysis and application of cannabinoids in various industries, focusing on agro-industrial transformation to increase their added value and optimize their therapeutic use.

Methodology: A systematic search was performed in the Scopus database on November 14, 2024, identifying keywords and their synonyms for each research question, using Boolean operators. Studies published between 2015 and 2025 related to cannabinoid extraction, identification and application methodologies were included, excluding non-scientific papers. The PRISMA methodology was applied to filter and select articles.

Results: The studies analyzed show that extraction and metabolomic analysis methodologies have gained relevance in recent years, especially for obtaining bioproducts for therapeutic purposes. It was identified that cannabinoids, mainly THC and CBD, have potential in the treatment of inflammatory, neurological and chronic pain diseases. In addition, the application of emerging technologies for the micro and nanoencapsulation of cannabinoids, optimizing their bioavailability, was evidenced. However, there are still gaps in the literature on the correlation between extraction operating conditions and the efficiency of the final product, which hinders its industrial scalability.

Conclusions: The growing interest in Cannabis sativa research has led to the exploration of various techniques for the extraction and analysis of its metabolites. However, despite advances in laboratory methodologies, the industrial application of these processes remains a challenge. The lack of studies correlating operational variables with extraction efficiency limits the standardization of bioproducts. Future research should focus on articulating technology and applied science to establish production models to improve the traceability and safety of Cannabis sativa extracts, favoring their integration into the pharmaceutical and agro-industrial industry.”

https://pubmed.ncbi.nlm.nih.gov/41291955

https://link.springer.com/article/10.1186/s42238-025-00350-3

Chemical Profile, Bioactive Constituents and In Vitro Growth Stimulation Properties of Cold-Pressed Hemp Seed Oils from Romanian Varieties: In Vitro and In Silico Evaluation

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“Industrial hemp (Cannabis sativa L.; Cannabaceae), traditionally cultivated for fiber, also represents a valuable source of nutrient-rich seed oil.

In this study, cold-pressed hemp seed oils from three Romanian varieties (Teodora, Silvana, and Armanca) were evaluated for their fatty acid composition, minor bioactive constituents, antioxidant activity, growth-promoting property toward probiotic strains in vitro, and molecular docking interactions with probiotic targets.

Gas chromatography revealed a fatty acid profile dominated by linoleic (49.4-51.9%), oleic (16.3-22.8%), and α-linolenic acids (9.8-14.4%), resulting in favorable PUFA/SFA ratios (5.17-6.39) and ω-6/ω-3 ratios (3.93-5.53).

The oils also contained phenolics (118-160 mg GAE/kg), chlorophylls (6.18-8.31 mg/kg), and carotenoids (2.58-3.37 mg/kg), which contributed to their antioxidant activity (DPPH inhibition 35.92 µM TE/100 g-43.37 µM TE/100 g).

Broth microdilution assays against Lacticaseibacillus rhamnosus GG, L. paracasei ATCC BAA-52, and L. acidophilus ATCC 4356 demonstrated strain- and dose-dependent potential to promote probiotic growth under in vitro conditions. While L. rhamnosus and L. paracasei were inhibited at low concentrations and only mildly stimulated at higher levels, L. acidophilus showed robust growth promotion, reaching +54.7% effect and CP = 1.55 with Teodora oil at 16 mg/mL.

Molecular docking highlighted strong binding affinities of γ-linolenic and linoleic acids with key metabolic enzymes involved in probiotic metabolism (hydratase, enolase, glyceraldehyde-3-phosphate dehydrogenase, ribonucleoside hydrolase), forming stable hydrophilic and hydrophobic interactions which are explored in defining the stability of the ligand-protein complexes.

These results indicate that both major fatty acids and minor bioactive constituents contribute to the nutritional and antioxidant value of Romanian hemp seed oils and reveal a potential to promote probiotic growth under in vitro conditions, as supported by complementary in silico evidence.”

https://pubmed.ncbi.nlm.nih.gov/41304617

“This study demonstrated that cold-pressed hemp seed oils from Romanian varieties are rich in polyunsaturated fatty acids, with favorable PUFA/SFA and ω-6/ω-3 ratios that support their role as health-promoting dietary fats. Alongside their fatty acid profile, the oils contain phenolic compounds, chlorophylls, and carotenoids, which contribute to antioxidant stability and may synergize with PUFAs to enhance biological effects.”

https://www.mdpi.com/2223-7747/14/22/3465


Chronic cannabis use in people with bipolar disorder is associated with comparable decision-making and functional outcome to healthy participants

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“Impaired decision-making is often seen in people with bipolar disorder (BD), even those undergoing treatment. Targeted therapeutics are therefore needed.

People with BD report that cannabis use (CU) attenuates such cognitive and behavioral symptoms.

We hypothesized that 1) people with BD who do not use cannabis would exhibit poor decision-making and functional capacity relative to healthy comparison (HC) participants and 2) CU in people with BD would be associated with decision-making and functional capacity comparable to that of HC participants who do not use cannabis.

HC and BD participants that either reported regular (≥4x/weekly) CU or no-CU were recruited (n = 87). Participants were tested on decision-making and functional capacity using the Iowa Gambling Task and UCSD Performance-based skills assessment (UPSA-2), respectively.

CU was associated with impaired decision-making in healthy participants while CU in participants with BD was associated with better decision-making than their non-using counterparts and equivalent to decision-making in non-CU HC participants.

Additionally, CU in people with BD was associated with UPSA-2 scores comparable to non-CU HC participants. Studies are needed to determine whether cannabinoid-related treatments improve such decision-making and function in people with BD.”

https://pubmed.ncbi.nlm.nih.gov/41309543

“In summary, people with BD who use cannabis had decision-making and functional capacity comparable to non-CU HC participants.”

https://www.nature.com/articles/s41398-025-03718-4