Author Archives: David Worrell

Cannabis Use and Risk of Chronic Rhinosinusitis and Sinus Surgery

Posted on by

“Objective: While cannabis’ link to asthma is well-studied, its impact on CRS is less clear. This study explores the association between cannabis use and rates of new-onset chronic rhinosinusitis (CRS), chronic rhinosinusitis with nasal polyps (CRSwNP), and functional endoscopic sinus surgery (FESS) rates.

Methods: The TriNetX Analytics Research Network was queried for adults ≥ 18 years old, stratified into cannabis user and non-user cohorts based on electronic health record data from January 2012 to December 2019. Separate cohorts of patients with pre-existing CRS-with and without cannabis use-were analyzed to evaluate associations with FESS. Primary outcomes were relative risks of new-onset CRS and CRSwNP encounter diagnosis and FESS 1, 2, and 5 years after initial cannabis use diagnosis.

Results: After 1:1 propensity score matching, cohorts analyzing CRS and CRSwNP included 73,091 patients each. Cannabis use was associated with reduced risk of unspecified CRS at 1 year (aRR = 0.87, 95% CI 0.80-0.95), 2 years (aRR = 0.84, 95% CI 0.78-0.90), and 5 years (aRR = 0.83, 95% CI 0.78-0.87). There was no difference in risk of CRSwNP at any timepoints. For FESS outcomes, matched cohorts included 5591 patients with pre-existing CRS; cannabis users had lower risk at 1 year (aRR = 0.67, 95% CI 0.47-0.96), 2 years (aRR = 0.64, 95% CI 0.46-0.88), and 5 years (aRR = 0.69, 95% CI 0.52-0.91).

Conclusions: Patients with cannabis use demonstrated significantly reduced risks in new-onset diagnoses of CRS and FESS compared to non-users. Further studies are warranted to examine the cause of this relationship.”

https://pubmed.ncbi.nlm.nih.gov/41323660

“Our findings suggest that cannabis use is associated with a reduced incidence of new-onset CRS and a lower need for FESS in patients already diagnosed with CRS.”

https://onlinelibrary.wiley.com/doi/10.1002/lio2.70320

“The Associative Impact of Recreational Cannabis Use on Sinonasal Diseases. Users demonstrated significantly lower odds of AR, CRS, and CR than never users. There is an inverse, associative relationship between cannabis use and sinonasal disease.”

https://pubmed.ncbi.nlm.nih.gov/41064579

Modulatory Effects of “Minor” Cannabinoids in an in vitro Model of Neuronal Hypersensitivity

Posted on by

“Aim: Effective treatment for neuropathic pain remains an unmet clinical need. The therapeutic benefits of the Cannabis plant are well known, especially for pain relief. Here, we have assessed ten “minor” cannabinoids for their analgesic effects in an established model of neuronal hypersensitivity, a key mechanism which underlies neuropathic pain.

Methods: Adult rat DRG neurons were cultured in medium containing 100 ng/mL nerve growth factor (NGF) and 50 ng/mL glial cell-line derived neurotrophic factor (GDNF) for 48 hours to sensitize the neurons. Ca2+ imaging was used to measure the responses to pain stimulation using capsaicin, and to determine the modulatory effects of the cannabinoids, in individual neurons.

Results: Control neurons (nociceptors) showed robust responses of Ca2+ influx to capsaicin application, while neurons treated with ten minor cannabinoids tetrahydrocannabiorcol (THCC), cannabitriol (CBT), cannabidivarin (CBDV), cannabinol (CBN), cannabichromene (CBC), cannabichromevarin (CBCV), cannabicitran (CBCT), cannabigerol monomethyl ether (CBGM), tetrahydrocannabutol (THCB) or tetrahydrocannabiphorol (THCP), at concentrations of 0.001-100 μM, showed differential dose-related effects on the responses to capsaicin. Ca2+ influx in response to capsaicin application was completely inhibited for each compound in 35-78% capsaicin-sensitive neurons, while other neurons showed reduced responses. The opioid receptor agonist morphine and α2δ1- Ca2+ channel inhibitor gabapentin were also tested for comparison and showed similar results. All the cannabinoids tested here inhibited calcium influx in response to capsaicin, and two, namely, CBN and THCC elicited calcium influx at higher doses. Inhibition of Ca2+ influx due to cannabichromene (CBC) was reversed by the potassium channel inhibitor Tertiapin Q.

Conclusion: All the cannabinoids tested here inhibited TRPV1 signalling. CBC targeted K+ channels to block TRPV1 mediated Ca2+ influx, demonstrating potential analgesic effects in vitro.”

https://pubmed.ncbi.nlm.nih.gov/41322279

“The therapeutic benefits of the Cannabis plant are well known, especially for pain relief.”

“In conclusion, our results show that the minor cannabinoids potently inhibit TRPV1 signaling in sensitized DRG neurons, and for CBC by blocking Ca2+ influx via K+ channel activation. This conclusion is based on the reversal of CBC-mediated inhibition in the presence of the K+ channel inhibitor Tertiapin Q. Further studies are necessary to confirm the mechanism, pathways and targets involved in the observed inhibitory effects of the other minor cannabinoids. This will facilitate the identification of cannabinoid combinations likely to have the maximum effect in providing analgesia for inhibiting neuronal sensitization that underlies chronic pain.”

https://www.dovepress.com/modulatory-effects-of-minor-cannabinoids-in-an-in-vitro-model-of-neuro-peer-reviewed-fulltext-article-JPR

Advances in Extraction and Quantification of Minor Phytocannabinoids

Posted on by

“Ever since the chemical structures of major phytocannabinoids, such as Δ9-tetrahydrocannabinol (THC) and cannabidiol (CBD), were elucidated, the majority of research has focused primarily on these compounds, often overlooking the other ~160 minor cannabinoids identified in Cannabis sativa to date. However, in recent years, these previously understudied cannabinoids have garnered increasing scientific attention due to advancements in highly sensitive analytical techniques that enable their detection in plant matrices.

Moreover, early-stage clinical trials have demonstrated that several minor cannabinoids exhibit promising therapeutic potential.

This review aims to provide a comprehensive summary of recent developments in the extraction, analysis, and potential applications of selected minor phytocannabinoids, with the goal of facilitating future research in this field. A thorough analysis of the latest data has been conducted to offer a detailed overview of current extraction and quantification methodologies for minor cannabinoids.”

https://pubmed.ncbi.nlm.nih.gov/41321142

https://analyticalsciencejournals.onlinelibrary.wiley.com/doi/10.1002/pca.70040

Structural and dynamic mechanisms of cannabinoid receptors

Posted on by

“Cannabinoids and their G protein-coupled receptors (GPCRs) within the endocannabinoidome are pivotal regulators of neuromodulation, inflammation, and metabolic homeostasis.

Dysregulation of this system has been associated with a wide spectrum of pathological conditions, including neuropsychiatric disorders, chronic pain, and immune dysfunction.

In this review, we summarize recent structural advances in cannabinoid receptors that have deepened our understanding of receptor activation, allosteric modulation, transducer coupling selectivity, and dynamic conformational mechanisms.

These structural insights will facilitate cannabinoid receptor-targeted drug discovery, enabling the development of therapeutics with improved subtype selectivity, enhanced signaling precision, and reduced off-target effects.”

https://pubmed.ncbi.nlm.nih.gov/41319927

“The medicinal use of phytocannabinoids has been documented for millennia, with applications across diverse cultures in the treatment of insomnia, pain, epilepsy, headaches, and inflammation. Modern scientific investigation into cannabis began in the 1930 s, culminating in the isolation and structural characterization of its major constituents.”

“Taken together, these findings highlight cannabinoid receptors as multifaceted and dynamic therapeutic targets positioned at the intersection of neurology, immunology, and metabolism. A deeper understanding of its structural and signaling mechanisms will be critical for the rational design of next-generation cannabinoid-based therapies that harness its extensive regulatory potential with precision.”

https://www.sciencedirect.com/science/article/abs/pii/S0006295225008330?via%3Dihub


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

Posted on by

“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

Posted on by

“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

Posted on by

“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

Posted on by

“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

Posted on by

“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

Posted on by

“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