Author Archives: David Worrell

Medical Cannabis for Best Supportive Care of Patients Affected by Cancers of the Head and Neck: A Narrative Review

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“Cancers of the head and neck, including malignancies of the oral cavity, pharynx, larynx, and salivary glands, are often associated with severe symptoms that negatively impact quality of life. Patients commonly experience pain, nausea, cachexia (severe weight loss), dysphagia (difficulty swallowing), and xerostomia (dry mouth), all of which can be exacerbated by both the disease and its treatments, such as surgery, radiation, and chemotherapy.

Research has demonstrated that medical cannabis can be effective in managing symptoms such as chronic pain, nausea, vomiting, and anxiety, making it a valuable option in cancer care. Its ability to interact with the endocannabinoid system to reduce nociception (pain perception) and inflammation makes it particularly suitable for the complex symptom burden of patients with head and neck cancer.

This review explores the role of the endocannabinoid system and medical cannabis in mitigating symptoms and improving patient outcomes, as well as its place within the comprehensive care of patients with cancers of the head and neck.”

https://pubmed.ncbi.nlm.nih.gov/41482365

“Medical cannabis is a very interesting and emerging tool in the supportive care of patients with head and neck cancers, offering relief from pain, nausea, loss of appetite, and psychological distress. It complements existing therapies and provides an alternative or adjunct to conventional symptom management strategies, particularly for patients who do not tolerate traditional medications well.”

https://iv.iiarjournals.org/content/40/1/50

Medical Cannabis and Opioid Receipt Among Adults With Chronic Pain

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“Question  Is participation in the New York State (NYS) medical cannabis program associated with reduced prescription opioid receipt among adults with chronic pain?

Findings  In this cohort study of 204 adults with chronic pain, participation in the NYS medical cannabis program, defined as monthly dispensation of medical cannabis reported by the dispensary pharmacist, was associated with significantly reduced prescription opioid receipt.

Meaning  These findings suggest that participation in a pharmacist-directed medical cannabis program may help reduce prescription opioid receipt among adults with chronic pain.

Abstract

Importance  Medical cannabis is increasingly considered a substitute for prescription opioid medications for chronic pain, driven by the urgent need for opioid alternatives to combat the ongoing epidemic.

Objective  To determine the association between participation in the New York State (NYS) medical cannabis program and prescription opioid receipt among adults with chronic pain.

Design, Setting, and Participants  This cohort study used data from the NYS Prescription Monitoring Program (PMP) from September 2018 through July 2023. Adults prescribed opioids for chronic pain who were newly certified for medical cannabis use in NYS were recruited from a large academic medical center and nearby medical cannabis dispensaries in the Bronx, New York. Monthly dispensation of medical cannabis to study participants was monitored for 18 months. Data analyses were performed from February 3, 2025, to July 15, 2025.

Exposure  Portion of days covered each month by pharmacist report of dispensed medical cannabis.

Main Outcomes and Measures  Prescription opioid receipt, defined as NYS PMP-reported prescription monthly opioid dispensation (mean daily dose in morphine milliequivalents [MME]), was assessed with marginal structural models adjusted for time-invariant and time-varying confounders, including self-reported unregulated cannabis use. Nonprescribed opioid use was also assessed during the study period.

Results  Among 204 participants, the mean (SD) age at baseline was 56.8 (12.8) years, and 113 (55.4%) were female. At baseline, participants’ mean (SD) pain severity score was 6.6 (1.8) out of 10, and mean (SD) pain interference score was 6.8 (1.9) out of 10. Baseline mean (SD) daily MME was 73.3 (133.0). During the 18-month follow-up period, participants’ mean (SD) daily MME decreased to 57.4 (127.8). This reduction in mean daily MME was associated with the monthly portion of days covered with medical cannabis; compared with no medical cannabis dispensed, participants dispensed a 30-day supply of medical cannabis were exposed to 3.53 fewer MME per day (β = −3.53; 95% CI, −6.68 to −0.04; P = .03).

Conclusions and Relevance  In this cohort study, participation in NYS’s medical cannabis program was associated with reduced prescription opioid receipt during 18 months of prospective follow-up, accounting for unregulated cannabis use.”

https://jamanetwork.com/journals/jamainternalmedicine/article-abstract/2842414

Medical Cannabis Program Lowers Chronic Pain Opioid Prescriptions

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“Access to medical cannabis through a state-regulated program was associated with significantly lower rates of opioid prescriptions among adults with chronic pain, according to findings recently published in JAMA Internal Medicine.

The study included 204 adults enrolled in the New York State medical cannabis program, which provided monthly access to medical cannabis through a dispensary pharmacist, and 142 ultimately obtained the treatment. The data spanned from September 2018 through July 2023. Researchers measured prescription opioid receipt via mean daily dose in morphine milliequivalents (MME) and compared it with how many days’ worth of cannabis individuals were dispensed each month based on pharmacists’ reports.

After 18 months, the mean daily MME decreased by 22%, from 73 to 57.

The authors noted that instead of measuring medical cannabis exposure via its legalization status, they directly analyzed pharmacy dispensation amounts, a more accurate indicator of uptake. Randomized clinical trials are needed to see whether medical cannabis reduces opioid use, they added.”

https://pubmed.ncbi.nlm.nih.gov/41481315

https://jamanetwork.com/journals/jama/fullarticle/2843608

Cannabidiol Enhances SIRT1 and Autophagy for the Maintenance of Human Mesenchymal Stem Cells

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“Background/aim: Mesenchymal stem cells (MSCs) are used to treat various degenerative diseases. However, their therapeutic potential is limited by cellular aging during in vitro cultivation. This study aimed to explore whether cannabidiol (CBD) can delay MSC aging by enhancing the expression of Sirtuin 1 (SIRT1) and autophagy, two key anti-aging regulators.

Materials and methods: CBD, the most important non-psychotomimetic phytocannabinoid derived from the Cannabis sativa plant, was used to up-regulate SIRT1 and autophagy in order to maintain MSC stemness. MSCs were treated with CBD and assessed for cell viability, doubling time, key gene/protein expression, relative senescence-associated β-galactosidase (SA-β-gal) assay, relative telomere length, and telomerase expression.

Results: CBD significantly increased the expression of SIRT1 and autophagy-related markers in MSCs. Furthermore, CBD preserved MSC stemness by promoting the deacetylation of SRY-box transcription factor 2 (SOX2) through SIRT1, and delayed cellular senescence by enhancing autophagy, reducing SA-β-gal activity, maintaining proliferation capacity, and supporting telomere function.

Conclusion: CBD promotes MSC stemness and delays cellular senescence, potentially through the activation of SIRT1 and autophagy. These findings suggest that CBD may serve as a promising agent for preserving MSC function in regenerative medicine.”

https://pubmed.ncbi.nlm.nih.gov/41482390

“Cannabidiol (CBD) is the major non-psychotomimetic phytocannabinoid derived from the Cannabis sativa plant. Numerous studies have demonstrated its broad pharmacological effects, including antidepressant, anti-inflammatory, antiemetic, neuroprotective, analgesic, antibacterial, anticonvulsant, anxiolytic, antipsychotic, antitumor, and immunomodulatory activities. Recently, CBD has been shown to extend lifespan and improve health span in various models”

“This study demonstrates that an optimal concentration of CBD enhances MSC proliferation and promotes SIRT1 activation, thereby inducing autophagy and maintaining stemness through the regulation of SOX2. Moreover, CBD was found to delay cellular senescence and preserve replicative potential in MSCs. Collectively, these findings highlight CBD as a promising modulatory agent for improving MSC longevity and therapeutic quality, with potential implications for regenerative and anti-aging applications.”

https://iv.iiarjournals.org/content/40/1/222

Phytocannabinoids as anti-inflammatory agents: Synergistic effects when combined with Cannabis sativa matrices

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“Ethnopharmacological relevance: Cannabis sativa L. has a long history of traditional use for the treatment of pain and inflammatory disorders in both Asian and European medical systems, which supports its investigation as a source of bioactive compounds with potential relevance for chronic immune-mediated diseases.

Aim of the study: This study evaluated the ten major non-psychotropic phytocannabinoids for their anti-inflammatory and antioxidant activities, and for synergistic interactions with non-cannabinoid matrices derived from the same plant (polar, non-polar and terpenoid).

Material and methods: Anti-inflammatory effects were assessed in macrophage-differentiated THP-1 cells by measuring pro-inflammatory cytokine production (ELISA) and nuclear factor kappa B (NF-κB) pathway activation (luciferase reporter assay).

Results: All tested phytocannabinoids demonstrated anti-inflammatory effects, in particular, cannabidivarin (CBDV) reduced IL-6, TNF-α production and also inhibited NF-κB activation. Several phytocannabinoids, especially their acidic forms, exhibited high oxygen radical absorption capacity (ORAC), but none showed significant cellular antioxidant activity (CAA), possibly due to limited bioavailability. Importantly, several phytocannabinoid-matrix mixtures displayed synergistic anti-inflammatory effects, with combinations containing cannabigerol (CBG) or cannabinol (CBN) being particularly potent.

Conclusion: These findings highlight the potential of lesser-known phytocannabinoids, especially in combination with specific C. sativa L. matrix components, to modulate inflammatory pathway supporting their development as functional ingredients for managing chronic gut-associated inflammation.”

https://pubmed.ncbi.nlm.nih.gov/41478536

“Full plant chemical complexity outperforms single phytocannabinoid alone.”

“Non-psychotropic phytocannabinoids present promising functional food ingredients.”

https://www.sciencedirect.com/science/article/abs/pii/S0378874125018276?via%3Dihub

Extract engineering of Cannabis sativa yields novel antibacterial cannabinoids targeting Staphylococcus aureus and methicillin-resistant Staphylococcus aureus

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“Cannabis sativa is a phytochemically rich plant producing over 500 compounds, with cannabinoids recognized as its most bioactive constituents.

However, the natural exploration and exploitation of novel, pharmacologically active cannabinoids remain limited due to their trace abundance in the plant. To address this challenge, we employed an extract engineering strategy in which enriched fractions of major cannabinoids were chemically transformed through oxone/acetone oxidation under mild conditions.

This approach enabled the purification of seven cannabinoid analogs, including rare and previously undescribed compounds, in appreciable quantities. The structures of these analogs were elucidated using high-resolution mass spectrometry combined with comprehensive 1D and 2D NMR spectroscopy.

Antibacterial susceptibility assay revealed that out of seven compounds, Compound 1, 5, and 7 exerted significant inhibitory activity against both Staphylococcus aureus and methicillin-resistant S. aureus (MRSA) pathogens.

A Checkerboard study revealed the synergistic interaction between active hits and Rifampin in both S. aureus and MRSA. The biofilm-based assay demonstrated the antibiofilm potential of the identified hits. The mechanistic exploration elucidated the cell membrane-based targeting of the potent hits, validated through scanning electron microscopy. Moreover, the Propidium iodide assay performed using flow cytometry and fluorescence microscopy revealed the membrane disruption effect of the identified hits. In addition, the ATP quantification study demonstrated a major decline in ATP levels along with an augmentation in ROS production in the MRSA pathogen.

Thus, this work establishes extract engineering as a powerful strategy to unlock rare cannabinoid scaffolds and highlights their potential as leads for combating multidrug-resistant Staphylococcus infections.”

https://pubmed.ncbi.nlm.nih.gov/41478197


“Cannabis sativa has diverse phytochemical composition and therapeutic potential.”

“In summary, comprehensive antistaphylococcal evaluation of the cannabinoid-based molecules demonstrated strong antibacterial activity against both S. aureus and MRSA pathogens, along with synergistic interaction when combined with standard drugs. Notably, the potent molecules expressed low propensity for the development of resistance in the MRSA strain. Moreover, the antibiofilm action of the potent hits highlighted their curative role…”

https://www.sciencedirect.com/science/article/abs/pii/S0045206825013288?via%3Dihub

Vaporized cannabis versus placebo for acute migraine: A randomized, double-blind, placebo-controlled crossover trial

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“Objective: To assess the efficacy of cannabis for the treatment of acute migraine.

Background: Preclinical and retrospective studies suggest cannabinoids may be effective in migraine treatment. However, there have been no randomized clinical trials examining the efficacy of cannabinoids for acute migraine.

Methods: In this randomized, double-blind, placebo-controlled, crossover trial, adults with migraine treated up to four separate migraine attacks, one each with vaporized (1) 6% Δ9-tetrahydrocannabinol (THC) (THC-dominant), (2) 11% cannabidiol (CBD) (CBD-dominant), (3) 6% THC + 11% CBD, and (4) placebo cannabis flower in a randomized order. Washout period between treated migraine attacks was ≥1 week. The primary endpoint was pain relief, and secondary endpoints were pain freedom and most bothersome symptom freedom, all assessed at 2-h post-vaporization.

Results: Ninety-two participants were enrolled and randomized, and 247 migraine attacks were treated. THC + CBD was superior to placebo at achieving pain relief (67.2% vs. 46.6%, odds ratio [95% confidence interval] 2.85 [1.22, 6.65], p = 0.016), pain freedom (34.5% vs. 15.5%, 3.30 [1.24, 8.80], p = 0.017), and most bothersome symptom freedom (60.3% vs. 34.5%, 3.32 [1.45, 7.64], p = 0.005) at 2 h, as well as sustained pain freedom at 24 h and sustained most bothersome symptom freedom at 24 and 48 h. THC-dominant was superior to placebo for pain relief (68.9% vs. 46.6%, 3.14 [1.35, 7.30], p = 0.008) but not pain freedom or most bothersome symptom freedom at 2 h. CBD-dominant was not superior to placebo for pain relief, pain freedom, or most bothersome symptom freedom at 2 h. There were no serious adverse events.

Conclusion: Acute migraine treatment with 6% THC + 11% CBD was superior to placebo at 2-h post-treatment with sustained benefits at 24 and 48 h.”

https://pubmed.ncbi.nlm.nih.gov/41469488

“Many people with migraine self-treat with cannabinoids or are interested in using cannabinoids to treat migraine. In this double-blind study, people with migraine treated up to 4 migraine attacks, 1 attack was treated with each of 3 vaporized cannabis flower treatments (THC 6%, CBD 11%, and THC 6% + CBD 11%) or placebo cannabis flower without THC or CBD, within the first 4 h of migraine attack onset. Four puffs of cannabis flower containing THC 6% + CBD 11% was superior to placebo at treating migraine attacks, though the study did not examine the long-term effects of frequent use.”

https://headachejournal.onlinelibrary.wiley.com/doi/10.1111/head.70025

Unveiling Neurological Benefits: A Review of Hemp Leaf, Flower, Seed Oil Extract, and Their Phytochemical Properties in Neurological Disorders

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“Neurological disorders such as epilepsy, Alzheimer’s disease, Parkinson’s disease, and multiple sclerosis present significant global health care challenges, with complex pathophysiology and limited therapeutic options that often carry substantial side effects.

Hemp-derived compounds, particularly from Cannabis sativa seeds, leaves, and flowers, have gained attention for their potential neuroprotective properties.

This review aims to synthesize the current evidence surrounding the therapeutic benefits of hemp-derived compounds, focusing on their bioactive phytochemical profiles, mechanisms of action, and therapeutic efficacy in treating neurological disorders.

A comprehensive review of pre-clinical and clinical studies was conducted, analyzing the phytochemical composition of hemp extracts, including cannabinoids (such as cannabidiol, CBD), terpenes, flavonoids, and polyunsaturated fatty acids. We explored their mechanisms of action through interactions with the endocannabinoid system, neurotransmitter receptors, inflammatory pathways, and oxidative stress mechanisms.

The review highlights the therapeutic potential of hemp-derived extracts in mitigating various neurological conditions. Pre-clinical and clinical studies have demonstrated their efficacy in reducing seizure frequency in epilepsy, protecting dopaminergic neurons in Parkinson’s disease, alleviating neuroinflammation and oxidative stress in Alzheimer’s disease, and promoting remyelination in multiple sclerosis.

The entourage effect, where cannabinoids, terpenes, and flavonoids work synergistically, enhances these therapeutic effects. Innovations in extraction technologies have optimized yield and preserved bioactivity, further enhancing clinical relevance.

Hemp-derived compounds exhibit significant neuroprotective and therapeutic potential for managing neurological disorders. However, challenges such as product standardization, safety profiles, and regulatory frameworks must be addressed for clinical translation. Further research is essential to optimize dosing, establish safety parameters, and develop standardized formulations, which will be crucial for fully harnessing the therapeutic potential of hemp-derived products in treating neurological conditions.”

https://pubmed.ncbi.nlm.nih.gov/41468178

https://www.liebertpub.com/doi/10.1177/25785125251410822


Targeting bladder cancer: Potent anti-cancer effects of cannabichromene and delta-9-tetrahydrocannabinol-rich Cannabis sativa strains

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“Objective: This study aimed to explore the anticancer potential of Cannabis sativa (C. sativa) strains, specifically PARIS, Dairy Queen (DQ), and super cannabidiol (sCBD), on bladder cancer cells. Given the increasing interest in cannabinoids like cannabichromene (CBC) and delta-9-tetrahydrocannabinol (THC) for their therapeutic properties, we evaluated their cytotoxic effects on urothelial carcinoma (UC) cell lines and their ability to inhibit cell migration and induce apoptosis in both two-dimensional cell models and three-dimensional ex vivo organ cultures (EVOCs).

Methods: C. sativa strains were screened for their cytotoxicity against UC cell lines (HTB-4 and HTB-9) using XTT assays. Their phytocannabinoid content was analyzed using high-performance liquid chromatography. We employed fluorescence-activated cell-sorting to determine apoptosis and cell cycle, migration assays to determine cell migration, and EVOCs to evaluate the cytotoxic effect on UC. Gene expression was determined by quantitative polymerase chain reaction.

Results: Three commercial C. sativa strains, PARIS, DQ, and sCBD, were found to have the most potent anticancer effects on bladder cancer cells. All extracts contain CBC and THC at different concentrations. In XTT assays on UC cell lines, PARIS had a half-maximal inhibitory concentration (IC50) of 21.58 μg/mL, while DQ and sCBD had similar cytotoxic activity with IC50 values for 48-h treatment of 17.99 μg/mL and 17.88 μg/mL, respectively. DQ and sCBD extracts were found to significantly reduce cell migration and increase the percentage of cells in S phase and G2/M phase within the cell population. In EVOCs, the extracts initiated cell death with the expression of apoptosis-related genes increased following exposure to treatment.

Conclusion: The findings suggest that C. sativa strains PARIS, DQ, and sCBD, containing CBC and THC, exhibit significant anticancer activity against UC cell lines and ex vivo models. These results underscore the therapeutic potential of CBC- and THC-rich C. sativa extracts in bladder cancer treatment.”

https://pubmed.ncbi.nlm.nih.gov/41467200

“This study highlights the potential of commercially available cannabis extracts in inhibiting UC tumors through programmed cell death, the expression of apoptosis-related genes, and cell migration inhibition. The findings emphasize the significance of cannabinoid-specific content over total cannabinoid concentrations in determining their cytotoxic effects. While personalized medicine based on specific strain compositions remains a distant goal, certain cannabinoids like CBC, THC, and CBD show promise in exerting cytotoxic effects.”

“Overall, these findings underscore the potential of cannabis-derived compounds as therapeutic agents in cancer treatment and warrant further investigation.”

https://www.sciencedirect.com/science/article/pii/S2214388225000335?via%3Dihub

Targeting Human Cancer Cells with Cannabidiol (CBD): Apoptotic Cytotoxicity in HeLa, MDA-MB-231, and CaCo-2 Lines

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“Cannabidiol (CBD), a phytocannabinoid derived from Cannabis sativa, has demonstrated therapeutic potential across various diseases, including cancer.

This study evaluates the cytotoxic effects of CBD on three human cancer cell lines (HeLa, MDA-MB-231, and CaCo-2) and two non-cancerous cell lines (HaCaT and HUVEC) used as a control. Cells were treated with CBD at concentrations of 5, 10, and 20 µM for 24, 48, 72, and 96 h. Cytotoxicity was assessed using MTT assays, nuclear morphology was evaluated via DAPI staining, and cell death mechanisms were analyzed through flow cytometry with apoptosis/necrosis markers. The LC50 values at 24 h were determined as follows: HeLa (9.4 µM), MDA-MB-231 (10.3 µM), and CaCo-2 (4.3 µM).

CBD treatment induced morphological changes characteristic of cell stress and death in cancer cells, observed by optical microscopy after 24, 48, 72, and 96 h of exposure. These findings highlight the potential of CBD as an adjunctive therapeutic agent for cancer treatment versus non-malignant cells.”

https://pubmed.ncbi.nlm.nih.gov/41465562

“The findings of this study confirm the potential of CBD as a cytotoxic agent with pro-apoptotic activity in cancer cells.”

“CBD appears to exert a multifaceted mechanism of action on tumor cells, involving both the endocannabinoid system and receptor-independent pathways.”

“In the present study, we demonstrated that CBD induces apoptosis in human cancer cells (HeLa, MDA-MB-231, and CaCo-2) while delaying apoptotic processes in non-malignant control cells (HaCaT and HUVEC). These findings underscore the potential of CBD as an adjunctive therapeutic agent for cancer treatment, highlighting its selective cytotoxic effects on malignant cells with limited impact on non-malignant cells.”

“These results underscore the potential of CBD as an adjunctive therapy in cancer treatment, particularly for colorectal adenocarcinoma, where it exhibited greater efficacy.”

https://www.mdpi.com/1422-0067/26/24/12136