Author Archives: David Worrell

In Vitro Antimicrobial Effect of Tetrahydrocannabinol on Streptococcus mutans and Its Anticariogenic Potential

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“Introduction and aims: With the increasing use of marijuana, it is vital to understand the effect of tetrahydrocannabinol (THC) on oral microbiota, especially the primary carious pathogen Streptococcus mutans.

Methods: The minimum inhibitory concentration (MIC) of THC against S mutans was determined by antimicrobial susceptibility testing. Bacterial acid production was evaluated. The effect of THC on S mutans biofilm formation and preformed biofilms was determined by crystal violet assay. The metabolic activity and viability of the biofilm were assessed using the methylthiazolyldiphenyl tetrazolium bromide assay and live/dead assay, respectively. Extracellular polysaccharide (EPS) was examined by Cascade Blue Dextran staining. S mutans membrane potential was detected by the Baclight Bacterial Membrane Potential Kit.

Results: The MIC of THC against S mutans was 2 µg/mL (P < .0001). A total of ≥2 µg/mL THC reduced bacterial acidogenicity and inhibited over 90% of biofilm formation (P < .0001). Additionally, ≥1 µg/mL THC reduced biofilm viability and EPS production (P < .0001), as assessed by fluorescence measurements and microscopy. While 1 to 64 µg/mL THC did not degrade preformed biofilm, metabolic activity was reduced by 16 to 64 µg/mL THC (P < .01), and 8 to 32 µg/mL THC reduced biofilm viability in a time- and dose-dependent manner (P < .001). Moreover, 2 to 8 µg/mL THC promoted membrane hyperpolarization after a 5-minute treatment (P < .01).

Conclusion: THC inhibits S mutans growth and biofilm formation while also reducing bacterial viability, EPS production, and acid production. Although it does not degrade preformed biofilm biomass, THC diminishes its metabolic activity and viability. These effects may be linked to THC-induced membrane hyperpolarization. This in vitro study suggests that THC may reduce the cariogenic capacity of S mutans.

Clinical relevance: This study shows that THC inhibits S mutans growth, biofilm formation, properties of preformed biofilms, and acid production. It provides preliminary scientific evidence on the impact of THC on oral health, specifically cannabinoid consumption on cariogenesis, and a potential new avenue for developing a new anticariogenic agent.”

https://pubmed.ncbi.nlm.nih.gov/41576726

“Among the cannabinoids, THC is the most abundant and exhibits a range of therapeutic effects, including analgesic, antiemetic, anti-inflammatory, anticancer, and antiseizure properties, as well as offering neuroprotective benefits in cases of neurodegeneration.”

Taken together, we herein provide evidence of the efficacy of THC in antibacterial and antibiofilm activity against S mutans by reducing planktonic growth of S mutans, inhibiting biofilm formation, and interfering with preexisting biofilm activity and function.

In addition, it may be a potential new avenue for developing new anticariogenic agents by suppressing the growth of S mutans and decelerating the acidification process that leads to enamel demineralization.”

https://www.sciencedirect.com/science/article/pii/S0020653925086678?via%3Dihub

“Anticariogenic (meaning “anti-cavity”) describes substances or practices that prevent or arrest the development of dental caries (tooth decay).”

Exploring the neuroprotective effects of phytocannabinoids on oxygen-glucose deprived neurons in an in vitro model of stroke

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“Stroke is a leading cause of death and disability worldwide, but therapeutic options to reduce or prevent neuronal damage are extremely limited.

Cannabinoids exhibit antioxidant, anti-inflammatory, and receptor modulatory actions that may offer neuroprotection.

While research on the potential of cannabinoids has expanded in epilepsy and neurodegeneration, the neuroprotective potential of this class of natural compounds in stroke remains underexplored. Here, we evaluated a panel of phytocannabinoids (PCs) for their ability to mitigate ischemia–reperfusion injury in an in vitro human model of stroke.

Methods

Human induced pluripotent stem cell (iPSC)-derived cortical neurons were subjected to 60 min of oxygen–glucose deprivation (OGD) followed by reperfusion. Neuronal survival was quantified over seven days using longitudinal live-cell imaging. Twenty-eight PCs were screened for their effect on reducing neuronal death.

Results

Among 28 PCs screened, seven demonstrated modest effects, with cannabigerorcinic acid (CBGOA) significantly improving post-OGD neuronal survival. While OGD exposure led to increased cell death via activation of caspase 3, CBGOA treatment did not impact that pathway, suggesting that other caspase-independent pathways may be implicated.

Conclusions

This pilot study identifies CBGOA as a candidate cannabinoid with neuroprotective potential in an in vitro model of ischemic stroke. The use of iPSC-derived human cortical neurons strengthens translational relevance, but the modest effects observed, and the limitations of in vitro systems, underscore the need for in vivo validation and further mechanistic studies.

Collectively, these results provide a foundation for exploring CBGOA and related cannabinoids as potential neuroprotective agents in stroke.”

https://pubmed.ncbi.nlm.nih.gov/41578349

https://link.springer.com/article/10.1186/s42238-026-00393-0

Plant Growth-Promoting Rhizobacteria Colonize Δ9-Tetrahydrocannabinolic Acid Drug-Type Cannabis sativa L. Roots and Modulate Cannabinoid Metabolism

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“Plant growth-promoting rhizobacteria (PGPR) establish beneficial associations with plants, enhancing nutrient uptake, growth, and stress tolerance.

Cannabis sativa L., a medicinal plant producing over 300 specialized metabolites with relevant medicinal properties, remains underexplored for PGPR influence on its metabolism. This study assessed the ability of four PGPR taxa: Bacillus, Pseudomonas, Flavobacterium, and Burkholderia to colonize roots and modulate cannabinoid metabolism.

Two Δ9-tetrahydrocannabinolic acid (THCA) drug-type C. sativa cultivars, Amnesia Haze and Gorilla Glue, were tested. Plants grown hydroponically were inoculated under controlled conditions. Root colonization was confirmed via endophyte-specific assays.

Phenotypic analyses revealed no effects on plant phenotype, while chemical analyses revealed a response shared across taxa and cultivars. Bacterial inoculation increased the precursor cannabinoid Cannabigerolic acid (CBGA) concentration significantly by +27.37% while reducing Δ9-tetrahydrocannabinol (Δ9-THC) by -15.76%. The CBGA/THCA and THCA/CBDA ratios shifted significantly, indicating a favored CBGA accumulation and CBDA production, respectively.

PGPR treatments reduced in vivo and post-harvest decarboxylation of THCA into Δ9-THC, preserving the acidic cannabinoid profile. Under a standardized, soilless hydroponic regimen with a single shared reservoir and identical fertigation across groups, PGPR colonization was associated with shifts in cannabinoid metabolism and reduced decarboxylation.

This study demonstrates that PGPR can influence the specialized metabolism of high-THCA C. sativa, offering insights into sustainable cultivation and pharmaceutical exploitation of this relevant medicinal plant species.”

https://pubmed.ncbi.nlm.nih.gov/41578722

“Plants and bacteria share a long history that spans over a 100 million years. Since then, they have co-evolved to form complex relationships that facilitate the survival of both.”

“PGPRs can promote growth in several ways.”

“The findings and methodology of this research lay the groundwork for further evaluating and exploiting the potential beneficial relationship between PGPRs and C. sativa and implementing their sustainable applications in the agricultural, biotechnological, and pharmaceutical sectors.”

https://onlinelibrary.wiley.com/doi/10.1111/ppl.70756

Cannabidiol mitigates high-fat-diet-induced early-stage inflammation in two adipose tissue fat depots of Wistar rats

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“Cannabidiol (CBD) has potential for treating obesity-induced inflammation; thus, we studied the influence of CBD on the accumulation of lipid precursors of inflammation, the, enzymes, and cytokine levels in the subcutaneous (SAT) and visceral adipose tissue (VAT) of animals with obesity-induced early-stage inflammation.

Our experiment was performed on rats fed a high-fat (HFD) or control diet, which received CBD or its vehicle. The accumulation and composition of lipid fractions were assessed via gas‒liquid chromatography, whereas the expression of inflammatory pathway enzymes and the cytokine content were evaluated via Western blot or multiplexing, respectively.

In addition to selective changes in the content of cytokines, the administration of CBD to HFD-fed rats also decreased the deposition of all the lipid fractions in VAT, whereas in SAT, only the free fatty acid and diacylglycerol fractions were affected. Moreover, CBD reduced the deposition of arachidonic acid and the expression of enzymes associated with the synthesis of lipid precursors of inflammation in both the SAT and VAT of HFD-fed rats.

Although the data revealed the beneficial influence of CBD on lipid precursors of inflammation metabolism in both fat depots, more pronounced changes were observed in VAT, which is a tissue that is more predisposed to metabolic disease development.”

https://pubmed.ncbi.nlm.nih.gov/41571764

https://www.nature.com/articles/s41598-026-36666-0

Ewing sarcoma-related pain: potential role of medical cannabis monotherapy in symptom management – a case report

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“Persistent, multimodal cancer pain remains a challenge, particularly in long-term survivors facing treatment-related complications. The management of high-dose opioid dependence concurrent with chronic, multi-drug resistant (MDR) periprosthetic infection presents a critical unmet need. This case reports the potential use and sustained efficacy of medical cannabis monotherapy, highlighting an unexpected temporal association with the resolution of inflammatory and infectious symptoms in a highly complex oncologic setting.

Case presentation

A 27-year-old male, a long-term survivor of high-risk Ewing Sarcoma of the proximal tibia, presented with intractable mixed pain (VAS 9–10) secondary to chronic, recurrent MDR periprosthetic osteomyelitis and multiple surgical revisions (2013–2024). Despite continuous use of high-dose opioids (up to 120 mg/day morphine equivalents), pain levels remained moderate-to-severe (VAS 6–7) and functional status was poor. The patient had previously found temporary relief with self-administered cannabis. In January 2025, after refusing limb amputation, supervised medical cannabis therapy (Bedrocan®, 22% THC, 1% CBD, 1 g/day) was initiated. Pain levels gradually stabilized at VAS 2–3, coinciding with complete opioid discontinuation within four weeks. Over nine months of follow-up, the patient maintained full autonomy and an active lifestyle. Notably, sustained cannabis monotherapy was associated with the complete closure of the chronic draining fistula and a reduction in systemic inflammatory markers (CRP from 9.6 to 2.3 mg/dL). No significant adverse effects were reported.

Conclusions

This case suggests that THC-rich medical cannabis may represent a feasible strategy for achieving opioid-free analgesia in selected patients with refractory oncologic pain. While causality cannot be established from a single observation, the correlation between cannabis initiation and the resolution of severe chronic inflammatory and infectious symptoms is intriguing and suggests a potential pleiotropic role extending beyond traditional pain management. While these findings align with emerging evidence highlighting the potent immunomodulatory and anti-inflammatory properties of cannabinoids, they contrast with some recent neutral meta-analyses in broader populations, an this would justify warrant urgent controlled investigation into the potential mechanisms of cannabinoids in complex inflammatory pain states and their role as a possible adjunct in managing long-term oncological complications.”

https://pubmed.ncbi.nlm.nih.gov/41572388

https://link.springer.com/article/10.1186/s42238-026-00388-x

Perceived impact of medicinal cannabis on pelvic pain and endometriosis related symptoms in Aotearoa New Zealand: an observational cohort study

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“Endometriosis, characterised by the growth of endometrial-like tissue outside the uterus, often causes severe pelvic pain, dysmenorrhea, and fatigue. Current medical treatments frequently provide incomplete symptom control and/or significant side effects. Many individuals with endometriosis report symptom improvements with cannabis use, but high-quality evidence remains limited.

Methods

A prospective, mixed-methods cohort study was conducted. Participants aged 18–50 years with surgically or clinically diagnosed endometriosis self-engaged with a specialist consultant and were prescribed medicinal cannabis (cannabidiol [CBD] oil alone or in combination with dried cannabis flower). Weekly pain scores, and health-related quality of life (measured by the Endometriosis Health Profile-30 [EHP-30]) were assessed via surveys and standardised questionnaires over three months. Completion interviews were conducted to explore participants’ experiences with medicinal cannabis in greater depth.

Results

Participants reported limited adverse events during the study period. Pelvic pain scores decreased over 12 weeks: ‘overall’ pain reduced from 5.46 ± 1.55 (95% CI 0.57) to 3.77 ± 2.25 (95% CI 0.83), and ‘worst’ pain decreased from 7.62 ± 1.51 (95% CI 0.56) to 5.38 ± 2.69 (95% CI 1.00). The mean total EHP-30 score significantly decreased from 68.77 ± 15.17 (95% CI 5.61) to 37.40 ± 16.66 (95% CI 6.17). Qualitative analysis identified four major themes: motivations for seeking medicinal cannabis, experiences of use, barriers to use, and stigma.

Conclusions

Medicinal cannabis use was associated with reduction in pain measures and improvements in quality of life among some individuals with endometriosis during this study. Qualitative findings highlighted both perceived benefits and ongoing challenges related to access, dosage and social stigma. These results support the need for larger controlled studies to further evaluate the safety, efficacy, and long-term outcomes of medicinal cannabis as an adjunctive therapy for endometriosis-related pain.”

https://pubmed.ncbi.nlm.nih.gov/41566248

https://link.springer.com/article/10.1186/s12906-025-05189-y

The psychoactive cannabinoid THC inhibits peripheral nociceptors by targeting NaV1.7 and NaV1.8 nociceptive sodium channels

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“Δ⁹-Tetrahydrocannabinol (THC), the primary psychoactive compound in cannabis, is widely recognized for its central effects mediated by cannabinoid receptors. Here, we uncover a distinct peripheral mechanism by which THC inhibits the excitability of nociceptive neurons.

We show that THC directly targets the nociceptive voltage-gated sodium channels NaV1.7 and NaV1.8 through the conserved local anesthetic binding site. This interaction reduces sodium currents and suppresses action potential generation in peripheral sensory neurons.

Our findings demonstrate that, beyond its central psychoactivity, THC exerts direct peripheral nociceptor inhibition via modulation of NaV1.7 and NaV1.8, offering new insight into cannabinoid-based analgesia independent of cannabinoid receptor signaling.”

https://pubmed.ncbi.nlm.nih.gov/41565997

“Cannabis has been used for centuries for its analgesic properties, and its clinical relevance in pain management continues to grow.”

 “These findings reveal a previously unrecognized mechanism for THC-mediated peripheral analgesia and establish a non-canonical molecular pathway through which the psychoactive cannabinoid can inhibit nociceptor excitability and thereby pain.”

https://www.nature.com/articles/s41386-026-02355-9

Cannabidiol-Ion Channel Interactions Represent a Promising Preventive and Therapeutic Strategy in Hepatocellular Carcinoma

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“Hepatocellular carcinoma (HCC) is the main type of liver cancer and one of the malignancies with the highest mortality rates worldwide. HCC is associated with diverse etiological factors including alcohol use, viral infections, fatty liver disease, and liver cirrhosis (a major risk factor for HCC). Unfortunately, many patients are diagnosed at advanced stages of the disease and receive palliative treatment only. Therefore, early markers of HCC and novel therapeutic approaches are urgently needed.

The endocannabinoid system is involved in various physiological processes such as motor coordination, emotional control, learning and memory, neuronal development, antinociception, and immunological processes. Interestingly, endocannabinoids modulate signaling pathways involved in cell survival, proliferation, apoptosis, autophagy, and immune response.

Consistently, several cannabinoids have demonstrated potential antitumor properties in experimental models.

The participation of metabotropic and ionotropic cannabinoid receptors in the biological effects of cannabinoids has been extensively described. In addition, cannabinoids interact with other targets, including several ion channels. Notably, several ion channels targeted by cannabinoids are involved in inflammation, proliferation, and apoptosis in liver diseases, including HCC.

In this literature review, we describe and discuss both the endocannabinoid system and exogenous phytocannabinoids, such as cannabidiol and Δ9-tetrahydrocannabinol, along with their canonical receptors, as well as the cannabidiol-targeted ion channels and their role in liver cancer and its preceding liver diseases. The cannabidiol-ion channel association is an extraordinary opportunity in liver cancer prevention and therapy, with potential implications for several environments that are for the benefit of cancer patients, including sociocultural, public health, and economic systems.”

https://pubmed.ncbi.nlm.nih.gov/41562849

“The endocannabinoid system (ECS) plays a crucial role in the development and functioning of several biological systems. Classically, the endocannabinoid system comprises receptors, endogenous ligands, and enzymes that synthesize, transport, and degrade such ligands. ECS regulates many biological processes, both in normal conditions like brain function, neurotransmitter release, sleep regulation, appetite, movement, and coordination, as well as pathological states such as neurodegenerative disorders, headaches, chronic pain, anxiety, depression, and cancer, among others.

Accordingly, pharmacological modulation of the endocannabinoid system may be a potential target for preventing disease progression or enhancing symptom relief in multiple conditions, including cancer “

“Dysregulation of voltage-gated sodium channels causes the development of several diseases. CBD is a non-selective Nav1.1–1.7 sodium channel inhibitor and is effective in the treatment of epilepsy.”

“Exploiting the cannabidiol-ion channel-transporters association represents an extraordinary opportunity for liver cancer prevention and therapy, which may help to reduce the high mortality from this malignancy and to involve sociocultural, public health, regulatory, and economic systems.”

“Taken together, preclinical, epidemiological, and clinical data converge to support CBD as a promising candidate for the prevention and management of liver diseases and HCC, with potential implications for sociocultural, public health, and economic systems.”

https://www.mdpi.com/1873-149X/33/1/8

Exploring the neuroprotective effects and underlying mechanisms of medical cannabinoids in ischemic stroke: a systematic meta-analysis with bibliometric mapping of cerebral ischemia research

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“Background: Ischemic stroke is an acute neurological disorder with limited treatment options. Medical cannabinoids (MCs), primary bioactive compounds extracted from cannabis plants, have shown therapeutic prospects for ischemic stroke. This study integrates bibliometrics and meta-analysis to comprehensively summarize the research landscape of MCs in cerebral ischemia and thoroughly investigate their role and potential mechanisms in ischemic stroke.

Methods: Bibliometric analysis was performed based on literature retrieved from Web of Science Core Collection (WoSCC), PubMed, and Scopus. For meta-analysis, a comprehensive search was conducted across four databases (WoSCC, PubMed, Embase, and Cochrane Library) and grey literature repositories. Studies were screened according to predefined criteria. Pooled standardized mean differences with 95% confidence interval were calculated, followed by subgroup analysis.

Results: A total of 241 publications were identified for bibliometric analysis. From 2000 to June 2025, the annual publication output on MCs in cerebral ischemia displayed a fluctuating yet overall upward trend. Keyword co-occurrence analysis revealed three major research topics: neuroprotective mechanisms of MCs, pathological models of cerebral ischemia, and bioactive components of MCs. Meta-analysis of 26 studies demonstrated that MCs provided significant neuroprotection in animal models of ischemic stroke, including cerebral infarct volume, neurological function score (NFS), cerebral blood flow (CBF), blood-brain barrier (BBB) permeability, brain water content, apoptosis (TUNEL-positive cells), oxidative stress markers, inflammation (TNF-α, IL-1β), and excitotoxicity (Glu/NAA, Lac/NAA ratio). Subgroup analysis revealed that intraperitoneal administration and a full-course of cannabidiol (CBD) treatment were associated with reduced heterogeneity and enhanced therapeutic benefit. Isoflurane was identified as a potentially suitable anesthetic.

Conclusion: MCs exert multi-target neuroprotection in ischemic stroke by improving CBF, reducing brain edema and BBB permeability, and inhibiting oxidative stress, neuroinflammation, apoptosis, and excitotoxicity. Future research should focus on high-quality clinical trials to validate these findings and translate MCs into clinical practice.”

https://pubmed.ncbi.nlm.nih.gov/41551042

“THC produces anti-inflammatory effects, reduces neuronal damage, and promotes hippocampal neurogenesis.”

“CBD acts as a negative allosteric modulator of cannabinoid receptors (CBR) and exerts brain-protective effects through multi-target regulatory properties “

 “Moreover, the results of meta-analysis consolidate preclinical evidence, demonstrating that MCs confer neuroprotection by mitigating multiple pathological processes, including cerebral tissue perfusion, BBB permeability and cerebral edema, oxidative stress, excitotoxicity, inflammatory responses, and apoptosis.”

https://www.frontiersin.org/journals/neuroscience/articles/10.3389/fnins.2025.1731738/full

The Evidence for Medical Cannabis in Chronic Musculoskeletal Pain Management

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“Chronic musculoskeletal pain (CMP) is a pervasive condition that can impair daily functioning and quality of life. Traditional pharmaceutical therapies, including non-steroidal anti-inflammatory drugs, gabapentinoids, and opioids, often yield suboptimal results and carry notable risks, such as adverse side effects and dependence.

Increasing interest has turned toward medical cannabis, particularly combined formulations of cannabidiol (CBD) and tetrahydrocannabinol (THC), as a potential alternative or complement to current pain management strategies.

Evidence suggests that cannabinoids interact with the endocannabinoid system to modulate nociception and inflammation, offering meaningful pain relief and possibly reducing opioid requirements.

However, heterogeneity in study designs, product formulations, and regulatory frameworks presents challenges in drawing definitive conclusions. Additionally, while most adverse effects, such as fatigue, dizziness, and mild cognitive changes, are generally reported as tolerable, concerns remain about long-term safety and standardization of dosing.

Taken together, the existing literature points to a promising role for medical cannabis in CMP management, underscoring the need for further high-quality research to establish best practices, clarify patient selection, and guide clinicians in safe and effective cannabinoid therapy.”

“This scoping review highlights the potential role of medical cannabis in managing musculoskeletal pain. Evidence suggests it may reduce pain, enhance well-being, and improve quality of life, particularly as an alternative or adjunct to opioids. Adverse effects are typically mild, supporting its use as a safer long-term option. However, data on long-term efficacy, especially for CBD, remain limited.

Given the risks of opioid dependence, cannabis offers a promising therapeutic alternative.”

https://surgicoll.scholasticahq.com/article/138573-the-evidence-for-medical-cannabis-in-chronic-musculoskeletal-pain-management