Author Archives: David

Full Spectrum Cannabis Oil for the treatment of chronic pain and sleep dysfunction in myofascial temporomandibular disorder: a case report

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“Medicinal cannabis has been the subject of extensive research, with recent studies demonstrating its potential in managing chronic pain and enhancing quality of life.

This case report examines the use of medicinal cannabis in a patient treated at the School of Dentistry of Araçatuba (FOA-UNESP). The patient, a 28-year-old female with no comorbidities, presented with chronic muscular TMD and reported poor sleep quality. Full-spectrum cannabis oil (1:1 ratio of THC to CBD), was prescribed for a period of 60 days, with a maximum dosage of 10 drops per day. Pain intensity was measured using the Visual Analog Scale (VAS), while sleep quality was assessed using the Pittsburgh Sleep Quality Index (PSQI). Evaluations were conducted at three intervals: baseline, day 30, and day 60. To ensure patient safety, pre- and post-treatment blood tests were performed, and dosage adjustments were made every three days under the supervision of the study’s medical team.

The results revealed significant improvements in pain management, with the patient’s orofacial pain score decreasing from 7 to 3 on the NRS. Additionally, sleep quality improved, as reflected by a lower PSQI score (global sleep quality at level 6 at the end), indicating more restorative sleep. Throughout the treatment period, the patient experienced mild side effects, including drowsiness and gastrointestinal discomfort, which were effectively managed through dosage modifications.

In conclusion, full-spectrum cannabis oil shows promise as a therapeutic strategy for managing orofacial pain and improving sleep quality, providing significant relief in conditions where other interventions are ineffective or poorly tolerated. Further research is warranted to better understand the therapeutic mechanisms and potential side effects of medicinal cannabis in the management of chronic pain and related conditions.”

https://pubmed.ncbi.nlm.nih.gov/41092177/

“In conclusion, the use of Full Spectrum Cannabis Oil in this case was associated with a clinically meaningful reduction in chronic orofacial pain and improvement in sleep quality, with no adverse effects or laboratory abnormalities observed during the treatment period. These outcomes suggest that individualized cannabinoid-based therapy may be a safe and effective approach for selected patients with temporomandibular disorders and comorbid sleep disturbances.”

https://www.scielo.br/j/bjb/a/bK69ZBYPSB4dJ9yqcFxSzcf/?lang=en

Antinociceptive, anti-inflammatory, and anti-dysmenorrheal activities of aerial parts of Cannabis sativa L. from the sub-middle region of the Vale do São Francisco

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“Introduction: Cannabis sativa L. has been used for thousands of years to treat intestinal and uterine diseases and as an anti-inflammatory, analgesic, and antiepileptic, among others. This study aimed to conduct preclinical studies based on the ethnopharmacological properties of C. sativa.

Methods: For this purpose, the police and health authorities provided the raw plant material, and a crude ethanolic extract of the aerial parts of C. sativa (APCs) was produced, which was subsequently chemically analyzed using combined chromatographic and spectrometric methods. Subsequently, APCs were administered to Swiss mice and Wistar rats for evaluation using the open field test, acetic acid-induced abdominal contraction model, hot plate test, formalin test, carrageenan-induced paw edema, Saccharomyces cerevisiae-induced fever, and primary dysmenorrhea models.

Results: Chemical analysis suggests the presence of classic cannabinoids, such as cannabidiol, tetrahydrocannabinol, and cannabigerol, as well as flavonoids and alkaloids. The doses used in the open field test were 1, 3, 10, 30, and 100 mg/kg (gavage, po), with the last two doses responsible for reducing mobility and inducing hypothermia in the animals. In subsequent pharmacological protocols, the doses used were 1, 3, and 10 mg/kg (gavage, po). In the abdominal contraction model, the number of writhing events was reduced by APCs at a dose of 10 mg/kg [median 0.5 (Q25 = 0; Q75 = 5.75, p < 0.05)]. In the hot plate test, the doses of 1, 3, and 10 mg/kg increased the latency time to 17.67 ± 1.33, 18.50 ± 1.31, and 17.33 ± 1.69 s (p < 0.05), respectively. In the formalin test, the effect was restricted to the first phase, with values of 42.33 ± 7.588, 45.50 ± 6.657, and 39.50 ± 7.869 s (p < 0.05) in paw-licking time. In paw edema, the doses of 1 and 3 mg/kg were more constant, restricting the volume to 0.168 ± 0.004 and 0.150 ± 0.004 mL (p < 0.05), respectively. In dysmenorrhea, the doses of 3 and 10 mg/kg reduced abdominal contractions [0 (Q25 = 0; Q75 = 3.0) and 1.0 (Q25 = 0; Q75 = 3.0)].

Conclusion: APCs at the tested doses did not promote an antipyretic effect. These data indicate that APCs have antinociceptive, anti-inflammatory, and anti-dysmenorrheal effects in animal models.”

https://pubmed.ncbi.nlm.nih.gov/41089847/

“Cannabis sativa L. is a plant from the family Cannabaceae and one of the oldest to be domesticated in the world, with its use dating back to approximately 12,000 years in the Central Asian region.”

“C. sativa has a variety of indications in traditional medicine, in the most diverse forms of use (tea, smoke, vapor, etc.), and is used as a wound healing agent, analgesic, anticonvulsant, hypnotic, tranquilizer, anesthetic, anti-inflammatory, antibiotic, antiparasitic, antispasmodic, digestive, appetite stimulant, diuretic, aphrodisiac, antitussive, and expectorant.”

“Our results suggest that APCs contain classic cannabinoids, flavonoids, and alkaloids, and that classic cannabinoids, THC, and CBD are present. The administration of APCs promoted behavioral changes in the animals consistent with the pharmacological effects of these substances, such as reduced ambulation and hypothermic effect at doses of 30 and 100 mg/kg. In pharmacological studies, antinociceptive, anti-inflammatory, and anti-dysmenorrheal effects were observed in different experimental models and in the 1–10 mg/kg dose range; however, the APCs failed to show an antipyretic effect at these doses.”

https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2025.1677987/full

Synergistic combination of cannabidiol and celecoxib or 2,5-dimethylcelecoxib exerts oxidative stress-mediated cytotoxicity and mitigates glioblastoma invasiveness

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“Glioblastoma remains one of the most aggressive and treatment-resistant malignancies. Current treatment options, such as radio- and chemotherapy, induce oxidative stress-mediated DNA damage leading to cancer cell death, but are also neurotoxic and not efficient in long term.

Our study investigated the effects of cannabidiol, celecoxib and 2,5-dimethylcelecoxib, individually and in combinations, on U-138 MG glioblastoma cell survival, oxidative stress, canonical and non-canonical Nrf2 pathway activation, cell migration and apoptosis.

Using the MTT and flow cytometry assay we found that the analyzed compounds and their combinations induce dose-dependent, synergistic, and oxidative stress-related cytotoxicity, with minimal impact (at the concentrations exhibiting anti-cancer effects) on non-cancerous human astrocyte (HA) cell line.

The Nrf2 ELISA assay was used for the analysis of the nuclear binding of the nuclear factor-2 erythroid related factor-2 (Nrf2), which followed by the RT-qPCR and Western blot analysis, confirmed the antioxidant response of cells to the applied treatments. Diminished migratory potential, and increase of the autophagy-related p62, LC3 and apoptosis-related caspase-3 protein levels were also observed in response to the treatment with the analyzed compounds.

Overall, our study provides evidence that cannabidiol combined with celecoxib or 2,5-dimethylcelecoxib may represent a promising strategy for glioblastoma treatment.”

https://pubmed.ncbi.nlm.nih.gov/41089524/

“In conclusion, the combination of CBD with celecoxib or 2,5-DMC represents a promising therapeutic strategy for glioblastoma. While CBD alone induces cytotoxicity, ROS production, and apoptosis, our synergy analysis demonstrates that combining CBD with celecoxib or 2,5-DMC allows effective killing of GBM cells at lower CBD concentrations. “

https://www.frontierspartnerships.org/journals/acta-biochimica-polonica/articles/10.3389/abp.2025.15062/full

In silico insights on the binding site and function of cannabinoids and cannabinoid acids on human 5-HT1A receptor

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“Previous studies reported that the acid congener of the cannabinoids, cannabidiolic acid, was approximately 1000 times more effective than the neutral congener, cannabidiol, in alleviating emesis.

The biological actions of cannabinoids were proposed to be mediated by the enhancement of somatodendritic 5-HT1A receptors. However, to date, the potential mechanism that may be involved in the enhancement of the 5-HT1A activity by the acid congener is still lacking. To address this gap, molecular docking and molecular dynamics simulations were performed on different pairs of neutral and acidic cannabinoids in a human 5-HT1A receptor model.

Analyses showed that simulated cannabinoid acids (cannabidiolic acid and tetrahydrocannabivarinic acid) and tetrahydrocannabivarin were preferentially bound at the allosteric site of 5-HT1A and were able to maintain the receptor in its active state when a full agonist, R(+)-8-OH-DPAT, was bound at the orthosteric site. Importantly, these results also suggest that the strong activity of cannabidiolic acid is not due to its strong affinity for the 5-HT1A receptor but its positive allosteric modulation of the agonist activity on 5-HT1A, presumably by blocking the exit of the orthosteric ligand, hence promoting continuous activation of the receptor. This study also demonstrates that cannabidiol and both neutral and acidic cannabigerol prefer binding at the orthosteric site and are potential partial agonists of 5-HT1A.

In conclusion, these findings propose that every cannabinoid, regardless of whether neutral or acidic, is unique on its own in terms of its binding and function.”

https://pubmed.ncbi.nlm.nih.gov/41056675/

“Importantly, these findings indicate that every individual cannabinoids, regardless of neutral or acid congeners, is unique on its own and deserves its investigation, on its binding, function and therapeutic potential.”

https://www.sciencedirect.com/science/article/pii/S1093326325002463?via%3Dihub

Bioinformatics differential expression analysis of the effect of cannabidiol in chronic myeloid leukaemia cell line

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“Chronic myeloid leukaemia (CML) is the first clonal myeloproliferative disorder of pluripotent stem cells to be associated with a specific genetic abnormality, the Philadelphia chromosome, bearing the BCR-ABL1 fusion oncogene. Tyrosine kinase inhibitors are used as first-line treatment for the chronic phase of CML, although alternative treatments are necessary for resistant cases.

Cannabidiol (CBD) is a major constituent of hemp oil that exerts a broad range of pharmacological effects in various malignancies. However, its molecular mechanisms in leukaemia remain unclear. In the present study, Imatinib-sensitive K-562S cells were subjected to CBD treatment (IC50: 17.69 μM) for 4 and 12 h, followed by RNA sequencing to identify differentially expressed genes (DEGs).

The subsequent transcriptomic profiling revealed 3518 DEGs at 12 h and 3433 DEGs at 4 h of treatment, including significant modulation of metallothionein-regulated oxidative stress responses (MT1, MT2, and SLC30A2) and p53-mediated apoptosis (TP53TG3, DDIT4, BBC3, CHAC1, NOXA1, and DAPK2). Additionally, the DEGs were enriched in alterations in immune signalling pathways-including type I interferon activation and PI3K-Akt-mTOR and Toll-like receptor signalling-crucial in leukaemia progression, as well as variations in lipid metabolism and mitochondrial homeostasis.

The results presented in this study validate the considerable potential of CBD to induce broad transcriptional and signalling alterations, related to immune modulation, apoptosis, and metabolic processes in K-562S cells. These findings provide novel insights into the therapeutic potential of CBD and lay the groundwork for further investigation into its precision applications in haematological malignancies.”

https://pubmed.ncbi.nlm.nih.gov/41080716/

“Cannabis sativa (marijuana, hashish) has been used for centuries as an herbal remedy for the treatment of various ailments, as well as for its psychotropic properties. More than 550 constituents have been identified in cannabis, of which greater than 100 are represented by the family of phytocannabinoids. The most abundant amongst them are the psychoactive Δ9-tetrahydrocannabinol (THC) and cannabidiol (CBD), which exhibit primary anti-cancer effects on various malignant diseases, including leukaemia.”

https://www.sciencedirect.com/science/article/pii/S2699940425000773?via%3Dihub

Should cannabis be used in the management of endometriosis?

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“Introduction: Endometriosis is a chronic inflammatory condition that affects around 1 in 7 women of reproductive age. Current medical treatments tend to be sub-optimal to manage the range of symptoms, with low levels of patient satisfaction. Cross-sectional and retrospective data suggests that people with endometriosis are consuming cannabis to help manage their symptoms.

Areas covered: This review discusses the evidence for consumption of medicinal cannabis to help manage endometriosis symptoms, including potential mechanisms of action from both animal models and human studies, usage in the community, the current evidence from clinical trials and observational studies, and the safety and potential drug interactions.

Expert opinion: While there is a lack of high-quality clinical trial evidence, significant self-reported evidence from cross-sectional surveys and retrospective observational data suggests that those consuming medicinal cannabis report reductions in endometriosis symptoms such as pelvic pain, dysmenorrhea and gastrointestinal symptoms, and improve mental health and sleep. Given the low levels of satisfaction with current treatment options, consideration should be given to trialing medicinal cannabis as part of the interdisciplinary management of endometriosis in those who express interest and who do not demonstrate any significant contraindications.”

https://pubmed.ncbi.nlm.nih.gov/41070712/

  • “Less than 25% of women with endometriosis report satisfaction with current conventional treatments with high discontinuation rates due to ineffectiveness and side effects.
  • Dysregulation of the endocannabinoid system in endometriosis, including reduced CB₁ receptors and elevated endocannabinoid levels, provides biological plausibility for therapeutic intervention through TRPV1 modulation and PPARγ activation.
  • Cannabis consumption is associated with self-reported reductions in pain, gastrointestinal symptoms and nausea, and improvements in sleep quality and mental health.
  • Cannabis consumption is associated with reductions in potentially addictive medications such as opioids and benzodiazepines; however these reductions should be done under the guidance of a physician.
  • Despite promising preclinical data and substantial observational evidence, robust randomized controlled trial data in humans remains lacking, preventing recommendation of more widespread adoption as a treatment.”

https://www.tandfonline.com/doi/full/10.1080/17446651.2025.2572339

The Associative Impact of Recreational Cannabis Use on Sinonasal Diseases

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“Objectives: With growing cannabis use in the US, it is crucial to understand the impact of recreational use on sinonasal diseases like chronic rhinosinusitis (CRS), allergic rhinitis (AR), and chronic rhinitis (CR).

Methods: This cross-sectional study leveraged the NIH AllOfUs database to query patient surveys assessing cannabis usage frequency (lifetime never, monthly, weekly, or daily within the past 3 months) and consumption route (smoking or non-smoking). Cannabis users were matched to never users for demographics, healthcare visit frequency, and insurance. A stringent logistic regression model calculated odds ratios (OR) of developing AR, CRS, or CR after survey completion. Cox regression hazard ratios (HR) compared consumption routes.

Results: Twenty-five thousand one hundred sixty-four cannabis users were matched with 113,418 never users. Users demonstrated significantly lower odds of AR, CRS, and CR than never users. For CRS, the ORs compared to never users are as follows: daily users 0.64 (95% CI 0.53-0.78), weekly users 0.61 (95% CI 0.48-0.77), and monthly users 0.80. For AR, the ORs were 0.64 (95% CI 0.58-0.71) for daily users, 0.62 (95% CI 0.54-0.71) for weekly users, and 0.69 (95% CI 0.58-0.80) for monthly users. For CR, the ORs were 0.61 (95% CI 0.47-0.79) for daily users, 0.64 (95% CI 0.47-0.87) for weekly users, and 0.41 (95% CI 0.26-0.65) for monthly users. There was no significant difference between smokers and non-smokers (HR 0.64, 95% CI 0.27-1.5).

Conclusion: There is an inverse, associative relationship between cannabis use and sinonasal disease. This relationship is insufficiently understood, and there remain significant concerns about the impact of cannabis use, especially smoking, on airway pathologies.”

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

“This is the largest study to specifically comment on the association between cannabis use and three of the most common sinonasal diseases—AR, CRS, and CR. We found lower odds of AR, CRS, and CR in patients who use cannabis compared to those who do not, which is strengthened by the size of our cohorts and by incorporating demographic and comorbidity information in our analysis. Route of consumption did not change CRS incidence. “

https://onlinelibrary.wiley.com/doi/10.1002/lio2.70261

Efficacy of non-psychotropic Cannabis sativa L. standardized extracts in a model of intestinal inflammation

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“Background: The use of Cannabis sativa L. (Cannabis) was reported by observational studies on inflammatory bowel diseases (IBD) patients. However, this indication is poorly supported by clinical trials. Several pre-clinical studies demonstrated the anti-inflammatory activity of Δ⁹-tetrahydrocannabinol (Δ⁹-THC) and cannabidiol (CBD) at intestinal level. On the contrary, minor cannabinoids, such as cannabigerol (CBG), were less investigated. Moreover, several authors suggested that complex Cannabis extracts might display a higher efficacy in respect to pure cannabinoids against inflammatory disorders.

Methods: This study was aimed at investigating the role of Cannabis extracts, standardized in CBD and CBG content, in a model of in vitro-induced intestinal inflammation using CaCo-2 cells. Inflammatory mediators at transcriptional (PCR arrays) and protein level (ELISA assays) were investigated and correlated with enterocyte layer permeability. The two evaluated extracts, A and B, come from the mix of the same Cannabis varieties (Cannabis sativa L. Chemotype III and Chemotype IV), and are standardized in CBD and CBG at the same level, by changing the polarity of the primary extraction solvents.

Results: Pro-inflammatory cytokines involved in IBD, such as IL-1β and IFN-γ, induced the expression and the release of chemokines for lymphocytes (CXCL-9, CXCL-10, CCL20) in CaCo-2, while Cannabis extracts (100 µg/mL) or individual compounds (8 µM) showed inhibitory activity. After simulated digestion, extract A abrogated the release of CCL-20, while extract B abrogated the release of CXCL-9 and CXCL-10. The inhibition of CXCL-9 was demonstrated at transcriptional level also. The inhibitory activity paralleled with the content of CBD or CBG, acting at least in part through NF-κB impairment (-42% and – 66%, respectively). However, Cannabis extracts showed greater effect in the CaCo-2-THP-1 co-culture inflammation model compared to individual cannabinoids, thus partially recovering the epithelial barrier measured by transepithelial electrical resistance (TEER), and zonula occludens (ZO-1) expression.

Conclusions: Data collected within this study showed the importance of standardization and extraction method reproducibility through manufacturing and process control, besides demanding future investigations focusing on the effect of Cannabis extracts against intestinal inflammation, which show in this context effects higher than individual cannabinoids.”

https://pubmed.ncbi.nlm.nih.gov/41053843/

“At the best of our knowledge, this is one of the few works in which the biological properties of standardized Cannabis extracts were compared with their major cannabinoids. More generally, the role of CBG in intestinal inflammation is matter of interest for its non-psychotropics nature, but it was investigated by few articles before. However, our data suggest that the use of Cannabis extracts against intestinal inflammation might be preferred in respect to single cannabinoids. Nevertheless, specific studies should be conducted with the aim to translate the evidence to in vivo models.”

https://jcannabisresearch.biomedcentral.com/articles/10.1186/s42238-025-00335-2

Rethinking Alzheimer’s: Harnessing Cannabidiol to Modulate IDO and cGAS Pathways for Neuroinflammation Control

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“Alzheimer’s disease (AD) has traditionally been associated with amyloid-β plaques, but growing evidence underscores the role of neuroinflammation in disease progression. The autoinflammatory hypothesis of AD suggests chronic immune dysfunction contributes to neuronal damage, making immune modulation a promising therapeutic strategy.Cannabidiol (CBD), a phytocannabinoid with anti-inflammatory properties, may offer therapeutic potential.

This study investigates how CBD independently influences two key neuroinflammatory regulators in AD: the Indoleamine 2,3-dioxygenase (IDO) pathway and the cyclic GMP-AMP synthase (cGAS) pathway.

Though mechanistically distinct, both shape CNS immune responses. Targeting these immune-metabolic axes provides a mechanistic alternative to amyloid- or tau-based approaches by addressing upstream drivers of neuroinflammation and immune dysregulation. Using the male 5XFAD transgenic AD mouse model, we administered CBD via inhalation and assessed IDO and cGAS expression using flow cytometry, immunofluorescence, and gene expression analysis. We evaluated cytokine levels and used STRING-based bioinformatics to identify CBD-target interactions.

CBD treatment significantly reduced IDO and cGAS expression, correlating with decreased pro-inflammatory cytokines, including TNF-α, IL-1β, and IFN-γ. Bioinformatics identified potential interactions between CBD and immune targets such as AKT1, TRPV1, and GPR55. These targets were prioritized based on their roles in neuroinflammatory signaling and high-confidence interactions with CBD. AKT1 regulates inflammatory signaling and cell survival, TRPV1 modulates nociception and neuroinflammation, and GPR55 influences immune cell activation.

These findings support CBD as a potential monotherapy or adjunctive treatment for AD by targeting distinct neuroinflammatory pathways, including IDO and cGAS. Further studies are warranted to fully explore its therapeutic potential.

Significance statement This study highlights the therapeutic potential of cannabidiol (CBD) in targeting neuroinflammation, a major driver of Alzheimer’s disease (AD) progression. By modulating the IDO and cGAS pathways-critical regulators of CNS immune responses-CBD reduces pro-inflammatory cytokines and ameliorates immune dysfunction. These findings support the emerging autoinflammatory hypothesis of AD, which posits that chronic inflammation underlies neuronal damage. The IDO/cGAS signaling axis, located at the intersection of innate immunity and metabolic regulation, remains underexplored in AD and represents a key intervention point to disrupt neuroinflammatory loops. This study positions CBD as a promising mono- or adjunctive therapy and reinforces the need to consider multi-targeted strategies that address upstream immune mechanisms in neurodegenerative disease.”

https://pubmed.ncbi.nlm.nih.gov/41052930/

https://www.eneuro.org/content/early/2025/09/26/ENEURO.0114-25.2025

Cannabidiol combined with GABAergic drugs but not with sodium channel blockers prevents the development of drug-resistance seizures in a preclinical model

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“Drug resistance affects 30% of patients with epilepsy. Cannabidiol (CBD) decreases the expression of drug-resistant seizures in specific syndromes. However, it is unknown if CBD prevents the development of drug-resistant condition in epilepsy.

This research was conducted to investigate if subchronic administration of CBD with sodium channel blockers modifies the mortality associated with clonic-tonic seizures and the development of the drug-resistant phenotype induced by subchronic administration of 3-mercaptopropionic acid (3-MP) in rats. These effects were compared with those elicited by antiseizure medications acting on the GABAA receptors.

Male Wistar rats were used to evaluate CBD combined with different antiseizure medications (phenobarbital, diazepam, valproic acid, lamotrigine and oxcarbazepine) during the repetitive administration of 3-MP. The mortality rate and development of drug-resistant seizures were estimated. Computational experiments explored interactions between CBD and sodium channel blockers in the NaV1.7 receptor.

Subchronic administration of CBD alone did not modify neither the mortality rate nor the development of drug-resistant seizures. CBD combined with phenobarbital or diazepam reduced the mortality rate and prevalence of drug-resistant seizures. In contrast, coadministration of CBD with valproic acid or lamotrigine did not modify neither the mortality rate nor the expression of drug-resistant seizures. Contrariwise, combining CBD with oxcarbazepine at ED50 increases the incidence of drug-resistant seizures. Computational experiments suggested that CBD acting on NaV1.7 interferes with the action of sodium channel blockers and precludes their inhibitory effects.

Our results indicate that repeated administration of CBD with GABAergic antiseizure medications, but not sodium channel blockers, decreases the mortality and prevents the development of the drug-resistant phenotype induced by repeatedly provoked severe seizures.”

https://pubmed.ncbi.nlm.nih.gov/41050418/

“The present study confirms that CBD alone does not modify the mortality rate induced by severe seizures. Our results also support that CBD combined with GABAergic drugs but not with sodium channel blockers reduces the mortality rate during the repetitive induction of clonic-tonic seizures and prevents the development of drug-resistance seizures in a preclinical model.”

https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2025.1644018/full