Author Archives: David Worrell

Marijuana Use for Symptom Control in Inflammatory Bowel Disease: Patients’ Perceptions and Patterns of Use

Posted on by

“Introduction: Many patients with inflammatory bowel disease (IBD) use marijuana for disease-related symptoms. Data regarding reasons for usage, impact, and perceptions on its effects is lacking. Our study aimed to understand patterns of marijuana use, underlying symptom response, and beliefs about marijuana in patients with IBD.

Methods: An anonymous REDCap survey comprised of 39 questions on demographics, disease features, patterns of marijuana use, symptoms, quality of life, and true/false statements about marijuana was administered to 108 participants recruited from University of Florida (UF) IBD clinic.

Results: Participants were 47.2% male and 51.9% female. While a significant percentage of subjects reported co-morbid depression/anxiety (61.1%), the percentages for PTSD and ADHD are both 19.4%. Patient characteristics are compared among three reasons of marijuana use (Recreational, Medical and Combination). There was a notable shift in reasons for use with both age (p = 0.0074) and duration of IBD diagnosis (p = 0.006): recreational use is more common among younger patients and those with a shorter duration of IBD diagnosis, medical use becomes predominant in middle-aged patients and those with an intermediate duration of diagnosis, and combination use increases among older patients and those with the longest duration of IBD diagnosis. Comparisons are also conducted based on the frequency of marijuana usage. Associations were found between marijuana use frequency and symptom relief. Daily or near-daily marijuana use was associated with self-reported relief of nausea/vomiting (82.1%; p = 0.003), arthralgias (81%; p = 0.013), and insomnia (80%; p = 0.02). Additionally, marijuana use was linked to an improved ability to live independently (p = 0.0075) and current employment (p = 0.04). Patients with a history of bowel surgery were more likely to report marijuana use lasting longer than 5 years (OR 21.94, CI [2.91, 250.18], p = 0.0059) and using marijuana at least once weekly (OR 11.13, CI [1.78, 97.69], p = 0.0163). Notably, 59.3% of respondents believed marijuana use had reduced their opioid consumption. Marijuana users with a history of IBD-related hospitalization had higher odds of reporting depression/anxiety (OR 14.3, CI [2.34, 143.2], p = 0.009) and diarrhea symptoms (OR 13.3, CI [2.2, 128.9], p = 0.01). When asked how marijuana use affected their ability to live independently, 61.3% of participants reported “improved.” Similarly, 87.6% respondents reported improvement in their quality of life with marijuana use.

Conclusions: Marijuana can be helpful for symptom control, reducing reliance on opioid pharmaceuticals, and may improve quality of life in patients with IBD. Participants demonstrated good insight regarding the role of marijuana in the management of their disease.”

https://pubmed.ncbi.nlm.nih.gov/42592634

“Inflammatory bowel disease is an autoimmune condition causing inflammation in the small intestines and colon. It can often lead to chronic pain, hospitalization, surgery, and poor quality of life. Data regarding marijuana use among patients with inflammatory bowel disease is lacking. We conducted an anonymous survey of 108 participants with inflammatory bowel disease who use marijuana. Most participants reported improvement in symptoms, decreased opioid usage, and accurate perceptions on marijuana effects in their disease process.”

https://karger.com/mca/article/9/1/211/951948/Marijuana-Use-for-Symptom-Control-in-Inflammatory

Synergistic In Vitro Effects of Minor Phytocannabinoids and Melatonin Combinations Against Human Glioblastoma Cells

Posted on by

“The prognosis of glioblastoma (GBM) patients remains dismal due to chemoresistance.

Repurposing of natural and endogenous compounds, such as the pineal hormone melatonin (MLT) and minor phytocannabinoids like cannabinol (CBN) or cannabigerol (CBG), represents a promising strategy.

This study investigates the cytotoxic potential of combining these phytocannabinoids with MLT, evaluating their efficacy both alone and synergistically with temozolomide (TMZ) to overcome drug resistance.

To achieve this, cytotoxicity, synergy (Bliss model), and selectivity were evaluated in U87, T98, and U251 GBM lines and normal astrocytes. Mechanisms of damage were characterized via Western blot (γH2AX and PARP-1), flow cytometry using fluorescent dyes/probes (DCFDA, JC-1, MitoBright, BODIPY, PI, and Annexin-V), or the protein marker COX IV and confocal analysis.

The results demonstrated that CBN-MLT and CBG-MLT regimens exerted synergistic cytotoxicity while sparing healthy astrocytes. Notably, combining these regimens (U87: MLT 0.3 mg/mL + CBN 25 µM; MLT 0.2 mg/mL + CBG 15 µM. T98: MLT 0.7 mg/mL + CBN 25 µM; MLT 0.6 mg/mL + CBG 30 µM. U251: MLT 0.4 mg/mL + CBN 20 µM; MLT 0.5 mg/mL + CBG 35 µM) with TMZ significantly enhanced chemotherapeutic efficacy, overcoming baseline effects of TMZ in these cell lines.

The combinations induced necrotic cell death characterized by severe double-strand DNA damage. This was driven by an early accumulation of intracellular ROS, which triggered mitochondrial depolarization, loss of organelle mass, and lipid peroxidation. CBN combinations consistently triggered more robust biochemical alterations than CBG-based treatments.

Taken together, this study provides a strong preclinical basis for utilizing minor cannabinoids combined with MLT in GBM management.

Crucially, this co-treatment emerges as a promising approach to potentiate TMZ efficacy, offering a novel and potentially effective therapeutic strategy to counter GBM resilience.”

https://pubmed.ncbi.nlm.nih.gov/42589431

“In recent years, the repurposing of endogenous compounds and natural products has emerged as a promising frontier in neuro-oncology. Among these, the pineal hormone melatonin (MLT) and phytocannabinoids derived from Cannabis sativa, most notably Δ9-tetrahydrocannabinol (THC) and cannabidiol (CBD), have shown strong individual anti-cancer effects “

“Crucially, phytocannabinoids are capable of inhibiting tumor growth, inducing cancer cell death, and modulating the immune microenvironment. Moreover, they have demonstrated a distinct ability to enhance the effectiveness of conventional therapies and sensitize chemotherapeutic treatments, helping to overcome established resistance mechanisms.”

https://www.mdpi.com/1422-0067/27/15/6774


Whole-Cell Transformation of Cannabidiol by Selected Filamentous Fungi into Novel Polar Derivatives

Posted on by

“Cannabidiol (CBD) is a bioactive phytocannabinoid with considerable pharmacological potential. However, its limited aqueous solubility and high lipophilicity remain significant barriers to its broader pharmaceutical application.

In this study, the enzymatic potential of selected filamentous fungi was investigated as a whole-cell biocatalytic platform for the regioselective functionalization of CBD.

Sixteen fungal strains were screened, and thirteen microorganisms successfully transformed CBD into more polar derivatives. Four strains showing distinct and promising chromatographic profiles were selected for scale-up biotransformation and product isolation: Mucor hiemalis KCh W2, M. hiemalis AM 450, Isaria fumosorosea KCh J2, and Metarhizium robertsii MU4. Eight CBD derivatives were isolated and identified by UHPLC-DAD, NMR spectroscopy, and HRESI-MS, including hydroxylated, glycosylated, and methylglycosylated products.

Among them, two metabolites, 2′-O-(4‴-O-methyl-β-D-glucopyranosyl)-cannabidiol and 2′-O-(4‴-O-methyl-β-D-glucopyranosyl)-5″-hydroxycannabidiol, are reported here as previously undescribed CBD derivatives. 

I. fumosorosea KCh J2 and M. robertsii MU4 demonstrated the ability to catalyse 4-O-methylglycosylation. An additional experiment using 2′-O-(β-D-glucopyranosyl)-cannabidiol as an intermediate supported a sequential pathway involving initial phenolic O-glycosylation followed by methylation of the sugar moiety. In silico analysis predicted reduced lipophilicity for the newly obtained derivatives compared with CBD; however, these computational results require experimental verification and should not be interpreted as evidence of improved aqueous solubility, bioavailability, or biological activity.

These findings demonstrate that filamentous fungi are useful whole-cell biocatalysts for generating structurally diverse CBD derivatives with increased polarity and provide new compounds for future physicochemical and biological evaluation.”

https://pubmed.ncbi.nlm.nih.gov/42589536

https://www.mdpi.com/1422-0067/27/15/6884

In Silico Screening of Cannabis sativa Phytochemicals as Potential Ornithine Decarboxylase Inhibitors for Anti-Leishmanial Drug-Prioritized Compound Development

Posted on by

“Leishmaniasis remains a major neglected tropical disease with limited therapeutic options, increasing drug resistance, and significant treatment-associated toxicity. Ornithine decarboxylase (ODC), which plays an essential role in polyamine synthesis and survival of parasites, is a potential molecular target for the discovery of anti-leishmanial agents.

In this study, 49 natural products with bioactive properties, such as cannabinoids, terpenoids, flavonoids, polyphenols, and alkaloids, are evaluated against ODC using computational approaches like molecular docking and molecular dynamics (MD) simulations.

During molecular docking analysis, some compounds showed good affinity binding to the ODC catalytic site, namely Sanguinarine (-8.53 kcal/mol), Rutin (-8.15 kcal/mol), Evodiamine (-7.83 kcal/mol), Cannabinol (-7.58 kcal/mol), and β-sitosterol (-7.56 kcal/mol). Analysis of protein-ligand complex interactions showed that these compounds formed hydrogen bonds, hydrophobic interactions, π-alkyl contacts, π-cation contacts, and van der Waals forces in the vicinity of the active-site amino acid residue. For further analysis, MD simulations were performed for 100 ns on the best-docking complexes. Comparative trajectory analysis of RMSD, RMSF, Rg, SASA, and hydrogen bonds was conducted, revealing that Rutin and Evodiamine exhibited relatively high structural stability and consistent interactions within the ODC binding cavity.

Overall, this study indicates that the natural compounds analyzed here could be considered promising hit compounds for anti-leishmanial drug discovery against ODC. However, further investigations using experimental techniques are required to confirm their biological properties and efficacy.”

https://pubmed.ncbi.nlm.nih.gov/42589139

“Leishmaniasis is considered a neglected tropical disease due to limited treatment options, increasing resistance to prioritized compounds, and high toxicity associated with treatment, necessitating the exploration of new potential treatment approaches with improved safety profiles.

In this research, computational tools were used to evaluate the efficacy of certain natural bioactive compounds on Ornithine Decarboxylase, which is a key enzyme involved in parasite viability. Molecular docking found several compounds, including Sanguinarine, Rutin, Evodiamine, Cannabinol, and β-sitosterol, with good binding energy and interaction patterns. Further, molecular dynamics studies showed that Rutin and Evodiamine had relatively stable interactions with the protein target.

Overall, the current findings suggest that selected natural compounds could serve as potential candidates for prioritized compound development in the treatment of leishmaniasis.”

https://www.mdpi.com/2079-7737/15/15/1272

Design, Synthesis, In Silico and In Vitro Pharmacological Profiling of Cannabidiol-like Synthetic Analogues as Multi-Target Anti-Alzheimer’s Agents

Posted on by

“Alzheimer’s disease (AD) is a multifactorial neurodegenerative disorder that requires therapeutic agents capable of targeting multiple pathological pathways.

In this study, a series of cannabidiol (CBD)-like hydrazone derivatives (3a–i) was synthesized and characterized by NMR, HRMS, and single-crystal X-ray diffraction for compound 3i.

In silico ADME analysis predicted favorable drug-like properties, including compliance with Lipinski’s Rule of Five, oral bioavailability, and blood-brain barrier permeability. The compounds were evaluated for cholinesterase inhibition, antioxidant activity, cytotoxicity in neuronal cell lines, and binding interactions with human butyrylcholinesterase (hBChE) by molecular docking. Biological evaluation revealed a marked preference for BChE over acetylcholinesterase (AChE).

Compound 3f was the most potent BChE inhibitor (IC50 = 1.67 ± 0.11 μM), while compounds 3b and 3f demonstrated high selectivity toward BChE. Antioxidant assays (DPPH, ABTS, FRAP, and FTC) indicated moderate, mechanism-dependent activity. Compounds 3b and 3e showed the strongest ABTS radical-scavenging effects, whereas compounds 3b and 3f provided the greatest protection against lipid peroxidation, surpassing CBD under the tested conditions. Several derivatives, particularly 3a, 3b, 3f, 3h, and 3i, exhibited favorable safety profiles in SH-SY5Y and Neuro-2a cells. Molecular docking supported the experimental findings.

Overall, compounds 3b and 3f emerged as promising multifunctional leads for the development of multitarget-directed anti-Alzheimer agents.”

https://pubmed.ncbi.nlm.nih.gov/42588505

“Cannabidiol (CBD), a non-psychoactive phytocannabinoid derived from Cannabis sativa, has emerged as a promising multitarget neuroprotective agent for Alzheimer’s disease (AD).”

https://www.mdpi.com/1420-3049/31/15/2657

Endocannabinoid system attenuates emotional stress-induced orofacial musculoskeletal pain in rats

Posted on by

“Orofacial musculoskeletal pain (OMP) is a common feature of temporomandibular disorders (TMD), a group of conditions affecting the temporomandibular joint, chewing muscles, and associated structures.

The etiology of muscular TMD is currently understood within a biopsychosocial model of pain, highlighting the complexity related to OMP. In this context, the objective of this study was to investigate the OMP induced by psychological/emotional stress (ES) in rats, regarding the role of the endocannabinoid system (ECS) through CB1 and CB2 receptors.

Male Wistar rats were divided into Control and ES groups. OMP was induced by ES using the communication box model and evaluated through the mechanical threshold in masticatory muscles. c-Fos, CB1, and CB2 immunostaining was evaluated in the trigeminal ganglion (TG) and in the trigeminal nucleus caudalis (Sp5C). The selective CB1 or CB2 antagonist (AM251 or AM630, respectively) or the cannabinoid receptor non-selective agonist (WIN55,212-2) were administered to both groups, and the OMP was evaluated. The mechanical sensitivity of the masticatory muscles increased in the ES group, accompanied by increased c-Fos expression in the TG and Sp5C. AM251 and AM630 increased mechanical sensitivity, while WIN55,212-2 decreased the OMP. Furthermore, ES increased CB1 density in the TG and elevated both CB1 and CB2 in the Sp5C. Additionally, CB2 was increased in the masseter muscle.

Thus, cannabinoid receptors played a protector role in OMP caused by ES, indicating that cannabinoid drugs or the modulation of the ECS may represent a promising approach for the treatment of OMP frequently observed in patients with TMD.”

https://pubmed.ncbi.nlm.nih.gov/42585375

https://www.scielo.br/j/bjmbr/a/DHTkCSCk5bcNGJrbWcb67Jz/?lang=en


Cannabidiol-induced Heme oxygenase-1 contributes to modulate the phenotype of hiPSC-derived cardiac fibroblasts from patients with Duchenne muscular dystrophy

Posted on by

“Duchenne muscular dystrophy (DMD) is a severe and progressive form of muscular dystrophy caused by mutations in the dystrophin gene. We previously observed that loss of dystrophin in human induced pluripotent stem cell-derived cardiac fibroblasts (hiPSC-cFib) dysregulated the actin network and induced a metabolic remodeling associated with an exacerbated myofibroblast phenotype.

The endocannabinoid signaling (ECS) system plays an important role in chronic inflammatory and fibrotic conditions and is dysregulated in skeletal muscle of DMD patients. Here, we investigated the effects of cannabidiol (CBD) on hiPSC-cFib from healthy controls and DMD patients.

CBD failed to modify metabolic responses in DMD hiPSC-cFib, while significantly promoting glycolysis and cell proliferation in control hiPSC-cFib. Despite these distinct metabolic responses, CBD significantly attenuated TGF-β-induced myofibroblast activation in both DMD and control hiPSC-cFib by lowering α-smooth muscle actin and collagen type I levels suggesting a metabolism-independent mechanism.

Additionally, CBD exerted strong antioxidant effects on both DMD and control hiPSC-cFib, markedly reducing intracellular reactive oxygen species (ROS) levels, increasing GSH levels and robustly inducing heme oxygenase-1 (HO-1) expression in a time- and dose-dependent manner which could not be mimicked by CB1R or CB2R agonists and blocked by their antagonists.

Pharmacological inhibition of HO-1 blunted CBD’s ability to suppress TGF-β-induced activation of DMD and control hiPSC-cFib, demonstrating that HO-1 is a key mediator of CBD’s anti-fibrotic action.

Together, these findings showed stimulation of glycolytic metabolism by CBD, regulation which is lost in DMD hiPSC-cFib. We uncovered a previously unrecognized HO-1-dependent pathway by which CBD dampens profibrotic activation in human DMD and control hiPSC-cFib, highlighting its potential as a therapeutic approach to limit cardiac fibrosis in Duchenne muscular dystrophy.”

https://pubmed.ncbi.nlm.nih.gov/42579928

“Dysregulation of the endocannabinoid system (ECS) was observed in both murine and human muscles affected by DMD.”

“Modulation to the endocannabinoid system has shown benefits in locomotor performance of dystrophic mdx making the endocannabinoid system a therapeutical target for treatment of Duchenne patients.”

“Cannabidiol exerted a protective effect against the over-activation of Duchenne hiPSC-derived fibroblasts associated with HO-1 induction, highlighting its therapeutic potential to mitigate cardiac fibrosis associated with Duchenne muscular dystrophy.”

https://www.sciencedirect.com/science/article/pii/S2213231726003320?via%3Dihub


Cholesterol-induced stimulation of platelet aggregation is prevented by a hempseed-enriched diet

Posted on by

“Hypercholesterolemia indirectly increases the risk for myocardial infarction by enhancing the ability of platelets to aggregate. Diets enriched with polyunsaturated fatty acids (PUFAs) have been shown to reduce the detrimental effects of cholesterol on platelet aggregation.

This study investigated whether dietary hempseed, a rich source of PUFAs, inhibits platelet aggregation under normal and hypercholesterolemic conditions.

Male New Zealand white rabbits were fed one of 6 dietary interventions: regular control diet (RG); control diet + 10% hempseed (HP); control diet + 10% partially delipidated hempseed (DHP); control diet + 0.5% cholesterol (OL); control diet + 0.5% cholesterol + 10% hempseed (OLHP); control diet + 5% coconut oil (CO). After 8 weeks, blood was collected to measure ADP- and collagen-induced platelet aggregation and plasma levels of fatty acids, cholesterol, and triglycerides.

The hempseed-fed animals (HP and OLHP) displayed elevated plasma levels of PUFAs and a prominent enhancement in 18:3n-6 (gamma-linolenic acid, GLA) levels, a unique PUFA found in hempseed. The cholesterol-supplemented groups (OL and OLHP) had significantly elevated plasma levels of cholesterol and triglycerides, but platelet aggregation was significantly augmented only in the OL group.

The addition of hempseed to this diet (OLHP) normalized aggregation. The direct addition of GLA to the OL platelet samples blocked the cholesterol-induced stimulation of platelet aggregation.

The results of this study demonstrate that when hempseed is added to a cholesterol-enriched diet, cholesterol-induced platelet aggregation returns to control levels. This normalization is not due to a reduction in plasma cholesterol levels, but may be partly due to increased levels of plasma GLA.”

https://pubmed.ncbi.nlm.nih.gov/18418423

https://cdnsciencepub.com/doi/10.1139/Y08-011

Cannabis Seed Oil Alleviates Experimental Atherosclerosis by Ameliorating Vascular Inflammation in Apolipoprotein-E-Deficient Mice

Posted on by

“In recent decades, epidemiological, clinical, and experimental studies have demonstrated that a diet with antioxidant or anti-inflammatory function plays a central role in the prevention of atherosclerosis (AS).

The purpose of this study was to explore the effects of Cannabis seed oil (CO) administration on in vitro antioxidant capacity as well as blood lipid profiles, lipid peroxidation, inflammatory response, and endothelial cell integrity. Female ApoE-/- mice were fed a high-cholesterol diet and administrated with CO or phosphate-buffered saline (PBS) and seal oil by gavage for 8 weeks.

The results show that CO administration reduced the levels of serum triglycerides and low-density lipoprotein cholesterol at week 6. Additionally, a decrease in serum tumor necrosis factor α and nitric oxide was also observed. Moreover, results from CD31 staining and scanning electron microscopy revealed that CO treatment alleviated the endothelial cell damage and lipid deposition induced by a high-cholesterol diet. The ratio of lesion area to the total aorta area was 19.57% for the CO group, which was lower than the PBS control group (24.67%).

Collectively, CO exerted anti-atherosclerotic effects by modulating serum lipid profiles and inflammatory responses and improving endothelial cell integrity and arterial lipid deposition. The results provide a promising preventive strategy for the early progression of AS.”

https://pubmed.ncbi.nlm.nih.gov/34037390

https://pubs.acs.org/jafcau/article-abstract/69/32/9102/506931/Cannabis-Seed-Oil-Alleviates-Experimental?redirectedFrom=fulltext

Stability of Cannabinoids in Cannabis: Plant Material, Extracts, Oil Formulations, and Isolates (CBD and Δ9-THC) Under Different Storage Conditions

Posted on by

“Background: The chemical stability of cannabinoids in Cannabis sativa plant material and formulated products is a critical factor for quality control, therapeutic efficacy, and regulatory compliance. Cannabinoids such as THC are prone to degradation over time, which is heavily influenced by storage conditions and the product matrix. Despite its importance, comprehensive long-term stability data comparing different plant chemovars (high THC, high cannabidiol [CBD], and intermediate) alongside processed products like extracts and isolates remains limited. This study aims to evaluate the stability of cannabinoids in plant material, extracts, oil formulations, and isolates (CBD and Δ9-THC) under distinct environmental temperatures to optimize storage guidelines.

Methods: Cannabis plant material representing three distinct chemovars-high THC, high CBD, and intermediate (balanced THC/CBD), extracts, pure isolates (THC and CBD) and CBD extract as oil formulation were subjected to extended stability testing over a prolonged period under three controlled temperature environments: room temperature, refrigeration, and freezing. Quantitative analysis of cannabinoid content was performed at regular intervals using gas chromatography (GC/FID) to track degradation and potency over time.

Results: The stability profiles varied depending on the cannabinoid profile, temperature, and matrix type. For the majority of cannabis-derived products, exposure to room temperature accelerated the degradation of THC into cannabinol (CBN), whereas storage at -20°C preserved cannabinoid integrity over the extended timeline. Notably, a distinct divergence was observed between the compounds: CBD-only products demonstrated robust long-term stability even when maintained at room temperature. Conversely, THC-rich matrices were highly susceptible to ambient degradation but exhibited the highest stability when formulated as ethanolic solutions and stored in the freezer (-20°C).

Conclusion: To maximize cannabinoid shelf-life and prevent degradation, storage temperatures must match product composition. While CBD-dominant products can tolerate room-temperature storage, THC-rich products require cold chain management, ideally stored in a freezer at -20°C for optimal long-term potency.”

https://pubmed.ncbi.nlm.nih.gov/42576671

https://journals.sagepub.com/doi/10.1177/25785125261478275