Author Archives: David

Combined effects of cannabidiol and Δ9-tetrahydrocannabinol alleviate migraine-like symptoms in mice

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“Background: The therapeutic use of cannabidiol (CBD) and Δ9-tetrahydrocannabinol (THC) to treat migraine has been understudied. Using three mouse models, we examined the impact of CBD and THC on migraine-relevant behaviors triggered by: 1) calcitonin gene-related peptide (CGRP), 2) sodium nitroprusside (SNP), and 3) cortical spreading depolarization (CSD).

Methods: Both male and female CD1 mice were treated with CBD (100 mg/kg) or THC (1 mg/kg) alone or in combinations of CBD (1, 30 or 100 mg/kg) and THC (1 mg/kg) prior to injection of CGRP or SNP. The mice were assessed for light aversion (photophobia), squint (non-evoked pain), and periorbital tactile hypersensitivity, as well as possible adverse effects. In a separate set of experiments, CSD events were optogenetically induced in familial hemiplegic migraine 1 (FHM1) mutant and wildtype littermates (WT) mice (C57BL/6 background), followed by grimace and motor assessments with and without combinations of CBD (30 or 100 mg/kg) and THC (1 mg/kg).

Results: In CD1 mice, a 100:1 CBD:THC combination mitigated light aversion induced by CGRP and SNP in males and females. Rescue of CGRP- and SNP-induced squint was observed only in male mice with 100:1 CBD:THC. None of the treatments rescued periorbital tactile hypersensitivity in either sex. In FHM1 mutant and WT mice, the 100:1 CBD:THC ratio did not affect CSD characteristics but did reduce CSD-induced grimace features (i.e., head pain mimic). No adverse effects of any of the cannabinoid treatments were observed using cognitive, emotional, or motor tests.

Conclusions: A 100:1 ratio of CBD:THC has a beneficial effect on some of the most bothersome migraine-related symptoms in three mouse models. Our findings support a potential therapeutic efficacy of combined CBD and THC treatments.”

https://pubmed.ncbi.nlm.nih.gov/39988876/

“Our preclinical findings suggest that cannabinoids may have therapeutic potential for treating migraine symptoms without causing adverse effects. These findings are in line with previous studies that have suggested that cannabinoids may be effective in treating pain and migraine.”

https://journals.sagepub.com/doi/10.1177/03331024251314487

Cannabidiol and sphingolipid metabolism – an unexplored link offering a novel therapeutic approach against high-fat diet-induced hepatic insulin resistance

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“Despite extensive research on insulin resistance, which is associated with type 2 diabetes and obesity, there remains a lack of effective and safe methods to treat it. Thus, we hypothesized that cannabidiol (CBD), which influences lipid accumulation and inflammatory response, may interact with sphingolipid metabolism and insulin signaling.

To investigate the effects of CBD, male Wistar rats were fed a standard rodent chow or high-fat diet for 7 weeks to induce IR and were treated with CBD or its vehicle administered intraperitoneally for the last two weeks of the experiment. High-Performance Liquid Chromatography (HPLC) was used to assess sphingolipid concentration in the liver, while multiplex assay and western blotting were used to investigate the level or expression of proteins in the insulin signaling pathway and sphingolipid metabolism.

Our results revealed that CBD prevented ceramide deposition in the liver of high-fat-fed rats through inhibition of the ceramide de novo synthesis pathway. Moreover, the accumulation of sphingosine-1-phosphate was notably increased with impaired catabolic pathway. Observed changes in the sphingolipid pathway coincided with improved insulin signaling after CBD treatment in animals fed a high-fat diet.

Considering the presented evidence, CBD exerted a beneficial effect on insulin sensitivity in a state of lipid overload through the modification of sphingolipid deposition.

Our study reveals the importance of broadening IR treatment methods, especially with natural substances that lack serious side effects such as CBD.”

https://pubmed.ncbi.nlm.nih.gov/39986634/

“Cannabidiol – a novel therapeutic for the treatment of liver diseases.”

https://www.sciencedirect.com/science/article/abs/pii/S0955286325000282?via%3Dihub

Cannabis Use in HIV: Impact on Inflammation, Immunity and the Microbiome

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“Purpose of review: This review explores how cannabis impacts the gut microbiome, immune system, and ART outcomes in people with HIV (PWH). Given the increasing prevalence of cannabis use among PWH, we investigated its potential to reduce chronic inflammation and enhance gut health, both of which can influence HIV pathogenesis.

Recent findings: Cannabis has immunomodulatory and anti-inflammatory effects, including reducing systemic inflammatory biomarkers (such as MCP-1 and IP-10) and improving gut barrier integrity through increased short-chain fatty acid (SCFA) production.

Studies have shown that cannabis use is associated with increased gut mucosal immunity, decreased immune activation, and a unique microbiome composition. Preliminary evidence indicates that cannabis may influence HIV reservoirs, although the results remain inconclusive.

Cannabis shows promise in managing inflammation, gut dysbiosis, and immune dysfunction in PWH. However, its effects on HIV reservoirs, adherence to antiretroviral therapy, and long-term outcomes need further investigation through rigorous clinical trials using standardized formulations.”

https://pubmed.ncbi.nlm.nih.gov/39984806/

https://link.springer.com/article/10.1007/s11904-025-00729-0

Impacts of vaping and marijuana use on airway health as determined by exhaled breath condensate (EBC)

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“Across the United States, there is increased use of cannabis products and electronic delivery systems for cannabis products and nicotine, yet little is known about their impacts on lung health.

We analyzed exhaled breath condensate of 254 participants who were non-users and users who used cannabis and tobacco products. The 132 participants reported using a product (“users”) were distributed into cohorts of tobacco products and cannabis products, with some participants following into multiple cohorts.

Targeted analysis of inflammatory oxylipins found up-regulation among persons using tobacco products, while cannabis users had concentrations closer to nonusers, and often down-regulated.

Untargeted screening of 403 significant metabolites found tobacco users had similar breath profiles, and that cannabis users had a similar profile that was closer to the profile of nonusers.

Metabolites were significantly higher in breath of people using combustion products (tobacco and cannabis) relative to nonusers, and significantly lower in e-device users (nicotine and THC). Our work demonstrates the relative impact of e-delivery systems and cannabis products compared to traditional cigarette smoking on lung metabolic profiles.”

https://pubmed.ncbi.nlm.nih.gov/39984952/

“Analysis of exhaled breath condensate was used to compare human metabolomic information of persons using tobacco and cannabis related products. Targeted measurements of oxylipin inflammatory markers found significant up-regulation among those using tobacco products relative to nonusers.

Cannabis users exhibited oxylipin levels closer to and often downregulated compared to nonusers. However, direct links to clinical outcomes such as lung disease or respiratory dysfunction were not established, limiting conclusions about the clinical impact of these biomarkers.

Untargeted screening of breath metabolites found that users of cigarettes, nicotine vapes, and any tobacco product had similar metabolite profiles, whereas cannabis smokers, vapers, and product users had a profile that was more similar to nonusers.”

https://respiratory-research.biomedcentral.com/articles/10.1186/s12931-025-03147-3


Sustainable protein concentrate from Cannabis sativa L. seeds: Green chemistry and new functional concentrates for the alternative protein industry

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“This research focused on developing a hemp protein concentrate through a potential sustainable method, with nutritional and industrial value for the emerging alternative protein industry.

By response surface methodology, the optimal processing conditions (100% ethanol, 50°C, and 10% w/v solid-to-solvents ratio) resulted in a hemp protein concentrate with 68.61% ± 1.71% protein. The process had a protein yield value of 94.11% ± 4.45%, which aligns with current sustainable food processing trends and is an excellent value compared to traditional methods for hemp seeds.

The concentrate met nutritional quality criteria for most examined parameters and showed positive results regarding essential amino acids absorption through in vitro digestion compared to nonessential amino acids. Furthermore, its techno-functional properties, particularly oil-holding capacity, emulsification properties, and gelling qualities achieved commercial standards.

This research validates the potential for producing new protein concentrates from dehulled hemp seeds through an innovative green chemistry-based method.

PRACTICAL APPLICATION: The research presents a method based on green chemistry for the obtention of hemp protein concentrate from hemp seeds. Hemp seeds are not considered a “novel food” according to the European Commission. Hemp protein concentrate had 95% protein yield and similar or better functional properties compared to commercial proteins. Thus, hemp protein is an important product for food industry applications.”

https://pubmed.ncbi.nlm.nih.gov/39980271/

https://ift.onlinelibrary.wiley.com/doi/10.1111/1750-3841.70071

Therapeutic potential of cannabinoids in neurological conditions: a systematic review of clinical trials

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“Overview: Cannabinoids have gained increasing attention for their therapeutic potential in treating several neurological conditions, including neurodegenerative diseases, chronic pain, and epilepsy. This review aims to assess the current clinical trials investigating cannabinoids, primarily Tetrahydrocannabinol and Cannabidiol, for neurological disorders. This review will aim to highlight the efficacy, safety, and outcome measures used in these trials.

Methods: Clinical trials were identified using ClinicalTrials.gov, focusing on studies that examined the effects of cannabinoids in treating neurological conditions. All trials that fulfilled the following criteria were included: Phase 1-4, focused on cannabinoids as primary intervention, and measured relevant outcomes such as pain relief, cognitive function, or spasticity reduction. Data on conditions, interventions, primary and secondary outcomes, and trial phases were extracted and analysed.

Results: A total of 47 clinical trials were identified, including different neurological conditions. The most frequently studied conditions were Multiple Sclerosis, Fibromyalgia, and Parkinson’s Disease. Most trials were in Phase 2, with the primary outcome measures focused on pain management, spasticity, and cognitive function. Secondary outcomes included safety and tolerability measures.

Conclusion: The review highlights the broad therapeutic potential of cannabinoids in neurology, with promising results in symptom management for conditions like Multiple Sclerosis and Fibromyalgia. However, the lack of standardized study protocols, dosing, and outcome measures presents challenges for broader clinical implementation.”

https://pubmed.ncbi.nlm.nih.gov/39981181/

“The results of this analysis showed that both CBD and THC have significant potential as therapeutic agents for neurological disorders, particularly in managing pain, motor dysfunction, and behavioural disturbances. However, their different pharmacological profiles and side effect risks mean that each cannabinoid may be better suited to different patient populations and conditions. While THC’s broader range of applications in cognitive and motor symptoms positions it as a more multipurpose treatment option, the psychoactive risks associated with its use should not be ignored. On the other hand, CBD’s safety and non-psychoactive nature make it more preferred option for managing chronic pain, but its therapeutic benefits may be more limited. Future research should focus on addressing the gaps in long-term safety and efficacy data, as well as exploring the full potential of lesser-known cannabinoids and combination therapies to further enhance the treatment of neurological disorders.”

https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2025.1521792/full

Effectiveness of a Cannabinoids Supplement on Sleep and Mood in Adults With Subthreshold Insomnia: A Randomized Double-Blind Placebo-Controlled Crossover Pilot Trial

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“Background and aims: Conduct a pilot randomized double-blind placebo-controlled crossover trial for adults with subthreshold insomnia symptoms to examine the effectiveness of a cannabinoids supplement on sleep quality and health outcomes.

Methods: Adults with subthreshold insomnia symptoms (N = 20, Mage = 47.40) were randomized to either the Cannabinoids Supplement (CS) or Placebo Condition (PC) for 10 days. The CS was an oral soft gel that contained 3 mg Δ9-tetrahydrocannabinol, 6 mg cannabinol, 10 mg cannabidiol, and 90 mg of a proprietary food-grade terpene blend. Following a 2-week washout, they completed the alternate condition. The following validated questionnaires were collected at baseline and following each condition: Insomnia Severity Index, Pittsburgh Sleep Quality Index, Bergen Insomnia Scale, Profile of Mood States (POMS), Perceived Stress Scale, Pain and Sleep Questionnaire. Trait Anxiety Inventory, Flinders Daytime Fatigue, and Health-related Quality of Life Scale. Clinical trial registry number = ISRCTN 15022302.

Results: When compared to PC, the CS Condition had significantly improved sleep quality/efficiency, insomnia symptoms, and health-related quality of life, p < 0.05. Nonsignificant improvements for the CS compared to the PC were found for the POMS mood subscales of tension, anger, fatigue, depression, and vigor, as well as anxiety. The Esteem subscale improved significantly from Baseline to Post for the PC. Both the CS and PC Vigor improved significantly from baseline. Anxiety improved significantly from Baseline to Post for the CS. No adverse events reported.

Conclusion: This cannabinoid-based formulation was a well-tolerated oral supplement that may improve adults’ sleep quality/efficiency and health-related quality of life. Larger controlled trials are encouraged to examine the longer-term effects of this supplement in a variety of populations and environments.”

https://pubmed.ncbi.nlm.nih.gov/39980821/

https://onlinelibrary.wiley.com/doi/10.1002/hsr2.70481

Proteomic and metabolomic analyses reveal the antibacterial mechanism of Cannabidiol against gram-positive bacteria

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“Cannabidiol (CBD), the primary non-psychoactive cannabinoid isolated from cannabis, exhibits promising antibacterial effects. However, the antibacterial mechanism of CBD remains poorly understood.

In this study, the mechanism was investigated using bacterial inhibition assays, label-free proteomics, and untargeted metabolomics, with Bacillus licheniformis (B. licheniformis), Staphylococcus aureus (S. aureus), and Enterococcus faecium (E. faecium) selected as representative Gram-positive bacteria.

The results revealed that CBD caused significant damage to bacterial cell walls and membranes, leading to notable changes in proteomic and metabolic profiles. Specifically, 437, 120, and 195 proteins, as well as 52, 153, and 94 metabolites, were differentially expressed in B. licheniformis, S. aureus, and E. faecium, respectively.

The antimicrobial mechanism of CBD shares similarities with previously known antibacterial agents, such as penicillin and cephalosporins, particularly in affecting the bacterial cell wall, but differs in its detailed mode of action. CBD disrupted the biosynthesis of primary and secondary metabolites and altered bacterial metabolism, contributing to its antibacterial activity.

This study provides valuable insights into the antibacterial mechanism of CBD, supporting its potential development as an antibiotic alternative and its application in food safety.

SIGNIFICANCE: It is crucial to find alternatives to antibiotics to mitigate the impact of pathogenic bacteria on food safety and reduce the use of antibiotics. CBD is the primary non-psychoactive cannabinoid derived from cannabis, and it has shown promising antibacterial effects. However, the antimicrobial mechanisms of CBD have not been well elucidated. This study provides a deep understanding of the antibacterial mechanism from the cellular to molecular level, which will contribute to the development of CBD as a novel antibacterial agent.”

https://pubmed.ncbi.nlm.nih.gov/39978755/

“CBD is a promising antibacterial agent for Gram-positive bacteria.”

https://www.sciencedirect.com/science/article/abs/pii/S1874391925000387?via%3Dihub

Cannabidiol Targets Colorectal Cancer Cells via Cannabinoid Receptor 2, Independent of Common Mutations

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“Cannabidiol (CBD) is a non-neurotoxic, phytocannabinoid from cannabis with reported medicinal properties, including antiepileptic and anti-inflammatory activity.

Several in vitro and in vivo studies have shown that CBD has antitumor potential against colorectal cancer (CRC), the third deadliest cancer in the world. However, as different mutations influence the antitumor effects and CBD can bind a variety of receptors, it is yet to be determined whether specific CRC mutations affect CBD’s efficacy in treatment of CRC.

To investigate this, we selected four CRC cell lines, including HCT116, HT-29, LS174T, and LS153, which harbor distinct mutations. Cells were treated with a range of concentrations of CBD to evaluate its cytotoxic effects and impact on cell proliferation, migration, and invasion by using a live-cell imaging system. IC50 values were then calculated for each parameter. The level of endoplasmic reticulum (ER) stress pathway markers was also measured using qRTPCR. The requirements for CB1 or CB2 receptor-medicated signaling were investigated using the selective inhibitors AM251 and SR144528, respectively.

Our results demonstrate that CBD induces apoptosis and halts proliferation, migration, and invasion of CRC cell lines in a concentration-dependent manner.

CBD showed potent antitumor effects in the tested cell lines with no obvious effect from different mutations such as KRAS, BRAF, APC, PTEN, etc. CBD also induced ER stress in CRC cells but not in healthy intestinal organoids. Cotreatment with SR144528 inhibited the effects of indicating involvement of CB2 receptor activation in the anticancer effects of CBD.

Together, these results demonstrated that CBD could be effective for CRC regardless of the underlying mutation through CB2 receptor activation.”

https://pubmed.ncbi.nlm.nih.gov/39974647/

https://pubs.acs.org/doi/10.1021/acsptsci.4c00644

Medical Cannabis for Patients Over Age 50: A Multi-site, Prospective Study of Patterns of Use and Health Outcomes

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“Objective: Cannabis is being used as a therapeutic option by patients around the globe, and older patients represent a rapidly growing subset of this population. This study aims to assess the patterns of medical cannabis use in patients over 50 years of age and its effect on health outcomes such as pain, sleep, quality of life, and co-medication.

Method: The Medical Cannabis in Older Patients Study (MCOPS) is a multi-site, prospective observational study examining the real-world impact of medical cannabis use on patients over age 50 under the guidance of a health care provider. The study included validated instruments, with treating physicians collecting detailed data on participant characteristics, medical cannabis and co-medication use, and associated impacts on pain, sleep, quality of life, as well as adverse events.

Results: Inclusion criteria were met by 299 participants. Average age of participants was 66.7 years, and 66.2% of respondents identified as female. Approximately 90% of patients used medical cannabis to treat pain-related conditions such as chronic pain and arthritis. Almost all patients reported a preference for oral cannabis products (e.g., extracts, edibles) rather than inhalation products (e.g., flower, vapes), and most preferred oral formulations high in cannabidiol and low in tetrahydrocannabinol.

Over the six-month study period, significant improvements were noted in pain, sleep, and quality of life measures, with 45% experiencing a clinically meaningful improvement in pain interference and in sleep quality scores. Additionally, nearly 50% of patients taking co-medications at baseline had reduced their use by the end of the study period, and quality of life improved significantly from baseline to M3 and from baseline to M6, with an incremental cost per quality-adjusted life-year (QALY) of $25,357.20. No serious adverse events (SAEs) were reported.

Conclusions: In this cohort of older patients, most of whom suffered from pain-related conditions, medical cannabis seemed to be a safe and effective treatment. Most patients experienced clinically significant improvements in pain, sleep, and quality of life and reductions in co-medication. The cost per QALY was well below the standard for traditional pharmaceuticals, and no SAEs were reported, suggesting that cannabis is a relatively safe and cost-effective therapeutic option for adults dealing with age-related health conditions.”

https://pubmed.ncbi.nlm.nih.gov/39968489/

https://publications.sciences.ucf.edu/cannabis/index.php/Cannabis/article/view/239