Category Archives: THC (Delta-9-Tetrahydrocannabinol)

Cannabis Improves Metabolic Dysfunction and Macrophage Signatures in Obese Mice

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“Obesity rates continue to rise, highlighting the need for new treatments that are effective, safe, and widely accessible. Aligned with the easing of restrictions on cannabis use, interest in its therapeutic potential is evolving. As such, we examined the effects of the cannabis plant with high cannabidiol (CBD) content or high Δ9-tetrahydrocannabinol (THC) content on metabolic and immune dysregulation in obese mice.

Briefly, female C57BL/6 mice were randomized into four groups (n=15/group): 1) Lean, 2) Obese Placebo, 3) Obese CBD, and 4) Obese THC. Lean mice consumed a low-fat diet for the study duration. Obese mice consumed a high-fat diet for 16 weeks prior to a 4-week cannabis (3x/week; high CBD = ~4.2 mg/kg and high THC = ~7.3 mg/kg) intervention.

Consistent with our hypothesis, obesity increased Homeostasis Model Assessment of Insulin Resistance (HOMA-IR) and metabolic dysfunction-associated steatohepatitis (MASH) both of which were significantly mitigated by either high (10.5%) CBD or high (18.16%) THC cannabis (p<0.05). Interestingly, these changes appeared to occur independent of significant weight loss or measurable changes in food intake.

Diet-induced obesity also increased infiltrating macrophages, pan macrophages, and M1-like pro-inflammatory macrophages in adipose tissue and liver. These effects were rescued by high CBD and high THC (p<0.05), providing evidence consistent with causation for the improvements in HOMA-IR and MASH.

Despite the legal complexities surrounding cannabis use, these data suggest both CBD and THC can be a viable therapy to target macrophages and improve metabolic health and immune dysregulation with obesity.”

https://pubmed.ncbi.nlm.nih.gov/40960937/

https://journals.physiology.org/doi/abs/10.1152/ajpcell.00503.2025

Effectiveness of cannabinoids on subjective sleep quality in people with and without insomnia or poor sleep: A systematic review and meta-analysis of randomised studies

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“Study objectives: This systematic review and meta-analysis assessed the efficacy of cannabinoids compared to placebo for improving sleep quality.

Methods: Searches were conducted in MEDLINE, Embase, and Cochrane databases for randomised controlled trials comparing cannabinoids vs. placebo for improving sleep quality in adults with or without insomnia or poor sleep. The primary outcome was self-reported sleep quality (PROMIS, PSQI, LSEQ, Sleep Diary). Secondary outcomes included actigraphy parameters, anxiety (GAD-7, STAI-T), well-being (WHO-5 index), and insomnia severity (ISI). Additional analyses focused on sleep quality in (1) participants with insomnia or poor sleep, and (2) cannabidiol (CBD) vs. non-CBD interventions. Statistical analysis was performed using RevMan 5.4.1, with p < 0.05 considered significant.

Results: Six trials (1077 patients) were included. Cannabinoids significantly improved sleep quality compared to placebo [SMD 0.53; 95 % CI 0.03-1.02; p = 0.04; I2 = 88 %], particularly in those with insomnia or poor sleep [SMD 0.60; 95 % CI 0.09-1.11; p = 0.02; I2 = 89 %]. Non-CBD cannabinoids demonstrated greater efficacy [SMD 0.82; 95 % CI 0.24-1.40; p = 0.005], whereas CBD-only therapies showed no significant effect [SMD 0.13; 95 % CI -0.38-0.65; p = 0.61].

Conclusion: Cannabinoids, particularly non-CBD formulations, improve sleep quality, justifying further investigation as therapeutic options for insomnia or poor sleep.”

https://pubmed.ncbi.nlm.nih.gov/40929927/

https://www.sciencedirect.com/science/article/abs/pii/S1087079225001091?via%3Dihub

Oromucosal as an Alternative Method for Administration of Cannabis Products in Rodents

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“Oral administration of drugs in laboratory rodents such as rats is conventionally performed using the gavage technique. Despite effectiveness, gavage can induce distress associated with restraint, especially following repeated animal handling.

To mitigate these adverse effects and reduce morbidity associated with traditional methods, we explored oromucosal/buccal administration of cannabidiol (CBD)-enriched Cannabis extract.

In this method, male rats were treated daily for 15 days with medium-chain triglycerides (TCM) derived from coconut oil or CBD-enriched Cannabis extract. Each treatment was administered individually while animals were gently immobilized using an affectionate touch technique. The administration involved the use of a micropipette to apply the oily formulation directly into the oral mucosa. The dosage was calculated based on the CBD concentration in the Cannabis extract, standardized at 3 mg/kg/day. To ensure accuracy, animals were weighed daily, allowing for dose adjustments in accordance with weight changes over the treatment period. This method offers non-invasive and stress-reducing treatment, potentially improving animal welfare in experimental settings.

The treatment with CBD-enriched Cannabis extract was safe, and the analysis of the hippocampus of these animals’ showed alterations in the expression levels of GluA1 and GFAP proteins, which are directly associated with glutamatergic receptor functionality and neuroinflammation, respectively. This suggests that Cannabis extract could be applied in pathological conditions where glutamatergic excitotoxicity and astrogliosis are observed.”

https://pubmed.ncbi.nlm.nih.gov/40920655/

https://app.jove.com/t/68104/oromucosal-as-an-alternative-method-for-administration-cannabis

Chitosan nanoparticles-encapsulated cannabis extracts and their antimicrobial potential against skin pathogens

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“Cannabis compounds are well-known for their therapeutic applications in the treatment of various health issues.

These substances, mainly cannabinoids, are known for their antimicrobial properties and ability to interact with various cells through endocannabinoid receptors. However, the limitations of cannabis extract, particularly its viscosity, stickiness, and low bioavailability when applied topically, limit its use in dermatology.

To enhance topical applications for treating bacterial infections and dermatophytosis, cannabis extracts were encapsulated in chitosan nanoparticles, an easily accessible and cost-effective. Cannabis extracts were prepared from three cannabis strains differing in content of major cannabinoids, namely Chocolope (THCA-A), Jonas 1 (CBDA), and Hemp G (CBGA), and subsequently were encapsulated in chitosan nanoparticles. The resulting particles were characterized, and antimicrobial and cytotoxic activity was evaluated. The mean size of particles ranged from 89.1 ± 24.8 nm for empty nanoparticles to 355.6 ± 101.6 nm for particles containing Hemp G extract. Considering the extract:chitosan ratio (1:10 w/w, 1:20 w/w respectively) and the encapsulation efficiency (EE) range from 44.65 ± 4.39% to 94.44 ± 0.93%, total amount of extracts encapsulated in chitosan nanoparticles ranged from 2.96 ± 0.05 to 5.61 ± 0.19% in 1 g of chitosan nanopowder.

Most significant antimicrobial effect was observed against the fungi Nannizzia fulva CCF 6025, where the MIC80 of the pure extract from Jonas 1 variety was 256 μg/mL while the encapsulated extract in chitosan nanoparticles (1:10 w/w extract:chitosan ratio) inhibited growth at a concentration of 256 μg/mL of nanoparticles (corresponding to 13.05 ± 0.13 μg/mL of extract).

Overall, encapsulation reduced the amount of extract required to inhibit the growth of pathogenic microorganisms by up to several times, notably in case of dermatophytes, compared to non-encapsulated extracts. Encapsulation also reduced the cytotoxic effects of the extracts on human keratinocytes. Furthermore, pure high-THCA-A extract and encapsulated extract in chitosan nanoparticles slightly increased cell viability after 72 h exposure in low concentrations compared to control.

These results may suggest the chitosan nanoparticles-encapsulated formulations as a suitable topical delivery form of cannabis extracts, offering a possible adjunctive treatment of dermatophytosis and wound healing.”

https://pubmed.ncbi.nlm.nih.gov/40917837/

https://www.frontiersin.org/journals/medicine/articles/10.3389/fmed.2025.1644502/full

UHPLC-Q-TOF-MS profiling and multifaceted antioxidant, antihyperglycemic and anticancer potential of Cannabis sativa sugar leaves: An unexplored source of cannabidiol, terpenes and polyphenols

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Pharmacological Research - Natural Products

“Cannabis sativa is one of the most extensively researched plant species that holds promising therapeutic and ethnomedicinal significance.

Various parts of the species including fan leaves, flowers and trichomes are well documented for their richness in cannabidiol (CBD) and tetrahydrocannabidiol (THC) contents. However, an overlooked part of C. sativa, the sugar leaves, which are wasted during harvesting has plethora of CBD and THC and yet to investigated.

In this study we investigated the ethanol extract of sugar leaves of C. sativa (CSLE) for chemical composition through UHPLC-Q-TOF-MS analysis and pharmacological potential by using various in vitro antioxidant, antidiabetic, nitric oxide inhibition and anticancer studies. Furthermore, in silicomolecular docking analysis was performed for 10 selected compounds against α-glucosidase and α-amylase.

The UHPLC-Q-TOF-MS profiling of CSLE revealed the tentative identification of 37 compounds including CBD, THC, terpenes and flavonoids. The cytotoxicity studies presented highest activity against breast cancer cell lines (MDA-MB-231, IC50= 18.12 ± 1.13 µg/mL) followed by lung, liver and colorectal cancer cell lines.

Similarly, CSLE showed significant antidiabetic activity by inhibiting α-glucosidase (IC50= 3.13 ± 2.78 µg/mL) and α-amylase. The in vitro antioxidant assays gave highest activity in ABTS followed by DPPH method as well as potentially inhibited nitric oxide (NO) formation. The computational analysis revealed good docking interaction of CBD, THC, selected terpene and flavonoids against α-glucosidase and α-amylase.

Overall, the findings present the sugar leaves of C. sativa as the undisputed rich source of CBD, THC, terpenes and flavonoids with multifaceted therapeutic potential in diabetes, inflammation and different types of cancers. However, there is need of further investigations on toxicity profile and in-depth pharmacological evaluation through in vivo disease bearing animal models.”

https://www.sciencedirect.com/science/article/abs/pii/S2950199725001429

“The research titled “UHPLC-Q-TOF-MS profiling and multifaceted antioxidant, antihyperglycemic and anticancer potential of Cannabis sativa sugar leaves: An unexplored source of cannabidiol, terpenes and polyphenols” identifies sugar leaves of Cannabis sativa as a potential source for multiple therapeutic compounds, including cannabidiol, terpenes, and polyphenols. Through UHPLC-Q-TOF-MS analysis, the study found that these sugar leaf extracts exhibit antioxidant, antihyperglycemic (anti-diabetic), and anticancer activities against various cancer cell lines. The specific compounds present in the sugar leaves, when combined with other plant compounds like terpenes and flavonoids, demonstrate a phenomenon known as the entourage effect, which could enhance their therapeutic potential.”

Cannabis administration is associated with reduced alcohol consumption: Evidence from a novel laboratory co-administration paradigm

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“Background: Alcohol and cannabis co-use is increasingly prevalent across the U.S., concomitant with trends towards recreational cannabis legalization. While some studies have shown that cannabis co-use is associated with reductions in alcohol consumption (i.e., substitution), others have observed increases in alcohol intake (i.e., complementarity) or no change. This study aims to address this gap in the literature through investigating the effects of legal-market cannabis on alcohol consumption and craving in the laboratory.

Method: Leveraging a within-subjects design, we enrolled non-treatment seeking individuals who use both alcohol and cannabis (n = 61) to complete two laboratory sessions, wherein they were provided an alcohol priming drink alone or after self-administering cannabis. Participants were then given the opportunity to self-administer up to 4 additional drinks. We assessed differences in alcohol self-administration and craving between sessions.

Results: Cannabis self-administration was associated with a significant reduction in number of drinks self-administered. Further, exploratory analyses revealed that individuals who drank less after using cannabis (“substituters”, n = 23) experienced reductions in craving after using cannabis and alcohol compared to alcohol alone, whereas individuals who drank the same number of drinks after using cannabis show minimal differences in craving. There were no significant group differences in blood-THC concentration post-cannabis use.

Conclusion: Results indicate that for some individuals who drink heavily, cannabis may serve as a substitute for alcohol, and craving reduction is a potential mechanism through which this could occur.”

https://pubmed.ncbi.nlm.nih.gov/40915022/

“Cannabis use was associated with a reduction in alcohol intake.”

https://www.sciencedirect.com/science/article/abs/pii/S0376871625003138?via%3Dihub

Effect of Preoperative Cannabis Use on Postoperative Pain and Outcomes Following Cardiothoracic Surgery

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“Cannabis use has grown both recreationally and medicinally in the United States over the past decades, alongside increased legalization and social acceptance. However, there remains little research investigating the effects of preoperative cannabis use on postoperative pain in patients undergoing surgery.

We conducted a single-center prospective study in adults undergoing cardiac surgery via sternotomy. Patients seen for preoperative consultation in clinic were asked a standardized survey about cannabis use. Clinical data was collected via chart review. Primary outcomes were morphine equivalents in the first 48 hours postoperatively and Visual Analog Scale (VAS) scores. Secondary outcomes were time to extubation, postoperative nausea/vomiting, ICU length of stay (LOS), reoperation, and in-hospital mortality. The non-cannabis user group had 50 patients, and the cannabis user group had 23 patients.

Average morphine equivalents in the first 48 hours were similar between cannabis users and non-users (60.98 vs 59.90; P = 0.93), as were VAS scores at 24 hours (5.52 vs 4.84; P = 0.414) and 48 hours (4.74 vs 3.90; P = 0.23). Average time to extubation (minutes) was nearly identical between cannabis users and non-users (718.41 vs 718.67; P = 0.99). There was also no significant difference in average LOS (days) between cannabis users and non-users (2.91 vs 3.48; P = 0.26). There were no differences in postoperative nausea/vomiting, reoperation, or in-hospital mortality.

In patients undergoing cardiac surgery via sternotomy, there was no effect of cannabis use on any outcomes, including morphine equivalents, Visual Analog Scale scores, time to extubation, ICU length of stay, postoperative nausea or vomiting, reoperation, or in-hospital mortality.”

https://pubmed.ncbi.nlm.nih.gov/40905360/

https://journals.sagepub.com/doi/10.1177/10892532251374952

Exploring therapeutic potential of Cannabis based therapy in autoimmune and rheumatic disorders

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“The medical use of cannabis is expanding across many countries, with some legalizing its use outright and others implementing medical licensure systems to approve treatment for eligible patients.

Despite this growing interest and utilization, there remains a lack of solid scientific evidence supporting its medical use, even though cannabis has been used therapeutically for thousands of years.

The goal of the following communication is to present updated data on the potential roles of cannabis-based treatments in various autoimmune and rheumatic conditions.

The information highlights that incorporating cannabis into the therapeutic armamentarium may offer benefits.

However, in many cases, despite encouraging perspectives and outcomes, the supporting evidence remains insufficient and requires further validation.

Due to social and legal barriers, the conduct of such rigorous clinical trials has been hindered, limiting the availability of high-quality evidence to guide medical practice.”

https://pubmed.ncbi.nlm.nih.gov/40907777/

https://www.sciencedirect.com/science/article/abs/pii/S1568997225001867?via%3Dihub

UK Medical Cannabis Registry: A Clinical Outcomes Analysis for Complex Regional Pain Syndrome

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“Background: Complex regional pain syndrome is characterized by severe, persistent pain. Emerging evidence suggests that cannabis-based medicinal products may represent a new therapeutic option. However, to date, no clinical studies have evaluated the effects of cannabis-based medicinal products in individuals with complex regional pain syndrome. The aim of this study is to assess changes in patient-reported outcome measures and the prevalence of adverse events associated with cannabis-based medicinal products prescribed for complex regional pain syndrome.

Methods: This case series assessed changes in patient-reported outcome measures over 6 months in complex regional pain syndrome patients enrolled in the UK Medical Cannabis Registry. Adverse events were measured and graded using the Common Terminology Criteria for Adverse Events version 4.0.

Results: A total of 64 patients were identified for inclusion. At baseline, pain severity measured by the Brief Pain Inventory Short Form was 6.69 ± 1.42. This improved at 1 (5.85 ± 1.73), 3 (5.91 ± 1.82), and 6 months (6.05 ± 1.72; p < 0.050). Participants also reported improvements in severity as measured by the Short Form-McGill Pain Questionnaire-2 and pain visual analogue scale at the same time points (p < 0.050). Participants also reported improvements in anxiety symptoms, sleep quality, and general health-related quality of life (p < 0.050), as measured by validated measures. Five patients (7.81%) reported 50 (78.13%) adverse events.

Discussion: This study represents the outcomes in individuals with complex regional pain syndrome prescribed cannabis-based medicinal products. These suggest initiation of cannabis-based medicinal products is associated with improvements in patient-reported outcome measures. While these findings are consistent with the literature, they must be interpreted with caution, considering the limitations of this study.

Conclusion: Cannabis-based medicinal products were associated with improvements in pain severity and interference. Participants also reported improvements in important metrics of health-related quality of life. This supports further research through high-quality randomized controlled trials to ascertain the efficacy of cannabis-based medicinal products in improving complex regional pain syndrome symptoms.”

https://pubmed.ncbi.nlm.nih.gov/40898690/

“In conclusion, the results imply that initiation of CBMPs was associated with improved pain relief and health-related quality of life in complex regional pain syndrome patients.”

https://onlinelibrary.wiley.com/doi/10.1002/brb3.70823

Supplementing HIV-ART with cannabinoids increases serotonin, BHB, and Ahr signaling while reducing secondary bile acids and acylcholines

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“Despite effective antiretroviral therapy (ART), people with HIV (PWH) experience persistent inflammation and metabolic dysfunction, increasing their risk for non-AIDS comorbidities. Accordingly, we evaluated the effects of long-term/low-dose Δ9-tetrahydrocannabinol (THC) supplementation in simian immunodeficiency virus (SIV)-infected, ART-treated rhesus macaques (RMs).

THC significantly increased plasma/jejunum serotonin and indole-3-propionate, enhancing gut-brain communication through up-regulation of serotonin receptors (HTR4/HTR7) and aryl hydrocarbon receptor (Ahr) signaling via a cannabinoid receptor (CBR)-2-mediated mechanism. Furthermore, THC enriched cholesterol-metabolizing Oscillibacter and reduced plasma cholesterol and toxic secondary bile acids (SBAs), thus improving cholesterol and SBA homeostasis.

Furthermore, THC increased β-hydroxybutyrate (BHB) levels via a CBR1-mediated mechanism, suggesting enhanced hepatic fatty acid oxidation for metabolic and cardiovascular health. THC restored ART/SIV-induced elevation of pro-inflammatory and cardiotoxic long-chain acylcholines to preinfection levels. THC-treated RMs maintained viral suppression despite reduced plasma ART levels, suggesting diminished ART-related toxicity.

Our findings demonstrate phytocannabinoids to be a safe adjunct therapy alongside ART to mitigate chronic inflammation and metabolic dysfunction in PWH.”

https://pubmed.ncbi.nlm.nih.gov/40901952/

“Taken as a whole, our findings uncover numerous hitherto unknown mechanisms of cannabinoid action and provide multiple lines of evidence for its utility as an effective and relatively safe adjunct therapy to ART.”

https://www.science.org/doi/10.1126/sciadv.adw4021