Category Archives: THC (Delta-9-Tetrahydrocannabinol)

Cannabis for Harm Reduction: Exploring Mental Health and Other Motivational Factors among Adults at Risk for Alcohol Use Disorder in Florida

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“Background: Prior research has suggested that cannabis may serve as a safer alternative to alcohol, this study examined “marijuana” (THC-dominant cannabis) and cannabidiol (CBD) use as strategies to reduce alcohol consumption among adults who report harmful levels of drinking.

Method: Online surveys were distributed to 451 Florida adults (≥18 years) who consumed ≥5 alcoholic drinks weekly and reported any lifetime cannabis use. Measures included comorbid health conditions, alcohol use severity (Alcohol Use Disorder Identification Test [AUDIT]), depressive symptoms (PHQ-8), anxiety (GAD-7), post-traumatic stress symptoms (primary care post-traumatic stress disorder [PC-PTSD]), childhood trauma (Adverse Childhood Experience Questionnaire [ACE-Q]), and readiness to change (Readiness to Change Questionnaire [RCQ-12]). Chi-square and ANOVA examined differences across alcohol use risk groups; logistic regression identified factors associated with marijuana and CBD use for alcohol reduction.

Results: High (AUDIT scores ≥16) were found in 61.4% of males and 40.9% of females. Higher alcohol use risk was significantly associated with younger age, higher PHQ-8 and GAD-7 scores, greater ACE-Q scores, PTSD positivity, more health conditions, and higher readiness to change (p < 0.001). Marijuana (37.9%) and CBD (32.2%) were the most frequently reported alcohol-reduction strategies; higher alcohol use severity was linked to greater perceived effectiveness. Factors associated with marijuana use for alcohol reduction included higher PTSD scores (OR = 1.76), more comorbid conditions (OR = 1.17), action-stage readiness to change (OR = 1.47), and higher AUDIT scores (OR = 1.83). Factors associated with CBD use for alcohol reduction included higher ACE-Q scores (OR = 1.14), more comorbid conditions (OR = 1.18), action-stage readiness (OR = 1.50), and higher AUDIT scores (OR = 1.95).

Conclusion: These findings identify key clinical and motivational correlates of cannabis use for alcohol harm reduction, informing future intervention development.

Plain language summary

“This study found that individuals with severe alcohol problems, especially those with trauma and mental health conditions, frequently use cannabis to reduce drinking. Many perceive these strategies as effective, particularly when traditional treatments are inadequate or inaccessible. Public health efforts should recognize this growing interest in cannabis-based harm reduction and address the unmet needs of individuals who wish to reduce alcohol consumption, exploring alternative, evidence-based strategies to improve outcomes for high-risk groups and reduce the broader burden of alcohol-related harm.”

https://www.tandfonline.com/doi/full/10.1080/10826084.2026.2670620

Phytocannabinoids as epigenetic regulators: bridging DNA methylation and redox homeostasis in glioblastoma

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“Glioblastoma, a primary brain tumor of the CNS, is the most malignant lesion among gliomas. It has a median survival time of about 12-15 months after diagnosis and limited treatment options.

That neoplastic processes result from changes in the cell’s redox potential and the overproduction of reactive oxygen species. As a consequence, the epigenetic marker, m5C of DNA, is oxidized with ROS to 5-hydroxymethylcytosine, but guanosine is damaged to 8-oxo-dG, a general probe of oxidative stress. If so, the m5C, as well as 8-oxo-dG content in DNA, are subject to dynamic changes induced by environmental and endogenous cellular factors. These markers can be used to evaluate new therapeutic agents, among others.

Currently, there are no effective drugs against human glioblastoma.

Cannabinoids, small, lipophilic molecular compounds, are increasingly being studied for their antitumor properties.

Using the precise nucleotide post-labelling method and thin-layer chromatographic analysis we monitored the effect of CBD, THC, and CFE, as well as their combination with temozolomide, on changes of global m5C and 8-oxo-dG contents.

These results show that cannabinoids alone or in combination with the current standard glioblastoma chemotherapeutic, TMZ, inhibit the progression of GBM and could be used for its clinical treatment. The mechanism of cannabinoids’ actions on glioblastoma cells is also proposed.”

https://pubmed.ncbi.nlm.nih.gov/42118523

“Recently, cannabinoids have gained attention for their anticancer properties. They are found, among others, in Cannabis sativa L.”

“This paper shows that CBD and THC induce hypermethylation and proposes a novel mechanism of action for cannabinoids in glioblastoma.”

https://link.springer.com/article/10.1007/s13353-026-01070-x

Δ9 Tetrahydrocannabinol and cannabis extracts differentially improve adipoinsular dysfunction in diet-induced obesity

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“Diet-induced obesity (DIO) is associated with dysregulated adipoinsular axis and endocannabinoid system (eCBS) function. Acute cannabis consumption stimulates appetite; however, chronic consumption is paradoxically associated with lower prevalence of human obesity and type 2 diabetes.

We investigated the impact of chronic exposure to Δ9 tetrahydrocannabinol (THC) and cannabis extracts on DIO and glucose homeostasis in mice.

Male mice were fed a high-fat/sucrose diet or a low-fat/no-sucrose diet for 60 days. At day 30, mice were administered THC (5 mg/kg) or cannabis extracts matched for THC content daily for 30 days. We assessed adipocyte biology, glucose tolerance, insulin sensitivity, eCBS expression, body weight, food intake and motor activity. Roles for the eCBS in cannabis-induced changes in metabolic processes, including cellular bioenergetics, were analysed in 3T3-L1 adipocytes.

THC and extracts reduced body weight and fat mass in DIO mice, and reversed DIO-associated changes in expression of adipokines that regulate the adipoinsular axis. Extracts normalized expression of adipokines more effectively than THC. Notably, extracts – but not THC – normalized glucose clearance in DIO mice to levels found in lean mice. In addition, THC and extracts promoted anti-adipogenic effects and changes in energy metabolism in 3T3-L1 cells in a concentration-dependent manner.

These studies suggest that chronic cannabinoid exposure improves metabolic function and dysregulated glucose homeostasis in DIO by a mechanism that includes restoring impaired adipoinsular axis function.

KEY POINTS: Δ9 Tetrahydrocannabinol (Δ9THC) and cannabis extracts reduce body weight and fat mass in obese mice. Cannabis extracts, but not Δ9THC alone, improve glucose homeostasis in obese mice. Extracts more effectively normalize expression of components of the adipoinsular axis in obese mice. Δ9THC and extracts promote anti-adipogenic effects in 3T3-L1 cells. Δ9THC and extracts alter cellular bioenergetics in 3T3-L1 cells.”

https://pubmed.ncbi.nlm.nih.gov/42113966

“In conclusion, this study demonstrates that chronic cannabinoid exposure, particularly with cannabis extract, reduces body weight, improves glucose homeostasis and normalizes adipose tissue function in a mouse model of DIO. Our findings highlight the potential therapeutic value of cannabinoids in managing obesity and related metabolic disorders, though further research is needed to fully understand the underlying mechanisms and translate these findings into clinical applications.”

https://physoc.onlinelibrary.wiley.com/doi/10.1113/JP290431

Cannabinoids for Dermatological Applications: Mechanistic Insights, Clinical Evidence, and Emerging Nanotechnology-Enabled Delivery Strategies

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“Cannabinoids (CBs) derived from Cannabis sativa have attracted growing interest for dermatological applications due to their anti-inflammatory, antiproliferative, antimicrobial, antifibrotic, and antipruritic properties. However, their clinical translation is significantly limited by physicochemical and pharmacokinetic challenges, including poor aqueous solubility, lipophilicity, instability, variable skin penetration, and inconsistent bioavailability.

At the molecular level, CBs modulate keratinocyte proliferation, sebocyte activity, fibroblast function, melanocyte balance, and immune signalling through CB1/CB2 receptors, TRP channels, and PPARγ pathways.

Evidence supports their potential in the treatment of psoriasis, atopic dermatitis, acne, allergic contact dermatitis, pruritus, scleroderma, and skin cancers. Clinical evidence remains preliminary: topical and oral formulations have demonstrated anti-inflammatory, antiproliferative, antibacterial, and antifibrotic effects, with improvements in pruritus, lesion severity, and quality of life in early-phase studies. However, most trials are small, uncontrolled, and lack placebo comparators, limiting generalisability.

To overcome formulation barriers and enhance dermal delivery, advanced pharmaceutical strategies such as liposomes, nanoemulsions, polymeric nanoparticles, micelles, and transdermal systems have been investigated to improve stability, controlled release, and targeted skin deposition while minimising systemic exposure.

This review integrates mechanistic insights, clinical evidence, and emerging nanotechnology-enabled delivery approaches, emphasising rational formulation design and translational considerations necessary for advancing CBs toward standardised and clinically reliable dermatological therapeutics.”

https://pubmed.ncbi.nlm.nih.gov/42076122

“In summary, cannabinoids represent a biologically plausible yet clinically evolving therapeutic class in dermatology. Advancing their role in patient care will depend on coordinated progress in mechanistic understanding, pharmaceutical design, and structured clinical validation.”

https://www.mdpi.com/1999-4923/18/4/469

Cannabinoid-Driven Rewiring of GPCR and Ion Channel Signaling in Lung Cancer

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“Lung cancer remains the leading cause of cancer-related mortality worldwide, with non-small cell lung cancer accounting for the majority of cases and exhibiting persistent challenges related to therapy resistance and metastatic progression. Increasing evidence indicates that dysregulated G protein-coupled receptor signaling and ion channel activity function cooperatively as master regulators of tumor cell proliferation, migration, survival, and therapeutic response.

Cannabinoids, including phytocannabinoids such as delta-9-tetrahydrocannabinol and cannabidiol, as well as endogenous endocannabinoids, are uniquely positioned to modulate both G protein-coupled receptors and ion channels, thereby influencing key oncogenic signaling networks.

This review synthesizes current knowledge on the role of major ion channel families, including transient receptor potential channels, potassium channels, and sodium channels, and principal G protein-coupled receptor pathways involved in lung cancer progression. We further discuss how cannabinoids reprogram these interconnected signaling systems through canonical cannabinoid receptors, non-classical targets such as G protein-coupled receptor 55 and adenosine receptors, and direct modulation of ion channel activity.

Special attention is given to G protein-coupled receptor-ion channel coupling within membrane microdomains and to the capacity of cannabinoids to act as biased ligands, redirecting downstream pathways, such as the phosphoinositide 3-kinase-protein kinase B-mechanistic target of rapamycin and epidermal growth factor receptor signaling, toward apoptosis and reduced metastatic potential. Emerging strategies, including cannabinoid-based combination therapies, selective receptor biasing, and targeted delivery systems, are also highlighted.

Altogether, cannabinoid-driven rewiring of G protein-coupled receptor and ion channel signaling represents a promising mechanistic framework for developing innovative therapeutic approaches against lung cancer.”

https://pubmed.ncbi.nlm.nih.gov/42072396

“While challenges remain (optimal dosing, patient selection, and regulatory hurdles), the insight that can simultaneously target GPCRs and ion channels to cripple lung cancer is a paradigm shift. The convergence of cancer signaling biology with cannabinoid pharmacology opens up exciting possibilities for combination treatments that might tackle tumor resistance and recurrence. In summary, cannabinoid-driven modulation of GPCR and ion channel signaling represents a promising multi-pronged strategy against lung cancer, warranting further investigation and translation into clinical trials.”

https://www.mdpi.com/2227-9059/14/4/856

Cannabinoid receptors orchestrate distinct anti-tumour pathways in gastric cancer via and beyond specialized pro-resolving mediators

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“Endocannabinoids (ECS) and specialized pro-resolving mediators (SPMs) are both lipid-based compounds, but differ significantly in origin, mechanisms, and functions. Their mechanistic interaction in cancer remains undefined, particularly in gastric cancer (GC). Several interconnections have been described between these two “bioactive lipids” involved in inflammation resolution, homeostatic and anti-tumour functions.

Cannabinoid signalling can modulate SPM biosynthesis in immune cells, thus we investigated whether this crosstalk operates in GC cells, and whether SPMs mediate part of the anti-tumour activity of cannabinoid receptors.

Using synthetic and selective agonists for the cannabinoid G-protein-coupled receptors CB1 and CB2 (ACEA and JWH133, respectively), we found that receptor activation in GC cells (AGS and MKN45) sustains the synthesis of two SPMs, Resolvin D1 and Lipoxin B4, which in turn suppresses the angiogenic potential of GC cells. These CB1/CB2-driven activities required a SRC/MAPK signalling. At physiological concentrations, these SPMs further enhanced the binding affinity of ACEA and JWH133 for CB1 and CB2, indicating a functional crosstalk between the two systems.

Beyond angiogenesis, CB1/2 stimulation reduced cell proliferation and viability, induced apoptosis, impaired the migration and the epithelial-to-mesenchymal program in GC cells. Only CB2 activation reduced the stemness properties of GC cells. Interestingly, while the anti-angiogenic properties of CB1 and CB2 required SPM production, their other anti-tumour actions were independent of the pro-resolving pathway.

Our results extend the current knowledge of the endocannabinoid system by defining a new dual mechanism, SPM-dependent and SPM-independent, that restrains GC progression and identify the ECS-SPM axis as a potential target for therapeutic intervention.”

https://pubmed.ncbi.nlm.nih.gov/41775095

“CB1 and CB2 activation sustain potent anti-tumour effects in gastric cancer (GC).”

“In conclusion, this work demonstrates that cannabinoid receptor activation restrains gastric cancer cell proliferation, migration, stemness, and angiogenesis through both SPM-dependent and SPM-independent mechanisms. By linking ECS activation to pro-resolving lipid metabolism via SRC-ERK signalling, our data position CB1 and CB2 as regulators of tumour control rather than progression. These findings open the way for preclinical in vivo studies aimed at exploiting cannabinoid-SPM crosstalk as a novel therapeutic axis in gastric cancer.”

https://www.sciencedirect.com/science/article/pii/S0753332226002192?via%3Dihub

Antiproliferative Effects of Cannabinoids and Cisplatin in Cervical Cancer Cells

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“Introduction: Cervical cancer remains a leading cause of cancer-related mortality among women globally, particularly in low- and middle-income countries. Cisplatin, a standard chemotherapeutic agent, is limited by severe toxicities and chemoresistance. This study aimed to assess the effects of cisplatin in combination with phytocannabinoids, Δ9-tetrahydrocannabinol (THC) and cannabidiol (CBD) on cell proliferation, morphology, cell cycle progression, cell death, and DNA damage.

Methods: Synergistic interactions between THC, CBD, and cisplatin were assessed in HeLa, SiHa, and MCF-12A cells using the checkerboard assay and SRB assay. Cell morphology, cell cycle progression, apoptosis induction, autophagic activity, and DNA repair gene expression were evaluated using various techniques.

Results: The THC-CBD-cisplatin combination exhibited the strongest apoptotic response in cancer cells (HeLa 53%, SiHa 58%), while minimally affecting MCF-12A cells (32%). Cannabinoid co-treatment amplified the antiproliferative and pro-apoptotic effects of cisplatin in HeLa and SiHa cells. The triple combination induced a G2/M arrest in HeLa cells and sub-G1 accumulation in SiHa cells. Autophagic activity, indicated by LC3B puncta formation, increased in HeLa and SiHa cells following THC and CBD exposure. DNA repair genes XRCC1 and RAD51 were downregulated by the cannabinoid-cisplatin combination.

Conclusion: These findings demonstrate that combining THC and CBD with cisplatin results in enhanced and mechanistically diverse anticancer effects, with a higher degree of selectivity for cervical cancer cells compared to non-cancerous MCF-12A cells by inducing apoptosis and autophagy while inhibiting DNA repair capacity. This study highlights the potential of cannabinoid-based combination therapies as a promising approach for cervical cancer treatment.”

https://pubmed.ncbi.nlm.nih.gov/42055476

“Cannabinoids, a diverse group of bioactive compounds from the cannabis plant, have been shown to inhibit cancer cell proliferation through mechanisms such as inducing apoptosis, arresting the cell cycle, and inhibiting angiogenesis.”

“This study demonstrates that the combination of cannabinoids, specifically THC and CBD, with cisplatin results in enhanced, selective, and mechanistically diverse anticancer effects in cervical cancer cells. The combined treatment induces apoptosis and autophagy while inhibiting DNA repair capacity, leading to significant cytotoxicity against cancer cells and minimizing damage to normal cells. These findings underscore the potential of cannabinoid-based combination therapies as a promising and safer approach for cervical cancer treatment.”

https://onlinelibrary.wiley.com/doi/10.1002/cnr2.70561

Evaluation of Dronabinol to Decrease Opioid Use for Cancer-Induced Bone Pain

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“Background: Bone metastases (BM) from breast cancer cause significant cancer-induced bone pain (CIBP). Management of CIBP is primarily with opioids, which have notable side effects. In preclinical models, cannabinoid receptor (CB)2 and CB1 agonists were shown to decrease CIBP and bone degradation. We hypothesized that the addition of CB2/CB1 agonists would decrease opioid requirements in patients with BM.

Methods: We conducted a single-arm study among breast cancer patients with BM on opioid therapy. Patients were treated with 10 mg dronabinol BID for 8 weeks. Our primary objective was to determine the proportion who decreased their opioid use by ≥ 20%. Participants completed the Brief Pain Inventory and the European Organization for Research and Treatment of Cancer quality of life questionnaires before and after treatment. Pre- and post-treatment blood and urine were collected for analysis of biomarkers of bone remodeling.

Results: We enrolled 14 evaluable patients, and 4 decreased opioid use by ≥ 20%, meeting the primary endpoint. Patients reported significant improvements in pain severity, interference scores, quality of life, and insomnia. There was one grade 3 adverse event (dizziness) related to the study drug. A significant decrease was noted in serum C-terminal telopeptide levels with therapy.

Conclusion: Our pilot study shows that the addition of dronabinol resulted in decreased opioid requirements for CIBP. Patient-reported outcomes also demonstrated improved pain and QOL with addition of dronabinol. Our results are promising and warrant further investigation into novel analgesics for CIBP to decrease opioid use.”

https://pubmed.ncbi.nlm.nih.gov/42050177

https://academic.oup.com/oncolo/advance-article/doi/10.1093/oncolo/oyag163/8664403

“Dronabinol, sold under the brand names Marinol and Syndros, is the generic name for the molecule of (−)-trans-Δ9-tetrahydrocannabinol (THC) in the pharmaceutical context. It has indications as an appetite stimulant and antiemetic and is approved by the US Food and Drug Administration (FDA) as safe and effective for HIV/AIDS-induced anorexia and chemotherapy-induced nausea and vomiting.”

Associations of Low-Level Prenatal Alcohol and Cannabis Exposure With Adolescent Cognitive Trajectories

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“Background: No studies have examined the differential and combined effects of prenatal alcohol and cannabis exposure (PAE/PCE) on longitudinal trajectories of adolescent cognitive development. Further, previous alcohol research is mixed, with some evidence for negative PAE effects on cognition and other studies reporting null or positive associations. This study examined associations between PAE, PCE, and growth trajectories of adolescent cognition in a large, diverse sample.

Methods: N = 11,029 adolescents from the Adolescent Brain Cognitive Development℠ Study completed the NIH Toolbox cognitive battery at baseline (Mage = 9.95), two-year follow-up (Mage = 11.95), and four-year follow-up (Mage = 14.07). Retrospective parent report of PAE and PCE was assessed at baseline. Univariate growth trajectories were estimated for cognitive measures: Pattern Comparison, Picture Sequence Memory, Oral Reading, Flanker Task, and Picture Vocabulary. Cross-product terms for PAE and PCE tested combined use.

Results: Most mothers reported no prenatal alcohol (n = 8257; 74%) or cannabis (n = 10,812; 94%) use. Overall, use was low: across pregnancy, women reporting any alcohol use averaged 33.31 drinks, and those reporting any cannabis use averaged 33.00 use occasions. Before including covariates, there were negative main effects of PCE and positive main effects of PAE on intercepts for all five cognitive domains. There was little evidence for PCE/PAE effects on slopes for cognition. After adding covariates, no negative effects of PCE remained. Small positive PAE effects on intercepts for multiple domains persisted. Cross-product terms for combined exposure were not significant.

Conclusions: Little evidence emerged for negative effects of low PAE, PCE, or combined exposure on adolescents’ cognitive development after accounting for sociodemographic factors. Light drinking in families with social features positively associated with cognitive ability may result in few negative consequences. This study is the first to demonstrate weak evidence for adverse differential and combined low-level PAE and PCE effects on the development of adolescent cognition.”

https://pubmed.ncbi.nlm.nih.gov/41947378

“Little evidence emerged for negative effects of low level prenatal alcohol, cannabis, or combined exposure on adolescents’ cognitive development after accounting for sociodemographic factors.”

https://onlinelibrary.wiley.com/doi/10.1111/acer.70297

Cannabis Use and the Risk of Incident Venous Thromboembolism Among People With HIV: A Longitudinal Cohort Study in the United States

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“People with HIV (PWH) are at an increased risk of venous thromboembolism (VTE), and cannabis use is common in this population. However, evidence of cannabis impact on VTE risk has been conflicting and not well evaluated in PWH.

Using data from five Centers for AIDS Research Network of Integrated Clinical Systems sites (2009-2020), we assessed the association between cannabis use and VTE risk.

Among 13,646 PWH, 30% reported current cannabis use. In adjusted Cox models, neither former (adjusted hazard ratio [aHR] 0.78, 95% confidence interval (CI) 0.57-1.07) nor current (aHR 0.74, 95% CI 0.51-1.06) cannabis use showed a significant increase in VTE incidence compared with never use. Additionally, no dose-dependent relationship was observed between cannabis use frequency and VTE.

Among PWH, cannabis use does not appear to be associated with an elevated risk of VTE.

Further research is needed to elucidate the relationship between cannabis and VTE risk in this population.”

https://pubmed.ncbi.nlm.nih.gov/42017672

https://journals.lww.com/janac/abstract/9900/cannabis_use_and_the_risk_of_incident_venous.255.aspx