Category Archives: THC (Delta-9-Tetrahydrocannabinol)

Transient CB2R modulation durably restricts breast cancer plasticity by stabilizing a luminal like cell identity

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New breast cancer research suggests that brief modulation of cannabinoid receptor 2 (CB2R), including with THC, may have lasting effects on tumor cell behavior. Researchers found reduced self-renewal, invasiveness, and tumor-initiating capacity, along with greater tamoxifen sensitivity and a durable shift toward a more stable luminal-like cell identity.

“Cancer cell plasticity enables therapy resistance and metastasis by allowing transitions between stem-like and differentiated states. Differentiation-based strategies aim to stabilize tumor cell identity, yet pharmacological approaches that induce durable lineage restriction remain limited.

Here, we show that transient modulation of cannabinoid receptor 2 (CB2R) durably restricts breast cancer cell plasticity by stabilizing a luminal-like cell state. Using patient-derived and murine tumor organoids, we demonstrate that brief, low-dose CB2R modulation reduces self-renewal, invasiveness and tumor-initiating capacity, while enhancing tamoxifen sensitivity and limiting the emergence of resistant phenotypes.

These effects persist under pro-dedifferentiation conditions, including TGFβ exposure, stromal co-culture, immune signaling and mechanical stress, and are maintained in vivo following orthotopic transplantation. RNA sequencing reveals a progressive transition from an early plastic state toward a stabilized luminal-like identity, supported by CUT&Tag profiling that uncovers chromatin remodeling associated with this stabilization.

Together, our findings redefine CB2R as a regulator of tumor cell state and establish transient CB2R modulation as a strategy to durably constrain breast cancer plasticity through differentiation-based therapy.”

https://www.nature.com/articles/s42003-026-10837-1

“Low-dose THC keeps breast cancer cells in tumor models from reverting to an aggressive state”

https://medicalxpress.com/news/2026-09-dose-thc-breast-cancer-cells.html

Benefits of cannabis in treating lower urinary tract symptoms: A scoping review

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Cannabis-based therapies may offer another approach to managing lower urinary tract symptoms such as urinary urgency, frequency, and incontinence. A 2026 scoping review found encouraging evidence that THC, CBD, and combined cannabinoid formulations can improve several urinary symptoms and quality-of-life measures, with the most consistent evidence found among patients with multiple sclerosis.

“Introduction: Anticholinergics and β3-agonists remain the mainstay for bladder dysfunction but are limited by side effects and poor adherence. Cannabinoids are a potential alternative given receptor distribution in bladder control pathways. Early studies suggested that cannabis may demonstrate benefits in overactive bladder (OAB) and lower urinary tract symptoms (LUTS), but findings are limited by small sample sizes and cross-sectionality. This review investigates the therapeutic utility of cannabis and its impact on LUTS.

Methods: This scoping review was conducted following Cochrane and PRISMA guidelines. Eligible studies included adults with OAB symptoms due to neurogenic disease, benign prostatic hyperplasia (BPH), or cystitis, treated with cannabis vs. placebo, no treatment, or active therapies. Outcomes included urinary function and quality of life. Databases searched included MEDLINE, EMBASE, and CENTRAL. Non-English studies were excluded.

Results: From 998 abstracts, 31 full-text articles were reviewed and 12 were included. Studies showed consistent evidence on the effectiveness of cannabis-based therapies for managing LUTS, particularly in patients with multiple sclerosis (MS). Cannabis interventions, including THC, CBD, and combined formulations, showed some improvements in incontinence episodes, frequency, and quality-of-life measures. Mild adverse effects, including dizziness and dry mouth, were common (2-18%) and sometimes led to treatment discontinuation. Nine of 12 studies were done on MS populations, and only three studies were randomized controlled trials.

Conclusions: Evidence for the benefits of cannabis in treating LUTS is limited and largely observational. While preliminary findings are encouraging, randomized trials focusing on patient-centered outcomes are needed to clarify its role in clinical practice.”

https://pubmed.ncbi.nlm.nih.gov/42678682

https://cuaj.ca/index.php/journal/article/view/9478

Effects of delta-9 tetrahydrocannabinol and cannabidiol on cognitive outcomes following acute use of cannabis for chronic pain

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In a study of 183 adults using edible cannabis for chronic low back pain, researchers found no significant acute changes in executive function, episodic memory, or processing speed after cannabis use. Participants using CBD-dominant products performed better on working memory than those using CBD + THC one hour after use, while the CBD group also showed more stable verbal-learning scores than participants using THC or mixed CBD/THC products. The findings add useful evidence to the discussion of how different cannabinoid profiles may affect cognition when cannabis is used for chronic pain.

“Rationale: An estimated two-thirds of medical cannabis users in the United States are motivated by chronic pain, but clinical guidance remains guarded as to whether the potential benefit of cannabinoids for pain outweighs potential risks, such as effects on cognition.

Objectives: In a study where participants experienced benefits of cannabinoids for pain and tension, we evaluated cannabis effects on executive function, processing speed, memory, and verbal learning following acute use for chronic, non-specific low back pain.

Methods: Participants were in one of three self-selected edible cannabis groups: a) CBD-dominant, b) THC-dominant, or c) a mixed ratio of CBD to THC and completed a battery of cognitive tasks at pre-use, 1 h post-use use, and 2 h post-use.

Results: Among 183 participants (56.8% female; Mage = 45.6), those in the group using CBD outperformed participants using CBD + THC 1 h post use in working memory and produced more stable scores in verbal learning after use than participants using THC or CBD + THC. Additionally, while older age was associated with better working memory in the CBD group before use, that relationship was progressively attenuated over the subsequent timepoints. There were no significant effects of cannabis use on cognition in the domains of executive function, episodic memory, or processing speed.

Conclusions: Given the ubiquity of cannabis use for chronic pain and the ongoing call for more data, this study is relevant for informing clinical guidance on whether, and how, cannabis could be used in this context. In particular, understanding the acute impact on cognition from cannabis is critical, as cognitive functioning directly affects patients’ daily lives and quality of life.”

https://pubmed.ncbi.nlm.nih.gov/42678518

“In summary, these findings support CBD’s potential to preserve cognitive performance in the context of chronic pain, contrasting with the more variable effects of THC across cognitive domains. The observed influence of age, particularly among those using CBD, suggests that both cannabinoid composition and individual factors shape cognitive outcomes following acute cannabinoid use.”

https://link.springer.com/article/10.1007/s00213-026-07157-x

Cannabinoid efficacy for pain: dose, chronicity and route

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Cannabinoid pain relief depends on more than whether THC or CBD is used. Dose, route of administration, treatment duration and the type of pain can all influence whether a cannabis-based therapy provides meaningful analgesia or produces unwanted effects. This review examines those variables across preclinical and clinical research, while also considering the independent and combined roles of cannabis-derived terpenes.

“Cannabis-based therapies are widely used for chronic pain, yet their mechanisms and therapeutic windows remain incompletely defined. This review synthesizes preclinical and clinical evidence on how dose, route of administration, treatment duration, and chemical composition shape analgesic efficacy and adverse-effect liability for Δ9-tetrahydrocannabinol (THC), cannabidiol (CBD), and select cannabis-derived terpenes.

Across rodent pain models, acute THC reliably produces antinociception, but its therapeutic window is narrow because analgesic doses overlap with CB1 receptor-mediated side effects such as sedation, hypothermia, hyperphagia, and motor impairment. Repeated THC exposure leads to tolerance and dependence.

In contrast, CBD shows limited acute efficacy in naïve and inflammatory models but demonstrates more consistent benefit with repeated dosing in neuropathic and chemotherapy-induced pain, often without cannabimimetic adverse effects.

Terpenes such as linalool, β-caryophyllene, myrcene, limonene, α-terpineol, and α-bisabolol exhibit independent antinociceptive and anti-inflammatory properties and are thought to pharmacologically interact with cannabinoids in a dose-, ratio-, and route-dependent “entourage” effect that either enhance or constrain therapeutic benefit.

This review also focuses on integrating machine learning-based behavioral phenotyping of rodents to refine cannabinoid analgesia preclinical research. Computer vision pose-estimation and unsupervised clustering approaches enable high-resolution quantification of spontaneous and evoked natural behaviors, allowing the analytical dissociation of true analgesia from sedation, ataxia, or reduced exploration. By coupling these behavioral pipelines with pharmacokinetic and circuit-level analyses, emerging frameworks will define therapeutic windows with greater precision and improve the translational relevance of cannabinoid-based pain therapeutics.”

https://pubmed.ncbi.nlm.nih.gov/42661783

“Cannabinoid-based therapeutics are among the most widely used treatments for pain indications, with nearly one-third of adults with chronic pain using Cannabis for pain management.”

“Taken together, the studies reviewed here demonstrate that the analgesic efficacy of THC, CBD, and Cannabis-derived terepenes is dependent on dose, route of administration, treatment chronicity, and chemical composition.”

https://www.frontiersin.org/journals/neuroscience/articles/10.3389/fnins.2026.1888863/full

Chronic THC exposure modulates behavioral outcomes and endocannabinoid signaling in HIV-1 Tg26 mice in a sex-dependent manner

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Researchers examined how chronic THC exposure affects behavior and endocannabinoid signaling in an HIV-1 mouse model.

Chronic THC helped attenuate the decline in motor coordination and was associated with increased CB1 receptor expression in the cerebellum. The study also found major sex-dependent differences, with female and male mice showing different patterns of motor impairment and endocannabinoid signaling.

THC did not produce detectable pain-relieving effects in this model, but the findings suggest that chronic THC can influence HIV-related neurological changes through the endocannabinoid system.

Overall, the study highlights the complex relationship between THC, HIV-associated neurological dysfunction, and biological sex.

“While combined antiretroviral therapy (cART) has transitioned HIV-1 into a manageable chronic condition, it fails to eradicate latent viral reservoirs in the central nervous system (CNS) that drive persistent neuroinflammation and synaptodendritic injury. Consequently, people living with human immunodeficiency virus type-1 (HIV-1) often utilize cannabis to manage neurological symptoms, yet the long-term impact of exogenous cannabinoids on the HIV-1-burdened brain remains poorly understood.

In this study, we utilized the HIV-1 Tg26 mouse model to evaluate how chronic Δ9-tetrahydrocannabinol (THC, 3mg/kg) exposure influences motor coordination, thermal nociception, and endocannabinoid (eCB) signaling in the context of constitutive viral protein expression.

Our results demonstrate that HIV-1 viral protein expression was associated with impaired acquisition of cerebellum-dependent motor learning in a sex-dependent manner. This deficit was primarily driven by females and coincided with altered markers of eCB plasticity, characterized by elevated monoacylglycerol lipase (MAGL) expression and a depletion of 2-arachidonoylglycerol (2-AG). Conversely, males exhibit increased cerebellar CB1R and CB2R expression, which paralleled preserved rotarod performance. In the spinal cord, viral protein expression was associated with thermal hyposensitivity and a reduction in 2-AG and cannabinoid receptor levels, a pattern consistent with HIV-1-associated alterations in sensory processing circuits.

While chronic THC failed to produce detectable antinociceptive effects, consistent with spinal CB1R downregulation, it successfully attenuated the temporal decline of motor coordination with upregulating cerebellar CB1R. Data from a separate acute THC cohort demonstrated detectable THC and metabolite concentrations in plasma and cortex, while also revealing sex- and genotype-dependent differences in these measures.

Together, these findings identify sex-specific eCB signaling as a critical factor associated with the neurobiological response to HIV-1 proteins and provide a biological framework for understanding sex-dependent variability in cannabinoid efficacy.”

https://pubmed.ncbi.nlm.nih.gov/42660238

“Collectively, these results provide a biological framework for understanding sex-dependent variability in cannabinoid responses and support the inclusion of sex as a key factor in the development of cannabinoid-based adjunct therapies for chronic neuroinflammatory conditions.”

https://www.sciencedirect.com/science/article/pii/S0361923026003862?via%3Dihub

Cannabis laws and health-related workplace absenteeism in the United States

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A new U.S. study examining more than three decades of employment data found that medical cannabis decriminalization was associated with fewer health-related work absences, with some of the strongest effects appearing in physically demanding occupations and industries where chronic pain is common.

The findings suggest that access to medical cannabis may have implications not only for individual patients, but also for workforce participation and productivity.

“This study evaluated the impact of medical and recreational cannabis laws in the United States on health-related workplace absenteeism across different demographics, occupations, and industries.

Using state-level variation in the timing of cannabis decriminalization and the onset of regulated sales, we applied a flexible difference-in-differences approach to monthly data from the Current Population Survey, covering the period from January 1990 to March 2025.

The findings indicate that medical cannabis decriminalization reduced the likelihood of health-related work absences by about 6.9%, with decriminalization having a larger quantitative effect and greater statistical significance than the commencement of regulated sales.

We found no significant effect of recreational cannabis legalization on health-related workplace absenteeism. The absenteeism-reducing effects of medical cannabis decriminalization were notable in occupations (e.g., manual laborers, machine operators) and industries (e.g., manufacturing, agriculture, construction) where conditions more predisposed to cannabis treatment (e.g., chronic pain associated with physical work) are prevalent.”

https://www.tandfonline.com/doi/full/10.1080/15555240.2026.2680016#abstract

“University of Georgia study links legal marijuana use to fewer sick days”

https://www.livenowfox.com/news/university-georgia-study-links-legal-marijuana-use-fewer-sick-days

Lower Rates of Hepatocellular Carcinoma Observed Among Cannabis Users: A Population-Based Study

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Hepatocellular carcinoma (HCC) is the most common form of primary liver cancer and remains a major cause of cancer death worldwide.

In a population-based study involving more than 101 million U.S. hospital patients, researchers found a striking association between cannabis use and HCC: after adjusting for multiple potential confounding factors, patients with documented cannabis use were 55% less likely to have hepatocellular carcinoma than patients without documented cannabis use.

The study adds large-scale human observational evidence to earlier preclinical research examining cannabinoids and liver cancer.

“Background: Hepatocellular carcinoma (HCC) is one of the most common malignancies worldwide and the fourth leading cause of cancer deaths in the world. The association between HCC and cannabis has been identified in mice; however, to our knowledge has not been identified in humans. Therefore, we aim to investigate the relation between HCC and cannabis use in humans.

Methods: Using data from the National Inpatient Sample (NIS) database between 2002 and 2014, we identified the patients with HCC and cannabis use diagnosis using the International Classification of Disease 9th version codes (ICD-9). Then, we identified patients without cannabis use as the control group. We adjusted for multiple potential confounders and performed multivariable logistic regression analysis to determine the association between cannabis abuse and HCC.

Results: A total of 101,231,036 patients were included in the study. Out of the total, 996,290 patients (1%) had the diagnosis of cannabis abuse versus 100,234,746 patients (99%) in the control group without cannabis abuse. We noticed that patients with cannabis abuse were younger (34 vs 48 years), had more males (61.7% vs 41.4%) and more African Americans (29.9% vs 14.2%) compared with the control group (P<0.001 for all). Besides, patients with cannabis use had more hepatitis B, hepatitis C, liver cirrhosis, and smoking, but had less obesity and gallstones, (P<0.001 for all). Using multivariable logistic regression, and after adjusting for potential confounders, patients with cannabis abuse were 55% less likely to have HCC (adjusted Odds Ratio {aOR}, 0.45, 95% Confidence Interval {CI}, 0.42-0.49, P<0.001) compared with patients without cannabis abuse.

Conclusion: Based on our large database analysis, we found that cannabis use patients were 55% less likely to have HCC compared to patients without cannabis use. Further prospective studies are needed to assess the role of cannabis use on HCC.”

https://pubmed.ncbi.nlm.nih.gov/35651376

“Our analysis revealed that cannabis users were 55% less likely to have HCC compared to non-cannabis users.” 

https://www.cureus.com/articles/90568-lower-rates-of-hepatocellular-carcinoma-observed-among-cannabis-users-a-population-based-study#!

Multiple binding modes underlie Cannabis sativa cannabinoids recognition by peroxisome proliferator-activated receptor gamma

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Cannabinoids interact with more than the classical cannabinoid receptors CB1 and CB2. One important target is PPARγ, a nuclear receptor involved in metabolism, inflammation, insulin sensitivity and several disease-related pathways.

In this study, researchers examined how multiple Cannabis sativa cannabinoids bind to and activate PPARγ. The results showed that different cannabinoids can engage the receptor through multiple binding modes, with acidic cannabinoids such as THCA and CBDA showing particularly strong activity.

The findings help clarify another molecular pathway through which cannabis compounds may influence biological processes relevant to metabolic, inflammatory and other disorders.

“Introduction: Peroxisome proliferator-activated receptor gamma (PPARγ) is a ligand-activated nuclear receptor with broad therapeutic relevance across various pathologies, including type 2 diabetes, obesity, cancer, and inflammatory disorders. Cannabinoids are a class of terpene-phenolic compounds from Cannabis sativa L. that have been shown to act as partial agonists of PPARγ. Among them, the acidic forms Δ9-tetrahydrocannabinolic acid (THCA) and cannabidiolic acid (CBDA) display higher potency than their decarboxylated counterp arts Δ9-tetrahydrocannabinol (THC) and cannabidiol (CBD). Despite experimental evidence supporting direct PPARγ-cannabinoid interaction, the molecular determinants governing ligand recognition within the binding pocket have not yet been comprehensively investigated.

Methods: A combination of molecular docking and molecular dynamics simulations was employed to characterize the binding modes of THC, CBD, THCA, and CBDA within the PPARγ ligand-binding domain. Docking calculations were performed on a curated set of 70 PPARγ crystal structures co-crystallized with structurally diverse ligands, exploiting thus the conformational variability of the binding pocket. The best-ranked solutions were subjected to 500 ns MD simulations and evaluated on the basis of ligand stability, persistence of polar and aromatic-aromatic interactions with the receptor, and energetic contributions estimated by MM/GBSA. Three candidate binding modes per ligand were selected and their trajectories extended to 1,000 ns.

Results: All four cannabinoids yielded at least one stable binding mode at the microsecond timescale. The cannabinoids THCA and CBDA displayed a greater number of stable binding modes than THC and CBD, a result consistent with the higher potency previously reported for these compounds in experimental studies. This behavior may be attributable to the formation of salt bridges with basic residues in the binding pocket.

Conclusion: Our findings provide a structural framework for understanding cannabinoid recognition by PPARγ. The ability of these compounds to adopt multiple binding modes may contribute to their partial agonist profile, opening new avenues for the rational design of selective PPARγ modulators with improved therapeutic properties.”

https://pubmed.ncbi.nlm.nih.gov/42639023

“This work provides a foundation for future studies addressing the molecular basis of cannabinoid action on PPARγ.

Moreover, these findings could serve as a starting point to explore the allosteric mechanism by which these small lipophilic molecules influence receptor structure and dynamics.

Finally, the strategy described here may also be applied to determine the binding modes of these natural compounds in other members of the nuclear receptor family, including PPARα and PPARδ, as well as to investigate the binding modes of minor cannabinoids, such as cannabichromene and cannabigerol.”

https://www.frontiersin.org/journals/bioinformatics/articles/10.3389/fbinf.2026.1893303/full


A matter of formulation: Efficacy and tolerability of nabiximols and cannabis decoction for the treatment of multiple sclerosis-related spasticity

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Cannabinoid medicines are used to help manage multiple sclerosis-related spasticity, but formulation can influence both effectiveness and tolerability. In this study, both nabiximols and cannabis decoction were effective for MS-related spasticity, while cannabis decoction may represent a viable option for patients who do not respond to or tolerate nabiximols.

“Background: Spasticity is one of the most disabling symptoms in multiple sclerosis (MS) and is often inadequately controlled by standard treatments. Nabiximols is an approved cannabinoid therapy for MS-related spasticity, while cannabis decoctions may offer alternative efficacy and tolerability profiles.

Methods: This retrospective single-centre study evaluated the efficacy and tolerability of nabiximols and cannabis decoction for MS-related spasticity, spasms, and pain, in particular in patients who switched from nabiximols to decoction. Patients initiating nabiximols between 2013 and 2024 were included. Modified Ashworth Scale (mAS), Numerical Rating Scale (NRS) for spasticity and pain, and Penn Spasm Frequency Scale (PSFS) were assessed at baseline and follow-up. Efficacy was analysed using within-group and mixed-model approaches, and Cox regression evaluated discontinuation risk.

Results: Sixty-three patients were included; 39 (61.9%) discontinued nabiximols and 14 switched to cannabis decoction. Both treatments significantly improved spasticity, spasms, and pain. In switchers, cannabis decoction led to significant improvements across all outcomes. Nabiximols showed a higher, though not statistically significant, discontinuation rate, with adverse effects reported in 27.0% versus 14.3% for cannabis decoction. Longer disease duration was associated with discontinuation due to inefficacy, while tetraspasticity predicted switching to cannabis decoction.

Conclusions: Both nabiximols and cannabis decoction are effective for MS-related spasticity. Cannabis decoction may represent a viable option for patients who do not respond to or tolerate nabiximols. Differences in cannabinoid composition and pharmacokinetics may explain variations in outcomes. Prospective studies are needed to confirm these findings and optimize treatment strategies.”

https://pubmed.ncbi.nlm.nih.gov/42594706

https://www.msard-journal.com/article/S2211-0348(26)00463-3/abstract

Biocompatible Cyclodextrin-Cannabinoid Agar-Xanthan Gum Hydrogels for Controlled Delivery and Antimicrobial Soft-Tissue Biomedical Applications

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Researchers developed biocompatible hydrogels containing CBD and CBN designed for controlled cannabinoid delivery to soft tissue. The formulations provided sustained release for up to 72 hours, showed selective antibacterial activity against Staphylococcus aureus, and remained noncytotoxic to human skin fibroblasts, supporting their potential use in localized drug delivery and tissue-engineering applications

“Agar/xanthan hydrogels incorporating hydroxypropyl-β-cyclodextrin (HP-β-CD) inclusion complexes of nonpsychoactive cannabinoids (cannabidiol, CBD; cannabinol, CBN) were developed as multifunctional biomaterials for controlled delivery and antimicrobial soft-tissue biomedical applications.

Physicochemical characterization showed improved thermal stability, tunable hydrophilicity, and a porous network suitable for loading and release. In vitro release studies demonstrated sustained cannabinoid delivery over 72 h, following first-order and Fu-Kao kinetic models.

The hydrogels exhibited selective antimicrobial activity against Staphylococcus aureus, while remaining inactive toward Escherichia coli. Cytocompatibility assays with human skin fibroblasts confirmed noncytotoxic behavior over 7 days for all hydrogel formulations tested.

These results highlight that cyclodextrin-cannabinoid-loaded agar/xanthan hydrogels are promising biocompatible platforms for controlled delivery with antimicrobial activity, suitable for tissue engineering applications.”

https://pubmed.ncbi.nlm.nih.gov/42597876

“All these results demonstrate that combining agar/xanthan hydrogels with HPβ-CD–cannabinoid inclusion complexes yields multifunctional, biocompatible materials with controlled release and selective antibacterial activity, making them promising candidates for soft-tissue local controlled-release applications.”

https://pubs.acs.org/acsodf/article/11/31/46955/5232225/Biocompatible-Cyclodextrin-Cannabinoid-Agar