Next-generation hybrid nanosystems for cannabidiol: From molecular challenges to site-specific preclinical applications

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CBD’s therapeutic potential is constrained by a fundamental delivery problem: it dissolves poorly in water, undergoes extensive first-pass metabolism, and typically has low oral bioavailability. Researchers are now developing hybrid nanosystems designed to protect CBD, improve its stability and absorption, control its release, and potentially deliver it directly to specific sites in the body.

“Cannabidiol (CBD) is a monoterpene phenolic compound extracted mainly from Cannabis sativa, which is produced in high amounts compared to other plants. The compound is regarded as a promising therapeutic agent with anti-inflammatory, analgesic, and neuroprotective effects for biomedical use. Furthermore, important advances have been obtained in dermatological and anticancer effects.

Nowadays, the major challenges to the development of new medicine based on CBD arise from its unfavorable physicochemical properties that include reduced solubility in aqueous media (∼0.01 mg/mL), significant degradation due to first-pass metabolism, very low oral bioavailability (typically 6-20%), and an adverse pharmacokinetic profile. Seeking to overcome these disadvantages, recent studies have focused on employing delivery systems, including liposomes, polymeric nanoplatforms, and inorganic nanoparticles, which have attracted considerable attention for their excellent biocompatibility, high encapsulation capacity, and controlled-release properties.

Although conventional single-nanoplatforms offer advantages such as a large number of potential applications, they also have serious drawbacks, including burst drug release and short-term instability. Therefore, with respect to systems that will possess improved properties, hybrid nanoparticle systems have emerged as a second-generation class of systems capable of encapsulating CBD and potentially providing characteristics not available from single-nanoparticle systems. These include higher load efficiencies and stability, controlled and targeted delivery profiles, lower levels of premature drug release and greater enhancement of bioavailability. They are further able to provide site-specific delivery (i.e., transdermal, oral, or CNS-targeted).

The aim of this review is to provide readers with a simple summary of the most recent information found within the literature concerning CBD-loaded hybrid nanoparticle systems. It also discusses current preclinical evidence, translational challenges, and future perspectives for the clinical development of these systems.”

https://pubmed.ncbi.nlm.nih.gov/42659806

“Cannabidiol (CBD) constitutes one of the most promising therapeutic agents against different human diseases, mainly related to pathological conditions related to chronic inflammation, oxidative stress, and neurological dysregulation and degeneration, with relevant clinical results in epilepsy, autism, and pain management.”

“In summary, hybrid nanosystems have tremendous potential to transition cannabidiol delivery from traditional formulations to functional therapeutic platforms that deliver controlled release at the desired site of action while enhancing therapeutic performance.”

https://www.sciencedirect.com/science/article/pii/S0753332226009133?via%3Dihub

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

Brain cannabinoid CB1 receptor signaling modulates reward responses and inhibitory control in humans

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Researchers using PET and fMRI brain imaging found that natural differences in cannabinoid CB1 receptor availability are associated with how strongly the brain responds to anticipated food rewards and how it engages inhibitory-control systems. The findings provide new human evidence connecting the endocannabinoid system with appetite-related behavior and suggest CB1 signaling as a potential therapeutic target for eating disorders and appetite regulation.

“The central endocannabinoid system, particularly the in vivo cannabinoid type 1 (CB1) receptor signaling, presents a promising target for treating eating disorders. However, its precise role in appetite control remains unclear.

This study aimed to determine how CB1 receptor signaling contributes to key aspects of appetite regulation, specifically anticipatory food reward responses and inhibitory control.

Forty-one healthy male participants underwent [18F]FMPEP-d2 positron emission tomography (PET) to quantify CB1 receptor availability. Functional magnetic resonance imaging (fMRI) was used to assess anticipatory neural responses to food cues, while inhibitory control was measured using a go/nogo task.

Data show that individuals with higher CB1 receptor availability exhibited stronger anticipatory reward-related neural responses and reduced activation during inhibitory control. Therefore, CB1 receptor signaling plays a distinct role in modulating reward and inhibitory processes related to feeding behavior.

The findings suggest that the CB1 receptor may serve as a therapeutic target for regulating appetite.”

https://pubmed.ncbi.nlm.nih.gov/42662580

“Brain cannabinoid CB1 receptor availability modulates reward responses and inhibitory control, key neural mechanisms involved in appetite regulation. The findings suggest that individuals with elevated CB1 receptor availability may require increased engagement of inhibitory control mechanisms to counteract reward-driven responses triggered by external cues, as opposed to enhanced internal satiety signals.

These insights have potential implications for developing therapeutic strategies targeting the endogenous cannabinoid system to address obesity epidemic.”

https://direct.mit.edu/imag/article/doi/10.1162/IMAG.a.1344/138067/Brain-cannabinoid-CB1-receptor-signaling-modulates

Quality by Design-Driven Formulation Development of Cannabidiol Orally Disintegrating Tablets

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Orally disintegrating tablets may offer a more convenient way to deliver cannabidiol, particularly for people who have difficulty swallowing conventional pills. In this study, researchers used a Quality by Design approach to optimize a CBD tablet formulation for rapid disintegration, dose consistency, and reliable pharmaceutical performance.

“The development of cannabidiol (CBD) orally disintegrating tablets (ODTs) is effective in treating anxiety in a patient-friendly manner. The application of Quality by Design (QbD) enhances the efficiency and robustness of the pharmaceutical development of CBD ODTs.

The objective of this work was to develop a formulation for CBD ODTs using a QbD-driven approach. Quality target product profile, critical quality attributes, and an initial risk assessment were identified and evaluated. Subsequently, a Box-Behnken design was employed to analyze the effects of varied compression force, the quantity of microcrystalline cellulose, and the quantity of croscarmellose sodium to create a design space and control space.

Results indicated that the design and control spaces produced tablets with hardness ranging from 4 to 6 kg-force, a disintegration time (DT) ≤ 30 s, and a friability ≤ 1%. All formulations contained 4% CBD (or 10 mg per tablet). The optimal formulation consisted of 35% microcrystalline cellulose and 1% croscarmellose sodium and was compressed at 1400 pounds per square inch.

This formulation exhibited a hardness of approximately 5 kg-force, a DT of 13-15 s, and a friability of approximately 0.3%. Verification data confirmed the accuracy of the predictions made by computer software. The content uniformity and assay determined using validated high-performance liquid chromatography ranged between 90% and 100%. CBD was released from the CBD ODT in 1% sodium lauryl sulfate solution, with approximately 76% dissolved within 3 h in the dissolution study.

In conclusion, the QbD-driven approach successfully facilitated the formulation development of CBD ODTs with the desired properties for the treatment of anxiety in a patient-friendly manner.”

https://pubmed.ncbi.nlm.nih.gov/42662497

“The present study demonstrates the successful development of CBD ODTs using the QbD approach, which has proven effective in enhancing both the efficiency and robustness of the formulation process.

Overall, this study demonstrates the successful implementation of a QbD-driven strategy for laboratory-scale formulation development and optimization of CBD ODTs.

The findings contribute to pharmaceutical development efforts involving cannabinoid-based formulations and may provide useful guidance for future studies related to scale-up, stability evaluation, and in vivo performance.

https://onlinelibrary.wiley.com/doi/10.1155/sci5/3553253


Differential Effects of Cannabidiol and Cannabigerol on Cognition, Neuroinflammation, and Blood-Brain Barrier Integrity in a Rat Model of Iron Overload

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Researchers comparing cannabidiol (CBD) and cannabigerol (CBG) found that both cannabinoids reversed recognition-memory impairment and restored a protein important to blood-brain barrier integrity in rats exposed to excessive iron early in life.

Both CBD and CBG reduced the inflammatory marker IL-1β, although their broader effects on inflammation differed. The findings suggest that the two phytocannabinoids may protect cognitive function through distinct but complementary mechanisms involving neuroinflammation and the blood-brain barrier.

“Iron is an essential micronutrient for brain development, participating in mitochondrial respiration, myelination, and neurotransmitter synthesis. However, previous studies have demonstrated that excessive iron during early postnatal life induces oxidative reactions, leading to mitochondrial dysfunction and synaptic failure. These alterations compromise energy metabolism and neuronal integrity, contributing to long-lasting cognitive dysfunction and increased brain vulnerability later in life.

This study evaluated the effects of cannabidiol (CBD) and cannabigerol (CBG) on behavioral, neuroinflammatory, and blood-brain barrier (BBB) outcomes in rats exposed to early-life iron overload.

Male Wistar rats received iron carbonyl (30 mg/kg, intragastrically) from postnatal day 12 to 14. At three months of age, they were treated intraperitoneally with CBD, CBG (both at 10 mg/kg), or vehicle for 21 days. Cognitive performance was assessed in the open field and object recognition tasks. We examined hippocampal levels of interleukin-1 beta (IL-1β), interleukin-6 (IL-6), tumor necrosis factor alpha (TNF-α), as proinflammatory markers, and occludin, a protein known to regulate BBB permeability.

Iron-exposed animals showed impaired recognition memory, with elevated TNF-α and IL-1β, while CBD reversed memory deficits and reduced IL-1β in iron-treated animals, without affecting TNF-α.

CBG restored memory, decreased IL-1β in both iron-treated and controls, and increased TNF-α in controls. Also, iron overload reduced occludin expression in vehicle-treated rats which was reversed by both CBD and CBG.

These findings highlight inflammation and BBB disruption as mediators of iron-induced cognitive dysfunction and show that both phytocannabinoids act through distinct but complementary mechanisms, supporting their therapeutic potential in neuroinflammation linked to iron overload.”

https://pubmed.ncbi.nlm.nih.gov/42663810

https://link.springer.com/article/10.1007/s12640-026-00826-x


A comparative network analysis to explore cancer patient experiences with cannabis

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This study examined how people with cancer described the benefits and barriers they encountered when using CBD-only products compared with products containing both CBD and THC.

The findings point to a meaningful difference in patient experience: pain relief was especially prominent among those using CBD+THC products, while participants across the study also reported benefits including improved sleep, physical relaxation, emotional regulation, and reduced use of other medications.

“Introduction: Approximately 20% of cancer patients report cannabis use, yet only 30% of oncologists feel sufficiently informed to make recommendations on its use. This study aimed to visualize the network of themes that arise within cancer patients’ reported experiences with cannabis.

Materials and methods: Data was collected via an online survey of 65 patients who self-reported the use of cannabis in their treatment for cancer, details about the cannabis product(s) being used, their perceived benefits and problems associated with cannabis use, their reasons for starting cannabis use, and any reasons for stopping cannabis use. Epistemic Network Analysis (ENA) was used to compare two groups of cancer patients: 1) those who only used CBD-dominant products (CBD-only group) versus 2) those who used cannabidiol (CBD)- and delta-9-tetrahydrocannabinol (THC)-containing products (either CBD-dominant and THC-dominant cannabis products or cannabis products containing a balanced ratio of both CBD and THC; CBD+THC group).

Results: Cannabis use conferred therapeutic benefits for several health issues commonly encountered by cancer patients. Common benefits reported across the cohort of patients included pain relief, improved sleep, physical relaxation, emotional regulation, and reduction of concomitant medication. The most frequently reported barriers to cannabis use were the stigma associated with THC use and the high cost of CBD-dominant and THC-dominant products. Pain relief emerged as the most prominent, interconnected theme reported by the CBD+THC group, whereas emotional regulation was the most prominent theme for the CBD-only group.

Conclusion: Symptom relief differed based on the cannabinoid composition of the cannabis products. The following trends emerged, which must be confirmed with larger samples: pain relief was more prominent in responses from users of CBD+THC, whereas emotional regulation was more prominent in only the users of CBD-only products. These findings are a step toward assisting cancer patients and providers with clinical decision-making on cannabis use. This study highlights the continued perception of stigma associated with THC use and the need for insurance coverage of medicinal cannabis to reduce the financial burden for this patient population. Finally, this study exemplifies the value of ENA in studying the therapeutic utility of cannabis with qualitative data.”

https://pubmed.ncbi.nlm.nih.gov/42666469

“Pain relief is more frequently reported among users of CBD+THC products.”

“Emotional regulation is more frequently reported among users of only CBD.”

“Overall, pain relief was the most frequently discussed benefit and was associated with other benefits: emotional regulation, sleep or physical relaxation, and medication reduction. Primary patient concerns were stigma and cost.”

https://www.frontiersin.org/journals/psychiatry/articles/10.3389/fpsyt.2026.1737119/full

Cannabidiol Suppresses Glioma Growth and Limits Invasion Partly Through an LOXL2-Associated EMT-Like Program

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A new study found that cannabidiol (CBD) suppressed glioma growth and reduced tumor-cell migration and invasion in laboratory and animal models. The researchers linked part of this effect to reduced LOXL2 activity, suggesting CBD may interfere with molecular programs that help glioma cells spread into surrounding brain tissue.

The study adds new mechanistic evidence to the growing body of research examining CBD as a potential therapeutic compound in glioma and glioblastoma.

“Background: Gliomas, particularly glioblastoma, remain difficult to control because diffuse infiltration into surrounding brain tissue limits complete resection and contributes to recurrence. Cannabidiol (CBD), a nonpsychoactive cannabinoid capable of entering the central nervous system, has shown antitumor activity in glioma models, but the mechanisms underlying its anti-invasive effects remain unclear. Lysyl oxidase-like 2 (LOXL2) regulates extracellular-matrix remodeling and mesenchymal phenotypes in several cancers. We therefore tested the hypothesis that CBD limits glioma growth and invasion partly by suppressing an LOXL2-associated extracellular-matrix and EMT-like program.

Methods: Human U87 and murine GL261 glioma cells were used to examine CBD effects on tetrazolium-based cell viability, clonogenic growth, cell-cycle progression, apoptosis, migration, and invasion. The two cell lines provided complementary human and murine models, and the immunocompetent intracranial GL261 model enabled syngeneic in vivo validation. RNA sequencing and public glioma datasets were used to identify and contextualize CBD-responsive molecules. Mechanistic involvement was tested by determining whether LOXL2 knockdown phenocopied and LOXL2 overexpression attenuated the anti-invasive effects of CBD.

Results: CBD reduced glioma-cell viability and clonogenicity, induced G1-phase arrest and apoptosis, and suppressed migration and invasion. C CCK-8-derived IC50 values (mean ± SD, n = 3) at 24, 48, and 72 h were 36.5 ± 0.3, 26.7 ± 0.3, and 21.4 ± 0.3 μM in U87 cells and 33.3 ± 0.2, 29.3 ± 0.2, and 25.5 ± 0.4 μM in GL261 cells, respectively. CBD treatment was accompanied by reduced MMP2 and MMP9 expression and increased TIMP3 expression. Transcriptomic profiling identified LOXL2 as a prominent CBD-downregulated molecule, and public datasets associated higher LOXL2 expression with aggressive molecular features and shorter overall survival. LOXL2 silencing reproduced the antimigratory and anti-invasive phenotype, whereas LOXL2 overexpression enhanced cell motility and partially attenuated the effects of CBD. The partial rescue involved vimentin, MMP9/TIMP3, EMT-related transcription factors, and F-actin-rich protrusions. In vivo, CBD reduced intracranial tumor burden and produced tissue changes consistent with lower proliferation, enhanced apoptosis, and suppression of the LOXL2-associated mesenchymal program.

Conclusions: CBD suppresses glioma growth and limits invasion, at least in part, by attenuating an LOXL2-associated EMT-like and extracellular-matrix-remodeling program. Because LOXL2 overexpression produced only a partial rescue and direct target engagement was not tested, LOXL2 should be interpreted as a functional mediator rather than the sole or direct molecular target of CBD. These findings support further validation in patient-derived and pharmacokinetically informed glioma models.”

https://pubmed.ncbi.nlm.nih.gov/42661582

https://onlinelibrary.wiley.com/doi/10.1155/bmri/6385332

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#!