Potential antitumor effect of cannabidiol (CBD) in canine oncology: a systematic review

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“Introduction: Preparations of Cannabis sativa have been used for medicinal purposes for many centuries Currently, it is known that the phytocannabinoids present in the Cannabis sativa plant can modulate the endocannabinoid system, producing a variety of effects. Among the most abundant phytocannabinoids are delta-9-tetrahydrocannabinol (19-THC) and cannabidiol (CBD). CBD lacks psychotropic properties and has been shown to inhibit cell proliferation and migration, while inducing apoptosis in various human tumor cells. Studies evaluating CBD in dogs are more recent than those in humans, and to date, fewer publications are available. However, CBD has been shown to be safe and well-tolerated in dogs, supporting its potential clinical use. Since approximately 2015, some studies have been conducted evaluating CBD in different types of canine cancer; however, no comprehensive review of these findings has been performed.

Methods: we conducted a systematic review Following the PRISMA 2020 guidelines.to compile the existing evidence on the anticancer effects of CBD in dogs.

Results: We found that the studies conducted so far are pre-clinical, mostly based on cellular models, and that available data are primarily in lymphoma, mammary cancer, glioma, prostate cancer, osteosarcoma, and urothelial carcinoma. These studies consistently show that CBD exerts antiproliferative and proapoptotic effects, in some cases by modulating intracellular signaling pathways, including ERK, JNK, and caspases. Additionally, some studies have evaluated the combination of CBD with other drugs, reporting both synergistic and antagonistic effects.

Overall, these findings highlight the potential of CBD as an anticancer agent across different cancer types.

Discussion: Further studies are required to better elucidate the mechanisms underlying the effects of CBD and to standardize concentrations and formulations, enabling reliable, comparable results and the development of clinical studies evaluating the role of CBD in canine oncology.”

https://pubmed.ncbi.nlm.nih.gov/42254894

“The findings from pre-clinical studies in dogs are consistent with those observed in humans, where CBD triggers antiproliferative and pro-apoptotic effects on several cancer cell types, which support clinical trials to elucidate the pharmacodynamics, pharmacokinetics, and potential antitumor efficacy of CBD in dogs with cancer.”

https://www.frontiersin.org/journals/veterinary-science/articles/10.3389/fvets.2026.1800410/full

High-dose cannabidiol for chronic neuropathic pain associated with spinal cord injury: a randomised clinical trial

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“Background: Chronic neuropathic pain is common after spinal cord injury (SCI), yet current treatments have limited efficacy and significant side effects. Cannabidiol (CBD), a non-intoxicating component of cannabis, has demonstrated efficacy in preclinical neuropathic pain models. Here, we investigated the effect of high-dose (up to 800 mg/day) CBD on chronic neuropathic pain in SCI.

Methods: This randomised, double-blinded, placebo-controlled, crossover clinical trial was conducted at Neuroscience Research Australia. Adults with SCI and neuropathic pain (≥three months duration) were recruited. Participants were randomised to one of two treatment orders by an unblinded investigator who had no participant contact. Participants and all other investigators were blinded. Participants consumed oral CBD and placebo over two six-week treatment periods separated by a four-week washout. Treatment was titrated up to 800 mg/day of CBD over two-weeks. The primary outcome was change in self-reported pain intensity on a zero (no pain) to ten (worst pain imaginable) Visual Analogue Scale. Statistical comparisons included CBD versus placebo treatment, and pre-treatment (inactive phase) versus on-treatment (active phase). Outcomes were analysed by modified intention-to-treat. The study is registered with anzctr.org.au, ACTRN12622000634774 (not recruiting).

Findings: Forty participants were randomised (August 1, 2022 to December 16, 2024) and 38 included in the primary analysis (n = 6 female). A significant treatment by phase interaction effect (p < 0.001) was observed on self-reported pain. Pairwise comparison showed lower pain intensity during the active phase with CBD (mean ± SEM: 3.82 ± 0.23) compared to placebo (mean difference = -0.54, SEM = 0.15, p < 0.001), with a 95% confidence interval for the difference of -0.88 to -0.21. Treatments did not differ during the inactive phase (mean difference <0.01, SEM = 0.17, p = 1.00, 95% CI = -0.38 to 0.38). Adverse events, nearly all minor, were reported by 68.4% of participants during CBD (n = 67 events), and by 52.6% during placebo (n = 51 events) treatment.

Interpretation: In this placebo-controlled trial, CBD significantly reduced the self-reported intensity of neuropathic pain and was generally well-tolerated. While modest in magnitude, the observed effect supports further research into high-dose CBD for chronic neuropathic pain.”

https://pubmed.ncbi.nlm.nih.gov/42256679

“This trial provides evidence that high-dose CBD is safe and effective in treating chronic neuropathic pain following SCI. Additionally, the study provides initial evidence of a subgroup effect, whereby CBD is more effective in some individuals than others: this also warrants further exploration.”

https://www.thelancet.com/journals/eclinm/article/PIIS2589-5370(26)00234-8/fulltext

Long-term follow-up of children with autism spectrum disorder and severe treatment-resistant behavioral symptoms treated with purified cannabidiol

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“Background: Autism spectrum disorder (ASD) is a heterogeneous neurodevelopmental condition often associated with severe behavioral disturbances and limited pharmacological treatment options. Cannabidiol (CBD) has emerged as a potential therapeutic option; however, evidence on its long-term effectiveness and safety in children with ASD is scarce.

Objective: To evaluate the long-term effectiveness and safety of purified CBD as addon therapy in children with severe ASD and treatment-resistant behavioral symptoms.

Material and methods: We conducted a prospective observational before-and-after study in children and adolescents (3-18 years) with ASD severity levels 2 or 3 and intellectual disability treated with add-on CBD. The primary outcome was change in caregiver-identified symptoms, while secondary outcomes included standardized behavioral scales (Repetitive Behavior Scale-Revised [RBS-R], Vineland Adaptive Behavior Scales-II maladaptive behavior domain, Aberrant Behavior Checklist [ABC], Pediatric Sleep Clinical Global Impressions-Severity, Autism Family Experience Questionnaire, and Parental Stress Scale). Safety and tolerability were assessed through caregiver-reported adverse events.

Results: Twenty children were enrolled, of whom 13 completed the long-term follow-up (mean 27.6 ± 1.3 months). Of the caregiver-identified symptoms, improvements observed during the initial short-term study were maintained or further improved during follow-up. Standardized scales showed modest but sustained improvements, particularly in irritability, social withdrawal, and hyperactivity. Mild, transient adverse events, mainly irritability or decreased appetite, did not recur during long-term followup, and concomitant medications were reduced in 40% of patients.

Conclusion: Long-term treatment with purified CBD in children with severe ASD was well tolerated and associated with sustained improvement in caregiver-reported outcomes and standardized scales.”

https://pubmed.ncbi.nlm.nih.gov/42248366

“Cannabidiol (CBD), a non-psychoactive cannabinoid, has gained increasing interest as a potential therapeutic option for both core symptoms of ASD and associated comorbidities, based on its anxiolytic, anti-inflammatory, and neuromodulatory properties, together with a generally favorable safety profile.”

“In this long-term follow-up of children with severe ASD treated with purified CBD, no significant differences were observed between the three-month and the 26-month evaluations, suggesting that the initial improvements were maintained over time. Among patients who completed the extended follow-up, purified CBD was well tolerated and associated with sustained improvement in several symptoms, particularly those identified by families as most disruptive in daily life.”

https://www.sciencedirect.com/science/article/abs/pii/S0091305726000754?via%3Dihub

Combined peripheral cannabinoid CB1 and CB2 receptor activation abolishes cystitis-induced bladder hyperalgesia

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“Cannabinoid agonists may ameliorate bladder pain associated with interstitial cystitis/bladder pain syndrome.

Visceromotor responses (VMRs) to bladder distension were recorded in urethane-anesthetised control and protamine/zymosan-treated guinea pigs. The peripherally restricted preferential CB1 receptor agonist PrNMI and the selective CB2 receptor agonist 4Q3C each reduced cystitis-induced enhancement of VMRs at high intravesical pressures.

Co-activation of CB1 and CB2 receptors abolished cystitis-induced bladder hyperalgesia.

These findings indicate that simultaneous targeting of peripheral CB1 and CB2 receptors may provide clinically meaningful benefits for the treatment of bladder pain associated with cystitis.”

https://pubmed.ncbi.nlm.nih.gov/42247877

“Combined activation of peripheral CB1 and CB2 receptors using peripherally restricted agonists effectively reverses bladder hyperalgesia in a preclinical model of IC/BPS.

These findings provide strong support for the development of peripherally acting combination therapies targeting both cannabinoid receptors as a strategy to treat bladder pain and associated symptoms in IC/BPS, while minimising central cannabinoid-related side effects.”

https://www.autonomicneuroscience.com/article/S1566-0702(26)00066-4/fulltext

Industrial Cannabis, Cannabic Residue or Industrial Cannabis Waste? Perspectives on the Utilization, Reutilization, and Recycling of Cannabis

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“Introduction: Cannabis sativa L. is an annual herbaceous plant with a long history of multipurpose use, including food, textile, and medicinal applications. The progressive legalization in several countries has significantly increased its large-scale cultivation, consequently generating a substantial amount of biomass waste. This scenario calls for innovative and sustainable strategies to valorize Cannabis residues, aiming at promoting the circular economy and technological innovation.

Materials and methods: An integrative review was conducted following Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Systematic searches were performed in SCOPUS, PubMed, and SciELO, complemented by specialized platforms such as CANNUSE and CONSENSUS. Peer-reviewed empirical studies were included if they addressed the utilization, reutilization, or recycling of C. sativa by-products or residues for the development of industrial products, processes, or inputs. The analysis considered thematic and commercial domains, geographic origin, and biomass type.

Results: A total of 262 studies were included, with 144 retrieved from indexed databases and 118 from alternative methods. The most commonly explored residues were stems (48.2%), seeds (21.0%), and postextraction residuum (9.7%). The majority of applications were related to technology and innovation (37.5%) and industrial sectors (36.9%). A total of 328 technologies were identified, highlighting applications such as textile fibers, bioplastics, biofuels, functional foods, adsorbents, and natural cosmetics. Italy, China, and the United States led in scientific production. Leaves (7.0%) and roots (0.9%) were significantly underexplored despite their bioactive potential.

Discussion: The findings demonstrate a growing global interest in the valorization of C. sativa residues, with promising applications in bioeconomy, regenerative agriculture, phytoremediation, and energy transition. The integration of traditional knowledge and green technologies is a key strategy to enhance sustainability and socioterritorial inclusion. Nonetheless, regulatory gaps and a lack of robust clinical and toxicological studies limit the use of by-products in food and feed chains.

Conclusion: The residual biomass of C. sativa holds high technological, environmental, and economic value. Strategic valorization demands regulatory advancement, the development of green technologies, and the strengthening of multidisciplinary research. Industrial Cannabis emerges as a driver of ecological, social, and economic transformation toward sustainable circular production systems.”

https://pubmed.ncbi.nlm.nih.gov/41652844

https://journals.sagepub.com/doi/10.1177/25785125261421439

Harnessing Cannabis sativa as a dual-use platform for biohydrogen production and pharmaceutical synthesis: a hypothesis and theory

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“Cannabis sativa, long established as a cornerstone of the pharmaceutical and industrial fiber markets, represents a radical and underexplored platform for renewable energy innovation.

In this Hypothesis and Theory framework, we introduce a novel, patented (Provisional Patent No. 63916615) dual-use bio-refinery paradigm. This model harnesses engineered cannabis photosynthesis to drive green hydrogen production without compromising its established value as a high-yield medicinal crop.

By strategically redirecting photosynthetic electron flow toward oxygen-protected hydrogenase activity, it is possible to generate molecular hydrogen at commercially relevant scales while maintaining plant viability.

Unique to this model is the ability to leverage over $10 billion in existing controlled-environment agriculture (CEA) infrastructure, bypassing the capital-intensive barriers that have hindered traditional algal biohydrogen systems. We outline a tripartite circular economy strategy that integrates hydrogen capture during the vegetative phase with the subsequent harvest of therapeutic cannabinoids and industrial biomass.

This convergence of synthetic biology, clean energy, and biomedicine positions cannabis as a uniquely versatile multipurpose crop capable of fueling both the pharmaceutical industry and the global transition to a sustainable hydrogen economy.”

https://pubmed.ncbi.nlm.nih.gov/42245109

“The global transition toward a net-zero carbon economy necessitates the development of scalable, carbon-negative energy sources. While hydrogen (H2) is a premier clean energy carrier, biological production methods have traditionally struggled with economic viability due to low feedstock density and high infrastructure costs. We propose that Cannabis sativa, a crop already optimized for high-density biomass and metabolic output, serves as the ideal biological “factory” to overcome these hurdles.”

“Cannabis sativa stands at the intersection of the most disruptive shifts in modern industry: the legalization of medicinal biotechnologies and the urgent need for carbon-negative energy transition.

By adopting this patented dual-use framework, we can transform one of the world’s most valuable crops into an engine for a sustainable, hydrogen-powered future.”

“Collaborative frameworks between synthetic biologists, agricultural engineers, and regulatory bodies will be essential to advance this platform toward commercial viability.”

https://www.frontiersin.org/journals/plant-science/articles/10.3389/fpls.2026.1833491/full

The Use of Cannabis sativa L. for Pest Control: From the Ethnobotanical Knowledge to a Systematic Review of Experimental Studies

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“Background: Despite the benefits that synthetic pesticides have provided in terms of pest and disease control, they cause serious long-term consequences for both the environment and living organisms. Interest in eco-friendly products has subsequently increased in recent years. 

Methods: This article briefly analyzes the available ethnobotanical evidence regarding the use of Cannabis sativa as a pesticide and offers a systematic review of experimental studies. 

Results: Our findings indicate that both ethnobotanical and experimental procedures support the use of C. sativa as a pesticide, as remarkable toxicity has been observed against pest organisms. The results included in the systematic review of experimental studies (n=30) show a high degree of heterogeneity, but certain conclusions can be extracted to guide further research. For instance, promising pesticide properties were reported for most of the groups of species tested, especially Arachnida and Insecta; the efficacy of C. sativa as a pesticide can be derived from a wide variety of compounds that it contains and possible synergistic effects; it is crucial to standardize the phytochemical profile of C. sativa plants used as well as to obtain easily reproducible results; appropriate extraction methods should be explored; and upper inflorescences of the plant may be preferred for the production of the essential oil, but further studies should explore better other parts of the plant. 

Conclusion: In the coming years, as new findings are produced, the promising potential of C. sativa as a pesticide will be elucidated, and reviews such as the present one constitute useful basic tools to make these processes easier.”

https://pubmed.ncbi.nlm.nih.gov/34612729

https://journals.sagepub.com/doi/10.1089/can.2021.0095

The potential of Allium sativum and Cannabis sativa extracts for anti-tick activities against Rhipicephalus (Boophilus) microplus

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“The efficacy of Allium sativum and Cannabis sativa against Rhipicephalus microplus ticks was evaluated using the adult immersion and the larval packet test. In addition, an in silico approach was utilized by performing a docking study in order to identify the active ingredients from both plants.

Results showed a comparatively high lethal effect of A. sativum and C. sativa on egg laying (index of egg laying = 0.26 and 0.24, respectively), egg hatching (33.5 and 37.1, respectively), and total larval mortality (100%, both), at 40 mg/mL.

When applied to cattle which had been inoculated with larvae ticks, it was observed that a 45% solution of both herbal extracts significantly reduced the number of ticks by 96 h post treatment.

We analyzed in silico 27 known active molecules from both plants and identified in the PubChem database to explore the hypothesis that the effect found on ticks was based on inhibition of acetylcholinesterase (AChE).

Vitamin E and cannabidiol are the most potent AChE inhibitors with docking scores of -15.85 and -14.38, respectively.

Based on these findings, we conclude that A. sativum and C. sativa may potentially be used for the control of R. microplus, and should be further investigated as a potential supplement to or replacement of synthetic acaricides.”

https://pubmed.ncbi.nlm.nih.gov/32886258

https://link.springer.com/article/10.1007/s10493-020-00540-z

Cannabidiol-thiosemicarbazone exhibits dual tyrosinase inhibition and antioxidant activity in human skin-derived cells

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“The search for modulators of melanogenesis with improved biological compatibility remains an active area of investigation, as existing tyrosinase (TYR) inhibitors are often limited by low potency, instability, or cytotoxicity.

Here, we investigated CBD-TSC1, a cannabidiol-based thiosemicarbazone derivative, as a TYR-targeting scaffold.

Structural characterization confirmed a single, stable E-isomer, and pKa profiling together with kinetic analyses indicated reversible mixed-type inhibition of human TYR, involving interactions with both free enzyme and enzyme-substrate complexes. CBD-TSC1 exhibited higher inhibitory activity than CBD and kojic acid under the tested conditions while maintaining low cytotoxicity in G361 melanoma and HaCaT keratinocyte cell lines. In addition, CBD-TSC1 reduced intracellular oxidative stress at low micromolar concentrations. In zebrafish larvae, treatment with CBD-TSC1 resulted in a dose-dependent reduction in melanin content, comparable to that of kojic acid under identical experimental conditions, supporting an association between thiosemicarbazone modification and the observed biological activity.

Overall, CBD-TSC1 demonstrated consistent activity across biochemical, cellular, and zebrafish-based assays under the tested conditions. Although the mechanistic relationship between TYR inhibition, redox modulation, and melanogenesis regulation remains to be fully clarified, the present findings support further investigation of cannabidiol-based thiosemicarbazone derivatives as modulators of TYR-related pathways.”

https://pubmed.ncbi.nlm.nih.gov/42235859

“CBD-TSC1 is a novel cannabidiol-thiosemicarbazone hybrid with dual anti-melanogenic activity.”

“Thiosemicarbazone modification is essential for superior enzymatic and redox performance.”

https://www.sciencedirect.com/science/article/abs/pii/S0960894X26001745?via%3Dihub

Cannabidiol attenuates tau hyperphosphorylation and cognitive deficits in an experimental model of Alzheimer’s disease and is associated with restoration of PP2A expression

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“Pathogenic tau hyperphosphorylation, together with reduced protein phosphatase 2 A (PP2A) expression, is associated with neurofibrillary tangle formation and cognitive deterioration in Alzheimer’s disease (AD).

Cannabidiol (CBD), a non-psychotropic phytocannabinoid, remains insufficiently studied for its potential to modulate the PP2A-tau axis in experimental AD.

This study evaluated whether CBD improves hippocampus-dependent spatial cognition in a D-galactose/AlCl₃ rat model of AD and whether these effects are associated with restoration of PP2A expression and attenuation of tau hyperphosphorylation.

AD-like pathology was induced in male Wistar rats by D-galactose (60 mg/kg i.p.) and AlCl₃ (200 mg/kg oral gavage) for 10 weeks, followed by CBD (20, 40 or 80 mg/kg) or donepezil (1 mg/kg) for three weeks. The Morris water maze, Jess Simple Western, and ELISA were used to assess cognition, PP2A expression, and p-tau levels, respectively.

CBD significantly improved spatial learning and memory. PP2A expression increased across all tested doses, with the highest mean level observed at 80 mg/kg. Hippocampal p-tau levels were significantly increased in the model group and significantly reduced by all CBD doses and donepezil (all p < 0.0001 vs. model). The inverse relationship between PP2A expression and p-tau levels suggests possible involvement of the PP2A-tau axis.

CBD attenuated cognitive deficits and tau hyperphosphorylation alongside restoration of PP2A expression, suggesting that the PP2A-tau axis may be a relevant therapeutic target in AD-related tauopathy.”

https://pubmed.ncbi.nlm.nih.gov/42240860

https://link.springer.com/article/10.1007/s11011-026-01894-w