Dietary Cannabidiol Supplementation on Growth Performance, Behavior, Blood Profile, Metabolomic Analysis, and Fatty Acid Composition in Rabbits: A Multi-Disciplinary Approach to Improve Welfare and Productivity

pubmed logo

“This study evaluated the effects of dietary cannabidiol (CBD) supplementation on behavior, blood parameters, oxidative status, metabolomic profile, and the fatty acid composition of meat and liver in rabbits.

A total of 42 New Zealand White × California rabbits (60 days old; 1:1 sex ratio; average weight 1621.3 ± 46.2 g) were randomly assigned to two groups (a control group, CTRL, and a CBD group, n = 21 each). Both groups received the same commercial diet, with the CBD group additionally supplemented with 0.1 mL of cannabis extract in coconut oil, corresponding to 10 mg CBD/animal/day. At 92 days of age, rabbits were slaughtered, and samples were collected for analyses.

Results showed that CBD supplementation significantly improved body weight gain, reduced plasma triglyceride levels, and enhanced oxidative status.

Behavioral observations indicated increased motor and grooming activities in CBD-supplemented animals, suggesting enhanced psychological well-being. The fatty acid profile of meat and liver was not significantly altered by CBD supplementation.

Overall, dietary CBD demonstrated the potential to positively influence physiological and behavioral responses, representing a promising strategy to enhance animal welfare and productivity in rabbit farming. Although no adverse effects on lipid profiles were observed, further studies are warranted to explore CBD’s role in lipid metabolism and cholesterol regulation.”

https://pubmed.ncbi.nlm.nih.gov/40905739/

“Animal health and welfare are essential for ethical farming and high-quality food production. This study evaluated the effects of dietary cannabidiol (CBD) supplementation on behavior, some blood parameters, and fatty acid composition in meat and liver of rabbits. CBD is gaining attention for its pharmacological properties and its role in the endocannabinoid system. The results suggest that CBD supplementation can influence behavioral and physiological responses in rabbits, offering potential benefits for both animal welfare and meat quality.”

https://www.mdpi.com/2306-7381/12/8/759

[Low Abuse Potential of Plant-Derived Highly Purified Cannabidiol: A Narrative Review]

pubmed logo

“Cannabidiol (CBD) is an abundant phytocannabinoid extracted from Cannabis sativa L., along with delta-9-tetrahydrocannabinol.

Plant-derived, highly purified CBD oral solution (100 mg/mL) is approved as Epidiolex® in the United States and as Epidyolex® in Europe for the treatment of seizures associated with Lennox-Gastaut syndrome, Dravet syndrome, or tuberous sclerosis complex with country-specific labels.

CBD appears to reduce the neuronal hyperexcitability through a multimodal mechanism of action, although the precise mechanism remains unknown. Notably, unlike delta-9-tetrahydrocannabinol, CBD has low affinity for the euphoria-inducing cannabinoid receptor type 1 therefore lacks euphoric effects.

Preclinical and clinical studies have demonstrated a low abuse and dependence potential, as well as an absence of withdrawal syndrome of CBD.

Despite the lack of abuse potential for CBD, there are concerns related to cannabis and consequently cannabis-derived pharmaceutical products in Japan. Plant-derived, highly purified CBD is currently under investigation for the treatment of drug-resistant seizures in Japanese patients with early-onset epilepsies (jRCT2031220041).

This narrative review aims to update healthcare professionals in Japan with results from preclinical and clinical studies evaluating the abuse and dependence potentials of CBD.”

https://pubmed.ncbi.nlm.nih.gov/40887246/

https://www.jstage.jst.go.jp/article/yakushi/145/9/145_25-00086/_article/-char/ja/

Cannabigerol Attenuates Memory Impairments, Neurodegeneration, and Neuroinflammation Caused by Transient Global Cerebral Ischemia in Mice

pubmed logo

“Evidence supporting the clinical use of neuroprotective drugs for cerebral ischemia remains limited. Spatial and temporal disorientation, along with cognitive dysfunction, are among the most prominent long-term consequences of hippocampal neurodegeneration following cerebral ischemia.

Cannabigerol (CBG), a non-psychotomimetic constituent of Cannabis sativa, has demonstrated neuroprotective effects in experimental models of cerebral injury.

This study investigated the neuroprotective mechanisms of CBG in mitigating memory impairments caused by transient global cerebral ischemia in C57BL/6 mice using the bilateral common carotid artery occlusion (BCCAO) model.

Mice underwent sham or BCCAO surgeries and received intraperitoneal (i.p.) injections of either a vehicle or CBG (1, 5, or 10 mg/Kg), starting 1 h post-surgery and continuing daily for 7 days. Spatial memory performance and depression-like behaviors were assessed using the object location test (OLT) and tail suspension test (TST), respectively. Additional analyses examined neuronal degeneration, neuroinflammation, and neuronal plasticity markers in the hippocampus.

CBG attenuated ischemia-induced memory deficits, reduced neuronal loss in the hippocampus, and enhanced neuronal plasticity.

These findings suggest that CBG’s neuroprotective effects against BCCAO-induced memory impairments may be mediated by reductions in neuroinflammation and modifications in neuroplasticity within the hippocampus.”

https://pubmed.ncbi.nlm.nih.gov/40869376/

“CBG Improves Memory Impairment Induced by BCCAO in Mice.”

https://www.mdpi.com/1422-0067/26/16/8056

Cannabis Derivatives as Ingredients of Functional Foods to Combat the COVID-19 Pandemic

“Lower respiratory infections predominantly affect children under five and the elderly, with influenza viruses and respiratory syncytial viruses (including SARS-CoV-2) being the most common pathogens. The COVID-19 pandemic has posed significant global public health challenges. While vaccination remains crucial, its efficacy is limited, highlighting the need for complementary approaches to mitigate immune hyperactivation in severe COVID-19 cases.

Medicinal plants like Cannabis sativa show therapeutic potential, with over 85% of SARS-CoV-2-infected patients in China receiving traditional herbal treatments. This review explores the antiviral applications of cannabis and its bioactive compounds, particularly against SARS-CoV-2, while evaluating their pharmacological and food industry potential.

Cannabis contains over 100 cannabinoids, terpenes, flavonoids, and fatty acids. Cannabinoids may block viral entry, modulate immune responses (e.g., suppressing pro-inflammatory cytokines via CB2/PPARγ activation), and alleviate COVID-19-related psychological stress.

There are several challenges with pharmacological and food applications of cannabinoids, including clinical validation of cannabinoids for COVID-19 treatment and optimizing cannabinoid solubility/bioavailability for functional foods. However, rising demand for health-focused products presents market opportunities. Genetic engineering to enhance cannabinoid yields and integrated pharmacological studies are needed to unlock cannabis’s full potential in drug discovery and nutraceuticals.

Cannabis-derived compounds hold promise for antiviral therapies and functional ingredients, though further research is essential to ensure safety and efficacy.”

https://pubmed.ncbi.nlm.nih.gov/40870742/

“Cannabis has been farmed for millennia as a source of traditional medicine and textile fiber, but it is now also being recognized as a source of a variety of secondary metabolites with value as medicines, flavoring compounds, and fragrances due to its unique composition and structure.”

“The cannabis food industry is poised for transformative growth as legalization expands globally and consumer acceptance increases.”

https://www.mdpi.com/2304-8158/14/16/2830

Unlocking the resorption potential of cannabidiolic acid: A comprehensive in vitro and in vivo bioavailability study

pubmed logo

“Phytocannabinoids, unique secondary metabolites of the plant Cannabis sativa L., are characterised by a wide spectrum of pharmacological activities and their use in medicine and food industry has increased exponentially in recent years.

In this study, the bioavailability of 10 representatives of neutral cannabinoids and cannabinoid acids was evaluated using an in vitro model of Caco-2 cells, as well as in vivo using an inbred mouse model. In the context of a possible increase in bioavailability, the influence of matrix components associated with the ‘cannabis synergy’ phenomenon was also investigated. The analysis of cannabinoids and non-cannabinoid matrix components was performed using a sensitive and validated method based on ultra-high performance liquid chromatography coupled with high-resolution tandem mass spectrometry (UHPLC-HRMS/MS). As a proof of concept for testing formulation effects on bioavailability, the most abundant cannabinoid and its corresponding acid (CBD and CBDA) were encapsulated in nanomicelles and the effect of the formulation was tested both in vitro and in vivo.

The experiments showed that cannabidiolic acid (CBDA) had a significantly better bioavailability compared to cannabidiol (CBD), especially in the in vivo model (CBDA concentrations in mouse plasma were approximately two orders of magnitude higher than those of CBD under the same dosing conditions).

These results demonstrate the great potential of CBDA as a previously overlooked and therapeutically underutilized substance.”

https://pubmed.ncbi.nlm.nih.gov/40858181/

https://www.sciencedirect.com/science/article/abs/pii/S0378517325009470?via%3Dihub

A novel cannabidiol:tetramethylpyrazine cocrystal (CBD:TMP, ART12.11) improves the efficacy and bioavailability of cannabidiol in reducing stress-induced depressive and anxiety symptoms

pubmed logo

“Clinical and pre-clinical research has reported promising outcomes for cannabidiol (CBD) in treating mood and anxiety disorder symptoms. However, the pharmacokinetic properties of CBD, such as low and variable bioavailability and low aqueous solubility, limit its therapeutic applications.

This study investigated the effects of ART12.11, a novel cannabidiol:tetramethylpyrazine (CBD:TMP) cocrystal, that aims to improve the pharmacotherapeutic potential of CBD by combining it with the co-former tetramethylpyrazine (TMP) to improve CBD’s pharmaceutical properties.

We used an integrative combination of translational behavioural pharmacology alongside targeted gene and protein expression analyses to characterize the potential anti-depressant and anxiolytic-like effects of ART12.11 in male Sprague Dawley rats, following exposure to chronic stress. In addition, we investigated blood plasma concentrations of CBD and TMP following oral administration of ART12.11 to examine bioavailability.

We report that oral administration of ART12.11 reversed stress-induced behavioural deficits and produced significant anti-depressant and anxiolytic-like behavioural effects, which were superior to oral administration of CBD alone, TMP alone, or the co-administration of a non-crystalline mixture of CBD and TMP. Further, we report that ART12.11 resulted in higher blood plasma levels of CBD and its major metabolite, indicating superior bioavailability. Finally, we demonstrate that ART12.11 increased activation of the endocannabinoid and serotonergic systems directly in the prefrontal cortex, ventral hippocampus, and nucleus accumbens.

Collectively, our findings indicate that ART12.11 may offer significant advantages over delivering CBD by more traditional approaches in the treatment of mood and anxiety disorders.”

https://pubmed.ncbi.nlm.nih.gov/40854502/

https://www.sciencedirect.com/science/article/abs/pii/S0278584625002325?via%3Dihub

Biotechnological potential of Cannabis sativa adventitious roots for producing immunomodulatory and anti-inflammatory bioactive compounds

pubmed logo

“Cannabis sativa L. (C. sativa), commonly known as hemp, is widely recognized for its diverse range of bioactive compounds with therapeutic potential in medicinal, industrial, and nutritional applications.

This study investigates the use of adventitious roots (ARs) derived from C. sativa as a scalable platform for producing bioactive metabolites with immunomodulatory and anti-inflammatory properties.

We first isolated extracts from C. sativa ARs (CS-AR) using various solvents: methanol (MeOH-E), chloroform (CHCl3-E), and hexane (Hexane-E), and explored their effects on dendritic cell (DC) maturation, a key process involved in immune responses.

Notably, MeOH-E demonstrated strong anti-inflammatory effects without inducing cytotoxicity in DCs, distinguishing it from the other extracts. Metabolomic analysis of these extracts annotated the presence of cannabinoid derivatives and metabolites, including cannabinoid glycoside derivatives, cannabigerolic acid-O-acetate (CBGA-O-acetate), cannabidiol diacetate derivatives, and cannabidiol mono-acetate mono-benzoate. Among these, cannabinoid glycoside derivatives and CBGA-O-acetate were found to be present at higher levels in MeOH-E.

Further investigation into the functional properties of MeOH-E revealed that it could suppress the expression of key surface molecules and antigen-presenting ability in mature DCs, alongside attenuating mitogen-activated protein kinase (MAPK) signaling pathways as well as nuclear factor kappa-B (NF-κB) signaling. Additionally, MeOH-E inhibited T cell proliferation and activation.

These findings underscore the CS-AR system as a promising, reproducible biotechnological platform for producing therapeutic bioactive compounds for inflammatory diseases, with significant potential for application in the pharmaceutical and nutraceutical industries.”

https://pubmed.ncbi.nlm.nih.gov/40847038/

“Cannabis sativa L. (C. sativa), commonly referred to as hemp, has been utilized for centuries in the medicinal, industrial, and nutritional domains, primarily owing to its broad spectrum of bioactive compounds1,2. Its various plant parts including roots, stems, leaves, and flowers possess distinct biological properties, such as anti-inflammatory, antioxidant, and antimicrobial activities, thus, positioning C. sativa as a versatile resource in diverse applications.”

https://www.nature.com/articles/s41598-025-16130-1

Release of delta-9-tetrahydrocannabinol from polyvinyl alcohol hydrogels and its safe interaction with human skin fibroblasts

pubmed logo

“This study aimed to design a THC-rich hydrogel to deliver cannabis derivatives topically. We developed hydrogels using polyvinyl alcohol (PVA) mixed with propylene glycol (PG), vegetable glycerin (VG), or both to facilitate the dissolution of delta-9-tetrahydrocannabinol (THC).

The hydrogels showed a brown color, confirming the presence of the cannabinoid. They exhibit a porous structure and better mechanical properties than PVA alone. Indeed, the hydrogel containing PG, VG, or both showed elastic deformation behaviors with lower water content. FTIR analysis demonstrated the presence of THC with two specific peaks at 1,575 and 1,619 cm-1, confirming the presence of THC in the hydrogels.

Human dermal fibroblast cultures onto the surface of all hydrogels confirmed the safety of the THC-rich hydrogel as the cell adhesion was comparable to the control (no THC). Furthermore, cells adhering to the hydrogels could proliferate, showing increased cell viability at 48 and 72 h, with a higher proliferation obtained with the THC-rich PVA-PG-VG hydrogels.

Such cell behavior could be due to the release of the THC in the culture medium, as demonstrated by ultra-high performance liquid chromatography (UPLC), showing the presence of THC in the culture medium, ranging from 203 to 290 μg after 24 h of incubation of the hydrogels containing PG and VG or both. In comparison, the released THC from the PVA hydrogel was higher, reaching 852 μg. It is interesting to note that the THC release at 24, 48, and 72 h was slower with the hydrogels containing PG, VG, and both, compared to PVA alone.

Overall, the present study has designed safe THC-rich PVA-PG-VG hydrogels as a functional delivery system for the topical use of cannabinoids to control tissue diseases, such as inflammation.”

https://pubmed.ncbi.nlm.nih.gov/40836986/

“Cannabis has long been used to relieve symptoms such as pain, fever, anxiety, and diarrhea in the context of numerous diseases. Furthermore, cannabis products were reported to reduce inflammatory diseases. Over the past decades, it has been demonstrated that cannabinoids have anti-inflammatory effects, as ascertained by the decrease in the secretion of inflammatory mediators. The human body is subjected to various conditions (stress, autocrine/endocrine changes, exposure to exogenous stimuli, etc.) leading to organ and tissue inflammatory disorders, such as those in the skin and the oral cavity. Such tissue inflammation could be controlled using cannabis products.”

“Altogether, our results demonstrated the possible combination of PVA with PG and VG to generate useful THC-rich hydrogels for cannabinoid delivery. Because THC is lipophilic, our study suggests the possible delivery of THC when in topical contact with the tissues, including skin and oral mucosa, as the cells have lipid-rich membranes. Our THC-rich PVA-PG-VG hydrogels, therefore, may have the potential as a drug carrier for topical use to treat tissue inflammation.”

https://www.frontiersin.org/journals/drug-delivery/articles/10.3389/fddev.2024.1303812/full

Therapeutic potential of cannabinoids for treating atopic dermatitis

pubmed logo

“This review aims to assess the therapeutic potential of cannabinoids as complementary treatments for atopic dermatitis. Atopic dermatitis (AD) is a skin disease characterized by the loss of skin barrier function that promotes subsequent symptoms such as intense itching, xerosis and inflammation. Several treatments are available, particularly topical approaches, which are crucial for both acute and chronic management of the disease.

The main objectives of topical treatments are to promote skin hydration and reduce itching and immune responses, typically through lotions and topical medications such as glucocorticoids. However, the long-term use of glucocorticoids presents certain disadvantages, highlighting the need for new therapeutic options to minimize adverse effects and providing a broader range of choices for both physicians and patients to find the best alternative for each case.

Research involving cannabinoids, which can be endogenous, plant-based or synthetic, has intensified in recent years to evaluate the therapeutic potential of these compounds for skin conditions, including AD. Studies suggest that phytocannabinoids such as cannabidiol (CBD) and Δ-9-tetrahydrocannabinol (THC), along with endogenous and synthetic compounds such as palmitoyletanolamide (PEA) and dronabinol, can improve AD symptoms, primarily because of their anti-inflammatory, antipruritic and antioxidant properties. Additionally, some cannabinoids exhibit antimicrobial effects.

Despite these promising results, the use of cannabinoids in AD treatment requires further investigation to better understand their efficiency and safety, necessitating high-accuracy clinical and preclinical trials.”

https://pubmed.ncbi.nlm.nih.gov/40818974/

“Cannabinoids, whether of plant, endogenous, or synthetic origin, clearly possess significant therapeutic potential and should be further explored as complementary treatments for AD. The development of cannabinoid-based formulations for skin conditions is not limited to products classified as medicines by pharmaceutical regulatory agencies, but also includes their use as active ingredients in cosmetic formulations, such as soaps, shampoos, and especially moisturizing lotions and creams, for individuals with AD and other conditions requiring enhanced skin hydration.

Beyond the therapeutical potential of the classical phytocannabinoids CBD and THC, other components such as CBG and CBC have also been investigated for their dermatological benefits, including anti-inflammatory, antibacterial, and antioxidant properties that may contribute to skin health and the treatment of various skin disorders, including AD .”

https://jcannabisresearch.biomedcentral.com/articles/10.1186/s42238-025-00317-4

Potential of Cannabidiol (CBD) to overcome extensively drug-resistant Acinetobacter baumannii

pubmed logo

“Extensively drug-resistant (XDR) Acinetobacter baumannii poses a serious clinical challenge due to its resistance to nearly all available antibiotics, including carbapenems and colistin. Cannabidiol (CBD), a non-psychoactive phytochemical from Cannabis sativa L., has recently shown promising antimicrobial activity.

This study evaluates the antibacterial and anti-biofilm effects of CBD against XDR A. baumannii isolates and explores its mechanism of action and potential as an adjunct therapeutic agent.

Twenty-six A. baumannii isolates collected from ICU medical devices were identified using MALDI-TOF/MS. Antimicrobial susceptibility was assessed by disk diffusion and broth microdilution to determine MICs and MBCs for CBD and standard antibiotics. Synergistic effects were evaluated via checkerboard assays and FICI values. Biofilm inhibition and eradication were assessed using crystal violet and MTT assays. Time-kill studies, membrane integrity assays (DNA/protein leakage, NPN uptake, membrane depolarization), and scanning electron microscopy (SEM) were employed to investigate bactericidal kinetics and membrane-disruptive mechanisms.

CBD exhibited activity against antimicrobial resistance isolates (MIC: 3.9 to > 500 µg/mL). Remarkably, CBD synergized with gentamicin, meropenem, and colistin, reducing their effective concentrations by up to 1,000-fold. Combination therapy significantly inhibited and eradicated biofilms. Time-kill assays demonstrated rapid, concentration-dependent killing, with complete bacterial clearance at 4× MIC within 2 h. Mechanistic assays and SEM confirmed that CBD induces extensive membrane damage.

These findings highlight CBD’s potential as an effective adjunct to conventional antibiotics for treating XDR A. baumannii infections, offering a novel strategy to counteract antimicrobial resistance.”

https://pubmed.ncbi.nlm.nih.gov/40817249/

“Acinetobacter baumannii is an opportunistic, Gram-negative bacterium that has emerged as a major cause of hospital-associated infections (HAIs) worldwide, with no standard therapeutic recommendation for its management and control. It primarily affects critically ill and immunocompromised patients, leading to severe infections such as ventilator-associated pneumonia, bloodstream infections, urinary tract infections, meningitis, and wound infections. A. baumannii’s remarkable ability to survive in hospital environments, resist desiccation, and persist on medical equipment—particularly in intensive care units (ICUs)—makes it a persistent challenge in healthcare settings.”

“Our study demonstrates that CBD exhibits potent antibacterial and anti-biofilm properties against XDR A. baumannii, particularly when used in combination with conventional antibiotics such as gentamicin, meropenem, and colistin. Notably, its ability to disrupt membrane integrity represents a key mechanism in overcoming drug tolerance.

These findings provide a strong foundation for further investigation of CBD as a novel therapeutic strategy to combat antimicrobial resistance in clinical settings.”

https://bmccomplementmedtherapies.biomedcentral.com/articles/10.1186/s12906-025-05056-w