“Background: Cannabidiol (CBD) has shown potential benefits in managing symptoms associated with autism spectrum disorder (ASD), although its underlying mechanisms of action remain unclear. This study investigated whether CBD improves ASD-like behavior in association with changes in lipid metabolic disturbances and apoptosis-related signaling in a prenatal valproic acid (VPA) rat model.
Methods: Male offspring from VPA-exposed rats received CBD (10 mg/kg, intraperitoneal, twice daily) for 7 days starting on postnatal day 21. Behavioral testing evaluated hyperactivity, social interaction, and repetitive behaviors. Hippocampal lipid profiles were quantified by UPLC-MS/MS. Candidate mechanisms were examined through a joint pathway analysis integrating lipidomics with curated target information, followed by targeted gene/protein validation (qPCR, Western blotting) and molecular docking.
Results: CBD treatment improved VPA-induced hyperactivity and repetitive behaviors and social interaction deficits. Lipidomics demonstrated remodeling of hippocampal lipid abnormalities after CBD treatment, with changes across major classes, including phosphatidylcholines, lysophosphatidylcholines, and sphingomyelins. Joint pathway analysis pinpointed potential targets-LDHA, LDHB, PKM, PTGS2, and EPHX2-linked to energy-related pathways (pyruvate metabolism, glycolysis/gluconeogenesis, propanoate metabolism) and arachidonic acid metabolism. CBD also modulated apoptosis-related protein dysregulation, with potential involvement of Akt-related signaling. Docking results suggested possible binding between CBD and the selected targets.
Conclusion: These results suggest that CBD improves ASD-like behaviors alongside hippocampal lipid metabolism remodeling and modulation of apoptosis-related signaling in VPA-exposed rats, providing preliminary insights into potential mechanisms underlying the effects of CBD in ASD models.”
“This study evaluated the therapeutic potential of raw hemp seed polysaccharides (HSP) and stir-fried hemp seed polysaccharides (FHSP) in a rat model of blood-deficiency syndrome induced by cyclophosphamide and acetylphenylhydrazine.
Both HSP and FHSP are acidic heteropolysaccharides primarily composed of arabinose, galacturonic acid, and galactose, but differ in molecular weight, monosaccharide ratios, and microstructure. Methylation and GC-MS analyses indicated that HSP and FHSP shared similar major glycosidic linkage types, predominantly including →5)-Araf-(1→, Galp-(1→, →4)-GalAp-(1→, and →6)-Galp-(1→, but differed in their relative molar proportions.
In vivo experiments showed that both HSP and FHSP significantly improved hematological parameters (RBC, WBC, HGB, and HCT), regulated cytokine levels (EPO, G-CSF, TNF-α, and IL-6), and alleviated splenic damage. Compared with HSP, FHSP produced more pronounced improvements in several evaluated indicators under the present experimental conditions.
Mechanistic analyses suggested that the beneficial effects of FHSP may be associated with the JAK1-STAT1 signaling pathway, amelioration of splenic metabolic dysfunction involving arachidonic acid, glutathione, riboflavin, and arginine and proline metabolism, and modulation of the gut microbial community.
These findings suggest that FHSP has potential for alleviating blood deficiency syndrome and provide new insights into the further development and application of hemp seed polysaccharides.”
“Cannabidiolic acid (CBDA) is a phytocannabinoid found in the Cannabis plant. Understanding the effects of CBDA is essential to uncover its full potential and possible health benefits.
The study was conducted on rats receiving standard rat chow (control) and a high-fat diet (HFD).
Half of the animals in each group were administered CBDA intragastrically. The total lipid fractions and arachidonic acid (AA) contents were measured in the frontal and posterior cortex, hippocampus, and subcortical nuclei using gas-liquid chromatography. The expression of proteins involved in neurodegenerative diseases and insulin signaling pathway proteins in the frontal and posterior cortex was measured using Immunoblotting. RT-PCR was used to assess the expression of pro-inflammatory pathway proteins in the same regions. Additionally, untargeted and targeted metabolomic analyses were performed on cerebrospinal fluid (CSF).
The results showed that a decrease in arachidonic acid levels and pro-inflammatory precursor proteins after CBDA treatment in high-fat-fed rats was simultaneous with improved insulin signaling, particularly in the posterior cortex.
Inactivation of glycogen synthase kinase 3 (GSK-3β) in this region was concomitant with changes in neurodegenerative biomarkers in the cortex and CSF. Metabolomic studies revealed a significant diminishment in creatinine, phenylalanine, and sarcosine levels in the HFD+CBDA group, suggesting it plays an important role in neurological disorders.
The results suggest that CBDA has anti-inflammatory properties by reducing the synthesis of lipid inflammatory mediators, which are concomitant with improved insulin signaling and probably reduced neurodegeneration.
Thus, CBDA could be considered as a part of future clinical treatment for many inflammatory conditions.”
“Our study demonstrated a preliminary analysis of the impact of CBDA on the inflammatory profile of the brain under conditions of excess calories from fat. The results suggest an anti-inflammatory role for this cannabinoid, particularly in inhibiting the synthesis of lipid inflammatory mediators.”
“Insulin Resistance (IR) is a central pathophysiological mechanism underlying obesity, type 2 diabetes mellitus, metabolic syndrome, and metabolic dysfunction-associated steatotic liver disease, with significant implications for skeletal muscle function, exercise capacity, and rehabilitation outcomes. Because skeletal muscle represents the primary site of insulin-stimulated glucose disposal, muscle insulin resistance is a key determinant of both metabolic health and physical performance.
Cannabidiol (CBD), a non-intoxicating phytocannabinoid derived from Cannabis sativa, has attracted increasing scientific interest due to its anti-inflammatory, antioxidant, and pleiotropic signaling properties.
This narrative review aims to examine the relationship between CBD and insulin resistance, with a particular focus on skeletal muscle biology and its relevance for exercise and rehabilitation medicine.
A structured literature search was conducted using major biomedical databases, including PubMed, Scopus, and Web of Science, to identify relevant preclinical and clinical studies. Evidence was synthesized narratively, with emphasis on skeletal muscle insulin resistance, endocannabinoid system signaling, potential mechanisms of CBD action, and clinical outcomes.
Preclinical data suggest that CBD may influence several pathways involved in skeletal muscle insulin resistance, including chronic low-grade inflammation, oxidative stress, lipotoxicity, and ceramide accumulation. However, current human studies remain limited and do not demonstrate consistent improvements in glycemic control or insulin sensitivity with CBD alone. Furthermore, evidence regarding its effects on muscle function, exercise performance, or rehabilitation outcomes is lacking.
In conclusion, CBD represents a biologically plausible but clinically unproven modulator of skeletal muscle insulin resistance. At present, it should be considered an experimental adjunct rather than an established therapeutic strategy. Future research should focus on well-designed clinical trials integrating metabolic and functional endpoints to determine its potential role alongside exercise-based interventions in rehabilitation medicine.”
“Roughly one-third of patients with epilepsy remain drug resistant, underscoring the need for novel therapeutic strategies. Although cannabidiol (CBD) has recently been approved for specific epileptic encephalopathies, its anticonvulsant mechanisms and the influence of biological sex on treatment response remain incompletely understood.
In this preclinical study, we evaluated the efficacy, tolerability, pharmacokinetics, and molecular effects of CBD in the GASH/Sal hamster, a genetic model of audiogenic generalized tonic-clonic seizures.
Animals received intraperitoneal CBD (200 mg/kg) either acutely or chronically for 14 days. CBD concentrations were measured in serum and brain, while seizure severity, latency, and neuroethological parameters were assessed following acoustic seizure induction. Safety was evaluated through body weight, hematological, and biochemical analyses, and gene expression profiling was performed in the inferior colliculus, the primary epileptogenic focus. CBD achieved measurable systemic and brain exposure after both acute and chronic administration, despite substantial inter-individual variability and no significant sex differences in drug concentrations.
CBD reduced audiogenic seizure severity in a time-dependent manner, with greater protection after chronic treatment.
CBD also prolonged latency to seizure onset in both sexes (earlier in females). Although complete seizure suppression was more frequent in females than males (37.5% vs. 12.5% after chronic treatment), direct sex comparisons did not reach statistical significance.
Notably, higher serum and brain CBD concentrations were associated with lower seizure severity. Chronic CBD administration was well tolerated in both sexes, affecting selected hematological parameters without altering body weight or liver function. Gene expression profiling revealed that transcriptional organization of the inferior colliculus was driven predominantly by biological sex rather than by seizure induction or CBD treatment. Marked sex-dependent differences were observed in serotonergic, endocannabinoid, purinergic, and Sigmar1-related neuroprotective pathways. Within this molecular context, seizure stimulation modulated Trpv1 and Slc29a1, whereas chronic CBD induced pathway-specific, sex-dependent changes involving 5-Htr1a, Adora1, and Cnr1, without eliciting widespread transcriptional remodeling.
Collectively, these findings identify CBD as a well-tolerated anticonvulsant in the GASH/Sal model and suggest that pharmacokinetic exposure and the sex-specific molecular organization of the epileptogenic focus contribute to variability in treatment response, highlighting the importance of considering biological sex in cannabinoid-based epilepsy research.”
“Cannabinoid receptors have traditionally been regarded as regulators of neuroinflammation. However, their anti-inflammatory effects alone are insufficient to fully elucidate their complicated roles in neurodegenerative diseases (NDDs).
Mounting evidence identifies disruptions in energy metabolism as key drivers of neurodegeneration, which has prompted a re-evaluation of the cannabinoid receptor system within the context of brain energy metabolism and pathophysiological processes. Accumulated findings from several independent preclinical studies have offered novel insights into the potential involvement of cannabinoid receptors in energy metabolism, mitochondrial function, and glial metabolic reprogramming.
This review focuses on the metabolic regulatory potential of classical cannabinoid receptors, including cannabinoid receptor type 1 (CB1R) and cannabinoid receptor type 2 (CB2R), with particular attention to mitochondrial CB1 receptors (mtCB1), as well as non-classical targets such as G protein-coupled receptor 55 (GPR55), G protein-coupled receptor 119 (GPR119), and peroxisome proliferator-activated receptors (PPARs). Additionally, the review explores the mechanisms by which astrocytes maintain neuronal support through cell-type-specific metabolic specialization and how metabolic reprogramming in microglia modulates neuroinflammatory phenotypes.
Although the current evidence is predominantly derived from preclinical models and several mechanistic links remain to be experimentally validated, we propose a novel conceptual model, namely the cannabinoid receptor-glial metabolic reprogramming-neuronal metabolic support failure axis, in which the breakdown of metabolic checkpoints is viewed as a crucial event in disease progression.
At the therapeutic level, we advocate shifting from conventional anti-inflammatory approaches to metabolic repair strategies, while also exploring emerging directions in the development of cannabinoid-based medications targeting metabolism.
Collectively, a deep understanding of the complex metabolic regulatory functions of cannabinoid receptors is critical for developing next-generation treatment strategies for NDDs.”
This study represents an important part of Olivia Newton-John’s legacy.
After experiencing medicinal cannabis personally during her long cancer journey, Olivia became an outspoken advocate not only for patient access, but for the scientific research needed to determine what cannabis could—and could not—do for people living with cancer.
The Olivia Newton-John Cancer Research Institute later stated that Olivia’s own experience with medicinal cannabis and her interest in pursuing the science behind its use in cancer helped lead the Institute to undertake its first medicinal-cannabis clinical trial.
That work developed into the RESONANCE trial, a Phase I/II double-blind, randomized controlled study examining medicinal cannabis in people with advanced cancer. The study is investigating its effects on quality of life and symptoms including pain, nausea, appetite loss, anxiety and sleep problems, as well as safety and how cannabinoids are metabolized by the body. The study protocol was published in Clinical Therapeutics in 2026.
Olivia repeatedly made clear that her personal experience was not enough. She wanted the science. She wanted researchers to investigate the benefits she believed she had experienced and determine whether other cancer patients could benefit as well.
The study is currently recruiting
As of August 2026, the RESONANCE trial is listed as open and recruiting in Victoria, Australia.
Potential participants may be eligible if they:
are 18 years of age or older;
have advanced cancer; and
have an estimated life expectancy of at least two months.
Additional inclusion and exclusion requirements apply, and final eligibility must be determined by the study team.
Two-thirds of participants receive medicinal cannabis and one-third receive placebo. Both are administered as an oral oil, beginning once daily and increasing, when appropriate, to a maximum of three times per day. Dosing is increased until symptoms are adequately controlled and is then maintained for up to one month. Participants provide blood samples and complete questionnaires, and researchers may also invite a participant’s caregiver to take part in aspects of the study.
After completion of the trial period, participants may be able to obtain medicinal cannabis through compassionate access.
Clinical trial registration: ACTRN12619001534178.
Interested in participating?
People interested in the trial should discuss participation with their doctor and contact the research center to determine whether they meet the complete eligibility requirements. Peter MacCallum Cancer Centre currently lists the study as open and recruiting and directs prospective participants to the full Australian clinical-trial registry criteria.
Dr. Jodie Palmer Olivia Newton-John Cancer Research Institute Level 5, ONJWRC 145 Studley Road Heidelberg, Victoria 3084, Australia Phone: +61 3 9496 3573 Email:trials@onjcri.org.au
Olivia spent the final years of her life asking that medicinal cannabis be taken seriously enough to study scientifically. She believed her own experience raised questions worth answering.
This study is part of the scientific legacy she helped set in motion.
“Purpose: Medicinal cannabis is increasingly used in cancer care despite limited high-quality evidence to inform practice. It is increasingly legalized around the world; however, this has outpaced high-quality research on cancer symptom outcomes, leading to patient and prescriber uncertainty. This trial evaluates the safety profile, tolerability, and impact of medicinal cannabis on quality of life in advanced cancer.
Methods: This is a Phase I/II multicenter clinical trial. The Phase I component is open-label and aims to determine the safety profile and tolerability of medicinal cannabis use by evaluating clinical outcomes and pharmacokinetic profile. The Phase II component is a double-blind, randomized clinical trial that aims to determine the impact of medicinal cannabis on quality of life and symptom control (pain, anorexia, anxiety, sleep, nausea, treatment satisfaction, toxicity, and caregiver burden) using validated instruments in people with advanced cancer.
Findings & implications: This trial is expected to generate important knowledge about the tolerability, efficacy, and adverse effects of medicinal cannabis in people with advanced cancer, with a particular focus on quality of life and symptom burden. Protocol adaptations aimed at enhancing inclusivity may be worth noting in future studies. Collectively, the findings have the potential to inform clinical practice, reduce decisional uncertainty among prescribers and patients, and affect care for the estimated 10 million people who die of advanced cancer annually worldwide. Australian New Zealand Clinical Trials Registry identifier: ACTRN12619001534178.”
“Dental caries is strongly associated with biofilm-forming bacteria such as Streptococcus mutans and Lactobacillus acidophilus, and improving the antimicrobial performance of restorative materials remains a major challenge in preventive dentistry.
Glass ionomer cements (GICs) exhibit favorable properties including chemical adhesion and fluoride release, yet their intrinsic antibacterial activity remains limited.
This study investigated the incorporation of four cannabinoid-rich fractions (F1, F2, F3, and F4) into glass ionomer cements and evaluated their structural, antimicrobial, and biological properties.
Cannabinoid fractions isolated from hemp flowers were incorporated into Ketac Cem Radiopaque and Ketac Molar Easymix formulations at 1 wt %. Data were analyzed using one-way ANOVA, Tukey’s post hoc test, and Kruskal-Wallis analysis (p < 0.05).
Attenuated Total Reflection-Fourier Transform Infrared Spectroscopy (ATR-FTIR) and X-ray diffraction (XRD) analyses demonstrated structural compatibility between the cannabinoid fractions and the glass ionomer matrix, indicating preservation of the original phase composition and the absence of disruption in the acid-base setting reaction. The modified cements exhibited strain-dependent antibacterial and antibiofilm activity, with KCR-F4 showing the strongest reduction in S. mutans viability (47.35%) and KME-F1 demonstrating the greatest activity against L. acidophilus (14.77%).
Significant differences were observed among GIC types and cannabinoid fractions for antimicrobial activity, fluoride release, and cytotoxicity. Scanning electron microscopy (SEM) imaging further confirmed decreased bacterial adhesion and disrupted surface colonization on cannabinoid-modified cement surfaces. Fluoride-release behavior was largely preserved following cannabinoid incorporation. However, cytotoxicity analysis revealed increased LDH release at the tested concentration, indicating a cytotoxicity trade-off associated with enhanced antimicrobial activity.
It is concluded that cannabinoid extract is promising as an additive to formulate bioactive glass-ionomer cements, although further optimization is required to balance antimicrobial efficacy with cytocompatibility.”
“Phytochemicals derived from medicinal plants have emerged as promising candidates for antimicrobial modification of dental biomaterials. Among these, cannabinoids isolated from Cannabis sativa L. have attracted increasing interest due to their diverse biological activities, including antimicrobial, anti-inflammatory, antioxidant, and antibiofilm effects.”
“Recent studies have also reported that cannabinoids may disrupt bacterial membrane integrity and inhibit biofilm formation, suggesting potential applications in oral health and dental biomaterials. “
“Wound healing is a complex process; therefore, new dressings are frequently required to facilitate it.
In this study, porous bacterial levan-based sponges containing cannabis oil (Lev@CBDs) were prepared and fully characterized.
The sponges exhibited a suitable swelling ratio, proper water vapor transmission rate, sufficient thermal stability, desired mechanical properties, and good antioxidant and anti-inflammatory properties. The obtained Lev@CBD materials were evaluated in terms of their interaction with proteins, human serum albumin and fibrinogen, of which fibrinogen revealed the highest binding effect.
Moreover, the obtained biomaterials exhibited antibacterial activity against Staphylococcus aureus and Pseudomonas aeruginosa, as well as being non-hemolytic material as indicated by hemolysis tests. Furthermore, the sponges were non-toxic and compatible with L929 mouse fibroblasts and HDF cells.
Most significantly, the levan sponge with the highest content of cannabis oil, in comparison to others, retained its non-hemolytic, anti-inflammatory, and antimicrobial properties after prolonged storage in a climate chamber at a constant temperature and relative humidity.
The designed sponges have conclusively proven their beneficial physicochemical properties and, at the preliminary stage, biocompatibility as well, and therefore can be considered a promising material for wound dressings in future in vivo applications.”
“The biomaterials consisting of levan sponges enriched with cannabis oil are expected to be suitable wound dressing due to their highly effective characteristics”
“Overall, these results showed that prepared sponges enriched with cannabis oil might have significant potential for applications in wound healing, tissue engineering, and cell culture.”
“Cannabidiol (CBD) has been shown to have antioxidant and antibacterial effects. The investigation into CBD’s potential as an antioxidant and antibacterial agent, meanwhile, is still in its initial stages.
The study goals were to prepare encapsulated cannabidiol isolate (eCBDi), evaluate the effect of eCBDi edible active coatings on the physicochemical properties of strawberries, and determine whether CBD and sodium alginate coatings could be used as a postharvest treatment to promote antioxidation and antimicrobial activity and prolong the strawberry shelf life.
A well-designed edible coating on the strawberry surface was achieved using eCBDi nanoparticles in combination with a sodium alginate polysaccharide-based solution. Strawberries were examined for their visual appearance and quality parameters.
In the results, a significantly delayed deterioration was observed in terms of weight loss, total acidity, pH, microbial activity, and antioxidant activity for coated strawberries compared to the control.
This study demonstrates the capability of eCBDi nanoparticles as an efficient active food coating agent.”
