A cannabidiol-containing alginate based hydrogel as novel multifunctional wound dressing for promoting wound healing

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“In addition to preventing infection and promoting angiogenesis, novel hydrogel dressings are highly expected to possess the potential to scavenge reactive oxygen species (ROS) and reduce inflammatory responses during the wound healing process.

In this study, we designed and fabricated a hydrogel dressing (CBD/Alg@Zn) containing cannabidiol (CBD) based on the ion crosslinked interaction between Zn2+ ions and the alginate polymer (Alg).

The as-fabricated hydrogel exhibited a suitable swelling ratio, sufficient thermal stability, and stable rheological property. In vitro biological activity experiments indicated that the hydrogel has good biocompatibility, antibacterial activity, and angiogenesis properties. Moreover, it could significantly scavenge DPPH (2,2-diphenyl-1-picrylhydrazyl) free radicals and reduce the inflammatory response.

In vivo studies revealed that the CBD/Alg@Zn hydrogel significantly facilitated the wound healing process by controlling the inflammatory infiltration, promoting collagen deposition and the granulation tissue, and benefiting the formation of blood vessels.

We, therefore, suggested that CBD/Alg@Zn hydrogel should be a potential candidate material for wound dressing and skin tissue engineering.”

https://pubmed.ncbi.nlm.nih.gov/35523648/

“A cannabidiol-containing alginate based hydrogel (CBD/Alg@Zn) was developed as novel multifunctional wound dressing.•

The Alg@Zn hydrogel not only acts as a drug carrier but also shows significantly anti-bacterial and angiogenic activities.•

The introduction of cannabidiol (CBD) endowed the hydrogels with antioxidant and anti-inflammatory effects.•

The CBD/Alg@Zn hydrogel showed accelerated wound healing effect in vivo.”

https://www.sciencedirect.com/science/article/abs/pii/S0928493121007001?via%3Dihub

Chitosan-based films with cannabis oil as a base material for wound dressing application

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“This study focuses on obtaining and characterizing novel chitosan-based biomaterials containing cannabis oil to potentially promote wound healing.

The primary active substance in cannabis oil is the non-psychoactive cannabidiol, which has many beneficial properties.

In this study, three chitosan-based films containing different concentrations of cannabis oil were prepared. As the amount of oil increased, the obtained biomaterials became rougher as tested by atomic force microscopy. Such rough surfaces promote protein adsorption, confirmed by experiments assessing the interaction between human albumin with the obtained materials. Increased oil concentration also improved the films’ mechanical parameters, swelling capacity, and hydrophilic properties, which were checked by the wetting angle measurement. On the other hand, higher oil content resulted in decreased water vapour permeability, which is essential in wound dressing. Furthermore, the prepared films were subjected to an acute toxicity test using a Microtox.

Significantly, the film’s increased cannabis oil content enhanced the antimicrobial effect against A. fischeri for films in direct contact with bacteria. More importantly, cell culture studies revealed that the obtained materials are biocompatible and, therefore, they might be potential candidates for application in wound dressing materials.”

https://pubmed.ncbi.nlm.nih.gov/36333591/

“In this study, novel chitosan-based biomaterials containing cannabidiol were obtained, with cannabis oil being used as a source of cannabidiol.”

“The results suggest that the cannabidiol-containing chitosan-based films (CBD-CS) possess the most prerequisites for a good dressing for wound healing applications.”

“Therefore, chitosan-based films incorporating cannabis oil might be an excellent candidate for wound treatment and dressing.”

https://www.nature.com/articles/s41598-022-23506-0

Self-reported cannabis use to manage opioid withdrawal symptoms and reductions in opioid use among people who use unregulated opioids: a cross-sectional analysis

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Background: Opioid withdrawal is a significant challenge for people seeking to reduce or eliminate opioid use, and unmanaged withdrawal increases the risk of relapse and overdose. Using cannabis to manage opioid withdrawal has been reported by people who use opioids, yet it is not clear whether this leads to reductions in opioid use. Moreover, because pain is prevalent among people who use unregulated opioids (PWUO) and may contribute to ongoing opioid use, the effects of cannabis use to manage withdrawal symptoms may differ among individuals experiencing moderate to severe pain. We investigated the relationship between cannabis use to manage unregulated opioid withdrawal and self-reported reductions in opioid use among PWUO.

Methods: Data were derived from a cross-sectional questionnaire administered to cannabis-using PWUO in Vancouver, Canada, between December 2019 and November 2021. Multivariable logistic regression estimated the associations between cannabis use for opioid withdrawal and self-reported reductions in opioid use. A sub-analysis explored if these associations varied among participants living with and without moderate to severe pain.

Results: Among 197 participants, 89 (45.2%) reported cannabis use to manage symptoms of opioid withdrawal in the past six months. In multivariable analysis, cannabis use for opioid withdrawal was significantly associated with self-reported reductions in opioid use (adjusted Odds Ratio [AOR] = 2.16, 95% Confidence Interval [CI]: 1.13-4.19) in the same time period. In a sub-analysis, this association was only significant among participants with moderate to severe pain (AOR = 6.55; 95% CI: 2.44-19.63).

Conclusions: We observed a significant association between self-reported use of cannabis to manage unregulated opioid withdrawal and reductions in opioid use among cannabis-using PWUO living with pain. Aligned with other studies, these findings support conducting experimental trials of cannabinoids to support individuals experiencing opioid withdrawal and living with pain.”

https://pubmed.ncbi.nlm.nih.gov/42343486

https://link.springer.com/article/10.1186/s42238-026-00458-0

Signaling pathways of inflammation in CIA model of rheumatoid arthritis regulated by cannabichromene

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“Background: Rheumatoid arthritis is a chronic autoimmune disease characterized by synovial inflammation, cytokine imbalance, and progressive joint destruction. The endocannabinoid system has emerged as a potential therapeutic target; however, the anti-inflammatory mechanisms of non-psychoactive cannabinoids such as cannabichromene (CBC) remain insufficiently defined. This study aimed to evaluate the anti-inflammatory effects of CBC in vitro and in a collagen-induced arthritis (CIA) rat model, with a focus on key inflammatory signaling pathways.

Methods: CBC effects were assessed in LPS-stimulated HUVEC cells by qPCR analysis of inflammatory markers. In vivo, female Wistar rats were assigned to four groups: CIA + saline (placebo), CIA + CBC, CIA + methylprednisolone, and non-immunized controls receiving saline. Disease progression was evaluated using clinical scoring, paw thickness, and body weight. Synovial tissues and serum were analyzed by qPCR, Western blotting, and ELISA to assess cytokines, inflammasome components, and signaling pathways, including NF-κB and JAK/STAT.

Results: CBC reduced TNF-α expression in vitro at low micromolar concentrations. In vivo, CBC significantly decreased arthritis scores compared to placebo and attenuated weight loss, although it did not significantly reduce paw swelling. Molecular analyses revealed downregulation of IL-6, STAT3, and IL-17 A, indicating suppression of the TNF-NF-κB-IL-6-STAT3-Th17 axis. CBC also significantly inhibited inflammasome components (NLRP3, NLRP1A, caspase-11). However, MMP-3 and MMP-9 levels were not significantly affected.

Conclusions: CBC exhibits significant anti-inflammatory activity in vitro and in vivo by modulating key cytokine and inflammasome pathways. While its effects on structural joint damage markers were limited, CBC represents a promising candidate for inflammatory arthritis therapy, warranting further investigation.”

https://pubmed.ncbi.nlm.nih.gov/42343451

https://link.springer.com/article/10.1186/s42238-026-00464-2

Efficacy and Safety of Cannabinoid-Based Products in Children and Adolescents with Autism Spectrum Disorder, Fragile X Syndrome and Rett Syndrome: A Systematic Review

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“Introduction: Neurodevelopmental disorders (NDDs), including Autism Spectrum Disorder (ASD), Fragile X syndrome (FXS), and Rett Syndrome (RTT), share impairments in cognitive and behavioral functioning and may involve an altered excitatory/inhibitory balance modulated by the endocannabinoid system. This systematic review evaluated the safety and efficacy of cannabinoid-based products (CBPs) in these pediatric NDDs.

Methods: We conducted a systematic review according to Preferred Reporting Items of Systematic Reviews and Meta-Analyses (PRISMA) 2020, including randomized and nonrandomized studies of patients under 18 years treated with cannabidiol (CBD), cannabidivarin (CBDV), tetrahydrocannabinol (THC), or their combinations. Outcomes were adverse events (AEs) and treatment discontinuation, seizure reduction, and behavioral and cognitive changes. Study quality and certainty of evidence were assessed using design-specific risk-of-bias tools and the GRADE approach.

Results: Seventeen studies (two randomized controlled trials, observational studies, and case series) met the inclusion criteria. Across diagnoses, CBPs were generally associated with mild-to-moderate AEs and low discontinuation rates. Descriptive pooled proportions suggested behavioral improvements in ASD and FXS and seizure reduction in RTT, with exploratory analyses indicating differential effects of CBD versus CBD + THC on behavioral and cognitive outcomes in ASD.

Conclusion: CBPs may offer potential benefits for selected behavioral symptoms and comorbid epilepsy in pediatric NDDs, but current evidence is insufficient to support routine clinical use. High-quality randomized controlled trials with standardized outcome measures and long-term follow-up are needed to clarify efficacy, safety, and syndrome-specific effects.”

https://pubmed.ncbi.nlm.nih.gov/42339654

https://journals.sagepub.com/doi/10.1177/10445463261462382

CBD-rich oil nanoemulsion mitigates long-term testicular and endocrine toxicity induced by prenatal valproic acid exposure in rats

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“Valproic acid is a widely used antiepileptic drug and a recognized model of developmental reproductive toxicity, as exposure during critical periods of testicular development can lead to persistent endocrine and reproductive dysfunction in adulthood.

Cannabidiol (CBD) has therapeutic potential in several pathological conditions but exhibits low oral bioavailability due to its lipophilic nature.

This study evaluated whether chronic treatment with a CBD-rich corn oil nanoemulsion could attenuate long-term testicular and endocrine alterations induced by prenatal valproic acid exposure in rats.

CBD-rich nanoemulsions were prepared and physicochemically characterized. On gestational day 12.5, pregnant rats received a single intraperitoneal dose of valproic acid (500mg/kg). In adulthood, male offspring from valproic acid-exposed dams were treated orally with CBD nanoemulsions at doses of 1 or 2mg/animal, administered twice daily. After euthanasia, testes were collected for morphometric, biochemical, and hormonal analyses.

Prenatal exposure to valproic acid induced persistent testicular alterations, including reduced Leydig cell number, decreased serum testosterone levels, reduced seminiferous epithelium height, and increased seminiferous tubule diameter. Increased activities of superoxide dismutase and glutathione S-transferase suggested an adaptive antioxidant response. These findings are consistent with long-term testicular and endocrine dysfunction following developmental exposure to an endocrine-disrupting drug.

Importantly, treatment with the CBD-rich nanoemulsion reversed the morphometric, hormonal, and oxidative alterations induced by valproic acid.

Overall, these results indicate that nanoformulated CBD may mitigate long-term reproductive toxicity induced by prenatal valproic acid exposure, highlighting the importance of drug formulation in determining the biological effects of cannabinoids on the male reproductive system.”

https://pubmed.ncbi.nlm.nih.gov/42342051

“In conclusion, our findings provide preclinical evidence that chronic treatment with a CBD-rich corn oil nanoemulsion attenuates several reproductive effects induced by prenatal exposure to valproic acid in male rats.”

https://www.sciencedirect.com/science/article/abs/pii/S0890623826001401?via%3Dihub

Development and clinical evaluation of a nanoemulsion for buccal delivery of cannabis extract in refractory chronic pain

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“Cannabinoid-based therapies have gained increasing attention for the management of chronic and treatment-resistant pain, although their clinical application is limited by the poor aqueous solubility and variable bioavailability of Δ9-tetrahydrocannabinol (THC).

In this study, we developed and characterized a nanoemulsion (THC-NE) for buccal administration of a Cannabis sativa L. extract (Bedrocan®), with the aim of improving solubility, stability and bioavailability.

The optimized formulation, composed of pharmaceutically acceptable excipients, showed a narrow droplet size distribution (DH ≈ 73 nm, PDI ≈ 0.2), a THC content consistent with the theoretical value (3.53 ± 0.56 mg/mL), and good physicochemical stability at 4°C for at least 90 days. The formulation maintained its properties upon extensive dilution in simulated buccal fluids and after spray nebulization, supporting its suitability for oromucosal delivery. In vitro release studies confirmed sustained THC release from THC-NE, whereas negligible release was observed from the oil extract, highlighting the role of nanoformulation in enhancing solubilization and controlled release.

An observational study was conducted in 18 patients with chronic pain unresponsive to standard treatments. After a median follow-up of 189 days, mean pain scores (NRS) decreased significantly from 8.6 ± 0.9 to 5.4 ± 2.8 (p < 0.001), with 83% of patients achieving a ≥ 20% reduction. Among responders, the mean NRS decreased by 45% and treatment persistence was found to be high, with 64% of patients still remaining under therapy after six months. A total of 17 adverse events were reported in 11 patients, most of which were mild to moderate and transient. Additionally, treatment interruption occurred in three patients due to adverse events, in other three owing to limited efficacy and in two for logistical reasons.

Overall, these findings indicate that buccal administration of THC-NE represents a promising patient-friendly approach for cannabis-based therapy, offering improved solubility, controlled release and meaningful clinical benefit in patients with refractory chronic pain.”

https://pubmed.ncbi.nlm.nih.gov/42336000

“Among the bioactive compounds found in Cannabis sativa, Δ9-tetrahydrocannabinol (THC) has been identified as the primary psychoactive component, exhibiting significant analgesic, antispastic, and neuroprotective properties. “

“This study demonstrates that NE technology can be successfully applied to develop a stable and efficient buccal formulation of Cannabis sativa extract. The optimized THC-NE proved to be physicochemically stable, robust under dilution, and suitable for administration via standard spray devices, while ensuring enhanced release of THC compared to the oily extract.”

https://www.sciencedirect.com/science/article/pii/S0939641126001839?via%3Dihub

Cannabidiol Limits Early Aβ-Induced Glial Activation and Preserves Synaptic Integrity in Primary Mouse Hippocampal Neuron-Glia Cultures

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“Alzheimer’s disease (AD) initiates with subtle neuroimmune alterations that precede overt synaptic loss and neuronal death, yet the early sequence linking Aβ exposure to glial activation remains incompletely understood.

To capture early neuroimmune dynamics with greater physiological relevance, we employed primary mixed neuron-glia cultures derived from the hippocampi of postnatal day 1 (P1) mice. Unlike conventional coculture systems, these hippocampal mixed cultures preserve intrinsic neuron-astrocyte-microglia communication and recapitulate key features of the in vivo hippocampal microenvironment.

Using this model, we investigated whether cannabidiol (CBD) modulates the initial pathogenic events triggered by Aβ25-35 during a 24h simultaneous cotreatment in cell culture.

Aβ exposure induced robust hippocampal glial activation, oxidative stress, and elevated levels of proinflammatory mediators, particularly IL-1β, IL-6, and TNF-α. Notably, hippocampal synaptic and neurogenic markers (5HT1A, Gria1, GRIN1, DCX, PSD-95) remained largely unaltered at this early stage, revealing a temporal dissociation in which glial-driven inflammation precedes synaptic dysfunction.

CBD significantly attenuated inflammatory and oxidative responses and prevented Aβ-induced cellular damage, indicating engagement of endocannabinoid-related mechanisms that constrain early hippocampal glial reactivity. Although CBD did not fully normalize all glial alterations, it preserved hippocampal synaptic integrity and halted progression toward neuronal dysfunction.

Together, these findings identify early hippocampal glial inflammation as a primary target of CBD and provide mechanistic insight into the temporal sequence linking Aβ exposure to neuroimmune activation.

These results highlight early glial responses as a critical window for therapeutic intervention and support cannabinoid-based strategies to modulate the initial stages of Alzheimer’s disease pathogenesis.”

https://pubmed.ncbi.nlm.nih.gov/42331352

https://onlinelibrary.wiley.com/doi/10.1111/ejn.70588

Cell death induction and intracellular vesicle formation in human colorectal cancer cells treated with Δ9-Tetrahydrocannabinol

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“Background: Δ9-Tetrahydrocannabinol (Δ9-THC) is a principal psychoactive extract of Cannabis sativa and has been traditionally used as palliative medicine for neuropathic pain. Cannabidiol (CBD), an extract of hemp species, has recently attracted increased attention as a cancer treatment, but Δ9-THC is also requiring explored pharmacological application.

Objective: This study evaluated the pharmacological effects of Δ9-THC in two human colorectal cancer cell lines. We investigated whether Δ9-THC treatment induces cell death in human colorectal cancer cells.

Methods: We performed an MTT assay to determine the pharmacological concentration of Δ9-THC. Annxein V and Western blot analysis confirmed that Δ9-THC induced apoptosis in colorectal cancer cells. Metabolic activity was evaluated using MitoTracker staining and ATP determination. We investigated vesicle formation by Δ9-THC treatment using GW9662, known as a PPARγ inhibitor.

Results: The MTT assay showed that treatment with 40 μM Δ9-THC and above inhibited the proliferation of colorectal cancer cells. Multiple intracytoplasmic vesicles were detected upon microscopic observation, and fluorescence-activated cell sorting analysis showed cell death via G1 arrest. Δ9-THC treatment increased the expression of cell death marker proteins, including p53, cleaved PARP-1, RIP1, and RIP3, suggesting that Δ9-THC induced the death of colorectal cancer cells. Δ9-THC treatment also reduced ATP production via changes in Bax and Bcl-2. Δ9-THC regulated intracytoplasmic vesicle formation by modulating the expression of PPARγ and clathrin, adding that antiproliferative activity of Δ9-THC was also affected.

Conclusion: In conclusion, Δ9-THC regulated two functional mechanisms, intracellular vesicle formation and cell death. These findings can help to determine how cannabinoids can be used most effectively to improve the efficacy of cancer treatment.”

https://pubmed.ncbi.nlm.nih.gov/37837516

 “Cannabinoid extracts exhibit pharmacological effects by regulating the endocannabinoid system.”

“Δ9-THC treatment shows cell death and morphological changes in human colorectal cancer cells.”

“Therefore, these results suggest that Δ9-THC treatment induced cell death by inhibiting cell growth and inducing cellular morphological changes.”

https://link.springer.com/article/10.1007/s13258-023-01466-7

Endocannabinoid System and Its Regulation by Polyunsaturated Fatty Acids and Full Spectrum Hemp Oils

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“The endocannabinoid system (ECS) consists of endogenous cannabinoids, their receptors, and metabolic enzymes that play a critical homeostatic role in modulating polyunsaturated omega fatty acid (PUFA) signaling to maintain a balanced inflammatory and redox state.

Whole food-based diets and dietary interventions linked to PUFAs of animal (fish, calamari, krill) or plant (hemp, flax, walnut, algae) origin, as well as full-spectrum hemp oils, are increasingly used to support the ECS tone, promote healthy metabolism, improve risk factors associated with cardiovascular disorders, encourage brain health and emotional well-being, and ameliorate inflammation.

While hemp cannabinoids of THC and CBD groups show distinct but complementary actions through a variety of cannabinoid (CB1 and CB2), adenosine (A2A), and vanilloid (TRPV1) receptors, they also modulate PUFA metabolism within a wide variety of specialized lipid mediators that promote or resolve inflammation and oxidative stress.

Clinical evidence reviewed in this study links PUFAs and cannabinoids to changes in ECS tone, immune function, metabolic and oxidative stress adaptation, and overall maintenance of a well-balanced systemic function of the body. Understanding how the body coordinates signals from the exogenous and endogenous ECS modulators is critical for discerning the underlying molecular mechanisms of the ECS tone in healthy and disease states.

Nutritional and lifestyle interventions represent promising approaches to address chronic metabolic and inflammatory disorders that may overlap in the population at risk. Further investigation and validation of dietary interventions that modulate the ECS are required in order to devise clinically successful second-generation management strategies.”

https://pubmed.ncbi.nlm.nih.gov/34067450

“Hemp oils derived from the cannabis plant (Cannabis sativa L.) are a rich source of lipid bioactive compounds, including cannabinoids, β-caryophyllene, and polyunsaturated fatty acids that potentially interact with the ECS.”

https://www.mdpi.com/1422-0067/22/11/5479