Optimization of seizure prevention by cannabidiol (CBD)

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“Objective: Cannabidiol (CBD) is one of the most prominent non-psychotropic cannabinoids with known therapeutic potentials. Based on its anti-seizure efficacy, the first cannabis derived pharmaceutical grade CBD-based medication was approved in the USA in 2018 for the treatment of seizures in patients 2 years and older. Despite the effectiveness in reducing seizures, there remain several major questions on the optimization of CBD therapy for epilepsy such as the optimal dosage, composition, and route of delivery, which are the main objective of this current study.

Methods: We evaluated the antiseizure effects of CBD through different compositions, routes of delivery, and dosages in a pre-clinical model. We used a kainic acid-induced epilepsy model in C57BL/6 mice, treated them with placebo and/or CBD through inhalation, oral, and injection (intraperitoneal) routes. We used CBD broad spectrum (inhaled and intraperitoneal) vs CBD isolate formulations. We employed the Racine scaling system to evaluate the severity of the seizures, flow cytometry for measuring immune biomarkers and neurotrophic factors, and histologic analysis to examine and compare the groups.

Results: Our findings showed that all forms of CBD reduced seizures severity. Among the combination of CBD tested, CBD broad spectrum via inhalation was the most effective in the treatment of epileptic seizures (p < 0.05) compared to other forms of CBD treatments.

Conclusion: Our data suggest that route and CBD formulations affect its efficacy in the prevention of epileptic seizures. Inhaled broad spectrum CBD showed a potential superior effect compared to other delivery routes and CBD formulations in the prevention of epileptic seizures, which warrants further research.”

https://pubmed.ncbi.nlm.nih.gov/40177581/

https://www.degruyterbrill.com/document/doi/10.1515/tnsci-2022-0362/html

The Neuroprotective Effects of Cannabis-Derived Phytocannabinoids and Resveratrol in Parkinson’s Disease: A Systematic Literature Review of Pre-Clinical Studies

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“Currently, there are no pharmacological treatments able to reverse nigral degeneration in Parkinson’s disease (PD), hence the unmet need for the provision of neuroprotective agents.

Cannabis-derived phytocannabinoids (CDCs) and resveratrol (RSV) may be useful neuroprotective agents for PD due to their anti-oxidative and anti-inflammatory properties.

To evaluate this, we undertook a systematic review of the scientific literature to assess the neuroprotective effects of CDCs and RSV treatments in pre-clinical in vivo animal models of PD. The literature databases MEDLINE, EMBASE, PsychINFO, PubMed, and Web of Science core collection were systematically searched to cover relevant studies. A total of 1034 publications were analyzed, of which 18 met the eligibility criteria for this review.

Collectively, the majority of PD rodent studies demonstrated that treatment with CDCs or RSV produced a significant improvement in motor function and mitigated the loss of dopaminergic neurons. Biochemical analysis of rodent brain tissue suggested that neuroprotection was mediated by anti-oxidative, anti-inflammatory, and anti-apoptotic mechanisms.

This review highlights the neuroprotective potential of CDCs and RSV for in vivo models of PD and therefore suggests their potential translation to human clinical trials to either ameliorate PD progression and/or be implemented as a prophylactic means to reduce the risk of development of PD.”

“To our knowledge, this is the first systematic review that has directly considered the effects of both selective CDCs and RSV in the neuroprotective treatment of PD. Collectively, in vivo rodent studies have demonstrated that these natural compounds are efficacious in their neuroprotection of PD and produced symptomatic benefits.”

https://www.mdpi.com/2076-3425/11/12/1573

Preventive Beneficial Effects of Cannabidiol in a Reserpine-Induced Progressive Model of Parkinsonism

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“Parkinson’s disease (PD) is characterized by motor and non-motor symptoms such as tremors, difficulty in initiating movements, depression, and cognitive deficits. The pathophysiology of PD involves a gradual decrease in dopaminergic neurons in the substantia nigra, increased inflammatory parameters, and augmented oxidative stress in this region.

Several new therapies aim to promote antioxidant and anti-inflammatory actions, including the use of cannabinoids, particularly cannabidiol (CBD). CBD is a non-psychotomimetic component of Cannabis sativa that acts broadly through several mechanisms.

The objective of this study was to investigate the potential protective effect of CBD in mice subjected to a low-dose (0.1 mg/kg) repeated reserpine protocol, which encompasses behavioral and neuronal alterations compatible with the progressiveness of PD alterations.

We used two approaches: (1) concurrent administration during the development of parkinsonism and (2) preadministration to explore possible preventive action. The effect of CBD (0.5 mg/kg) on reserpineinduced alterations was investigated on behavioral (catalepsy and vacuous chewing movements) and neuronal (immunolabeling for tyrosine hydroxylase -TH) parameters.

Overall, groups that were treated with CBD and reserpine presented motor alterations later during the protocol compared to the groups that received only reserpine (except for vacuous chewing evaluation in the concomitant treatment). Additionally, CBD attenuated reserpine-induced catalepsy (preventive treatment) and prevented the decrease in TH labeling in the substantia nigra pars compacta in both concurrent and preventive protocols.

Based on these data, we observed a beneficial effect of CBD in motor and neuronal alterations reserpine-induced progressive parkinsonism, particularly after preventive treatment.”

https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2025.1539783/abstract

Intravitreal CBD-Loaded niosomes enhance retinal neuroprotection in ischemic injury

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“Cannabidiol (CBD) has emerged as a promising treatment for conditions like retinal ischemia, characterized by reduced blood flow to the retina and significant vision loss. Despite its therapeutic potential, CBD’s clinical application could be limited by due to its low bioavailability.

This study investigates the efficacy of CBD-loaded niosomes as a neuroprotective formulation for the use in ocular therapies related to retinal ischemia. We investigated the neuroprotective effects of CBD using a nanodispersed system (niosomes) administered via intravitreal injection in rats’ eyes.

Niosomes underwent characterization for size, distribution, zeta potential, morphology, and encapsulation efficiency. Safety and neuroprotective activity were assessed by electroretinography (ERG), confocal and transmission microscopy and histology. Niosomes exhibited nanometric size (100-400 nm) and stability, showing good tolerance in animals.

ERG results demonstrated higher b-wave amplitudes in animals pre-treated with niosomes + CBD compared to the control group following ischemic injury induced by a sudden increase in IOP. Histological and confocal microscopy analyses of retinas from the niosomes + CBD group showed preserved structure compared to the ischemic control group, suggesting significant retinal protection by intravitreally injected niosomes + CBD before ischemia. CBD-loaded niosomes effectively preserved retinal function, highlighting the neuroprotective potential of CBD against retinal ischemia.

This formulation presents a promising and innovative treatment for ischemic retinal diseases.”

https://pubmed.ncbi.nlm.nih.gov/40174680/

“Cannabidiol (CBD), a non-psychoactive compound derived from Cannabis sativa, shows promise in treating retinal ischemia due to its previously described combined anti-inflammatory and neuroprotective effects.”

“This study highlights the neuroprotective potential of CBD encapsulated in niosomes against retinal ischemia. Our findings indicate that pre-treatment with CBD-loaded niosomes effectively preserved retinal function, as demonstrated through histological, fluorescence, and electroretinography analyses.”

“CBD-loaded niosomes offer a new approach for treating ischemic retinal diseases.”

https://www.sciencedirect.com/science/article/abs/pii/S0939641125000827?via%3Dihub

Cannabidiol on aggression in betta fish (Betta splendens)

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“Cannabidiol (CBD) was first isolated in the 1940s and its drug structure was established in the 1960s. It has risen significantly in popularity since then and has been observed to reduce inflammation and anxiety in patients.

CBD is easy to obtain and consume, therefore, its common use is rising and has spread to use in pets and children. Few studies have focused on the use of CBD as a solution to aggression.

In our study, we tested if CBD is effective in reducing aggression in Siamese fighting fish (Betta splendens) induced by territorial interactions.

Betta fish were exposed to controls (water or acetone) and CBD treatments ranging from low, medium, and high (2, 10, and 20 mg CBD/L, respectively), and their behaviors after the visual introduction of an intruder fish were recorded. CBD reduced the odds of aggressive behavior in treated fish. Seventy-five percent of all control fish exhibited aggressive behaviors, while only 17% of CBD-treated fish displayed aggression.

Especially, the low CBD dose seemed effective at preventing aggressive behaviors but fish also appeared more lethargic than in any of the other treatments. However, when CBD-treated fish displayed aggressive behaviors, CBD did not appear to reduce the amount of time fish spent being aggressive compared to aggressive fish that did not receive any CBD treatment.

While the long-term effects of CBD still have to be examined, our study indicates that CBD might be effective in reducing aggression in Betta fish and potentially other pets.”

https://pubmed.ncbi.nlm.nih.gov/40172839/

Improvements in health-related quality of life are maintained long-term in patients prescribed medicinal cannabis in Australia: The QUEST Initiative 12-month follow-up observational study

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“Aims: Since 2016, more than one million new patients with chronic health conditions have been prescribed medicinal cannabis in Australia. We aimed to assess overall health-related quality of life (HRQL), pain, fatigue, sleep, anxiety, depression, and motor function in a large real-world sample of patients prescribed medicinal cannabis. We previously found all patient-reported outcomes improved in the first 3-months and hypothesised that improvements would be maintained to 12-months.

Methods: The QUEST Initiative, a multicentre prospective study, recruited adult patients with any chronic health condition newly prescribed medicinal cannabis oil between November 2020 and December 2021. Participants identified by 114 clinicians across Australia completed validated questionnaires at baseline, then 2-weeks titration, and 1-,2-,3-,5-,7-,9- and 12-months follow-up.

Results: Of 2744 consenting participants who completed baseline assessments, 2353 also completed at least one follow-up questionnaire and were included in analyses, with completion rates declining to 778/2353 (38%) at 12-months. Ages ranged between 18-97 years (mean 50.4y; SD = 15.4), 62.8% were female. Chronic conditions commonly treated included musculoskeletal pain (n = 896/2353; 38.1%), neuropathic pain (n = 547/2353; 23.2%), insomnia (n = 546/2353; 23.2%), anxiety (n = 520/2353; 22.1%), and mixed depressive and anxiety disorder (n = 263/2353; 11.2%). Clinically meaningful improvements were observed in HRQL: EQ-5D-5L index (d = 0.52) and QLQ-C30 summary scores (d = 0.91), PROMIS fatigue (d = 0.51) and sleep disturbance (d = 0.76). Participants diagnosed with chronic pain experienced clinically meaningful improvement in scores on QLQ-C30 pain (d = 0.5), PROMIS pain intensity (d = 0.76), and PROMIS pain interference (d = 0.76). There was significant improvement in DASS anxiety (d = 0.69) and DASS depression (d = 0.65) for those with anxiety or depressive conditions, but no motor function improvements observed for participants with movement disorders. All observed improvements were statistically significant.

Conclusions: Statistically significant and clinically meaningful improvements in overall HRQL, fatigue, and sleep disturbance were maintained over 12-months in patients prescribed medical cannabis for chronic health conditions. Anxiety, depression, insomnia, and pain also improved over time for those with corresponding health conditions.”

https://pubmed.ncbi.nlm.nih.gov/40173146/

https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0320756

Cannabinoid receptor deficiencies drive immune response dynamics in Salmonella infection

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“This study investigated the roles of cannabinoid receptors 1 and 2 (CB1R and CB2R) in regulating host responses to Salmonella Typhimurium in C57BL/6 mice.

The absence of both receptors significantly impaired host resilience, as evidenced by increased weight loss, deteriorated body condition, and reduced survival following infection.

Notably, CB1R deficiency resulted in more pronounced weight loss and heightened susceptibility to bacterial proliferation, as demonstrated by increased Salmonella dissemination to organs. In addition, both CB1R and CB2R knockout mice exhibited alterations in immune cell recruitment and cytokine production. CB1R-KO mice displayed increased T cell and macrophage populations, whereas CB2R-KO mice showed a reduction in NK cells, indicating receptor-specific effects on immune cell mobilization.

Cytokine profiling of macrophages post-infection revealed that CB1R-KO mice had reduced IL-10 levels, along with increased IL-6 and TGF-β, suggesting a dysregulated polarization state that combines pro-inflammatory and regulatory elements. In contrast, CB2R-KO mice exhibited a profile consistent with a more straightforward pro-inflammatory shift.

Furthermore, microbiota analysis demonstrated that CB2R-KO mice experienced significant gut dysbiosis, including reduced levels of beneficial Lactobacillus and Bifidobacterium species and an increase in pro-inflammatory Alistipes species post-infection. Functional microbiome analysis further indicated declines in key metabolic pathways, such as the Bifidobacterium shunt, L-glutamine biosynthesis, and L-lysine biosynthesis, suggesting microbiota-driven immune dysregulation.

Together, these findings highlight the distinct, non-redundant roles of CB1R and CB2R in modulating innate immunity, host defense, and microbiota composition during bacterial infections.

Significance statement: Understanding the role of cannabinoid receptors in immune regulation is important for identifying new therapeutic targets for bacterial infections. Our study demonstrates that CB1R and CB2R play distinct, non-redundant roles in host defense against Salmonella Typhimurium. The absence of these receptors impairs host resilience, increases bacterial dissemination, and alters immune cell recruitment and cytokine production. Notably, CB1R deficiency leads to enhanced weight loss, increased bacterial spread, and a dysregulated macrophage cytokine profile-characterized by reduced IL-10 and elevated IL-6 and TGF-β-while CB2R deficiency is associated with reduced NK cell numbers and a more pronounced pro-inflammatory cytokine profile. These findings reveal a receptor-specific balance in immune responses, suggesting that cannabinoid signaling modulates infection outcomes.

Targeting CB1R and CB2R pathways may offer novel strategies to enhance host immunity and improve treatments for bacterial infections in the future.”

https://pubmed.ncbi.nlm.nih.gov/40161677/

https://www.biorxiv.org/content/10.1101/2025.03.10.642352v1

[Real-life study with pharmaceutical cannabidiol in refractory epilepsy]

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“Pharmaceutical-grade cannabidiol (CBD) is an alternative treatment for patients with drug-resistant epilepsy (DRE). In 2022, the Italian Hospital of Buenos Aires implemented a non-medical change (NMC) of treatment, replacing one commercial pharmaceutical-grade CBD product with another, the latter also being the initial option for new patients.

Our objective was to evaluate the clinical outcomes of the commercial product change in this population.

Methods: Retrospective cohort of DRE patients who either switched from one commercial pharmaceutical-grade CBD product to another or started treatment with the new product. The clinical response was evaluated by changes in seizure frequency, perception of change with the Patient Global Impression of Change (PGIC) scale, and safety considering discontinuation and/or the presence of adverse effects.

Results: Nineteen patients were included, 12 in the change group and 7 in the new start group (7 pediatric and 12 adults). One patient discontinued treatment due to lack of response. Among those who completed follow-up, 8 (44%) reduced seizure frequency, 6 (33%) showed no change, and 4 (22%) increased seizure frequency. According to the PGIC scale, 9 (50%) remained unchanged, 5 (28%) reported barely noticeable changes, and 4 (22%) reported improvement. Adverse events were mild and transient.

Conclusion: The new commercial pharmaceutical-grade CBD product is a safe and valid option both for substitution and initial treatment in patients with DRE. During the treatment period, patients perceived stability or improvement according to the PGIC scale.”

https://pubmed.ncbi.nlm.nih.gov/40163830/

Cannabidiol and Its Effects on Patients with COVID-19 Infection

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“Background: The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) disease pathway is heavily influenced by different inflammatory cytokines. There is ample evidence of cannabidiol (CBD) immunomodulation effects.

Objectives: To investigate the effect of CBD on patients with SARS-CoV-2 and to measure the impact on inflammatory cytokines.

Methods: A double blind, placebo-controlled study to compare the clinical outcomes and selected serum cytokine levels in patients with SARS-CoV-2 that received sublingual CBD extraction. Seven patients were randomized to the treatment arm and three to the placebo group.

Results: Clinical outcomes were better in the patient group that received sublingual CBD vs. patients receiving placebo treatment. Serum cytokine mean concentration levels showed differences between the two groups but of mixed trends.

Conclusions: Patients presenting with SARS-CoV-2 and receiving CBD sublingually had better outcomes than those receiving a placebo, although these results did not reflect in selected serum cytokines. Further study is needed.”

https://pubmed.ncbi.nlm.nih.gov/40170643/

Cannabinoids in Chronic Pain Management: A Review of the History, Efficacy, Applications, and Risks

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“Background/Objectives: Chronic pain remains a pervasive and challenging public health issue, often resistant to conventional treatments such as opioids, which carry substantial risks of dependency and adverse effects. Cannabinoids, bioactive compounds derived from the Cannabis sativa plant and their synthetic analogs, have emerged as a potential alternative for pain management, leveraging their interaction with the endocannabinoid system to modulate pain and inflammation. 

Methods: The current, evolving literature regarding the history, efficacy, applications, and safety of cannabinoids in the treatment of chronic pain was reviewed and summarized to provide the most current review of cannabinoids. 

Results: Evidence suggests that cannabinoids provide moderate efficacy in managing neuropathic pain, fibromyalgia, cancer-related pain, and multiple sclerosis-related spasticity. Patient-reported outcomes further indicate widespread perceptions of cannabinoids as a safer alternative to opioids, with potential opioid-sparing effects. However, the quality of existing evidence is limited by small sample sizes and methodological inconsistencies. Regulatory barriers, including the classification of cannabis as a Schedule I substance in the United States, continue to hinder robust research and clinical integration. Moreover, the risks associated with cannabinoids, such as psychiatric effects, addiction potential, and drug interactions, necessitate cautious application. 

Conclusions: Cannabinoids represent a promising, albeit complex, alternative for chronic pain management, particularly given the limitations and risks of traditional therapies such as opioids. However, significant deficiencies remain in the research. While smaller trials and systematic reviews indicate therapeutic potential, the quality of evidence is often low due to limited sample sizes, short study durations, and methodological inconsistencies. Large-scale, randomized controlled trials with long-term follow-up are urgently needed to confirm efficacy and safety across diverse patient populations and pain etiologies.”

https://pubmed.ncbi.nlm.nih.gov/40149508/

“The future for cannabis research is bright, and as regulatory frameworks adapt to balance access and oversight, cannabinoids may transition from an experimental adjunct to a well-established option in chronic pain care, provided scientific rigor and evidence-based policymaking remain at the forefront.”

https://www.mdpi.com/2227-9059/13/3/530