Cannabidiol-Rich Cannabis sativa L. Extract Alleviates LPS-Induced Neuroinflammation Behavioral Alterations, and Astrocytic Bioenergetic Impairment in Male Mice

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“Neuroinflammation is a hallmark of various neurodegenerative disorders, yet effective treatments remain limited.

This study investigates the neuroprotective potential of a cannabidiol (CBD)-Rich Cannabis sativa L. (CS) extract in a lipopolysaccharide (LPS)-induced neuroinflammation mouse model.

The effects on anxiety-like behavior, cognitive function, and locomotor activity were assessed using behavioral tests (open field, elevated plus maze, novel object recognition, and Morris water maze). Antioxidant activity was measured by assaying glutathione (GSH) levels and lipid peroxidation by-products (TBARs). Anti-inflammatory properties were evaluated using quantitative reverse transcription polymerase chain reaction (QRt-PCR) for proinflammatory cytokines (IL-6 and TNF-α), glial fibrillary acidic protein (GFAP), and cannabinoid receptor 1 (CB1) mRNAs in the prefrontal cortex (PFC). Astrocytic bioenergetics were analyzed using extracellular flux assays. Additionally, computational inference with a deep learning approach was conducted to evaluate the synergistic interactions among CS phytocompounds on the CB1 receptors.

Compared with synthetic CBD, the CS extract (20.0 mg/kg) demonstrated superior efficacy in mitigating LPS-induced anxiety-like behavior, cognitive deficits, and locomotor impairments. It also significantly mitigated oxidative stress (increased GSH, reduced TBARs) and suppressed proinflammatory cytokines and GFAP mRNAs, indicating potent anti-inflammatory properties.

The extract modulated CB1 receptor expression and preserved metabolic homeostasis in cortical astrocytes, preventing their shift from glycolysis to oxidative phosphorylation under neuroinflammatory conditions. Computational modeling highlighted conformational changes in CB1 receptor residues induced by Delta-9-THC that enhanced CBD binding.

These findings underscore the potential of CS extract as a therapeutic candidate for managing neuroinflammation and its associated neurodegenerative consequences, warranting further clinical exploration.”

https://pubmed.ncbi.nlm.nih.gov/40195769/

https://onlinelibrary.wiley.com/doi/10.1002/jnr.70035

Effects of cannabinoids on immune checkpoint inhibitor response: CCTG pooled analysis of individual patient data

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“Background: Immune checkpoint inhibitors (ICIs) benefit patients across various tumor types. ICIs block cancer and T-cell interactions whereas cannabinoids may inhibit T-cell activation, reducing lysis of tumor cells. Interactions between cannabinoid use and dual ICI treatment remain unknown.

Methods: Individual patient data from 4 Canadian Cancer Trials Group (CCTG) trials of patients treated with dual ICI ± chemotherapy (n = 684) were pooled. Cochran – Mantel – Haenszel and log-rank tests (stratified by trial/treatment arms) correlated cannabinoid use with clinicopathologic characteristics, Best Overall Response (BOR)/iBOR per RECIST 1.1/iRECIST, Progression-Free Survival (PFS)/iPFS, Overall Survival (OS) and immune-related adverse events (irAEs).

Results: Sixty-five (9.5%) patients took cannabinoids at any time on trial, 32 (4.7%) of which were using cannabinoids at baseline. By multivariate analysis, cannabinoid use at baseline was significantly associated with improved iPFS (0.05), but not iBOR (p = 0.15), PFS (p = 0.12), OS (p = 0.35) or incidence of grade 1/2 or 3/4 irAEs (p = 0.96 and 0.65 respectively). Results were not significantly different with cannabinoid use at any time on trial.

Conclusion: Improved iPFS with cannabinoid use in patients treated with durvalumab plus tremelimumab ± chemotherapy did not translate into OS benefits. This study supports the safe use of cannabinoids in the context of combination ICI therapy.”

https://pubmed.ncbi.nlm.nih.gov/40184324/

“Plain Language Summary

Immune checkpoint inhibitors (ICI) have become an important treatment option for cancer patients and has been associated with improved survival outcomes across various tumor types. Cannabinoids are active components of cannabis and include tetrahydrocannabinol (THC) and cannabidiol (CBD). Cannabis use has increased in Canadian cancer patients and is often used for symptom management. Some studies have suggested that cannabinoids can alter the function of the immune system, which could impact the effectiveness of immune checkpoint inhibitors. Therefore, we aimed to evaluate whether cannabinoid use might impact the effectiveness of combination ICI treatment with durvalumab plus tremelimumab (with/without chemotherapy) using data from four clinical trials completed through the Canadian Cancer Trials Group (CCTG). We found no significant difference in response, survival outcomes or adverse events in patients who used cannabinoids with combination ICI treatment compared to cannabinoid non-users. This study supports the safe use of cannabinoids in the context of combination ICI therapy.”

https://www.tandfonline.com/doi/full/10.1080/1750743X.2025.2485012

Multifunctional cosmetic potential of extracellular vesicle‑like nanoparticles derived from the stem of Cannabis sativa in treating pigmentation disorders

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“While natural products and synthetic chemicals are used in functional cosmetics, their potential side effects remain a concern.

This has driven the need safer and more effective agents to treat skin disorders. Therefore, the present study aimed to explore the functional properties of Cannabis sativa stem‑derived nanoparticles (CSS‑NPs) and evaluate their potential as a cosmetic ingredient.

Using nanoparticle analysis, CSS‑NPs, with a mean diameter of ~120 nm exhibited notable resistance to external stress conditions, including pH fluctuation and enzymatic degradation by DNase, RNase and proteinase K. They also contained 48 distinct biochemical components. In vitro assays revealed that CSS‑NPs significantly downregulated the expression of genes and proteins associated with melanin synthesis in mouse B16F10 melanoma cells under α‑melanocyte stimulating hormone (α‑MSH)‑induced hyperpigmentation. These inhibitory effects were mediated by the activation of ERK and Akt signaling pathways. Furthermore, CSS‑NPs improved the viability of α‑MSH‑treated B16F10 cells; this was accompanied by the upregulation of antioxidant‑associated enzymes and a decrease in α‑MSH‑induced reactive oxygen species levels.

Collectively, these findings suggested that CSS‑NPs carry out a key role in mitigating skin pigmentation and enhancing antioxidant defenses by modulating the ERK/Akt axis during excessive melanin synthesis. Thus, CSS‑NPs represent a promising multifunctional cosmetic ingredient with potential in treating pigmentation disorders and protecting skin cells.”

https://pubmed.ncbi.nlm.nih.gov/40183388/

https://www.spandidos-publications.com/10.3892/mmr.2025.13512

Characterizing the Population of a Medical Cannabis Clinic in a Pediatric Hospital

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“Background: Medical cannabis (MC) is increasingly in use due to recent cultural and political changes. Other than patients with Lennox-Gastaut and Dravet syndrome, there is inadequate literature to provide evidence-based support for prescribing MC in pediatric patients. 

Objectives: Characterize the population receiving an MC recommendation in an ambulatory pediatric palliative care setting and quantify patient/family-reported outcomes. 

Design: Retrospective chart review of electronic medical record (EMR) data. Setting/Subjects: Total n = 46 consecutive patients receiving medical advice regarding MC (n = 42) in a specialized ambulatory clinic embedded in a palliative care division and n = 4 inpatient in a midwestern U.S. hospital between 2019 and 2022. Measurements: Demographics, diagnosis, symptoms, adverse reactions, patient-reported outcomes, and barriers abstracted from EMR. 

Results: Our sample included 46 palliative care patients with a mean age of 11.7 years (SD 5.4); 50% had a neurological diagnosis (n = 25); 37% (n = 14) hematological/oncologic; and 13% (n = 6), chronic pain. The most common type of MC recommended was 1:1 Cannabidiol (CBD): tetrahydrocannabinol (THC) tincture. There was a statistically significant decrease in inpatient floor days and cost. Totally, 35% of patients were able to decrease or discontinue other medications. Thematic analysis identified four barriers to use (product unavailable, difficulty obtaining state MC card, cost, and organizational) and subjective symptom improvement. 

Conclusions: These data characterize the palliative care MC clinic population at our pediatric hospital. Positive outcomes were noted across several symptom domains. MC seems to be associated with lower health care utilization, reduced polypharmacy, and increased quality of life and was used without significant adverse events. In a value-conscious health care environment, the data warrant further exploration.”

https://pubmed.ncbi.nlm.nih.gov/40180570/

https://www.liebertpub.com/doi/10.1089/jpm.2024.0533

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