Category Archives: Cerebral palsy

A Balanced Cannabinoids Mixture Protects Neural Stem/progenitor Cells from CoCl2 Induced Injury by Regulating Autophagy and Inflammation: An in Vitro Study

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“Although tetrahydrocannabinol (THC) and cannabidiol (CBD) have been individually studied for their neuroprotective roles, few studies have addressed the effects of their balanced 1:1 formulation Satinex (STX) under pathologic conditions like hypoxia. Moreover, the effect of STX on embryonic neural stem/progenitor cells (ENS/PCs) derived from the rat embryonic brain, which are highly vulnerable during early development, remains unexplored.

Considering the pivotal role of hypoxia in numerous neuropathological situations, this study examined the impact of STX on rat ENS/PCs exposed to chemically induced hypoxia.

ENS/PCs were isolated from rat embryos and subjected to hypoxia using 100 µM cobalt (II) chloride hexahydrate (CoCl₂0.6 H₂O) for 48 h. Cytotoxic activity of STX andCoCl2was assessed using the 3-(4,5-Dimethyl-2-thiazolyl)-2,5-diphenyl-2 H-tetrazolium (MTT) assay, while stem cell identity was confirmed via flow cytometry (Nestin, SOX2). STX (0.1 and 0.5 µM) was applied under both normoxic and hypoxic conditions. Expression levels of hypoxia-inducible factor 1-alpha (Hif1α) mRNA, autophagy markers (Beclin-1, microtubule-associated protein 1 light chain 3-II [LC3-II]), and pro-inflammatory proteins nuclear factor kappa B [NF-κB], Toll-like receptor 2 [TLR2], Toll-like receptor 4 [TLR4]) were assessed using reverse transcription polymerase chain reaction (RT-PCR) and western blot techniques following STX treatment.

Based on flow cytometric assays, over 70% of cultivated cells were positive for Nestin and SOX2. Hypoxia significantly reduced cell viability and proliferation, accompanied by increased Hif1α mRNA expression. Treatment with STX (0.1 µM and 0.5 µM) significantly reversed these changes, restoring cell viability and proliferation while reducing Hif1α levels. Hypoxia also elevated autophagy markers (Beclin-1, LC3-II) and pro-inflammatory proteins (NF-κB, TLR2, TLR4), which STX suppressed in a dose-dependent manner.

This study provides novel evidence that STX mitigates hypoxia-induced neural damage by downregulating Hif1α and its downstream inflammatory and autophagic signaling pathways. The use of a clinically relevant cannabinoids mixture and a developmentally sensitive cell model underline the translational potential of balanced THC/CBD formulations in the treatment of hypoxia-related neurodegenerative and neurodevelopmental conditions.”

https://pubmed.ncbi.nlm.nih.gov/41240218

https://link.springer.com/article/10.1007/s12640-025-00770-2

CB1 Receptors In NG2 CELLS MEDIATE CANNABINOID-EVOKED FUNCTIONAL MYELIN REGENERATION

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“Defects in myelin homeostasis have been reported in many neuropathological conditions. Cannabinoid compounds have been shown to efficiently promote myelin regeneration in animal models of demyelination. However, it is still unknown whether this action relies mostly on a cell autonomous effect on oligodendroglial-lineage-NG2 cells.

By using conditional genetic mouse models, here we found that cannabinoid CB1 receptors located on NG2 cells are required for oligodendroglial differentiation and myelin regeneration after demyelination. Selective CB1 receptor gene depletion in NG2 cells following toxin-induced demyelination disrupted oligodendrocyte regeneration and functional remyelination and exacerbated axonal damage. These deficits were rescued by pharmacological blockade of the RhoA/ROCK/Cofilin pathway.

Conversely, tetrahydrocannabinol administration promoted oligodendrocyte regeneration and functional remyelination in wild-type but not Ng2-CB1-deficient mice.

Overall, this study identifies CB1 receptors as essential modulators of remyelination and support the therapeutic potential of cannabinoids for promoting remyelination in neurological disorders.”

https://pubmed.ncbi.nlm.nih.gov/39528076/

“Cannabinoids have been shown to modulate myelin development and regeneration in mice. Here, using OPC-specific reporter mouse lines in combination with models of toxin-induced demyelination, we found that CB1 receptors located on NG2 cells, by modulating RhoA/ROCK/cofilin and mTORC1 signaling in a coordinated manner, exert an essential function in controlling NG2 cell differentiation, OL regeneration, myelin regeneration and functional recovery following demyelination, thus supporting the therapeutic potential of cannabinoids for promoting remyelination in neurological disorders.”

https://www.sciencedirect.com/science/article/abs/pii/S0301008224001199?via%3Dihub

Purified cannabidiol as add-on therapy in children with treatment-resistant infantile epileptic spasms syndrome

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“Objective: The aim of this study was to assess efficacy, safety, and tolerability of highly purified cannabidiol oil (CBD) as add-on therapy for the treatment of a series of patients with infantile epileptic spasms syndrome (IESS) who were resistant to antiseizure medications and ketogenic dietary therapy.

Material and methods: We conducted a retrospective analysis of the medical records of 28 infants with treatment-resistant IESS aged 6 to 21 months who received highly purified CBD between July 2021 and June 2023. Data were collected on neurological examinations, EEG, Video-EEG and polygraphic recordings, imaging studies, laboratory testing, and seizure frequency, type, and duration, and adverse effects. As the primary outcome, a reduction of frequency of epileptic spasms (ES) was assessed. ES freedom was considered after a minimal time of 1 month without ES.

Results: Sixteen male and 12 female patients, aged 6-21 months, who received CBD for treatment-resistant IESS were included. The etiology was structural in 10, Down syndrome in seven, genetic in nine, and unknown in two. Initial CBD dose was 2 mg/kg/day, which was uptitrated to a median dose of 25 mg/kg/day (range, 2-50). Prior to CBD initiation, patients had a median of 69 ES in clusters per day (range, 41-75) and of 10 focal seizures per week (range, 7-13). After a mean and median follow-up of 15 and 12.5 months (range, 6-26 months), seven patients were ES free and 12 had a >50 % ES reduction. Five of seven patients (71 %) with Down syndrome and 3/5 (60 %) with cerebral palsy responded well. Adverse effects were mild. EEG improvements correlated with ES reductions.

Conclusion: In this study evaluating the use of CBD in children with IESS, 19/28 (67.8 %) had a more than 50 % ES reduction with good tolerability.”

https://pubmed.ncbi.nlm.nih.gov/38237316/

https://www.seizure-journal.com/article/S1059-1311(24)00018-9/fulltext

Efficacy and safety of medical cannabinoids in children with cerebral palsy: a systematic review

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“Introduction: The increasing popularity of cannabinoids for treating numerous neurological disorders has been reported in various countries. Although it reduces tetrahydrocannabinol psychoactivity, it helps patients tolerate higher doses and complements the anti-spasmodic effects of tetrahydrocannabinol. One of the most important potential of cannabinoids are related to its potential to help children with cerebral palsy, a contributor of lifelong disability. Therefore, this systematic review aimed to assess the efficacy and safety of medical cannabinoids in children with cerebral palsy.

Methods: This review adhered to The Preferred Reporting Items for Systematic Reviews and Meta-analysis 2020 guidelines. Seven databases, namely, Scopus, PubMed, EBSCO Host, ProQuest, Google Scholar, Semantic Scholar, and JSTOR, were used to identify relevant studies. Studies examining pediatric patients with cerebral palsy and reporting the efficacy and safety of medical cannabinoids through clinical trials, observational cross-sectional studies, or cohort designs were included. The outcomes of the studies included the efficacy of medical cannabinoids administered for spasticity, motor components, pain control, sleep difficulties, adverse effects, and seizure control.

Results: Of 803 identified articles, only three met the inclusion criteria for data synthesis. One study exhibited a moderate risk-of-bias. A total of 133 respondents, mainly from Europe, were investigated. Overall effectiveness and safety were considered good. However, the results are inconsistent, especially regarding spasticity treatment variables.

Conclusion: The anti-spasticity, anti-inflammatory, and anti-seizure properties of cannabinoids might be beneficial for patients with cerebral palsy, although their effectiveness has not been widely studied. Further studies with larger sample sizes and various ethnicities are warranted.”

https://pubmed.ncbi.nlm.nih.gov/37991091/

https://journal.einstein.br/article/efficacy-and-safety-of-medical-cannabinoids-in-children-with-cerebral-palsy-a-systematic-review/

Cannabidiol Use Patterns and Efficacy for Children Who Have Cerebral Palsy

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“Cannabidiol (CBD)-containing supplements are used by children with cerebral palsy (CP), but the prevalence and efficacy of their use have not been studied. We sought to describe CBD use patterns and perceived efficacy in the pediatric population with CP, evaluating any association between CBD use and health-related quality of life. Patients with CP were prospectively enrolled, and caregivers were offered the Caregiver Priorities and Child Health Index of Life with Disabilities (CPCHILD) Questionnaire and a survey assessing CBD use. Of 119 participants, 20 (16.8%) endorsed CBD use (CBD+) and 99 (83.2%) denied it (CBD-). Participants in the CBD+ group had worse functional status (85% Gross Motor Function Classification System level IV-V for CBD+ vs 37.4% for CBD-, P<.001) and lower health-related quality of life (mean CPCHILD score of 49.3 for CBD+ vs 62.2 for CBD-, P=.001). Spasticity was the rationale most cited for CBD use (29%), followed by pain and anxiety (both 22.6%). CBD was perceived to be most effective for improving emotional health, spasticity, and pain. Fifty percent of the patients in the CBD+ group underwent surgery in the previous 2 years and most endorsed a general benefit in the postoperative setting. The most common side effects noted were fatigue and increased appetite (both 12%). Most participants endorsed no side effects (60%). CBD may serve as a useful adjunct for some children with CP, especially those with worse disease severity. Caregivers perceive CBD as offering some benefits, particularly in the domains of emotional health, spasticity, and pain. We found no evidence of severe adverse events in our small cohort.”

https://pubmed.ncbi.nlm.nih.gov/37216564/

https://journals.healio.com/doi/10.3928/01477447-20230517-06

The Endocannabinoid System: A Potential Target for the Treatment of Various Diseases

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ijms-logo“The Endocannabinoid System (ECS) is primarily responsible for maintaining homeostasis, a balance in internal environment (temperature, mood, and immune system) and energy input and output in living, biological systems.

In addition to regulating physiological processes, the ECS directly influences anxiety, feeding behaviour/appetite, emotional behaviour, depression, nervous functions, neurogenesis, neuroprotection, reward, cognition, learning, memory, pain sensation, fertility, pregnancy, and pre-and post-natal development.

The ECS is also involved in several pathophysiological diseases such as cancer, cardiovascular diseases, and neurodegenerative diseases. In recent years, genetic and pharmacological manipulation of the ECS has gained significant interest in medicine, research, and drug discovery and development.

The distribution of the components of the ECS system throughout the body, and the physiological/pathophysiological role of the ECS-signalling pathways in many diseases, all offer promising opportunities for the development of novel cannabinergic, cannabimimetic, and cannabinoid-based therapeutic drugs that genetically or pharmacologically modulate the ECS via inhibition of metabolic pathways and/or agonism or antagonism of the receptors of the ECS. This modulation results in the differential expression/activity of the components of the ECS that may be beneficial in the treatment of a number of diseases.

This manuscript in-depth review will investigate the potential of the ECS in the treatment of various diseases, and to put forth the suggestion that many of these secondary metabolites of Cannabis sativa L. (hereafter referred to as “C. sativa L.” or “medical cannabis”), may also have potential as lead compounds in the development of cannabinoid-based pharmaceuticals for a variety of diseases.”

https://pubmed.ncbi.nlm.nih.gov/34502379/

https://www.mdpi.com/1422-0067/22/17/9472

“Cannabis sativa L. as a Natural Drug Meeting the Criteria of a Multitarget Approach to Treatment”

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7830475/

Cannabidiol Administration Prevents Hypoxia-Ischemia-Induced Hypomyelination in Newborn Rats.

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Image result for frontiers in pharmacology“Neonatal hypoxia-ischemia (HI) is a risk factor for myelination disturbances, a key factor for cerebral palsy.

Cannabidiol (CBD) protects neurons and glial cells after HI insult in newborn animals.

We hereby aimed to study CBD’s effects on long-lasting HI-induced myelination deficits in newborn rats.

In conclusion, HI injury in newborn rats resulted in long-lasting myelination disturbance, associated with functional impairment. CBD treatment preserved function and myelination, likely as a part of a general neuroprotective effect.”

https://www.ncbi.nlm.nih.gov/pubmed/31611802

“In conclusion, our study confirms that a HI insult in rats at a brain developmental stage equivalent to term infants leads to long-lasting myelination disturbance which is directly related to long-term functional disturbances. The administration of CBD single dose after the neonatal HI insult protects the maturational process of OL cells, as well as the mOL function and relationship with axons, thus, preserving normal myelination and restoring neurobehavioral function. Those results open exciting perspectives regarding a possible role for CBD in NHIE and other demyelinating pediatric conditions.”

https://www.frontiersin.org/articles/10.3389/fphar.2019.01131/full

Treatment of human spasticity with delta 9-tetrahydrocannabinol.

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Image result for J Clin Pharmacol. “Spasticity is a common neurologic condition in patients with multiple sclerosis, stroke, cerebral palsy or an injured spinal cord. Animal studies suggest that THC has an inhibitory effect on polysynaptic reflexes. Some spastic patients claim improvement after inhaling cannabis. We tested muscle tone, reflexes, strength and performed EMGs before and after double-blinded oral administration of either 10 or 5 mg THC or placebo. 10 mg THC significantly reduced spasticity by clinical measurement (P less than 0.01). Responses varied, but benefit was seen in three of three patients with “tonic spasms.””
 https://www.ncbi.nlm.nih.gov/pubmed/6271839
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