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Official websites use. Share sensitive information only on official, secure websites. Mezzanine Jl. Iskandarsyah Raya No. This is an Open Access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. 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. 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. Of identified articles, only three met the inclusion criteria for data synthesis. One study exhibited a moderate risk-of-bias. A total of respondents, mainly from Europe, were investigated. Overall effectiveness and safety were considered good. However, the results are inconsistent, especially regarding spasticity treatment variables. 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. Prospero database registration: www. Complex movement disorders are a heterogeneous group of neurological disorders characterized by different types of abnormal movements and postures, including spasticity and dystonia. These abnormal movements and postures are generally associated with severe orthopedic problems, chronic pain, eating difficulties, constipation, sleep disturbances, epilepsy, and a poor quality of life. The estimated prevalence is 2—3 per 1, live births. Cannabinoid-based therapies have been investigated for the treatment of various neurological disorders, particularly drug-resistant epilepsy and movement disorders. Cannabinoid-based drugs, phytocannabinoids, and synthetic cannabinoids have multiple mechanisms of action including interactions with endocannabinoid receptors. Cannabidiol may also complement the anti-spasmodic effects of THC e. Synthetic cannabinoids, such as nabilone, dronabinol, and Sativex, are cannabinoid receptor agonists with effects similar to those of THC. They have been approved for clinical indications including spasticity, pain, and refractory epilepsy. This systematic review aimed to assess the efficacy and safety of medical cannabinoids in children with CP. The search terms used in each database are listed in Appendix 1 42KB, pdf. No time restrictions were imposed on the literature search. Manual search was also conducted by examining the citations of selected articles to identify relevant publications that were not indexed in the aforementioned databases. Studies examining pediatric patients with CP and reporting the efficacy and safety of medical cannabinoids through clinical trials, observational cross-sectional studies, or cohort designs were included. Systematic reviews, meta-analyses, narrative reviews, case reports, case series, opinion pieces, conference abstracts, and grey literature were excluded. The titles and abstracts of unique studies were independently screened using Rayyan QCRI, an online software used for abstract and title screening. Full-text articles were obtained and two reviewers independently conducted eligibility assessments. No reviewers were blinded to the bibliographic information of the studies. Cerebral palsy should be assessed using validated tests and internationally standardized diagnostic criteria. Several tools were used to assess the risk-of-bias based on the study type. The tool can be assigned for the following areas: i entanglement bias, ii study participant selection bias, iii exposure measurement bias, iv exposure misclassification bias during follow-up, v bias in outcome measurement, vi bias in missing data, and vii bias in the selection of the results. The risk-of-bias was assessed on 0—4 scale points following the severity of the bias risk. The randomized studies used the RoB-2 tool. The five following domains were assessed: i randomization, ii deviation from the intended intervention, iii outcome measures, iv missing outcome data, and v selection from reported outcomes. The following five domains were assessed: i representative population, ii adequate response rate, iii missing data, iv clinically sound, and v reliability and validity of the survey instrument. Two reviewers independently assessed the risk-of-bias and the strength of evidence in all relevant studies. Any disagreements between the two researchers were resolved through consultation with a third researcher. The authors of this article did not conduct human or animal studies. Therefore, ethical approval was not required. Therefore, patient and publication consent was not required. The search strategy yielded articles, of which the titles and abstracts of unique articles were evaluated for eligibility after deduplication. A total of articles were considered ineligible and were excluded in the first screening phase. The full texts of the remaining 74 articles were reviewed to assess their eligibility for inclusion and 71 articles were excluded. Three studies met the inclusion criteria for data synthesis Figure 1. Table 1 presents the characteristics of the included studies. This systematic review included three research projects, one of which was an observational study and two were experimental studies RCT and non-RCT. There were respondents range: 19—70 participants. Each study included a European population. Only two studies provided information on the average age of participants and duration of treatment, with a mean ages of All studies used various cannabinoid substances and administration methods. Fairhurst et al. The medications were administered orally or sublingually for 12 weeks. Meanwhile, Libzon et al. Furthermore, an observational study by Morosoli et al. The effects of medical cannabis on patient complaints varied. In contrast, Libzon et al. Along with pain duration and frequency, pain intensity decreased, as evidenced by an improvement in the visual analog scale VAS score. Meanwhile, Morosoli et al. Medical cannabis is particularly safe for pediatric patients with CP. The adverse events were mild-to-moderate, with no long-term consequences. Serious adverse events included changes in seizure characteristics, 11 , 12 disorientation, euphoria, hypotonia, distress, hallucinations, psychotic symptoms, food aversion, elevated liver enzymes, and viral upper respiratory tract infections. The overall risk-of-bias was moderate-to-low. The moderate results in the study by Morosoli et al. This was not observed in the other included studies. The risk-of-bias assessment is shown in figure 2. Reports on the benefits of medical cannabis are increasing. Despite the controversy over its safety and efficacy, studies have suggested that cannabis may have the therapeutic potential to improve several disorders, including neurological diseases. However, concerns regarding the adverse effects of cannabis have emerged. Non-serious adverse effects may occur even before cannabis initiation. Cannabis plants contain more than known cannabinoid compounds. Cerebral palsy refers to a set of persistent movements and postural disorders that restrict activity and is caused by non-progressive disruptions in the developing brain. It is primarily related to movement disorders the basis of CP , musculoskeletal problems, and repeated exposure to painful procedures, including surgery. The effect of cannabinoid administration in patients with CP is uncertain despite its high potential. CB1 is found in the central nervous system and peripheral tissues, whereas CB2 is mainly found in the immune cells. They are also abundant in brain areas associated with nociceptive perception, such as the thalamus and amygdala. Cannabinoids presynaptically hinder glutamate release. Several animal studies have identified CB1 as a receptor that modulates the anti-spasticity effects of cannabinoids. These substances exhibit low toxicity and high tolerability. Considering the synergistic relationship between seizures and inflammation, the cannabinoid system offers a novel strategy for targeting both sectors of this feedback mechanism. Cannabidiol may exert anti-seizure effects by reducing glutamate release. CBD also minimizes epileptiform events in the hippocampus in an in vitro model in a CB1-independent, concentration-dependent, and region-specific manner. This systematic review has some limitations. The number of studies included in this systematic review was limited to those with different study designs. Of the three studies, only one was an RCT. The small sample sizes of the included studies may not represent real-world efficacy and safety. In addition, the study focused mainly on the European population, making generalizability challenging to achieve. Cannabinoids may be beneficial in patients with cerebral palsy; however, their effectiveness has yet to be thoroughly studied. The proposed modes of action of cannabinoids in cerebral palsy include anti-spasticity, anti-inflammatory, and anti-seizure features. Although mild-to-moderate adverse events have been reported, there have been no reports of long-term adverse events, indicating a favorable safety profile. Further research with a larger sample size, extended study period, and individuals of various ethnicities is required to determine the role of cannabinoids in cerebral palsy. As a library, NLM provides access to scientific literature. Einstein Sao Paulo. Find articles by Widya Murni. Find articles by Tungki Pratama Umar. Find articles by Kevin Tandarto. Find articles by Abraham Simatupang. Find articles by Armedy Ronny Hasugian. Find articles by Reza Yuridian Purwoko. Find articles by Sri Idaiani. Find articles by Bella Stevanny. Find articles by Caroline Oktarina. Find articles by Reganedgary Jonlean. Find articles by Tamara Tango. Find articles by Kevin Surya Kusuma. Find articles by Sagita Pratiwi Sugiyono. Find articles by Aditya Putra. Widya Murni : conceptualized a research project, The corresponding author ensured accuracy and agreement. Tungki Pratama Umar : handled methodology, software, data, and played a key role in writing and visualization. Kevin Tandarto : curated data and contributed to writing. Abraham Simatupang : supervised and investigated. Armedy Ronny Hasugian : conceptualized a research project. Reza Yuridian Purwoko : supervised and conceptualized. Sri Idaiani : validated. Bella Stevanny : validated, wrote, and edited. Caroline Oktarina : engaged in formal analysis. Reganedgary Jonlean : engaged in formal analysis. Tamara Tango : engaged in formal analysis. Kevin Surya Kusuma : provided resources. Sagita Pratiwi Sugiyono : performed thorough reviews. Aditya Putra : performed thorough reviews. Received Nov 17; Accepted Mar 19; Collection date PMC Copyright notice. Open in a new tab. VAS score improved in addition to pain duration, frequency, and dystonia. Adverse effects were rarely reported including seizure deterioration. There were no changes in ECG or blood tests Morosoli et. No long-term side effects are witnessed. Similar articles. Add to Collections. Create a new collection. Add to an existing collection. Choose a collection Unable to load your collection due to an error Please try again. Add Cancel. Fairhurst et. Libzon et. NRS for spasticity improved from baseline in the entire study population regardless of treatment assignment. There were no changes in ECG or blood tests. Morosoli et. Medical cannabinoids including cannabis oil, dronabinol solution, cannabis tincture, and cannabis spray.
Efficacy and safety of medical cannabinoids in children with cerebral palsy: a systematic review
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Efficacy and safety of medical cannabinoids in children with cerebral palsy: a systematic review
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Efficacy and safety of medical cannabinoids in children with cerebral palsy: a systematic review
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