The quest for innovative and effective treatments for rare childhood neurological disorders drove the beginning of the use of cannabis-based medications in children. Currently, refractory epilepsy is the best-studied application of cannabidiol (CBD), with results nothing short of life-changing.

The history of CBD’s application in pediatric neurology faced pivotal moments that have shaped its path. In the early 1970s, Israeli researcher Dr. Raphael Mechoulam, renowned for his work in cannabis research, joined forces with Brazilian scientist Dr. Elisaldo Carlini. Together, they conducted groundbreaking research into the anti-seizure properties of CBD. Their collaborative efforts yielded early insights into CBD’s potential as an anticonvulsant agent, setting the stage for further investigations.

A poignant chapter in this journey is the story of Charlotte Figi, a young girl whose battle with Dravet syndrome – a severe and rare form of pediatric epilepsy – resonated with the world. Charlotte’s remarkable response to CBD treatment (she went from having hundreds of seizures a week to a few episodes a month)  became a symbol of hope and a catalyst for further research. Her story served as a stark reminder of the need for rigorous scientific investigation into the efficacy and safety of CBD as a potential treatment for these conditions.

In 2018, the FDA gave Epidiolex, a pharmaceutical-grade CBD formulation, the green light for managing seizures in children with Dravet syndrome, Lennox-Gastaut syndrome, and tuberous sclerosis complex. Clinical trials of Epidiolex demonstrated a significant reduction in monthly seizures compared to placebo groups, with minimal adverse effects reported. This approval signifies a leap forward in cannabis-based treatments and lays the groundwork for further investigation into its potential in neurology.

Research has continued to demonstrate the efficacy of cannabis for these conditions. A 2023 systematic review and meta-analysis demonstrated that CBD is highly efficacious both as standalone and adjunct therapy with clobazam for controlling seizures in DS, LGS, and TSC conditions while limiting side effects.

The mechanisms underlying the reduction in seizure activity in these neuro-syndromes after CBD treatment are still not completely understood, though they are likely multifactorial. It is widely accepted that the endocannabinoid system plays a vital role in the development and well-being of the nervous system. Studies have shown that there are various signaling pathways that involve neurotransmitters and the endocannabinoid system, through which cannabinoids may exert therapeutic effects. Further pharmacodynamic investigation of cannabis-derived drug actions, drug interaction assessments, and therapeutic management guidelines are warranted.

Beyond seizure control, research has elucidated cannabis’ broader spectrum of benefits for children.

Researchers are exploring various neurological targets in children that can be treated with cannabis, with a focus on CBD. Studies suggest that CBD has significant efficacy as an anti-inflammatory, antipsychotic, neuroprotector, antidepressant, analgesic, and even as an antioxidant. The existing research indicates several possible ways CBD interacts with the brain to bring about therapeutic changes. Clinical trials and preclinical studies are underway to provide crucial answers for the proper use of cannabis in a clinical setting for young patients.

An open-label trial suggested that CBD may have additional beneficial effects on patient quality of life, distinct from its seizure-reducing properties. This paralleled a review of children with severe epilepsies treated with artisanal CBD preparations, where a majority reported improved mood, behavior, language, alertness, and sleep.

Autism Spectrum Disorder (ASD) is of particular focus. The endocannabinoid system (ECS) has a key role in neurodevelopment as well as in normal inflammatory responses, and it is not surprising that many preclinical and clinical studies account for alterations of the endocannabinoid signaling in ASD. Research has shown that phytocannabinoids might be effective in reducing some of the symptoms of ASD, such as difficulty with social interaction and communication, hyperactivity, anxiety, and sleeping disorders. Studies have demonstrated significant improvement in behavior and symptoms in patients using medicinal cannabis, with 61-93% of participants experiencing benefits. These findings open new avenues of exploration for enhancing the lives of children with ASD.

Cannabis has shown promise in treating other pathologies in pediatric patients, including Fragile X syndrome, Tourette’s syndrome, Fetal Alcohol Spectrum Disorder, Epidermolysis bullosa, and anxiety. Ongoing trials and investigations indicate CBD’s multifaceted potential in managing these conditions. For example, CBD may help alleviate anxiety symptoms in children while also improving their cognitive function and reducing their levels of hyperactivity. Similarly, CBD can effectively reduce tics and other behavioral symptoms associated with Tourette’s syndrome. Additionally, CBD has shown potential in improving the social and communication skills of children with Fragile X syndrome. These findings suggest that cannabis may be a valuable treatment option for a wide range of pediatric neurological conditions.

As the journey unfolds, CBD research not only offers potential benefits but also necessitates a close examination of safety and long-term usage. Therefore, ongoing research is imperative.

In the world of pediatric neurology, the cannabis journey is one of collaboration, resilience, and hope. From the pioneering work of Dr. Mechoulam and Dr. Carlini to the approval of Epidiolex and the expanding horizons in treating various conditions, the story continues to evolve, offering a brighter future for children facing rare and challenging disorders.

References:

• Anderson, C. L., & Carney, P. R. (2021). Cannabidiol – A new fixture in childhood neurology. Current Opinion in Pharmacology, 61, 142–146. https://doi.org/10.1016/J.COPH.2021.10.002
• Aran, A., Cassuto, H., Lubotzky, A., Wattad, N., & Hazan, E. (2019). Brief Report: Cannabidiol-Rich Cannabis in Children with Autism Spectrum Disorder and Severe Behavioral Problems—A Retrospective Feasibility Study. Journal of Autism and Developmental Disorders, 49(3), 1284–1288. https://doi.org/10.1007/S10803-018-3808-2
• Bar-Lev Schleider, L., Mechoulam, R., Saban, N., Meiri, G., & Novack, V. (2019). Real life Experience of Medical Cannabis Treatment in Autism: Analysis of Safety and Efficacy. Scientific Reports, 9(1). https://doi.org/10.1038/S41598-018-37570-Y
• Barchel, D., Stolar, O., De-Haan, T., Ziv-Baran, T., Saban, N., Fuchs, D. O., … Berkovitch, M. (2019). Oral cannabidiol use in children with autism spectrum disorder to treat related symptoms and Co-morbidities. Frontiers in Pharmacology, 9(JAN). https://doi.org/10.3389/FPHAR.2018.01521
• da Silva Rodrigues, D., Santos Bastos Soares, A., & Dizioli Franco Bueno, C. (2023). The use of cannabinoids in children with epilepsy: A systematic review. Epilepsy & Behavior : E&B, 145. https://doi.org/10.1016/J.YEBEH.2023.109330
• Efron, D., & Freeman, J. (2018). Medical cannabis for paediatric developmental–behavioural and psychiatric disorders. Journal of Paediatrics and Child Health, 54(7), 715–717. https://doi.org/10.1111/JPC.13902
• Efron, D., & Taylor, K. (2023). Medicinal Cannabis for Paediatric Developmental, Behavioural and Mental Health Disorders. International Journal of Environmental Research and Public Health, 20(8). https://doi.org/10.3390/IJERPH20085430/S1
• Efron, D., Taylor, K., Payne, J. M., Freeman, J. L., Cranswick, N., Mulraney, M., … Williams, K. (n.d.). Does cannabidiol reduce severe behavioural problems in children with intellectual disability? Study protocol for a pilot single-site phase I/II randomised placebo controlled trial. https://doi.org/10.1136/bmjopen-2019-034362
• Elliott, J., DeJean, D., Clifford, T., Coyle, D., Potter, B. K., Skidmore, B., … Wells, G. A. (2019). Cannabis-based products for pediatric epilepsy: A systematic review. Epilepsia, 60(1), 6–19. https://doi.org/10.1111/EPI.14608
• Fletcher, S., Pawliuk, C., Ip, A., Huh, L., Rassekh, S. R., Oberlander, T. F., & Siden, H. (2022). Medicinal cannabis in children and adolescents with autism spectrum disorder: A scoping review. Child: Care, Health and Development, 48(1), 33–44. https://doi.org/10.1111/CCH.12909
• Kwan Cheung, K. A., Mitchell, M. D., & Heussler, H. S. (2021). Cannabidiol and Neurodevelopmental Disorders in Children. Frontiers in Psychiatry, 12, 643442. https://doi.org/10.3389/FPSYT.2021.643442
• Pawliuk, C., Chau, B., Rassekh, S. R., McKellar, T., & Siden, H. (2021). Efficacy and safety of paediatric medicinal cannabis use: A scoping review. Paediatrics & Child Health, 26(4), 228–233. https://doi.org/10.1093/PCH/PXAA031
  Treves, N., Mor, N., Allegaert, K., Bassalov, H., Berkovitch, M., Stolar, O. E., & Matok, I. (123AD). Efficacy and safety of medical cannabinoids in children: a systematic review and meta-analysis. Scientific Reports |, 11, 23462. https://doi.org/10.1038/s41598-021-02770-6