Could Cannabidiol be a Treatment Option for Intractable Childhood and Adolescent Epilepsy?

Koo, Chung Mo; Kang, Hoon Chul

doi:10.14581/jer.17003

Cited by 18 publications

(14 citation statements)

References 29 publications

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“…Adverse reactions were reported in 199 children and young adults treated with 2-5 mg/kg/day CBD for uncontrolled seizures [72] and in 424 children and young adults treated with 0.5-50 mg/kg/day CBD for refractory epilepsy [73]. The most common AEs were drowsiness, somnolence, and fatigue.…”

Section: Changes In Behaviormentioning

confidence: 99%

“…In a CBD trial on Dravet's syndrome, 120 children and young adults were randomly receiving 20 mg/kg/day oral CBD or placebo for 14 weeks, AEs included diarrhea (31% vs 10%), loss of appetite (28% vs. 5%), and much less commonly vomiting [71]. Diarrhea and weight and appetite loss were also reported in 199 children and young adults treated with 2-5 mg/kg/day CBD for uncontrolled seizures [72], and in 424 children and young adults treated with 0.5-50 mg/kg/day CBD for refractory epilepsy [73].…”

Section: Gastrointestinal Effectsmentioning

confidence: 99%

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Cannabidiol Adverse Effects and Toxicity

et al. 2019

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Background: Currently, there is a great interest in the potential medical use of cannabidiol (CBD), a non-intoxicating cannabinoid. Productive pharmacological research on CBD occurred in the 1970s and intensified recently with many discoveries about the endocannabinoid system. Multiple preclinical and clinical studies led to FDA-approval of Epidiolex®, a purified CBD medicine formulated for oral administration for the treatment of infantile refractory epileptic syndromes, by the US Food and Drug Administration in 2018. The World Health Organization considers rescheduling cannabis and cannabinoids. CBD use around the world is expanding for diseases that lack scientific evidence of the drug’s efficacy. Preclinical and clinical studies also report adverse effects (AEs) and toxicity following CBD intake. Methods: Relevant studies reporting CBD’s AEs or toxicity were identified from PubMed, Cochrane Central, and EMBASE through January 2019. Studies defining CBD’s beneficial effects were included to provide balance in estimating risk/benefit. Results: CBD is not risk-free. In animals, CBD AEs included developmental toxicity, embryo-fetal mortality, central nervous system inhibition and neurotoxicity, hepatocellular injuries, spermatogenesis reduction, organ weight alterations, male reproductive system alterations, and hypotension, although at doses higher than recommended for human pharmacotherapies. Human CBD studies for epilepsy and psychiatric disorders reported CBD-induced drug-drug interactions, hepatic abnormalities, diarrhea, fatigue, vomiting, and somnolence. Conclusion: CBD has proven therapeutic efficacy for serious conditions such as Dravet and Lennox-Gastaut syndromes and is likely to be recommended off label by physicians for other conditions. However, AEs and potential drug-drug interactions must be taken into consideration by clinicians prior to recommending off-label CBD.

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Section: Changes In Behaviormentioning

confidence: 99%

Section: Gastrointestinal Effectsmentioning

confidence: 99%

Cannabidiol Adverse Effects and Toxicity

et al. 2019

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“…Indeed, recent clinical and preclinical evidence have demonstrated that CBD is able to prevent THC-induced psychotic-like effects and improve positive symptoms of schizophrenia without inducing the well- known deleterious side effects provoked by classical antipsychotics ( 108 – 116 ). CBD has also been shown to be an effective treatment for epilepsy, with very few adverse effects ( 117 ). However, the phytochemical profile of illicit cannabis has profoundly changed over the past three decades: with THC content dramatically increasing along with a relative decrease in CBD content ( 2 ).…”

Section: Adolescence Cannabis Use Gabaergic System and Schizophreniamentioning

confidence: 99%

Effects of Adolescent THC Exposure on the Prefrontal GABAergic System: Implications for Schizophrenia-Related Psychopathology

2018

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Marijuana is the most commonly used drug of abuse among adolescents. Considerable clinical evidence supports the hypothesis that adolescent neurodevelopmental exposure to high levels of the principal psychoactive component in marijuana, -delta-9-tetrahydrocanabinol (THC), is associated with a high risk of developing psychiatric diseases, such as schizophrenia later in life. This marijuana-associated risk is believed to be related to increasing levels of THC found within commonly used marijuana strains. Adolescence is a highly vulnerable period for the development of the brain, where the inhibitory GABAergic system plays a pivotal role in the maturation of regulatory control mechanisms in the central nervous system (CNS). Specifically, adolescent neurodevelopment represents a critical period wherein regulatory connectivity between higher-order cortical regions and sub-cortical emotional processing circuits such as the mesolimbic dopamine (DA) system is established. Emerging preclinical evidence demonstrates that adolescent exposure to THC selectively targets schizophrenia-related molecular and neuropharmacological signaling pathways in both cortical and sub-cortical regions, including the prefrontal cortex (PFC) and mesolimbic DA pathway, comprising the ventral tegmental area (VTA) and nucleus accumbens (NAc). Prefrontal cortical GABAergic hypofunction is a key feature of schizophrenia-like neuropsychopathology. This GABAergic hypofunction may lead to the loss of control of the PFC to regulate proper sub-cortical DA neurotransmission, thereby leading to schizophrenia-like symptoms. This review summarizes preclinical evidence demonstrating that reduced prefrontal cortical GABAergic neurotransmission has a critical role in the sub-cortical DAergic dysregulation and schizophrenia-like behaviors observed following adolescent THC exposure.

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“…Uncontrolled seizures often affect one's quality of life, especially when they occur at a young age. 1 2 3 4 5 In particular, in epileptic encephalopathies such as Lennox-Gastaut syndrome (LGS) and Dravet syndrome (DS), epileptic activity causes severe cognitive and behavioral disorders to worsen over time. 6 …”

Section: Introductionmentioning

confidence: 99%