Category Archives: Epilepsy

Off-label use of cannabidiol in genetic epileptic and developmental encephalopathies: A case report

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“Developmental Epileptic encephalopathies (DEEs) are severe neurological conditions where cognitive functions appear modulated by both seizure and interictal epileptiform activity.

Cannabidiol (CBD) has been shown to be highly effective in the treatment of drug-resistant seizures in patients with DEEs.

Along with its antiseizure effects, CBD demonstrated clinical beneficial effects in patients’ quality of life, sleep and numerous adaptive behaviors. However, based on the available phase III studies, the indications for this treatment have so far been restricted to Lennox-Gastaut syndrome (LGS), Dravet syndrome (DS) and tuberous sclerosis complex (TSC) by regulatory authorities.

We present the case of a 30-year-old girl with a rare genetic DEE, experiencing relevant seizure frequency reduction together with striking improvement in sleep quality, mood, behavior, language and motor skills after introducing off-label CBD.”

https://pubmed.ncbi.nlm.nih.gov/39040437/

  • “•Cannabidiol exerts also clinical beneficial non-seizure outocomes.
  • •Cannabidiol should be considered in other developmental epileptic encephalopathies.
  • •Cannabidiol presents antiepileptic, neuroprotective and anti-inflammatory effect.”

“Besides its antiseizures effect, CBD might lead to clinical beneficial effects in patients’ quality of life, sleep, cognition and numerous adaptive behaviors. Hopefully, the growing interest in the CBD antiepileptic activity will lead to its use in other developmental and epileptic encephalopathie.”

https://www.sciencedirect.com/science/article/pii/S2589986424000443?via%3Dihub


Historical perspective on the therapeutic potential of cannabidiol

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“Cannabidiol (CBD) is one of over 200 cannabinoids present in the Cannabis plant. Unlike the plant’s primary cannabinoid, delta-9-tetrahydrocannabinol (THC), CBD does not produce psychotomimetic effects nor induce dependence. Initially considered an inactive cannabinoid, interest in its pharmacological properties and therapeutic potential has grown exponentially over the last 20 years.

Currently employed as a medication for certain epileptic syndromes, numerous pre-clinical and clinical studies support its potential use in various other disorders. In this chapter, we provide a brief historical overview of how this compound evolved from an “inactive substance” to a multifunctional clinical agent. Additionally, we discuss the current challenges in researching its potential therapeutic effects.”

https://pubmed.ncbi.nlm.nih.gov/39029980/

“In the sixty years that separate the initial studies with CBD from the current state of knowledge, understanding of its therapeutic potential has advanced remarkably. However, much of this potential still needs to be explored through randomized clinical trials to better establish CBD’s role in clinical therapy. This need, though, poses a significant obstacle to its development due to the high costs involved in conducting these trials and the difficulty of obtaining patents.”

https://www.sciencedirect.com/science/article/abs/pii/S0074774224000515?via%3Dihub


Cannabidiol and epilepsy

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“Cannabidiol (CBD) has been investigated as a pharmacological approach for treating a myriad of neurological and psychiatric disorders, the most successful of them being its use as an antiseizure drug (ASD). Indeed, CBD has reached the clinics for the treatment of certain epileptic syndromes.

This chapter aims to overview the pharmacology of CBD and its potential mechanisms of action as an ASD. First, we give an outline of the concepts, mechanisms and pharmacology pertaining to the field of study of epilepsy and epileptic seizures. In the second section, we will summarize the effects of CBD as an ASD. Next, we will discuss its potential mechanisms of action to alleviate epileptic seizures, which seem to entail multiple neurotransmitters, receptors and intracellular pathways. Finally, we will conclude and present some limitations and perspectives for future studies.”

https://pubmed.ncbi.nlm.nih.gov/39029983/

“Five decades ago, early studies noted the potential effects of CBD in alleviating epileptic seizures. However, a prolonged period passed before scientific and social interest in this phytocannabinoid experienced a resurgence. This delay in exploration hindered a comprehensive understanding of its clinical profile, but mechanisms of action could finally be addressed. After a long journey starting from the bench, today CBD has become an additional therapeutic option for patients diagnosed with epilepsy”

https://www.sciencedirect.com/science/article/abs/pii/S0074774224000527?via%3Dihub

The Relationship between Muscarinic and Cannabinoid Receptors in Neuronal Excitability and Epilepsy: A Review

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“Background: Of the seventy million people who suffer from epilepsy, 40 percent of them become resistant to more than one antiepileptic medication and have a higher chance of death. While the classical definition of epilepsy was due to the imbalance between excitatory glutamatergic and inhibitory γ-aminobutyric acid (GABA)-ergic signalling, substantial evidence implicates muscarinic receptors in the regulation of neural excitability.

Summary: Cannabinoids have shown to reduce seizure activity and neuronal excitability in several epileptic models through the activation of muscarinic receptors with drugs which modulate their activity. Cannabinoids also have been effective in reducing antiepileptic activity in pharmaco-resistant individuals; however, the mechanism of its effects in temporal lobe epilepsy is not clear.

Key messages: This review seeks to elucidate the relationship between muscarinic and cannabinoid receptors in epilepsy and neural excitability.”

https://pubmed.ncbi.nlm.nih.gov/39015608/

“Cannabis has been used as a traditional treatment of epilepsy since the 1800s.”

https://karger.com/mca/article/7/1/91/907741/The-Relationship-between-Muscarinic-and

Comparison of various doses of oral cannabidiol for treating refractory epilepsy indications: a network meta-analysis

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“Aim: To evaluate the comparative efficacy and safety of various doses of oral cannabidiol (CBD) in treating refractory epilepsy indications, thus providing more informative evidence for clinical decision-making.

Methods: A literature search of PubMed, Embase, the Cochrane library, and Web of Science (WoS) was performed to retrieve relevant randomized controlled trials (RCTs) that compared different doses of oral CBD with placebo or each other in refractory epilepsy indications. The search was limited from the inception of each database to January 3, 2023. Relative risk [RR] with a 95% confidence interval [CI] was used to express results. STATA/SE 14 was employed for network meta-analysis.

Results: Six RCTs involving 972 patients were included in the final data analysis. Network meta-analysis showed that, CBD10 (10 mg/kg/day) (RR: 1.77, 95%CI: 1.28 to 2.44), CBD20 (20 mg/kg/day) (RR: 1.91, 95%CI: 1.49 to 2.46), CBD25 (25 mg/kg/day) (RR: 1.61, 95%CI: 0.96 to 2.70), and CBD50 (50 mg/kg/day) (RR: 1.78, 95%CI: 1.07 to 2.94) were associated with higher antiseizure efficacy although the pooled result for CBD25 was only close to significant. In addition, in terms of the risk of treatment-emergent adverse events (TEAEs), the difference between different doses is not significant. However, CBD20 ranked first in terms of antiseizure efficacy, followed by CBD50, CBD10, and CBD25. For TEAEs, CBD25 ranked first, followed by CBD10, CBD50, CBD5, and CBD20.

Conclusion: For refractory indications, CBD20 may be optimal option for antiseizure efficacy; however, CBD25 may be best for TEAEs. Therefore, an appropriate dose of oral CBD should be selected based on the actual situation. Due to the limitations of eligible studies and the limited sample size, more studies are needed in the future to validate our findings.”

https://pubmed.ncbi.nlm.nih.gov/38994494/

https://www.frontiersin.org/journals/neurology/articles/10.3389/fneur.2024.1243597/full

Effectiveness of Highly Purified Cannabidiol in Refractory and Super-Refractory Status Epilepticus: A Case Series

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“Introduction: Refractory and super-refractory status epilepticus are medical emergencies that must be promptly treated in consideration of their high mortality and morbidity rate. Nevertheless, the available evidence of effective treatment of these conditions is scarce. Among novel antiseizure medications (ASMs), highly purified cannabidiol (hpCBD) has shown noteworthy efficacy in reducing seizures in Lennox-Gastaut syndrome (LGS), Dravet syndrome (DS), and Tuberous Sclerosis Complex (TSC).

Case presentation: Here, we present two cases of effective use of hpCBD in both refractory and super- refractory status epilepticus. The administration of the nasogastric tube permitted the resolution of status epilepticus without adverse events. At 6-month follow-up, both patients were on hpCBD treatment, which continued to be efficacious for treating seizures.

Conclusion: According to our experience, hpCBD should be taken into consideration as an add-on therapy of RSE and SRSE while also considering the possibility of maintaining this treatment during the follow-up of patients. However, more studies and real-world experiences are needed to better understand its effectiveness in this setting and the interaction with other ASMs.”

https://pubmed.ncbi.nlm.nih.gov/38910424/

https://www.eurekaselect.com/article/141195

The Use of Compounds Derived from Cannabis sativa in the Treatment of Epilepsy, Painful Conditions, and Neuropsychiatric and Neurodegenerative Disorders

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“Neurological disorders present a wide range of symptoms and challenges in diagnosis and treatment. Cannabis sativa, with its diverse chemical composition, offers potential therapeutic benefits due to its anticonvulsive, analgesic, anti-inflammatory, and neuroprotective properties.

Beyond cannabinoids, cannabis contains terpenes and polyphenols, which synergistically enhance its pharmacological effects. Various administration routes, including vaporization, oral ingestion, sublingual, and rectal, provide flexibility in treatment delivery.

This review shows the therapeutic efficacy of cannabis in managing neurological disorders such as epilepsy, neurodegenerative diseases, neurodevelopmental disorders, psychiatric disorders, and painful pathologies.

Drawing from surveys, patient studies, and clinical trials, it highlights the potential of cannabis in alleviating symptoms, slowing disease progression, and improving overall quality of life for patients. Understanding the diverse therapeutic mechanisms of cannabis can open up possibilities for using this plant for individual patient needs.”

https://pubmed.ncbi.nlm.nih.gov/38891938/

https://www.mdpi.com/1422-0067/25/11/5749


Infant formula as a solid lipid dose form for enhancement of the oral bioavailability of cannabidiol for paediatric patients

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“Cannabinoids can save paediatric patients from harmful psychological conditions caused by epilepsy. However, the limited aqueous solubility of the drug presents a limitation to oral absorption and bioavailability.

Previous studies have shown the enhancement of oral bioavailability for poorly water-soluble drugs using milk or milk-based products like infant formula as a novel lipid-based formulation, due to digestion of the lipids to enhance drug solubility. that is particularly well suited to infants and in low economy settings.

Therefore, this study has investigated the in vitro solubilization enhancement of cannabidiol (CBD) in milk-based products during digestion using synchrotron small angle X-ray scattering, followed by pharmacokinetic studies to determine the relative oral bioavailability. The in vitro results, coupled with in vivo data, demonstrate a two-fold increase in the oral bioavailability of CBD in bovine milk as well as infant formula.

The results of this study indicate the potential for infant formula to be considered as a novel formulation approach for CBD. Further study is encouraged for more drugs with infant formula to strengthen the correlation between the solubilization of drug and their oral bioavailability.”

https://pubmed.ncbi.nlm.nih.gov/38782154/

https://www.sciencedirect.com/science/article/pii/S0378517324004915?via%3Dihub

Use of cannabidiol in the treatment of drug-refractory epilepsy in children and young adults: A systematic review

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“Objectives: Epilepsy poses a significant challenge in pediatric and adolescent populations, impacting not only seizures but also psychological and cognitive comorbidities, leading to higher mortality rates than the general population. Drug-refractory epilepsy, resistant to conventional treatments, affects a range of 7-20% of pediatric patients. The search for alternative therapies has led to exploring the therapeutic potential of Cannabis sativa L. compounds, particularly cannabidiol (CBD). Examine the use of CBD for treating drug-refractory epilepsy in children and young adults, summarizing existing evidence on its efficacy.

Materials and methods: A systematic review, following Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines, assessed studies from 2018 to 2023, focusing on CBD’s efficacy and safety for treatment-resistant epilepsy in pediatric and juvenile populations. The search spanned seven databases, and the studies underwent rigorous screening and data extraction.

Results: Out of 6351 identified articles, eight were selected for review. The included studies reported positive outcomes, with CBD leading to a reduction in seizure frequency ranging from 50% to complete seizure freedom. Adverse effects were mostly mild and reversible, including drowsiness, diarrhea, and loss of appetite.

Conclusion: The CBD emerges as a promising tool for refractory epilepsy in pediatric patients, showing efficacy in reducing seizure frequency and improving overall quality of life. Despite mild and reversible adverse effects, CBD’s benefits outweigh the risks. However, more research on long-term effects is needed to fully understand its implications.”

https://pubmed.ncbi.nlm.nih.gov/38746511/

“The use of cannabis is a tool for refractory epilepsy when first-line therapies do not have the expected efficacy. The benefits of the crisis are clear, in the reduction and even elimination or blocking of seizures, impacting positively their quality of life such as sleep, behavior, and cognitive functions. There is great efficacy against different types of epileptic seizures, such as tonic, tonic-clonic, epileptic encephalopathy, focal seizures, and generalized seizures, making its use advisable for patients, without forgetting that more information is still required regarding its long-term use. As for the adverse effects, it can be noted that, despite being almost constant, these mainly appear due to the interaction of CBD with the medications used by these patients, although it is clear that none of these adverse effects turned out to be a reason not to stop the treatment that was presented during the different studies.”

https://ruralneuropractice.com/use-of-cannabidiol-in-the-treatment-of-drug-refractory-epilepsy-in-children-and-young-adults-a-systematic-review/

CBD in the Treatment of Epilepsy

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“It has been several years since highly purified cannabidiol (CBD) was registered as a medication that can be used in children of at least 2 years of age to treat different types of seizures related to Lennox-Gastaut syndrome (LGS), Dravet syndrome (DS), and more recently tuberous sclerosis complex (TSC).

During this time, 39 randomized clinical trials (RCTs) and 13 meta-analyses on the efficacy and safety of CBD treatment have been published. Each of the meta-analyses had its own criteria for the RCTs’ inclusion and, therefore, slightly different interpretations of the analyzed data.

Each of them contributed in its own way to the understanding of CBD pharmacology, mechanisms of therapeutic action, development of adverse reactions, and drug-drug interactions. Hence, it seemed reasonable to gather the most relevant data in one article and present all the current knowledge on the use of CBD in epilepsy.

The results of the 13 meta-analyses presented herein confirmed the effectiveness and safety of CBD in children and adolescents with DREs. In adults, reliable conclusions cannot be drawn due to insufficient data.”

https://pubmed.ncbi.nlm.nih.gov/38731471/

https://www.mdpi.com/1420-3049/29/9/1981