“Background: Cannabidiol (CBD) has become a promising therapeutic option in the treatment of epilepsy. Recent studies provide robust evidence that CBD is effective and safe. Limitations in current knowledge and regulatory issues still limit CBD use. CBD use regarding epilepsy types still lacks clear guidelines.

Objective: To critically review the main current pharmacological features and clinical issues regarding CBD use in epilepsy, to provide current regulatory background regarding CBD use in Brazil, and to suggest a practical CBD therapeutic guide in Brazil.

Methods: Non-systematic literature review (up to February 2022) of current concepts of CBD and epilepsy, including the authors’ personal experience.

Results: Five pivotal trials have led to CBD approval as an adjunctive treatment for Dravet and Lennox-Gastaut syndromes, and for the tuberous sclerosis complex. Efficacy of CBD in other drug-resistant epilepsies remains not completely understood. CBD adverse event profile and drug interactions are better understood. CBD is well tolerated. In Brazil, CBD is not classified as a medication, but as a product subject to a distinct regulatory legislation. CBD is still not offered by the National Brazilian health system, but can be purchased in authorized pharmacies or imported under prescription and signed informed consent.

Conclusion: CBD is a recognized novel treatment for epilepsy. Future well-designed studies and public health strategies are needed to offer widespread access to CBD, and to improve the quality of life of people living with epilepsy in Brazil.”

https://pubmed.ncbi.nlm.nih.gov/35976327/

“In conclusion, epilepsy burden, especially medically refractory epilepsy, affects patients and families, particularly for medically refractory epilepsy. CBD offers hope in treating epilepsy. Current evidence demonstrates efficacy and safety in prescribing CBD for Dravet and Lennox-Gastaut syndrome and Tuberous Sclerosis Complex.”

https://www.scielo.br/j/anp/a/Hw3WJKnhvbxvdCqxc9tNDNd/?lang=en

“The use of cannabidiol (CBD) in childhood refractory seizures has become a common therapeutic approach for specific seizure disorders in human medicine. Similarly, there is an interest in using CBD, cannabidiolic acid (CBDA) or cannabinoid-rich hemp products in the treatment of idiopathic epilepsy in dogs.

We aimed to examine a small cohort in a pilot investigation using a CBD and CBDA-rich hemp product for the treatment of refractory epileptic seizures in dogs.

Fourteen dogs were examined in a 24-week randomized cross-over study being provided placebo or CBD/CBDA-rich hemp extract treatment at 2 mg/kg orally every 12 h for each 12-week arm of the study. Serum chemistry, complete blood counts, serum anti-seizure medication (ASM) concentrations and epileptic seizure frequency were followed over both arms of the cross-over trial.

Results demonstrated that besides a mild increase in alkaline phosphatase, there were no alterations observed on routine bloodwork at 2, 6, and 12 weeks during either arm of the study.

Epileptic seizure frequency decreased across the population from a mean of 8.0 ± 4.8 during placebo treatment to 5.0 ± 3.6 with CBD/CBDA-rich hemp extract (P = 0.02). In addition, epileptic seizure event days over the 12 weeks of CBD/CBDA-rich hemp treatment were 4.1 ± 3.4, which was significantly different than during the 12 weeks of placebo treatment (5.8 ± 3.1; P =0.02). The number of dogs with a 50% reduction in epileptic activity while on treatment were 6/14, whereas 0/14 had reductions of 50% or greater while on the placebo (P = 0.02).

No differences were observed in serum zonisamide, phenobarbital or bromide concentrations while on the treatment across groups. Adverse events were minimal, but included somnolence (3/14) and transient increases in ataxia (4/14) during CBD/CBDA-rich hemp extract treatment; this was not significantly different from placebo. This further indicates that providing CBD/CBDA-rich hemp extract during refractory epilepsy (only partially responsive to ASM), in conjunction with other ASM appears safe.

Based on this information, the use of 2 mg/kg every 12 h of a CBD/CBDA-rich hemp extract can have benefits in reducing the incidence of epileptic seizures, when used concurrently with other ASMs.”

https://pubmed.ncbi.nlm.nih.gov/35967998/

“Since the 1970’s or earlier, cannabinoids have been found to have anti-epileptic effects in animal seizure models. In conclusion, there appears to be a population of dogs that respond favorably to CBD/CBDA-rich hemp products for epileptic seizure reduction similar to other human, dog and rodent data.”

https://www.frontiersin.org/articles/10.3389/fvets.2022.939966/full

“Microglia, the dynamic innate immune cells of the central nervous system, become activated in epilepsy. The process of microglial activation in epilepsy results in the creation of an inflammatory environment around the site of seizure onset, which contributes to the epileptogenic process and epilepsy progression. Cannabidiol (CBD) has been effective for use as an adjunctive treatment for two severe pediatric seizure disorders. Newly recognized as an Food and Drug Administration (FDA)-approved drug treatment in epilepsy, it has gained in popularity primarily for pain management. Although CBD is readily available in stores and online retailers, its mechanism of action and specifically its effects on microglia and their functions are yet fully understood. In this study, we examine the effects of commercially available CBD on microglia inflammatory activation and neurogenic response, in the presence and absence of seizures. We use systemic administration of kainate to elicit seizures in mice, which are assessed behaviorally. Artisanal CBD is given in different modes of administration and timing to dissect its effect on seizure intensity, microglial activation and aberrant seizure-related neurogenesis. CBD significantly dampens microglial migration and accumulation to the hippocampus. While long term artisanal CBD use does not prevent or lessen seizure severity, CBD is a promising adjunctive partner for its ability to depress epileptogenic processes. These studies indicate that artisanal CBD is beneficial as it both decreases inflammation in the CNS and reduces the number of ectopic neurons deposited in the hippocampal area post seizure.”

https://pubmed.ncbi.nlm.nih.gov/35700815/

https://www.sciencedirect.com/science/article/abs/pii/S0306452222003049?via%3Dihub

“Background: Purified cannabidiol (CBD), a non-psychoactive phytocannabinoid, has gained regulatory approval to treat intractable childhood epilepsies. Despite this, artisanal and commercial CBD-dominant hemp-based products continue to be used by epilepsy patients. Notably, the CBD doses used in these latter products are much lower than that found to be effective in reducing seizures in clinical trials with purified CBD. This might be because these CBD-dominant hemp products contain other bioactive compounds, including phytocannabinoids and terpenes, which may exert unique effects on epilepsy-relevant drug targets. Voltage-gated sodium (Na_V) channels are vital for initiation of neuronal action potential propagation and genetic mutations in these channels result in epilepsy phenotypes. Recent studies suggest that Na_V channels are inhibited by purified CBD. However, the effect of cannabis-based products on the function of Na_V channels is unknown.

Methods: Using automated-planar patch-clamp technology, we profile a hemp-derived nutraceutical product (NP) against human Na_V1.1-Na_V1.8 expressed in mammalian cells to examine effects on the biophysical properties of channel conductance, steady-state fast inactivation and recovery from fast inactivation.

Results: NP modifies peak current amplitude of the Na_V1.1-Na_V1.7 subtypes and has variable effects on the biophysical properties for all channel subtypes tested. NP potently inhibits Na_V channels revealing half-maximal inhibitory concentration (IC₅₀) values of between 1.6 and 4.2 μg NP/mL. Purified CBD inhibits Na_V1.1, Na_V1.2, Na_V1.6 and Na_V1.7 to reveal IC₅₀ values in the micromolar range. The CBD content of the product equates to IC₅₀ values (93-245 nM), which are at least an order of magnitude lower than purified CBD. Unlike NP, hemp seed oil vehicle alone did not inhibit Na_V channels, suggesting that the inhibitory effects of NP are independent of hemp seed oil.

Conclusions: This CBD-dominant NP potently inhibits Na_V channels. Future study of the individual elements of NP, including phytocannabinoids and terpenes, may reveal a potent individual component or that its components interact to modulate Na_V channels.”

https://pubmed.ncbi.nlm.nih.gov/35689251/

https://jcannabisresearch.biomedcentral.com/articles/10.1186/s42238-022-00136-x

“Compounds present in Cannabis sativa L. preparations have recently attracted much attention in the treatment of drug-resistant epilepsy. Here, we screened two olive oil extracts from a non-psychoactive C. sativa variety, fully characterized by high-performance liquid chromatography and gas chromatography. Particularly, hemp oils with different concentrations of terpenes were administered at the same dose of cannabidiol (25 mg/kg/day orally), 1 h before the 6-Hz corneal stimulation test (44 mA). Mice were stimulated once a day for 5 days and evaluated by video-electrocorticographic recordings and behavioral analysis. Neuronal activation was assessed by FosB/ΔFosB immunoreactivity. Both oils significantly reduced the percentage of mice experiencing convulsive seizures in comparison to olive oil-treated mice (p < 0.050; Fisher’s exact test), but only the oil enriched with terpenes (K2) significantly accelerated full recovery from the seizure. These effects occurred in the presence of reduced power of delta rhythm, and, instead, increased power of theta rhythm, along with a lower FosB/ΔFosB expression in the subiculum (p < 0.050; Duncan’s method). The overall findings suggest that both cannabinoids and terpenes in oil extracts should be considered as potential therapeutic agents against epileptic seizures and epilepsy.”

https://pubmed.ncbi.nlm.nih.gov/34959660/

https://www.mdpi.com/1424-8247/14/12/1259

“Objective: We report our findings regarding effectiveness, safety, and tolerability of cannabidiol (CBD)-enriched medical cannabis as add-on therapy in children with drug-resistant epileptic encephalopathies (DEEs) after a median follow-up of 20 months.

Methods: A prospective cohort study was conducted to assess effectiveness, safety, and tolerability of CBD-enriched medical cannabis oil added to standard antiseizure medications in children with drug-resistant DEE seen at a single center.

Results: Between October 2018 and March 2020, 59 patients were enrolled. Mean age at enrollment was 10.5 years (range, 2-17 years). Median treatment duration was 20 months (range, 12-32). Median age at first seizure was 8 months (range, 1 day – 10 years). At the end of follow-up, 78% of the children had a ≥ 50% decrease in seizure frequency and 47.5% had a > 75% decrease. Seven patients (11.9%) were seizure free. The number of seizures was reduced from a median of 305/month to 90/month, amounting to a mean reduction of 57% and a median reduction of 71% (p < 0.0001). Adverse effects were mostly mild or moderate. CBD was discontinued in 17 patients (28.8%) due to lack of response to treatment, increased seizure frequency, intolerance to the drug, or poor compliance.

Conclusion: In children with drug-resistant DEEs, long-term treatment of CBD-enriched medical cannabis as an adjuvant therapy to antiseizure therapy was found to be safe, well tolerated, and effective. Sustained reductions in seizure frequency and improvement of aspects of daily living were observed compared to our preliminary findings.”

https://pubmed.ncbi.nlm.nih.gov/34999381/

• “•Long-term use of CBD-enriched medical cannabis as add-on treatment seems safe and effective in DEE.
• •The drug was well tolerated and had a positive impact on aspects of daily living.
• •Good results were found in patients with LGS and DS, as well as those with DEEs other than LGS and DS.
• •No tolerance to CBD-enriched medical cannabis was observed in any of the children.”

https://www.seizure-journal.com/article/S1059-1311(22)00001-2/fulltext