Cannabis constituents reduce seizure behavior in chemically-induced and scn1a-mutant zebrafish
| Autor: | Kristine L. Willett, Dennis R. Carty, Nicole M. Ashpole, Kennedy Dickson, Cammi Thornton |
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| Rok vydání: | 2020 |
| Předmět: |
Drug
Cannabidivarin Acyclic Monoterpenes media_common.quotation_subject Cannabinol Pharmacology Article Animals Genetically Modified 03 medical and health sciences Behavioral Neuroscience chemistry.chemical_compound Epilepsy 0302 clinical medicine Dravet syndrome Seizures medicine Animals Cannabidiol Dronabinol 030212 general & internal medicine Adverse effect Zebrafish Cannabis media_common Dose-Response Relationship Drug biology Cannabinoids business.industry Zebrafish Proteins biology.organism_classification medicine.disease NAV1.1 Voltage-Gated Sodium Channel Neurology chemistry Pentylenetetrazole Anticonvulsants Neurology (clinical) business 030217 neurology & neurosurgery medicine.drug |
| Zdroj: | Epilepsy Behav |
| ISSN: | 1525-5050 |
| DOI: | 10.1016/j.yebeh.2020.107152 |
| Popis: | Current antiepileptic drugs (AEDs) are undesirable for many reasons including the inability to reduce seizures in certain types of epilepsy, such as Dravet syndrome (DS) where in one-third of patients does not respond to current AEDs, and severe adverse effects that are frequently experienced by patients. Epidiolex, a cannabidiol (CBD)-based drug, was recently approved for treatment of DS. While Epidiolex shows great promise in reducing seizures in patients with DS, it is used in conjunction with other AEDs and can cause liver toxicity. To investigate whether other cannabis-derived compounds could also reduce seizures, the antiepileptic effects of CBD, Δ9-tetrahydrocannabinol (THC), cannabidivarin (CBDV), cannabinol (CBN), and linalool (LN) were compared in both a chemically-induced (pentylenetetrazole, PTZ) and a DS (scn1Lab−/−) seizure models. Zebrafish (Danio rerio) that were either wild-type (Tupfel longfin) or scn1Lab−/− (DS) were exposed to CBD, THC, CBDV, CBN, or LN for 24 h from 5 to 6 days postfertilization. Following exposure, total distance traveled was measured in a ViewPoint Zebrabox to determine if these compounds reduced seizure-like activity. Cannabidiol (0.6 and 1 μM) and THC (1 and 4 μM) significantly reduced PTZ-induced total distance moved. At the highest THC concentration, the significant reduction in PTZ-induced behavior was likely the result of sedation as opposed to antiseizure activity. In the DS model, CBD (0.6 μM), THC (1 μM), CBN (0.6 and 1 μM), and LN (4 μM) significantly reduced total distance traveled. Cannabinol was the most effective at reducing total distance relative to controls. In addition to CBD, other cannabis-derived compounds showed promise in reducing seizure-like activity in zebrafish. Specifically, four of the five compounds were effective in the DS model, whereas in the PTZ model, only CBD and THC were, suggesting a divergence in the mode of action among the cannabis constituents. |
| Databáze: | OpenAIRE |
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