Abstracts

Rationale: Intoxicating tetrahydrocannabinol (THC) and non-intoxicating cannabidiol (CBD) are the two most prevalent phytocannabinoids found in cannabis sativa plants. CBD is well studied in multiple disease models, especially as anti-convulsant in treating intractable forms of epilepsy1. However, in many strains of cannabis, over 90% of phytocannabinoids are synthetized as non-intoxicating acidic cannabinoids2. 'Raw hemp oil' extracts prepared using cold temperatures are often dominated by acidic cannabinoids, such as cannabidiolic acid (CBDA), which is the precursor of CBD. Recent evidence suggests that CBDA is an effective anti-emetic (acting through serotonin receptors)3, anti-inflammatory (Cox-2 inhibition)4 , and it abrogates cancer cell growth5. However, it is unknown what role CBDA plays in the central nervous system (CNS). Methods: Using single cell and network electrophysiological recordings, we compared effects of synthetic CBD (30M) and CBDA (25M) on seizure-like activity and neuronal excitability in the hippocampal slices. Results: Both, CBD and CBDA reduced zero magnesium-induced seizure-like activity by reducing action potential firing in the excitatory pyramidal cells. CBDA actions were typically as effective, but delayed by 10-15 minutes, compared to CBD. Only CBDA significantly increased afterhyperpolarizations following the action potentials. Conclusions: Our studies reveal that CBDA can effectively control seizure-like excitability in vitro. Further studies with CBDA and other acidic cannabinoids are needed to determine their effectiveness and anti-epileptic potential in vivo. Funding: Dravet Syndrome Foundation (J..)