Cannabidiol (CBD) in combination with a 5-HT2B receptor agonist, an amphetamine or an amphetamine derivative, preferably fenfluramine, for use in the treatment of epilepsy is provided. Preferably the combination is for use in the prevention or reduction of side effects associated with agonism of the 5-HT2B receptor, in particular heart valve disease. The CBD may be present as a synthetic compound or may be in the form of a highly purified extract of cannabis which comprises at least 98% (w/w) CBD, less than 0.15% tetrahydrocannabinol (THC) and up to 1% cannabidivarin (CBDV). Preferably the epilepsy is treatment resistant epilepsy, in particular one of: Dravet syndrome, myoclonic-absence epilepsy, Lennox-Gastaut syndrome, generalized epilepsy of unknown origin, CDKL5 mutation, Aicardi syndrome, tuberous sclerosis complex, bilateral polymicrogyria, Dup15q, SNAP25, febrile infection related epilepsy syndrome (FIRES), benign rolandic epilepsy, juvenile myoclonic epilepsy, infantile spasm (West syndrome) and Landau-Kleffner syndrome. Preferably the ratio of CBD to 5-HT2B receptor agonist, amphetamine or amphetamine derivative is between 20:1 to 1:20, in particular 3:1 to 1:3.
