Box 1 Unanswered questions and directions for future studies

1. How do the pro and anti-epileptic effects of cannabis change with development? Are there age-specific differences in responsiveness, side effects, and target receptor expression? 2. What are the long-term effects of cannabis/cannabidiol use? 3. Are certain types of seizures or genetic channelopathies more likely to respond to cannabidiol than others? 4. What is the safety of cannabidiol in patients with special conditions (pregnancy, recent or planned surgery, vagus nerve stimulation, etc.)? 5. How do synthetic cannabinoids (“spice” or “K2”) dysregulate the central nervous system to induce seizures? What is their relative safety and toxicity relative to cannabis?