Cannabinoids and CBD in clinical practice

Abstract

Derivates are phytocannabinoids with active properties on the endocannabinoid system. Cannabidiol (CBD) antiepileptic effects were described in animal models, recently leading to clinical application. High quality data on efficacy of CBD enriched compounds as adjunctive therapy in epilepsy patients derives from RCTs with plant-derived pure CBD solution (10-20 mg/kg/day) in children/adolescents with Dravet or Lennox Gastaut Syndromes; 25-50 mg/kg/day in Tuberous Sclerosis. A 50% seizure reduction was observed in 36–49% of cases compared to 15–27% in placebo groups, supporting current clinical guidelines. Responder rates of 42–62% were reported in observational studies including a wider spectrum of ages and epilepsies. Frequent (78–92%), mild-moderate adverse effects (AE) are usually early and transient; serious AE were mostly associated to concomitant valproate (hepatic toxicity) or clobazam (sedation, pneumonia, respiratory failure). Deleterious cognitive and behavioural long-term effects of prolonged exposure to cannabinoids (mostly tetrahydrocannabinol-THC) during brain development are well described. No significant changes were found after 1-year of CBD treatment. Positive effects on alertness, communication, mood and sleep could be additional benefits, with impact on quality of life. CBD undergo a complex metabolism including CYP2C19, CYP3A4 inhibition, favouring pharmacokinetic interactions; therefore, drugs monitoring is recommended. Few observational studies using CBD enriched extracts (CBD:THC 1:50, 1:20) reported similar efficacy. Synthetic and plant-derived CBD seem to have similar pharmacokinetics, efficacy and AE profile. Current challenges in clinical practice include limited data on: efficacy, predictive factors of response/AE, safety and dosing of many currently used compounds. Costs, availability, cultural factors and local regulations are additional barriers to face.