Marilyn A. Huestis, Renata Solimini, Simona Pichini, Roberta Pacifici, Jeremy Carlier and Francesco Paolo Busardò* Pages 974 - 989 ( 16 )
Background: Currently, there is a great interest in the potential medical use of cannabidiol (CBD), a non-intoxicating cannabinoid. Productive pharmacological research on CBD occurred in the 1970s and intensified recently with many discoveries about the endocannabinoid system. Multiple preclinical and clinical studies led to FDA-approval of Epidiolex®, a purified CBD medicine formulated for oral administration for the treatment of infantile refractory epileptic syndromes, by the US Food and Drug Administration in 2018. The World Health Organization considers rescheduling cannabis and cannabinoids. CBD use around the world is expanding for diseases that lack scientific evidence of the drug’s efficacy. Preclinical and clinical studies also report adverse effects (AEs) and toxicity following CBD intake.
Methods: Relevant studies reporting CBD’s AEs or toxicity were identified from PubMed, Cochrane Central, and EMBASE through January 2019. Studies defining CBD’s beneficial effects were included to provide balance in estimating risk/benefit.
Results: CBD is not risk-free. In animals, CBD AEs included developmental toxicity, embryo-fetal mortality, central nervous system inhibition and neurotoxicity, hepatocellular injuries, spermatogenesis reduction, organ weight alterations, male reproductive system alterations, and hypotension, although at doses higher than recommended for human pharmacotherapies. Human CBD studies for epilepsy and psychiatric disorders reported CBD-induced drug-drug interactions, hepatic abnormalities, diarrhea, fatigue, vomiting, and somnolence.
Conclusion: CBD has proven therapeutic efficacy for serious conditions such as Dravet and Lennox-Gastaut syndromes and is likely to be recommended off label by physicians for other conditions. However, AEs and potential drug-drug interactions must be taken into consideration by clinicians prior to recommending off-label CBD.
Cannabidiol, adverse effects, toxicity, animal studies, in vitro studies, in vivo studies, studies in humans.
Lambert Center for the Study of Medicinal Cannabis and Hemp, Institute of Emerging Health Professions, Thomas Jefferson University, Philadelphia, PA, National Centre on Addiction and Doping, Istituto Superiore di Sanita, Rome, National Centre on Addiction and Doping, Istituto Superiore di Sanita, Rome, National Centre on Addiction and Doping, Istituto Superiore di Sanita, Rome, Unit of Forensic Toxicology (UoFT), Department of Anatomical, Histological, Forensic and Orthopedic Sciences, Sapienza University of Rome, Rome, Section of Legal Medicine, Universita Politecnica delle Marche, Ancona