(169) Post-Marketing Safety Profile of Cannabis Products: Signals from The FDA Adverse Event Reporting System

Publication Number: 500

Background: Although cannabis preparations are increasingly available across jurisdictions worldwide, evidence concerning their risk-benefit profile is far from conclusive. Post-marketing monitoring plays an essential role in investigating their safety because of novelty and heterogeneity in formulations and uses.

Objectives: Using the FDA Adverse Event Reporting System (FAERS), we aim to characterize post-marketing cannabis-related adverse drug events (ADEs).

Methods: FAERS quarterly data (January 2004-September 2021) were downloaded and deduplicated to identify cannabis products, namely cannabidiol (CBD), tetrahydrocannabinol (THC), and cannabinoids not otherwise specified (cannabinoids-NOS). Reports of cannabis-related ADEs were described and compared to other FAERS reports. The reporting odds ratio (ROR) with 95% confidence interval (CI) was calculated to detect signals of disproportionate reporting for the three different products. Product labels were used to highlight unexpected signals.

Results: We retrieved 25,686 cases of cannabis-related ADEs, of which 40.5% involved CBD and 25.5% THC. Compared to other reports, cases were more often reported by physicians (p=0.002, 30% vs 24%) and involved men (p < 0.001, 52% vs 39%) and the 18-30 years age group (p=0.002, 18% vs 8%). Patients with cannabinoids-NOS ADEs were younger (median: 37 years; IQR: 25-53) than those with THC ADEs (56 years; 42-67). Death was more often recorded (p=0.002, 14% vs 9%), especially for THC (19%) and cannabinoids-NOS (22%), with only 4% for CBD. Known cannabis-related ADEs were mood, psychotic and behavioral conditions, sedation, seizures, abuse, vomiting, rhythm alteration, infections, hypersensitivity, hypophagia, myalgia, rashes, asthenia, and hemodynamic instability. CBD had fewer signals, followed by THC, and cannabinoids-nos. New signals, peculiar to THC, concerned pancytopenia (ROR = 3.51, 95%CI= 2.7-4.5), osteoporosis (4.2, 3.2-5.4), renal failure (2.19, 1.81-2.63), and deep vein thrombosis (2.64, 2.06-3.33).

Conclusions: According to this pharmacovigilance analysis, known safety issues were confirmed, and CBD seems to bear an overall safer profile. Specific concerns for THC-related cytopenia, osteoporosis, renal failure, and thrombosis deserve further investigation.