Safety of cannabidiol versus placebo in healthy population: a systematic review and meta-analysis

Cannabidiol (CBD) has gained significant attention for its potential therapeutic benefits, but its safety profile in healthy populations remains underexplored. This systematic review and meta-analysis aim to evaluate the safety of CBD compared to placebo in healthy adults. A comprehensive search of PubMed, Embase, Cochrane CENTRAL, and ClinicalTrials.gov identified four randomized controlled trials (RCTs) involving 269 healthy adults. The primary outcome was headache, with secondary outcomes including fatigue, abdominal pain, diarrhea, upper respiratory tract infection (URTI), and dizziness. The results revealed that CBD use was associated with a significantly higher risk of diarrhea (RR = 5.85; 95% CI = 1.14-30.02; <i>P</i> = 0.03). While there was a trend toward increased abdominal pain and headache, these results were not statistically significant. Fatigue, dizziness, and URTI showed no significant differences between the CBD and placebo groups. These findings suggest that while CBD appears safe for short-term use in healthy adults, gastrointestinal side effects, particularly diarrhea, should be monitored. Further large-scale studies with longer follow-up periods are warranted to confirm these results and explore long-term safety.