Adverse effects of cannabidiol: a systematic review and meta-analysis of randomized clinical trials
Chesney et al.·NeuropsychopharmacologyImpact 4.4
HarmGRADEHigh278 citations
Samplek = 12 Studien n = 803 Pat.
Duration≥7 days
ControlPlacebo
EndpointAdverse events
Blindingdoppelblind
DesignMeta-Analyse
Cannabinoidcbd
Routeoral
”Key finding
CBD was associated with an increased likelihood of study discontinuation, serious adverse events (especially in childhood epilepsy), diarrhoea, somnolence and sedation compared to placebo.
Summary
Systematic review + meta-analysis on CBD safety across k=12 double-blind RCTs (n=803). CBD vs. placebo: increased risk for study discontinuation (OR 2.61, 95% CI 1.38-4.96), serious adverse events (OR 2.30, 95% CI 1.18-4.48), abnormal liver values (OR 11.19, 95% CI 2.09-60.02), pneumonia (OR 5.37, 95% CI 1.17-24.65), decreased appetite (OR 3.56, 95% CI 1.94-6.53), diarrhoea (OR 2.61, 95% CI 1.46-4.67), somnolence (OR 2.23, 95% CI 1.07-4.64). Liver value abnormalities, somnolence, sedation and pneumonia limited to childhood epilepsy studies (possible interaction with clobazam/valproate). After exclusion of childhood epilepsy: only diarrhoea associated (OR 5.03, 95% CI 1.44-17.61).
P
PopulationAdults and children with various medical indications (including epilepsy), pooled n=803
I
InterventionCannabidiol (CBD), oral administration, various dosages
C
ControlPlacebo
O
OutcomeCBD increased, compared to placebo, the risk for study discontinuation (OR 2,61; 95% CI: 1,38–4,96), serious adverse events (OR 2,30; 95% CI: 1,18–4,48), liver function impairment (OR 11,19; 95% CI: 2,09–60,02), decreased appetite (OR 3,56; 95% CI: 1,94–6,53), diarrhoea (OR 2,61; 95% CI: 1,46–4,67), somnolence and sedation; after exclusion of paediatric epilepsy studies only diarrhoea remained significantly associated (OR 5,03; 95% CI: 1,44–17,61)
Confidence in the evidence
Very lowLowModerateHigh
High
The highest of four GRADE levels, the effect estimate is very reliable.
Cannabidiol (CBD) is being investigated as a treatment for several medical disorders but there is uncertainty about its safety. We conducted the first systematic review and meta-analysis of the adverse effects of CBD across all medical indications. Double-blind randomized placebo-controlled clinical trials lasting >/=7 days were included. Twelve trials contributed data from 803 participants to the meta-analysis. Compared with placebo, CBD was associated with an increased likelihood of withdrawal for any reason (OR 2.61, 95% CI: 1.38-4.96) or due to adverse events (OR 2.65, 95% CI: 1.04-6.80), any serious adverse event (OR 2.30, 95% CI: 1.18-4.48), serious adverse events related to abnormal liver function tests (OR 11.19, 95% CI: 2.09-60.02) or pneumonia (OR 5.37, 95% CI: 1.17-24.65), any adverse event (OR 1.55, 95% CI: 1.03-2.33), adverse events due to decreased appetite (OR 3.56, 95% CI: 1.94-6.53), diarrhoea (OR 2.61, 95% CI: 1.46-4.67), somnolence (OR 2.23, 95% CI: 1.07-4.64) and sedation (OR 4.21, 95% CI: 1.18-15.01). Associations with abnormal liver function tests, somnolence, sedation and pneumonia were limited to childhood epilepsy studies, where CBD may have interacted with other medications such as clobazam and/or sodium valproate. After excluding studies in childhood epilepsy, the only adverse outcome associated with CBD treatment was diarrhoea (OR 5.03, 95% CI: 1.44-17.61). In summary, the available data from clinical trials suggest that CBD is well tolerated and has relatively few serious adverse effects, however interactions with other medications should be monitored carefully. Additional safety data from clinical trials outside of childhood epilepsy syndromes and from studies of over-the-counter CBD products are needed to assess whether the conclusions drawn from clinical trials can be applied more broadly.