TY - JOUR
T1 - Cannabidiol-associated hepatotoxicity
T2 - A systematic review and meta-analysis
AU - Lo, Lindsay A.
AU - Christiansen, April
AU - Eadie, Lauren
AU - Strickland, Justin C.
AU - Kim, David D.
AU - Boivin, Michael
AU - Barr, Alasdair M.
AU - MacCallum, Caroline A.
N1 - Publisher Copyright:
© 2023 The Authors. Journal of Internal Medicine published by John Wiley & Sons Ltd on behalf of Association for Publication of The Journal of Internal Medicine.
PY - 2023/6
Y1 - 2023/6
N2 - Background: Findings of liver enzyme elevations in recent cannabidiol studies have raised concerns over liver safety. This study aimed to determine the association between cannabidiol use, liver enzyme elevation, and drug-induced liver injury (DILI). Methods: In this systematic review and meta-analysis, a search of EMBASE, CENTRAL, CINAHL, Clinicaltrials.gov, Medline, medRxiv, and Web of Science of records up to February 2022 was conducted. Clinical trials initiating daily cannabidiol treatment with serial liver enzyme measures were included. The proportion of liver enzyme elevations and DILI were independently extracted from published reports. Pooled proportions and probability meta-analyses were conducted. Results: Cannabidiol use was associated with an increased probability of liver enzyme elevation (N = 12 trials, n = 1229; OR = 5.85 95% CI = 3.84–8.92, p < 0.001) and DILI (N = 12 trials, n = 1229; OR = 4.82 95% CI = 2.46–9.45, p < 0.001) compared to placebo controls. In participants taking cannabidiol (N = 28 trials, n = 1533), the pooled proportion of liver enzyme elevations was 0.074 (95% CI 0.0448–0.1212), and DILI was 0.0296 (95% CI 0.0136–0.0631). High-dose CBD (≥1000 mg/day or ≥20 mg/kg/day) and concomitant antiepileptic drug use were identified as risk factors. No cases were reported in adults using cannabidiol doses <300 mg/day. No cases of severe DILI were reported. Conclusions: Cannabidiol-associated liver enzyme elevations and DILI meet the criteria of common adverse drug events. Clinicians are encouraged to screen for cannabidiol use and monitor liver function in patients at increased risk.
AB - Background: Findings of liver enzyme elevations in recent cannabidiol studies have raised concerns over liver safety. This study aimed to determine the association between cannabidiol use, liver enzyme elevation, and drug-induced liver injury (DILI). Methods: In this systematic review and meta-analysis, a search of EMBASE, CENTRAL, CINAHL, Clinicaltrials.gov, Medline, medRxiv, and Web of Science of records up to February 2022 was conducted. Clinical trials initiating daily cannabidiol treatment with serial liver enzyme measures were included. The proportion of liver enzyme elevations and DILI were independently extracted from published reports. Pooled proportions and probability meta-analyses were conducted. Results: Cannabidiol use was associated with an increased probability of liver enzyme elevation (N = 12 trials, n = 1229; OR = 5.85 95% CI = 3.84–8.92, p < 0.001) and DILI (N = 12 trials, n = 1229; OR = 4.82 95% CI = 2.46–9.45, p < 0.001) compared to placebo controls. In participants taking cannabidiol (N = 28 trials, n = 1533), the pooled proportion of liver enzyme elevations was 0.074 (95% CI 0.0448–0.1212), and DILI was 0.0296 (95% CI 0.0136–0.0631). High-dose CBD (≥1000 mg/day or ≥20 mg/kg/day) and concomitant antiepileptic drug use were identified as risk factors. No cases were reported in adults using cannabidiol doses <300 mg/day. No cases of severe DILI were reported. Conclusions: Cannabidiol-associated liver enzyme elevations and DILI meet the criteria of common adverse drug events. Clinicians are encouraged to screen for cannabidiol use and monitor liver function in patients at increased risk.
KW - CBD
KW - adverse events
KW - cannabidiol
KW - drug-induced liver injury
KW - liver
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U2 - 10.1111/joim.13627
DO - 10.1111/joim.13627
M3 - Article
C2 - 36912195
AN - SCOPUS:85150655917
SN - 0954-6820
VL - 293
SP - 724
EP - 752
JO - Journal of Internal Medicine
JF - Journal of Internal Medicine
IS - 6
ER -