Observed Impact of Long-Term Consumption of Oral Cannabidiol on Liver Function in Healthy Adults

Abstract

Introduction: Previous studies have suggested that prescribed cannabidiol (CBD) products may cause elevations in liver tests (LT). This study compared the prevalence of elevated LT in an adult population self-administering CBD with the normal and general adult population prevalences. Materials and Methods: Adults 18–75 years of age across the United States taking CBD orally for a minimum of 30 days were recruited from 12 individual CBD product companies in this decentralized, observational study and sent their standard CBD regimen from the company of their choice. An app-based, 21CFR Part 11 decentralized clinical study platform (ValidCare Study) was used to securely automate consent inclusion/exclusion criteria and collect all the data for this study, including: demographic information, medical history, reasons for taking, dosage, current medications dosage, adverse effects, and efficacy. At the end of 30 days, LTs were obtained. Follow-up LTs were offered to all individuals with elevated alanine transaminase (ALT) values. Results: A total of 28,121 individuals were invited to participate in this study, 1475 enrolled, and 839 (female: 65.3%, male: 34.7%) completed the study. Full-spectrum hemp oil was used by 55.7%, CBD-isolate by 40.5%, and broad spectrum by 3.8%. The mean±SD daily dose of CBD was 50.3+40.7 mg. The prevalence of elevated ALT was 9.1%, aspartate aminotransferase (AST) 4.0%, alkaline phosphatase 1.9%, total bilirubin 1.7%, with 85.5% of the ALT elevations <2×the upper limit of normal (ULN) with only 0.3% having ALT levels >3× ULN. The prevalence of ALT and AST elevations (9.1% and 4.0%) were not significantly different from known adult general population prevalences (8.9% and 4.9%). There was no significant association between CBD dosage and LT values. Thirty-three individuals with elevated ALT levels had follow-up LT performed with 21 having normal LT, 8 having the same severity of ALT elevation, and 4 having an increase in severity, 1 of which ultimately became normal. Conclusions: Self-medication of CBD does not appear to be associated with an increased prevalence of LT elevation and most of the LT elevations are likely due to the conditions/medications for which the individuals are taking CBD.

Cannabidiol and Cannabidiol Metabolites: Pharmacokinetics, Interaction with Food, and Influence on Liver Function

“…It appears likely that non-clinical doses of commercially available CBD are unlikely to represent an appreciable risk to liver function. A similar sentiment was recently expressed in a large study of 839 healthy adults who regularly self-administered CBD (approximately 50 mg/day for 30 days); the authors speculated that the very few examples of unfavorable liver markers could be explained by co-existing medical conditions and/or the use of other supplements and medications [ 60 ].…”

“…In addition, in clinical trials of Epidiolex, indicators of liver dysfunction/damage were noted in four reports [ 56 , 57 , 58 , 59 ]. Alternatively, in a recent cross-sectional study of 839 habitual CBD users, no association was identified between CBD and multiple markers of liver health and function [ 60 ]. Furthermore, based on a review of the potential contribution of the endocannabinoid system to liver disease, others have called for CBD to be included in comprehensive treatments for liver disorders [ 24 ].…”

Safety and Tolerability of Oral Cannabinoids in People Living with HIV on Long-Term ART: A Randomized, Open-Label, Interventional Pilot Clinical Trial (CTNPT 028)

“…Transient CBD-related elevations of ALT and AST are commonly reported in clinical studies [ 40 , 46 , 47 , 48 , 50 , 54 , 56 ]. Transient transaminase abnormalities do not seem to be of critical long-term clinical significance for the liver as they tend to normalize following dose reduction or treatment discontinuation [ 57 , 58 ]. On the other hand, the second participant who experienced abnormally high elevated transaminases was a 62 years old white man with underling fatty liver disease with elevated levels of transaminases (ALT and AST) and blood glucose before the initiation of CBD treatment, along with alcohol binging which was not openly disclosed to the study team.…”

Cannabidiol-enriched cannabis extraction product in Parkinson’s disease: A randomized, double-blind, and placebo-controlled trial in Buriram Hospital

“…Another study showed that 50.3 mg/day of cannabidiol in the healthy population did not affect liver function. [20] Studies on cannabidiol use for PD treatment are limited, and most studies have a small sample size. Hence, this trial was conducted to examine the efficacy of a cannabidiol-enriched cannabis extraction product (CBDEP) on disease severity, QOL, functional performance, anxiety, depression, and renal and liver functions in patients with PD.…”

“…Another study showed that 50.3 mg/day of cannabidiol in the healthy population did not affect liver function. [ 20 ]…”