Short-term repeated oral intake of low dose cannabidiol: effects on liver enzyme activity and creatinine concentration during intense exercise

• Published in: Archives of toxicology Vol. 99; no. 2; pp. 815 - 824
• Main Authors: Isenmann, Eduard, Lachenmeier, Dirk W., Flenker, Ulrich, Lesch, Alessio, Veit, Sebastian, Diel, Patrick
• Format: Journal Article
• Language: English
• Published: Berlin/Heidelberg Springer Berlin Heidelberg 01.02.2025; Springer Nature B.V
• Subjects: Administration, Oral; Adult; adverse effects; alanine transaminase; Alanine Transaminase - blood; Aspartate Aminotransferases - blood; Athletes; Biomedical and Life Sciences; Biomedicine; Cannabidiol; Cannabidiol - administration & dosage; Cannabidiol - adverse effects; Cannabidiol - toxicity; Cannabinoids; Creatinine; Creatinine - blood; Cross-Over Studies; Double-Blind Method; Environmental Health; Enzymatic activity; Enzyme activity; exercise; Exercise - physiology; Female; gamma-glutamyltransferase; gamma-Glutamyltransferase - blood; hepatotoxicity; Humans; Liver; Liver - drug effects; Liver - enzymology; Male; Occupational Medicine/Industrial Medicine; oils; Oils & fats; Organ Toxicity and Mechanisms; oxaloacetic acid; Pharmacology/Toxicology; Physiological effects; Placebos; Pyruvic acid; Side effects; Toxicity; Transaminase; Transaminases; Young Adult; γ-Glutamyltransferase; Liver function; Cannabidiol; Exercise; Toxicity; Kidney function
• DOI: 10.1007/s00204-024-03904-1
• ISSN: 0340-5761; 1432-0738

The side effects and safety of cannabidiol (CBD) products are currently discussed in different contexts. Of all adverse effects, hepatotoxic effects have been reported most frequently in previous studies. However, the threshold for liver toxicity of CBD in humans is uncertain due to the lack of adequately designed studies in humans below the lowest observed adverse effect level (LOAEL) of 300 mg/day. In a randomised, three-arm, double-blind, crossover study, the effects of two CBD products (oil and solubilisate (solu) containing 60 mg CBD) were investigated during a high-intensity exercise protocol. Seventeen well-trained subjects (26±4 years, 181±5 cm, 85.6±9.4 kg) participated in the intervention. All subjects were healthy and had no physiological or psychological injuries. Participants were divided into advanced (Ad) and highly advanced (Hi) athletes … They consumed 60 mg of the compound in each microcycle over 7 days. To evaluate possible effects of short-term repeated use of 60 mg CBD on oxaloacetate transaminase (GOT), glutamate pyruvate transaminase (GPT), gamma-glutamyl transferase (GGT) and creatinine (CREA) were analysed before and after each microcycle. GOT increased significantly in both performance levels of the placebo groups (Ad: p≤0.001; Hi: p=0.003). This increase was significantly reduced in the Ad group by both CBD oil (p=0.050, ES=0.66) and CBD solu (p=0.027; ES=0.75). GPT also increased significantly in both placebo groups (Ad: p≤0.001; Hi: p=0.032). This increase was significantly reduced in the Ad group by both CBD oil (p=0.027; ES=0.75) and CBD solu (p=0.023; ES=0.77). These effects were not observed in the Hi group for either parameter. Our results show that short-term repeated use of 60 mg CBD can inhibit exercise-induced liver activity. Furthermore, under the conditions of the present study, there was no evidence for hepatotoxic effects of oral intake of CBD at 60 mg for seven days. Nevertheless, despite the inhibitory effect on exercise-induced liver activity, the study provides evidence for the pharmacological effects of CBD on the liver even at low CBD dose and does not exclude adverse effects in sensitive individuals.