Potentially harmful interactions between ∆9- tetrahydrocannabinol (THC) and irinotecan

Irinotecan (IRI) is one of the most important cytostatics used in the treatment of advanced colon cancer. Some of its side effects such as acute and delayed cholinergic syndrome deteriorate the quality of life in patients. To improve their overall wellbeing, patients often use various supplements, including illegal ∆9- tetrahydrocannabinol (THC) preparations, sometimes containing more than 80% THC [1]. Our study investigated the interactions of IRI and THC at the cellular and organ level of Wistar rats by integrating biochemical, molecular biology and analytical methods. The obtained results provide evidence of a synergistic increase in the acute toxicity of IRI tested at a single intraperitoneal dose of 100 mg/kg under the influence of THC taken per os at a daily dose of 7 mg/kg for one, three and seven days. Concomitant administration of IRI and THC enhances the degree of oxidative stress and genotoxic effects of IRI in liver cells [2]. In rats given the combined treatment, a lowering of leukocyte counts was observed compared with the group treated with single IRI [3]. Concomitant administration of THC with irinotecan enhanced the urinary excretion of THC compared with the group of rats treated with single THC, also suggesting a possible interaction of the tested compounds [4]. From the results obtained, we concluded that concomitant administration of IRI with high doses of THC leads to adverse pharmacokinetic and pharmacodynamic effects. Although the results obtained cannot be directly extrapolated to humans, they indicate a number of undesirable and potentially dangerous side effects as well as the need for extreme caution in the administration of THC in oncology patients. References 1. Kopjar, N. et al, Clinical Drug Investigation, 2020, 40, 775- 787. 2. Lucić Vrdoljak, A. et al., Molecules, 2018, 23, 1332. 3. Prester, Lj. et al., Chemico- Biological Interactions, 2018, 294, 128-134. 4. Fuchs, N. et al. Arhiv Hig Rada Toksikol, 2019, 70, 325-331. Acknowledgment – This study was funded through the programme of cooperation between the Institute for Medical Research and Occupational Health (Zagreb, Croatia) and the University North (Varaždin, Zagreb).