Metabolism of (-)-∆9-Tetrahydrocannabinol (THC) in Chicken and Potential Exposure of THC and Its Metabolites to Humans

• Published in: The Journal of pharmacology and experimental therapeutics 2023-06, Vol.385, p.176-177
• Main Authors: Wang, Ziteng, Soo, Chock Ying, Goh, Evelyn Mei Ling, Moy, Hooi Yan, Chan, Eric Chun Yong
• Format: Article
• Language: English
• ISSN: 0022-3565
• DOI: 10.1124/jpet.122.152520

Abstract ID 15252 Poster Board 176 One recent study reported fewer cases of avian bronchitis and higher quality of meat when chicken were fed daily supplementation of cannabis.1 The exposure to primary substances of cannabis, namely (-)-∆9-tetrahydrocannabinol (THC) and its psychoactive metabolite, 11-OH-THC, in meat and egg of these supplemented chickens rarely received attention. Notably, these substances could be consumed by humans, raising health and legal issues. To explore the potential impact, we aimed to comprehensively investigate the pharmacokinetics (PK) of THC and 11-OH-THC in chicken and humans via in vitro and in silico approaches. In vitro metabolism experiments were performed to characterize metabolism of THC and 11-OH-THC using chicken liver microsomes (CLM). Kinetic parameters were calculated and compared with those derived from human liver microsomes (HLM). Thermal stabitilties of THC and 11-OH-THC were further assessed by mimicking the cooking process. PK of THC and 11-OH-THC and their distribution to muscle and egg were predicted via physiologically-based pharmacokinetic (PBPK) modeling. Oral consumption of 11-OH-THC in meat or egg was simulated under fed condition to predict its exposure to humans. The depletion of THC in CLM was slower than that in HLM (Fig. 1A). Intrinsic clearances (CLint) were estimated as 0.49 and 54.03 ml/min/g of chicken and human liver, respectively. Similarly, 11-OH-THC was more metabolically stable in CLM than in HLM, where UGT and P450 enzymes accounted for 67.5% and 32.5% of 11-OH-THC depletion in CLM, with CLint of 0.33 and 0.16 ml/min/g liver, respectively (Fig.1B). PBPK modeling predicted elimination half-lives of THC and 11-OH-THC in chicken as 79.3 and 27.2 h, respectively, demonstrating that both compounds were slowly eliminated (Fig. 1C and D). Their extensive distribution to chicken muscle and egg were simulated as well. However, high temperature incubation degraded most THC within 30 min, suggesting its substantial loss in a cooked chicken meal. Conversely, 11-OH-THC remained thermally stable (Fig. 1E). Subsequent PBPK modeling in humans simulated 1.68-fold increase in systemic exposure of 11-OH-THC in the presence of meal, suggesting food effect on systemic absorption of 11-OH-THC (Fig. 1F). Our study established the PK of THC and 11-OH-THC in chicken, and revealed that 11-OH-THC may reside in chicken products even after cooking. Oral absorption of 11-OH-THC in humans could be significantly augme