(148) Tacrolimus Variability With Cannabis Use After Alcohol-Associated Liver Transplant

Background & Introduction: Approximately 23% of liver transplant recipients report cannabis use, yet there is limited guidance on how to clinically manage ongoing cannabis use after transplantation in a manner that balances patient safety, graft outcomes, and engagement in care [1-3]. Interactions between cannabis and tacrolimus have previously been described in case reports, but a recent Phase I clinical trial was the first to prospectively demonstrate an increase in tacrolimus levels with oral cannabinoid administration, highlighting the importance of more rigorous quantitative research in this area [5]. Guidelines from societies such as the AASLD and EASL recommend a formal psychosocial assessment pre-transplant that includes a comprehensive substance use history treatment not just limited to alcohol but also other substances [1,2]; however, there is limited guidance on managing ongoing cannabis use post-transplant. This case illustrates the critical need to incorporate comprehensive substance use screening, counseling, and management through a multidisciplinary and harm-reduction approach in liver transplant recipients.

Case Description: A 43-year-old male with a history of alcohol use disorder (AUD), end-stage renal disease, and acute liver failure from alcohol-associated liver disease presented with refractory hepatic encephalopathy. He reported daily alcohol use and occasional cannabis use. Following a liver-kidney transplant, the patient was started on tacrolimus and enrolled in a multidisciplinary transplant clinic (METRIC). While he maintained abstinence from alcohol, his cannabis use escalated from once every few weeks to 5–10 blunts daily, triggered by psychosocial stressors, including familial loss and housing instability. Concurrently, marked tacrolimus trough variability was observed, with levels reaching 30 ng/mL (target 8–10 ng/mL), temporally associated with escalation in cannabis use. This required a decrease in his tacrolimus dose from 16mg to 9mg daily. In METRIC, he met with a psychologist and transplant psychiatrist with expertise in substance use disorders, who explored psychosocial drivers of increased cannabis use and provided counseling on risks including invasive fungal infection and potential drug–drug interactions between cannabinoids and tacrolimus metabolism. He was both counseled on stress management techniques and connected to a medical cannabis program for edible options. A longitudinal therapeutic alliance allowed the patient to disclose that limited accessibility and affordability of non-inhaled cannabis products contributed to continued inhalation despite understanding associated risks.

Conclusion & Discussion: This case highlights the growing clinical challenge of managing cannabis use after liver transplantation, an area where evidence and standardized post-transplant guidance remain limited. The rates of increased cannabis use in cases of alcohol cessation have not yet been studied and is a gap in the current literature. This patient’s clinically significant tacrolimus level variability raises concern for a potential pharmacokinetic interaction between cannabinoids and calcineurin inhibitors for the transplant population. An early phase-I trial with a small sample size of 15 patients showed a 4.2‐fold increase in tacrolimus level even with oral cannabinoids. However, trials of non-ral formulations and dose-dependent effects are lacking [5]. Addressing these gaps will allow evidence-based counseling, the ability to anticipate dose adjustment and limit toxicity in patients who continue cannabis use post-transplant.

This case also highlights the benefits of a multidisciplinary, harm-reduction-oriented transplant model. The established therapeutic relationship with a METRIC psychologist and psychiatrist allowed for continued patient engagement, early identification of risk, and the transparent disclosure of cannabis use which informed shared clinical decision making.

References: 1. Yan K, Forman L. Cannabinoid use among liver transplant recipients. Liver Transplantation. 2021;27(11):1623–1632. doi:10.1002/lt.26103.
2. Likhitsup A, Saeed N, Winder GS, et al. Marijuana use among adult liver transplant candidates and recipients. Clinical Transplantation. 2021;35(7):e14312. doi:10.1111/ctr.14312.
3. Guorgui J, Ito T, Markovic D, et al. The impact of marijuana use on liver transplant recipients: A 900-patient single-center experience. Clinical Transplantation. 2021;35(4):e14215. doi:10.1111/ctr.14215.
4. Substance Abuse and Mental Health Services Administration. Key Substance Use and Mental Health Indicators in the United States: Results from the 2023 National Survey on Drug Use and Health. HHS Publication No. PEP24-07-021. Rockville, MD: Substance Abuse and Mental Health Services Administration; 2024.
5. So GC, Lu JBL, Cheng Y-H, et al. A Phase I trial of the pharmacokinetic interaction between cannabidiol and tacrolimus. Clin Transl Sci. 2025;18(2):e70152. doi:10.1111/cts.70152.