P-062 - (Poster #62) Cannabis and Cancer Pain: A Case of Respiratory Depression with Concomitant Use of Opioids and Cannabinoids

The purpose of this case report is to provide insights for specialists in pain-management on the pharmacodynamic relationship between THC and opioids, and propose the following observations: 

1. 
   

   The importance of obtaining a thorough social history with emphasis on cannabinoid use
   



2. 
   

   The need to proactively counsel patients with history of cannabinoid use about the risks of concurrent opioid therapy
   

Patient: A 39-year-old female with stage IV rhabdomyosarcoma metastasized to the peritoneum, lungs, liver, and bones, presenting to the hospital due to increased abdominal distention and severe pain in her lower abdomen, rectum, and pelvic region.

Setting: Palliative care was consulted to manage cancer-related pain and goals of care conversation in the setting of her terminal diagnosis.

Privacy: All sensitive identifying information for the patient and the primary team was removed from the description of this case.

Results: The patient’s home pain regimen consisting of oral morphine, hydromorphone, fentanyl, pregabalin, and duloxetine were not providing her with adequate management, her average Morphine Equivalent Daily Dose (MEDD) prior to hospitalization was 350-500. She described the pain as 8/10 constant “labor-like” pain focally around her abdomen and pelvic region with no alleviating factors. Palliative discontinued oral morphine and transdermal fentanyl in favor of starting her on  methadone with a hydromorphone patient-controlled analgesia (PCA) with a concurrent continuous hydromorphone rate. The dose for the PCA and continuous rate were decreased to account for incomplete cross tolerance and the methadone dosing was started at a 20:1 ratio from her 3 day average MEDD.  Prior to transition to the PCA, her MEDD was 400 and after the first 24 hours on the PCA regimen, her MEDD was 325. The plan was to use the PCA to bridge her until methadone could reach its full action in 5 days, after which she would be deescalated from PCA and converted to oral pain medications prior to discharge. On the second day of methadone utilization, in light of recent rapid progression of disease, the team held a goals-of-care conversation with the patient to broach the topic of her unfavorable prognosis. Confronting her new prognosis left the patient feeling significant anxiety. That evening, outside the care team’s knowledge, her partner provided her with a home dose of 100mg combined THC and CBD tincture for stress relief. This tincture contained 35% total THC, 45% total CBD, 5% total terpenes and was of the Juanita La Lagrimosa strain. Later that evening, the patient developed bradypnea and unresponsiveness leading to two administrations of Naloxone. The patient became responsive and regained spontaneous respiratory drive. Immediately following, the PCA dosing was decreased and methadone discontinued for one day. Two days after the episode of respiratory depression, the hydromorphone PCA dosing was again increased and methadone restarted with no further respiratory depression or somnolence for the rest of the hospital course despite higher total opioid levels, with her average daily MEDD at 600.

Conclusions/Implications for future research and/or clinical care: Given that the patient was receiving lower opioid doses than her previous regimen, there is concern that the 100mg cannabinoid product was a significant contributing and potentially inciting factor in the episode of acute opioid toxicity. In-vitro modeling with human liver microsomes have shown that THC, CBD, and their metabolites are active inhibitors of UGT2B7, the primary enzyme responsible for morphine glucuronidation. Thus the substrates of morphine are increased when co-administered with CBD and THC, leading to potential adverse events.5 In our case, the patient’s opioid regimen was unchanged on the day of the event and she tolerated higher doses in prior and subsequent days, with the only episode of respiratory depression occurring within several hours of THC/CBD administration and the respiratory depression was reversed immediately with Naloxone administration. Our case underscores the importance of obtaining a thorough social history, including substance use, in the palliative care setting. For patients who use cannabis, explicit counseling regarding the risks of combining high-dose opioids with high-dose cannabinoids is needed. Proactive counseling with patients in this changing landscape of cannabinoid use will become essential for their safety in the setting of high-dose opioids in the treatment of cancer-related pain.