Cannabidiol May Interact With Methadone, Increasing Sleepiness, Fatigue

By Marilynn Larkin

May 26, 2020

NEW YORK (Reuters Health) - A "significant" drug-drug interaction between methadone and cannabidiol was described in a recent case report.

"We are finding out that cannabidiol can have profound effects on the metabolism of other medications that people take," Dr. Kevin Madden of MD Anderson Cancer Center in Houston told Reuters Health by email.

In their report in Pediatrics, Dr. Madden and colleagues describe a 13-year-old girl with metastatic cancer and chronic pain who experienced increasing sleepiness and fatigue, despite having been stable for four months on oral methadone 7.5 mg twice daily for pain control.

Discussion with her parents revealed that the mother had been giving her daughter 5 mL of cannabidiol oil (25 mg/mL) by mouth three times daily for the previous two months. A couple of weeks prior to the current visit, she learned that her daughter's intracranial metastatic lesions were shrinking.

After reading on various websites about cannabidiol's alleged antitumor properties, she assumed that more cannabidiol would shrink her daughter's tumors further. She continued to give 5 mL orally and increased the frequency from three to six times daily.

As a result, her daughter's serum methadone level rose to 271 ng/mL. Two weeks after stopping the cannabidiol, her serum methadone level decreased to 125 ng/mL. The drop coincided with a significant decrease in sleepiness and fatigue.

"Cannabidiol inhibits CYP3A4 and CYP2C19, both of which are involved in the metabolism of methadone," the authors state. "Pediatricians should be aware of this potential interaction and inquire if their patients are receiving cannabidiol."

Dr. Madden said, "I think the general view most of our patients - and many of our colleagues - have is that cannabidiol can be helpful, and at the same time, benign. People may use it with the idea that if it does not help with their particular symptom, at least there are no significant side effects - a 'no harm, no foul' philosophy, if you will."

"Unfortunately, thinking this way, combined with the fear that their healthcare provider may judge them, can lead to a cone of silence, and potentially serious consequences for the patient," he said.

Dr. Santhanam Suresh, Chair, Department of Pediatric Anesthesiology at the Ann and Robert H. Lurie Children's Hospital of Chicago, commented in an email to Reuters Health that recreational use and easy access to medicinal cannabinoids has made the issue of drug-drug interactions, particularly in children, more complicated. "Thirty-three states have approved the medicinal use of marijuana and 11 states, including the District of Columbia, have legalized recreational use."

"Unfortunately, due to the metabolism of opioids by the cytochrome P450 system, the indiscriminate administration of cannabinoids can significantly increase the risk of higher levels of opioids in the serum in this highly vulnerable population," he said.

At Lurie Children's Hospital, he said, "We often create an opioid contract for patients to whom we prescribe opioids for long-term pain control. In addition, it is imperative that parents and caregivers are given other options for reducing anxiety, as opposed to choosing non-FDA approved drugs."

SOURCE: Pediatrics, online May 22, 2020.