The world of addiction has a deeply embedded image of the oft-cited elephant in the room: substance use disorder in a family member, a fellow employee, a loved one; bigger than life, but not mentioned. The elephant in the room.
For opioid treatment programs (OTPs), the elephant is often alcohol, which, when combined with opioids (including therapeutic methadone or buprenorphine) can be dangerous, and even deadly. AT Forum talked about this problem with Lorenzo Leggio, MD, PhD, Chief of the Section on Clinical Psychoneuroendocrinology and Neuropsychopharmacology, a joint NIAAA (National Institute on Alcohol Abuse and Alcoholism) and NIDA (National Institute on Drug Abuse) laboratory.
Alcohol kills 89,000 people a year in the United States—double the rate of opioid overdoses, Dr. Leggio noted.
The problem isn’t only that the combination of alcohol and methadone or buprenorphine is a bad one—it’s the high comorbidity rate of alcohol use disorder and opioid use disorder, Dr. Leggio said. “Roughly 30 to 40 percent of patients who are on agonist maintenance also drink an excessive amount of alcohol—maybe even 50 percent.” And this may be a low estimate—the actual percentage may be much higher. This is based on epidemiological data from the United States and Europe. “It’s a remarkable number, unfortunately,” he said.
From a clinical perspective, the numbers are concerning. First, alcohol has an effect on the way the body metabolizes many drugs. Here’s how it works: the alcohol prevents the methadone from being metabolized, so the levels of methadone in the blood rise.
Sedation

There is also the problem of sedation. In the case of methadone, alcohol would potentiate the effect of the medication—and in turn, the methadone would potentiate the effect of the alcohol. “Think about someone who is on methadone and is also drinking and is driving,” he said. “There’s the risk of sedation,” even if the methadone alone is not sedating (and it isn’t, for stable patients in OTPs). Alcohol, on its own, has a risk of sedation, of course. “By mixing methadone and alcohol, you can have an amplification of this effect,” said Dr. Leggio.
Sedation is a known side effect of methadone. Central nervous system (CNS) depression is also a side effect, and combining methadone with alcohol could be lethal because the person stops breathing—just as they do after an opioid overdose.
“The best way to explain alcohol to patients is to make it clear: this is not trivial,” said Dr. Leggio. “We are talking about the effect of these drugs in your body that may lead to respiratory depression—your brain is not able to handle this, and you can die.”
Be clear to the patient who is taking methadone or buprenorphine that they are increasing their risk of death by drinking alcohol, he said.
On the bright side, methadone and buprenorphine patients, by definition, have been bought into treatment. “They are already committed to try to improve their health,” said Dr. Leggio.
So what can an OTP do? According to Dr. Leggio:
- Screening. First, the assessment must be clinically oriented and comprehensive, including alcohol screening. “You can use CAGE, you can use AUDIT, but you need to use some well-validated tool.”
- Patient education. “Patients may not recognize that alcohol is problem for them.” Lorenzo Leggio,
- Treatment. Depending on the level of care needed, providing brief intervention, motivational interviewing, or contingency management may be effective. Cognitive behavioral therapy is more complex and requires more time, but is also effective. “Try to do the treatment as part of a comprehensive approach,” said Dr. Leggio. For example, if the patient is coming into the OTP for methadone dosing, perform the alcohol counseling at the same time. And remember, it could be as simple as a brief intervention; if patients learn about the dangers, they may stop drinking, or at least reduce their drinking.
- Medications. This can be a complex issue, said Dr. Leggio, moving on to discuss three medications indicated for alcohol use disorder: naltrexone, acamprosate, and disulfiram. Patients on buprenorphine or methadone can’t take naltrexone, a medication that is only for patients who are opioid-free, but does reduce alcohol cravings. However, the patient may want to taper off methadone and buprenorphine (this is unlikely, but just in case a patient is interested in doing that, the naltrexone would be a good solution to prevent opioid use and reduce or prevent alcohol use). However, it’s important to remember that naltrexone reduces alcohol cravings in only 30% of patients—and nobody knows ahead of time which 30%.
There are no studies in which acamprosate, indicated for alcohol use disorders, has been studied in the context of methadone, said Dr. Leggio, but it would also be a possible treatment. He flatly ruled out disulfiram (which causes the patient to become very ill temporarily when combined with alcohol). “I would be concerned about the disulfiram syndrome in the context of opioid use disorder,” he said.
Finally, Dr. Leggio pointed to the fact that so few people get treatment for substance use disorder. “If we provided treatment to only 10 percent of people with breast cancer, it would not be accepted, but with addiction, it is accepted,” he said. “At the end of the day, we tend to put our head under the sand, until we are hit personally” by addiction. “It doesn’t help that we are so far beyond other medical fields, like cancer and infectious disease; it doesn’t help that there is so much we don’t understand.”
And criticism is more pointed in addiction than in the rest of the field. A Nobel Prize in Physiology or Medicine was awarded for cancer immunotherapy, a treatment that helps one-third of patients—the same success rate as naltrexone for alcohol, noted Dr. Leggio. However, for the cancer treatment, a molecular analysis can be done to predict whether a patient will respond or not. “For naltrexone, we don’t have that knowledge yet,” he said.
NIAAA is currently funding clinical trials looking at ondansetron and topiramate for alcohol use disorder. “But a trial is very expensive, with multiple sites needed,” said Dr. Leggio. Of course, physicians are free to use approved medications off-label.
If the most an OTP can do is get a patient to reduce his or her drinking, that would be a “clinical success,” said Dr. Leggio. “If a patient were to drop from five drinks a day to one, would that be a success?” we asked. “That would be a wonderful success, I would sign off on that,” he said. “You have to be practical and compromise, and sometimes do baby steps. Abstinence should be the real goal, but reduction is an important goal.”