A new study investigates three smoking cessation drugs.
A clinical trial to see whether three established smoking cessation treatments might also decrease alcohol use showed no differences between the medications, although rates of behavior change for both alcohol consumption and smoking were high in all treatment groups. According to the findings, these medications may be crucial in helping people quit smoking and drinking at the same time. Unexpectedly, both the prescription drugs cytisine and varenicline as well as nicotine replacement therapy worked.
400 Russians living with HIV participated in the study, which was conducted by researchers from the First Pavlov State Medical University of St. Petersburg, Russia, Boston University School of Medicine, Boston Medical Center, and Vanderbilt University Medical Center (VUMC). The study was recently published in the journal JAMA Network Open. Volunteers who self-identified as engaged in risky drinking and daily smoking were sought out by the researchers, which included HIV researchers and addiction experts. Following their enrolment in the clinical trial, participants were followed up with for up to a year. Because the medications were placebo-controlled, neither the participants nor the researchers knew which patients were receiving which medicine.
The research revealed that regardless of whether subjects received nicotine replacement therapy, varenicline, or cytisine after three months, alcohol consumption dropped. The primary outcome was the number of days with heavy drinking in the previous month at three months, while the secondary outcomes were alcohol abstinence at three months and smoking abstinence at six months.
“A single medication to treat both risky drinking and smoking could improve health efficiently and significantly. Risky drinking and smoking frequently co-occur, and they both threaten health by increasing risk of cardiovascular disease, cancer, and other important health outcomes,” said the study’s lead author, Hilary Tindle, MD, MPH, the William Anderson Spickard, Jr., MD, Professor of Medicine, and associate professor of Medicine at VUMC.
Researchers are increasingly focusing on comorbidities among people living with HIV, such as cardiovascular disease and cancer, to improve their longevity because there are now effective treatments for the virus.
“It was gratifying to see high-risk research participants being included in NIH-funded research,” said. Matthew Freiberg, MD, MSc, a study principal investigator, Dorothy and Laurence Grossman Chair in Cardiology, and professor of Medicine at VUMC. “They are not only living with HIV but also have a high burden of hepatitis, multi-substance use, and mental health issues. Such participants are often excluded from drug trials. If a medication as simple as nicotine replacement could help them, that would be a win.”
Freiberg noted that when investigators had designed the study, they envisioned nicotine replacement as the “control” arm for alcohol consumption. Nicotine replacement therapy has been available in the United States to treat tobacco addiction since the early 1980s and is not used for the reduction of alcohol consumption.
The study enrolled participants who engaged in five or more heavy drinking days in the past month (defined as five or more drinks in one day for a man or four or more drinks in one day for a woman) and who smoked five or more cigarettes a day.
VUMC researchers worked with Jeffrey Samet, MD, MA, MPH, John Noble, MD, Professor in General Internal Medicine and professor of Community Health Science at Boston University Schools of Medicine and Public Health, and colleagues on the study. Samet’s research focuses on substance abuse and HIV infection.
“Another important observation in our posthoc analysis was that rates of alcohol consumption were lower, and rates of alcohol abstinence were higher, among the people who quit smoking as compared to those who continued to smoke. These results need further study to understand if findings were due to the medications directly, quitting smoking, or both,” said Samet, the senior author of the study.
Tindle added that there is much to be learned about how the study drugs—termed nicotinic acetylcholine receptor agonists—may work to reduce voluntary alcohol intake. Studies in animal models show that stimulation of a very specific receptor type containing the alpha-four subunit is required. Importantly, all three of the study medications target these very receptors.
The investigators concluded that the results of the study, which was conducted from July 2017 to December 2020, extend prior work in several ways. Notably, this is the largest trial to study nicotinic acetylcholine receptor partial agonists to target alcohol consumption and the first to examine cytisine to treat both alcohol and tobacco. Cytisine is not yet approved by the U.S. Food and Drug Administration to treat tobacco use but it has been used widely in Eastern Europe for decades and is under active study globally.
Reference: “Effectiveness of Varenicline and Cytisine for Alcohol Use Reduction Among People With HIV and Substance Use
A Randomized Clinical Trial” by Hilary A. Tindle, MD, Matthew S. Freiberg, MD, Debbie M. Cheng, ScD, Natalia Gnatienko, MPH, Elena Blokhina, MD, Tatiana Yaroslavtseva, MD, Sally Bendiks, MPH, Gregory Patts, MPH, Judith Hahn, Ph.D., Kaku So-Armah, Ph.D., Michael D. Stein, MD, Kendall Bryant, Ph.D., Dmitry Lioznov, MD, Evgeny Krupitsky, MD and Jeffrey H. Samet, MD, 5 August 2022, JAMA Network Open.
The study was funded by the National Institute on Alcohol Abuse and Alcoholism.