Methamphetamine abuse is known to be bad for many reasons; one of the least known is its association with pulmonary arterial hypertension (PAH). Roham Zamanian, MD (associate professor, pulmonary & critical care medicine), has followed the geographic spread of the meth epidemic, including both production and use, from its US origin in the California Central Valley across isolated areas of the American West to current hotbeds in Appalachia and the Ohio Valley. It turns out that many of his patients with PAH admit to a history of meth abuse.

Methamphetamine abuse is a much larger problem than people realize. According to Zamanian, “A United Nations World Drug Report a few years ago found methamphetamine and amphetamine abuse to be second most common to marijuana worldwide. It is beyond cocaine and far greater globally than the opioid abuse problem was just two or three years ago.”

The worldwide spread of methamphetamine abuse is daunting. Zamanian finds that his European colleagues don’t think of it as a serious drug problem but, he says, “the European Monitoring Centre for Drugs and Drug Addiction has quantified a substantial portion of the population, especially in Scandinavia and the United Kingdom, as abusers of methamphetamine. The main production areas for methamphetamine in Europe are in Czechoslovakia and Slovenia. Five percent of European 15 to 34 year olds and 3.8 percent of adult Europeans have reported lifetime use of amphetamines. South East Asian and Middle East markets are rampantly drug trafficking and abusing.”

A corollary to those facts is that Stanford’s clinic that treats patients with PAH is also growing.

California’s first methamphetamine epidemic actually peaked in 2006. By then the Department of Justice had put a response in place, greatly increasing enforcement of existing laws and rooting out known meth labs. Although the abuse declined until 2010, it began to increase again, especially in 2013 and 2014, and has now surpassed the peak of 2006. At the same time, meth has become cheaper and purer and therefore more addictive. As someone who deals with the fallout of the problem, Zamanian shares recent data from the Department of Justice that foretells another major epidemic in California in 2017 and 2018.

Breaking Bad introduced many people in America to the sad story of methamphetamine use, and a lot of viewers saw it as glorifying the abuse. Zamanian didn’t see it that way. He explains, “I saw from Breaking Bad the recognition that this is a major epidemic in at least part of the United States. It is a disease of people not in urban or even suburban areas but in the farmlands or very isolated areas of the country. A lot of experts realize that methamphetamine abuse is a class-dependent drug problem.”

He continues: “Unfortunately, we at Stanford are at the epicenter of methamphetamine abuse in the United States, and so we see a greater number of methamphetamine-related PAH patients than we would like. Up to 30 to 40 percent of our patients who come in with this rare disease have a methamphetamine history."

As a research group, Zamanian and his colleagues started tracking their patients with meth-associated PAH In 2003. “The paper that we are working on now,” he says, “demonstrates that they do worse over 5 to 10 years than other PAH patients. We don’t know the exact mechanism, perhaps through the serotonin pathway, by which methamphetamine use leads to pulmonary hypertension. It is very hard to show an association, but it will be even harder to show causation.

To better define their PAH patients with a history of methamphetamine use and differentiate them from pulmonary hypertension patients without such a history, Zamanian and his colleagues “compared 97 patients with idiopathic PAH (iPAH) and 90 patients with methamphetamine-associated PAH. Pulmonary hypertension is a female-dominant disease and only 17 percent of our iPAH patients were men, but 37 percent of our meth-associated PAH patients were men. Compared with the iPAH patients, the meth-using PAH cohort was less of Hispanic and Asian Islander background, and thus more white. Their age at presentation was similar at 45 years.”

Zamanian further delineates his two patient groups: “What is very interesting is that in both groups of patients, the percent with median household income below the poverty level and the percent with a college degree were the same. Followed long term, fewer methamphetamine-associated PAH patients were adherent to physician recommendations regarding taking their prescribed medications and stopping methamphetamine use.”

With data now available on these patients from 2003 to 2015, the group is currently writing a manuscript for publication. Zamanian explains that “our statistical modeling pointed to the patients with methamphetamine-associated PAH being worse than other patients, such as pulmonary hypertension in patients with HIV or scleroderma or liver disease. The natural history of methamphetamine-associated PAH is far worse than that of iPAH or pulmonary hypertension associated with these other diseases.”

Having an excellent partnership with translationally-minded physician scientists like Dr. de Jesus Perez allows for us to increase the impact and breadth of our clinical research.

The manuscript has two distinct aims. First, it identifies methamphetamine-associated PAH as a distinct phenotype: “methamphetamine-associated PAH is a highly fatal condition that has prognostic outcome implications. These patients do worse than other PAH patients.” Its second aim is to answer the question: Is meth-associated pulmonary arterial hypertension a different disease or the same disease but in an unusual cohort? According to Zamanian, “We argue that it is a different disease than idiopathic pulmonary arterial hypertension.”   At present, efforts to further understand the genetic basis for methamphetamine-associated PAH are being carried out by Vinicio de Jesus Perez, MD (assistant professor of medicine, pulmonary & critical care medicine), whose genotyping of these patients led to the discovery of pathogenic variants that could enhance the risk of disease development in carriers who are exposed to methamphetamine. Zamanian feels that his collaboration with de Jesus Perez highlights the power of clinical observations and how they can lead to cutting-edge clinical translational discoveries in a nurturing academic environment: “Having an excellent partnership with translationally-minded physician scientists like Dr. de Jesus Perez allows for us to increase the impact and breadth of our clinical research.”

When the TV series Breaking Bad ended in 2013 after a five-year run, it entered the Guinness Book of World Records as the most critically acclaimed show of all time. We can only hope it impressed upon its viewers the downsides of methamphetamine abuse especially, as it is turning out, pulmonary arterial hypertension.