Methamphetamine use may increase an individual’s relative risk of developing Parkinson’s disease by as much as 76%, based on the results of a large retrospective database study.
"Our epidemiological data showing, in hospitalized methamphetamine users, increased risk of subsequent diagnosis of PD [Parkinson’s disease] in hospitalization or death records provides support to the long-hypothesized notion, based on animal data, that methamphetamine exposure might lead to enduring damage of brain dopamine neurons in humans," Dr. Russell C. Callaghan and his coinvestigators wrote in Drug and Alcohol Dependence.
More than 30 years ago, researchers discovered that methamphetamine and its metabolite amphetamine can harm brain dopamine neurons in animal testing. The animal findings raise the concern that use of methamphetamine might damage dopamine neurons in humans and thereby increase the risk of developing PD.
To assess the risk of PD among patients who had used methamphetamine and amphetamine-like drugs, the investigators searched hospital inpatient admission data from 1990 until 2005 from the Patient Discharge Database of the California Office of Statewide Health Planning and Development. These data contain records with demographic information and diagnoses for each inpatient discharged from a California-licensed hospital, including general acute care, acute psychiatric care, chemical dependency recovery, and psychiatric health facilities. The inpatient data were then linked to death records from the California Vital Statistics Database.
Dr. Callaghan of the Centre for Addiction and Mental Health, Toronto, and his associates pulled together three cohorts for the study: 207,831 patients admitted for appendicitis, 35,335 patients admitted for a cocaine-related ICD-9 code, and 40,472 patients admitted for ICD-9 codes related to amphetamine or other psychostimulants (Drug Alcohol Depend. 2011 [doi:10.1016/j.drugalcdep.2011.06.013]).
Patients in the appendicitis group had to be at least 30 years old with a diagnosis of an appendicitis-related condition. They could have no recorded indications or signs of PD or methamphetamine or cocaine use.
Likewise, patients in the cocaine group had to be at least 30 years old and had an ICD-9 code related to cocaine dependence, abuse, or poisoning. They could have no recorded indications or signs of PD, other alcohol or drug use, or HIV.
For the methamphetamine group, the researchers noted that it is not possible to distinguish between methamphetamine and other amphetamine-like stimulants based on ICD-9 codes. However, based on previous studies "we argue that it is reasonable to expect that the bulk of the admissions in our study are specific to methamphetamine."
The methamphetamine cohort had a significantly greater risk of a PD outcome – with a hazard ratio 1.76 – than did the appendicitis group. A PD outcome was measured as an inpatient admission with a diagnosis of PD or an underlying cause of death listed as PD. This result was based on a competing risks analysis using a 1:1 matched sample.
The increased risk "means that if we followed 10,000 methamphetamine users (at least 30 years of age) and 10,000 people of similar age, race, and sex from a California population-based sample for 10 years, we would expect approximately 21 cases of PD in the methamphetamine group and approximately 12 in the population group."
Similarly, the methamphetamine group had a greater risk of developing PD than did the cocaine group (hazard ratio, 2.41). But the cocaine group did not have a higher risk of developing PD than did the appendicitis group (HR, 1.04).
One important limitation of the study is its lack of information on the age of initiation, frequency, dose, or duration of drug use. "Nevertheless, it is reasonable to assume that the drug users in our study were, for the most part, ‘moderate to heavy’ stimulant users having clinically significant problems as indicated by a formal hospital diagnosis of a methamphetamine-use disorder," the investigators concluded.
"While our study does raise the question of whether licit amphetamines might also increase the risk of Parkinson’s disease, it is important to emphasize that our findings might not at all relate to those individuals who take much lower doses of amphetamine drugs for therapeutic purposes (e.g., for ADHD)."
All of the authors reported that they have no conflicts of interest.