Project 6E: Neuroadaptive Circadian Rhythm Changes with Methamphetamine Dependence

Melissa Weimer, D.O., Principal Investigator

Methamphetamine (MA) use is epidemic in the United States. In Oregon, substance abuse treatment admissions for MA are the highest in the country. These are important statistics because MA dependency is associated with high morbidity and mortality including depressive symptoms and increased risk for suicide above that of other chemical dependencies. Strong evidence also supports correlations between circadian misalignment and symptoms of depression and anxiety. Despite these associations very little is known about the correlation between MA dependency and circadian misalignment. In rats, MA administration has been shown to affect circadian oscillators and induce circadian misalignment, which can be measured by the phase angle difference (PAD).

This study proposes to translate these neuroadaptive observations to humans. We hypothesize that preclinical observations of MA-induced circadian phase delay is also present in humans with MA dependence and can be reliably assessed by previously validated circadian misalignment measures (PAD). We will accomplish this in three studies: 1) a feasibility study assesses the success using these techniques in MA dependent subjects; 2) a cross-sectional study assesses the correlation between PAD and MA dependence; 3) a cross-sectional study assesses PAD correlation to severity of MA dependence, depression, anxiety, and delayed discounting in MA dependent subjects. If successful, the study will provide data to support a larger trial investigating the use of melatonin for the treatment of circadian phase delay in MA dependent people. Treatment of a phase delay may improve MA recovery and help repair the maladaptive neuroadaptation that occurs with repeated MA use.