Introduction: The misuse of stimulant drugs such as
methamphetamine is a global public health issue. One important neurochemical mechanism of
methamphetamine use disorder may be altered dopaminergic neurotransmission. For instance, previous studies using positron emission tomography (PET) have consistently shown that striatal
dopamine D2-type receptor availability (quantified as binding potential; BPND) is lower in
methamphetamine use disorder. Further,
methamphetamine use is known to induce chronic
neuroinflammation through multiple physiological pathways. Upregulation of D2-type receptor and/or attenuation of
neuroinflammation may therefore provide a
therapeutic effect for this disorder. In vitro studies have shown that blockage of
adenosine 2A (A2A) receptors may prevent D2-receptor downregulation and
neuroinflammation-related brain damage. However, no study has examined this hypothesis yet. Methods and Analysis: Using a within-subject design, this trial will assess the effect of the selective A2A receptor antagonist,
istradefylline, primarily on D2-type BPND in the striatum, and secondarily on
neuroinflammation in the whole brain in individuals with
methamphetamine use disorder. The research hypotheses are that
istradefylline will increase striatal D2-type BPND and attenuate
neuroinflammation. Twenty participants with
methamphetamine use disorder, aged 20-65, will be recruited to undergo [11C]
raclopride PET (for every participant) and [
11C]DAA1106 PET (if applicable) once before and once after administration of 40 mg/day
istradefylline for 2 weeks. Neuropsychological measurements will be performed on the same days of the PET scans.