Abstract:
To date, magnetic resonance spectroscopy (MRS) and diffusion-weighted imaging (DWI) studies investigating the effects of methamphetamine addiction on the human brain have only been carried out in abstinent participants; the effects of current use on markers of cellular integrity and white matter microstructure are largely unknown. Furthermore, the association between these markers and methamphetamine use status has not been determined, and the changes that may occur pursuant to agonist replacement therapy have not been investigated. To investigate the changes associated with current use, two studies were performed. The first comprised MRS and DWI investigations of 18 active methamphetamine users and 22 healthy control participants. MRS analysis revealed significantly higher choline-containing compounds in the anterior cingulate cortex of current methamphetamine users; however, no changes in diffusion indices were observed in white matter regions. These findings differ from those reported in abstinent users and suggest that current methamphetamine use has different effects than those observed following abstinence. It is possible that methamphetamine-induced changes may become evident upon drug cessation. In a follow-up sub-study, participants in the methamphetamine users group were enrolled in a randomised, placebo-controlled trial of agonist replacement therapy with sustained-release methylphenidate, and MRI scans were repeated after 10 weeks. Due to high dropout rates, the follow-up component was underpowered to detect whether methylphenidate treatment was associated with positive effects on MRS and diffusion markers; however, further investigation is warranted. The second study was a preliminary investigation of the association between MRS and diffusion markers, and methamphetamine use status. A cross-sectional observational study of 17 female methamphetamine users (11 current, 6 recently abstinent) and 10 female control participants was carried out. MRS analysis revealed no significant differences between groups; however, DWI analysis showed significant changes in diffusion indices within some white matter tracts of abstinent users compared to current users. These initial results suggest that drug-induced changes in white matter microstructure are associated with early abstinence from methamphetamine.