Can Brain Spectroscopy Measure Stimulant Effects Without Measuring Impairment?

Magnetic resonance spectroscopy detected changes in selected brain metabolites after stimulant administration. Those measurements were neither blood drug concentrations nor direct measurements of driving impairment or synaptic neurotransmitter release.

A controlled comparison of two different drugs

White and colleagues enrolled healthy volunteers in a double-blind crossover study of oral d-amphetamine, 20 mg, methamphetamine, 20 mg, and placebo. Spectroscopy focused on the dorsal anterior cingulate cortex approximately 140–150 minutes after ingestion. Although 26 participants were enrolled, the principal spectroscopy analysis described 24 participants with usable data across 66 scans.

Which results were established

D-amphetamine increased glutamate, the pooled glutamate-plus-glutamine measure called Glx, and total creatine. Methamphetamine showed a significant interaction with gender for glutamate, including an increase in women. Neither drug established changes in total N-acetylaspartate, choline or myo-inositol after correction for multiple comparisons. The two drugs should not be assigned identical results.

The biological compartment matters

The authors emphasized that the spectroscopy signal largely represents intracellular metabolite pools over a relatively large tissue volume. It does not isolate moment-to-moment synaptic release. Glx is also a combined measure, not a synonym for glutamate alone. These distinctions are necessary before proposing a mechanism.

What the study cannot diagnose

Some metabolite changes correlated with subjective drug responses, but correlations do not validate an individual intoxication test. Only one brain region and a particular post-dose interval were studied. The experiment provides no conversion between these imaging units and amphetamine or methamphetamine concentrations in forensic whole blood, serum or urine. It supports an acute regional neurochemical effect under the tested conditions, not a universal impairment rule.

Related evidence

For a different perspective on interpreting stimulant evidence, see our analysis of the Swedish amphetamine concentration study. Its study population and outcome should remain separate from the present findings.

Primary research

Psychostimulant drug effects on glutamate, Glx, and creatine in the anterior cingulate cortex and subjective response in healthy humans. Original human research. doi:10.1038/s41386-018-0027-7.