Does Methamphetamine Change Anticipation of Loss More Than Reward?

A controlled human experiment found that methamphetamine changed selected brain responses while participants anticipated losing money. It did not produce a uniform increase in responses to rewards, and the imaging findings do not establish impaired judgment in an individual.

A task separating anticipation from outcome

Molla and colleagues analyzed 43 healthy adults in a double-blind, within-person comparison of oral methamphetamine, 20 mg, and placebo. During functional MRI, participants completed a monetary incentive delay task. Cues signaled potential gains, losses or neutral outcomes, allowing investigators to distinguish waiting for an outcome from receiving it.

The positive result was specific

Methamphetamine increased ventral-striatal and anterior-insular activation during anticipation of loss compared with non-loss. The corresponding effects during anticipation of gains and feedback for wins or losses were not significant. Exploratory whole-brain analyses also did not establish significant drug-related clusters. A finding in a selected region is not interchangeable with a positive whole-brain result.

Brain activation is a measured signal, not a behavior

Arterial spin labeling showed reduced regional cerebral blood flow. That matters because functional imaging depends on physiological signals; greater task-related activation does not simply mean more dopamine, more neurons or better decisions. The study did not validate a methamphetamine concentration in blood, urine or oral fluid as a threshold for any of these imaging outcomes.

What the experiment can explain

The results support a narrowly defined effect on processing potentially important negative events. They cannot show that a particular person became more cautious, more reckless or unable to drive. A single oral dose in healthy volunteers differs from repeated use, dependence and sleep deprivation. The healthy, relatively homogeneous sample and task-specific analysis limit generalization.

Related evidence

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

Primary research

Methamphetamine Enhances Neural Activation During Anticipation of Loss in the Monetary Incentive Delay Task. Original human research. doi:10.1093/texcom/tgad014.