An experiment linked drug-free reward-cue activation to later methamphetamine-induced euphoria, while the corresponding activation under methamphetamine did not show the same association. A baseline correlate and a drug-induced brain change are different findings.
Molla and colleagues used a randomized, double-blind, within-participant design comparing 20 mg oral methamphetamine with placebo in healthy adults. Eighty-eight participants contributed to the imaging analysis after exclusions.
During fMRI, a monetary incentive task separated anticipation and receipt of gains and losses. Questionnaires assessed subjective effects, including euphoria. Brain responses to monetary cues and the pleasurable effects of the drug were measured separately.
Caudate activation during reward anticipation in the placebo session correlated with methamphetamine-induced euphoria. The corresponding drug-related activation measure did not significantly correlate with euphoria.
Methamphetamine reliably increased subjective euphoria but had minimal effects on the examined reward-gain activation measures. Its significant ventral-striatal effect during loss anticipation was not significantly associated with euphoria. A proposed common reward mechanism therefore cannot be inferred simply because both measures are called rewarding.
A correlation in this dataset is not a validated personal test for drug liking or future dependence. Nor does failure to detect the drug-state correlation prove that the mechanisms are wholly independent. The task sampled monetary incentives, a single oral dose and a selected healthy population.
The imaging and questionnaire endpoints were not drug concentrations or impairment thresholds. The paper supports separating baseline responsivity, drug-induced change and subjective experience when evaluating a claimed reward biomarker.
See earlier loss-anticipation research with a different question.
Effects of methamphetamine on two measures of reward: Euphoria and neural activation to reward cues. doi:10.1038/s41386-025-02110-6.