A controlled 2021 study found that oral methamphetamine changed some connections between resting brain networks without producing a statistically significant change within networks under the study’s corrected analysis. “Altered brain connectivity” therefore needs a more precise description than a claim that the drug increased or decreased connectivity everywhere.
What did the experiment involve?
Malina and colleagues studied 22 healthy adults, including 12 women, aged 18–35. Each participant received 20 mg oral methamphetamine and placebo on separate sessions at least four days apart, in counterbalanced order under double-blind conditions.
The administered drug was prepared in an oral syrup. Participants were escorted to a 45-minute imaging session after a post-dose assessment; resting-state scans were collected as part of the larger imaging protocol. These were measurements after a defined acute dose in selected healthy volunteers, not scans diagnosing chronic methamphetamine injury.
What does functional connectivity measure?
The analysis examined relationships among time-varying functional MRI signals. Functional connectivity in this setting describes statistical coordination of signals. It is not a direct count of anatomical connections, a measure of nerve-fiber loss or a blood methamphetamine concentration.
The researchers used independent-component analyses of placebo scans to identify networks, then compared drug and placebo conditions. They distinguished connectivity among regions within a network from connectivity between separate networks. The final analysis included 23 resting-state networks.
The corrected within-network result was nonsignificant
Methamphetamine did not significantly alter within-network connectivity under the Bonferroni-corrected analysis. The paper also examined results at more liberal thresholds. Those exploratory or nominal findings should not replace the main corrected null result.
A nonsignificant result does not prove that within-network effects are impossible. The authors noted that a broad analysis with stricter significance thresholds may miss weaker effects. It does mean this experiment did not establish the broad within-network change under its primary corrected criteria.
Between-network changes went in both directions
| Pattern | Connections reported |
|---|---|
| Increased connectivity | Five pairs involving thalamus or cerebellum and selected sensorimotor, postcentral or middle-temporal networks |
| Decreased connectivity | Two pairs connecting the lateral sensorimotor network with middle-temporal or posterior middle-temporal networks |
The seven affected pairs were not seven new groups of participants. They were network-pair findings from the same 22-person experiment. Increased coordination with a subcortical network could coexist with decreased coordination between cortical networks.
Neither direction is inherently a clinical improvement or injury. Assigning a benefit or deficit requires evidence connecting the specific change to a meaningful functional outcome.
Subjective effects did not provide that bridge
Methamphetamine increased stimulant-like subjective ratings, heart rate and mean arterial pressure. The study did not find significant correlations between subjective responses and the examined connectivity changes.
That observation does not establish a universal separation between experience and brain function. It means these measured changes did not show a significant relationship in this sample. A participant’s subjective response cannot be inferred from an individual network-pair result using this study.
What limits its forensic use?
The sample was small and homogeneous. Resting-state measurements do not necessarily describe connectivity while a person drives, reasons or responds to an emergency. Residual movement remained a possible influence, and the study did not include a perfusion measurement to assess global blood-flow effects.
Network definition and analytic strategy also matter. Findings from this data-driven approach need not duplicate results from studies selecting particular seed regions in advance. Different stimulant drugs, doses and administration routes cannot be silently substituted for one another.
The experiment establishes specific group-level changes under controlled conditions. It does not supply an impairment cutoff, determine the cause of an individual’s behavior, or turn a scan into a measure of permanent damage.
Primary scientific source
Malina M, Keedy S, Weafer J, Van Hedger K, de Wit H. Effects of Methamphetamine on Within- and Between-Network Connectivity in Healthy Adults. Cerebral Cortex Communications. 2021;2:tgab063. doi:10.1093/texcom/tgab063. Original commentary on the supplied controlled human study; citation follows the paper’s author list.
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