Acute neurocognitive and subjective effects of oral methamphetamine with low doses of alcohol: A randomised controlled trial

Background: Methamphetamine is often recreationally co-consumed with alcohol due to desirable off-target effects; however, the acute neurocognitive and subjective consequences of combined use are unclear. Methods: In a randomised, placebo-controlled, counterbalanced, cross-over study design, the effects of acute oral methamphetamine (0.42 mg/kg) were assessed with and without low doses of alcohol (target 0.04% blood-alcohol concentration, BAC) on subjective intoxication, alertness, physiological outcomes and neurocognition during the ascending and descending phases of the BAC curve. Sixteen healthy adults (mean age = 30.4 years, SD +/- 4.4, 67% male) completed four experimental sessions over 4 weeks involving a one-week washout period. Results: Cardiovascular measures [heart rate (beats/minute), blood pressure (mmHg)] were predictably elevated following methamphetamine, but unaffected by combined alcohol use. Methamphetamine and alcohol produce divergent effects on subjective alertness and sedation across time, yet their combination produced predominantly sustained stimulative effects independent of the biphasic alcohol curve. At a peak BAC of 0.029%, alcohol alone impaired performance across most functional neurocognitive domains relative to placebo and methamphetamine only, and the addition of methamphetamine attenuated these effects. Methamphetamine alone produced isolated improvement in psychomotor speed consistent with peak drug effects. Conclusion: Methamphetamine combined with alcohol does not substantially alter the physiological or metabolic profile compared to either drug alone. Strong stimulative effects of methamphetamine appear to mask the biphasic sedative and performance effects of low doses of alcohol, which may underlie motivations for co-consumption in recreational settings and increase propensity for harm.