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Controlled Clinical Trial
. 2011 Dec 15;119(3):187-93.
doi: 10.1016/j.drugalcdep.2011.06.006. Epub 2011 Jul 6.

Physiological and subjective effects of acute intranasal methamphetamine during extended-release alprazolam maintenance

Joshua A Lile  1 , William W Stoops, Paul E A Glaser, Lon R Hays, Craig R Rush
Affiliations
Controlled Clinical Trial

Physiological and subjective effects of acute intranasal methamphetamine during extended-release alprazolam maintenance

Joshua A Lile et al. Drug Alcohol Depend. .

Abstract

Background: Medications development for methamphetamine dependence is ongoing, but no widely accepted, effective pharmacotherapy has been identified. Previous studies have demonstrated neurobiological perturbations to central GABA(A) activity following chronic stimulant use, and that positive modulation of GABA(A) receptors attenuates the neurochemical and behavioral response to stimulant drugs such as methamphetamine. Therefore, GABA(A) modulators could be useful as pharmacotherapies for stimulant-use disorders.

Methods: This study tested the hypothesis that intranasal methamphetamine would be safe and well tolerated during maintenance on extended-release alprazolam (XR), and that the effects of methamphetamine would be attenuated. Eight non-treatment-seeking, stimulant-dependent individuals completed an inpatient experiment in which ascending doses of intranasal methamphetamine (0, 5, 10, 20 and 30 mg) were administered after four days of alprazolam XR maintenance (0 and 1mg/day).

Results: Intranasal methamphetamine produced prototypical effects (e.g., increased positive subjective ratings and elevated cardiovascular signs). The combination of intranasal methamphetamine and alprazolam XR was safe and well tolerated. Alprazolam XR produced small, but orderly, reductions in some of the subjective effects of methamphetamine, and performance impairment.

Conclusions: The present results demonstrate that methamphetamine use during alprazolam XR treatment would not pose a significant safety risk. Given the potential of GABA(A) positive modulators to manage certain aspects of stimulant abuse and dependence (i.e., drug-induced seizures, anxiety and stress), but the relatively small impact on the acute abuse-related effects of methamphetamine observed here, additional research with GABA(A) positive modulators is warranted, but should consider their use as an adjunct component of combination behavioral and/or drug treatment.

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Figures

Figure 1
Figure 1
AUC dose-response functions for methamphetamine during maintenance on placebo (squares) and 1 mg/day alprazolam XR (circles) for the number of symbols attempted and correct on the DSST, systolic pressure and heart rate. Data were divided by the coefficient used for AUC calculation (5, which corresponds to the number of post-methamphetamine time points). X-axis: Intranasal methamphetamine dose. PL denotes placebo. Data points represent means for eight subjects. Filled symbols indicate the data point differs significantly from the placebo condition (i.e., 0 mg methamphetamine during maintenance on 0 mg alprazolam XR). An asterisk indicates that the data point is significantly different from the corresponding dose of methamphetamine during maintenance on 0 mg alprazolam XR. Error bars represent 1 S.E.M.
Figure 2
Figure 2
Area-under-the-curve (AUC) dose-response functions for methamphetamine during maintenance on placebo (squares) and 1 mg/day alprazolam XR (circles) for VAS ratings of Any Effect, Stimulated and High on the Drug-Effect Questionnaire and scores from the Stimulant scale of the Adjective Rating Scale. Other details are as in Figure 1.
See this image and copyright information in PMC

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