TY - JOUR
T1 - Physiological and subjective effects of acute intranasal methamphetamine during extended-release alprazolam maintenance
AU - Lile, Joshua A.
AU - Stoops, William W.
AU - Glaser, Paul E.A.
AU - Hays, Lon R.
AU - Rush, Craig R.
N1 - Funding Information:
This research and the preparation of this manuscript were supported by grants from the National Institute on Drug Abuse ( R01 DA025591 to Craig R. Rush and K01 DA018772 to Joshua A. Lile) and a grant from the University of Kentucky Center for Clinical and Translational Science . These funding sources had no further role in study design; in the collection, analysis and interpretation of data; in the writing of the report; or in the decision to submit the paper for publication.
PY - 2011/12/15
Y1 - 2011/12/15
N2 - 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 1. mg/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.
AB - 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 1. mg/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.
KW - Alprazolam
KW - Benzodiazepine
KW - Human
KW - Methamphetamine
KW - Pharmacotherapy
KW - Subjective effects
UR - http://www.scopus.com/inward/record.url?scp=82555192458&partnerID=8YFLogxK
U2 - 10.1016/j.drugalcdep.2011.06.006
DO - 10.1016/j.drugalcdep.2011.06.006
M3 - Article
C2 - 21737214
AN - SCOPUS:82555192458
SN - 0376-8716
VL - 119
SP - 187
EP - 193
JO - Drug and Alcohol Dependence
JF - Drug and Alcohol Dependence
IS - 3
ER -