Inhaled vs. oral alprazolam: subjective, behavioral and cognitive effects, and modestly increased abuse potential.
Inhaled vs. oral alprazolam: subjective, behavioral and cognitive effects, and modestly increased abuse potential.
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DOI：
10.1007/s00213-014-3721-0
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发表时间：
2015-03
影响因子：
3.4
通讯作者：
Griffiths, Roland R.
中科院分区：
文献类型：
--
作者：
Reissig, Chad J.;Harrison, Joseph A.;Carter, Lawrence P.;Griffiths, Roland R.
对人体和人的研究表明，药物滥用可能性的决定因素是主观效应的发生率。本研究旨在确定与口服途径相比，通过吸入途径给药时阿普唑仑的主观效应发作率和滥用可能性是否会增加。安慰剂，吸入阿普唑仑（0.5，1，2毫克），口服阿普唑仑（1，2，4毫克），在双盲，双模拟条件下，使用交叉设计，在14个健康的参与者与药物滥用史。参与者和观察者的评级，行为和认知性能的措施进行了评估，在9小时的会议。两种给药途径均产生有序的剂量和时间相关效应，剂量越高，效应越大，持续时间越长。吸入阿普唑仑后主观效应的发作非常迅速（例如，2 mg吸入与口服后2分钟与49分钟）。关于滥用可能性的衡量标准（例如，喜欢和良好的效果），吸入阿普唑仑更有效，如剂量反应曲线的显著移动所证明的。尽管存在效力差异，但在最高剂量下，与滥用可能性相关的主观效应的峰值评级（例如，“药物喜好”）在两种途径中相似。关于其他措施（例如，镇静和性能）的途径是等效的。吸入给药途径适度增加了阿普唑仑的滥用潜力，尽管其发病率显著增加。如果上市销售，吸入性阿普唑仑的可用性降低和成本增加可能会降低滥用增加的社会风险。
Infrahuman and human studies suggest that a determinant of the abuse potential of a drug is rate of onset of subjective effects. This study sought to determine if the rate of onset of subjective effects and abuse potential of alprazolam would be increased when administered via inhalation vs. the oral route. Placebo, inhaled alprazolam (0.5, 1, 2 mg), and oral alprazolam (1, 2, 4 mg) were administered under double-blind, double-dummy conditions using a cross-over design in 14 healthy participants with histories of drug abuse. Participant and observer ratings, and behavioral and cognitive performance measures were assessed repeatedly during 9 hour sessions. Both routes of administration produced orderly dose and time-related effects, with higher doses producing greater and longer lasting effects. Onset of subjective effects following inhaled alprazolam was very rapid (e.g., 2 vs. 49 minutes after 2 mg inhaled vs. oral). On measures of abuse potential (e.g., liking and good effects), inhaled alprazolam was more potent, as evidenced by a leftward shift in the dose response curve. Despite the potency difference, at the highest doses, peak ratings of subjective effects related to abuse potential (e.g., “drug liking”) were similar across the two routes. On other measures (e.g., sedation and performance) the routes were equipotent. The inhaled route of administration modestly increased the abuse potential of alprazolam despite significantly increasing its rate of onset. If marketed, the reduced availability and increased cost of inhaled alprazolam may render the societal risk of increased abuse to be low.
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影响因子：
7.6
作者：
Carter, Lawrence P.;Richards, Brian D.;Griffiths, Roland R.
通讯作者：
Griffiths, Roland R.
影响因子：
2.7
作者：
BALSTER, RL;SCHUSTER, CR
通讯作者：
SCHUSTER, CR
影响因子：
4.2
作者：
Nelson, RA;Boyd, SJ;Gorelick, DA
通讯作者：
Gorelick, DA
影响因子：
3.4
作者：
GRIFFITHS, RR;MCLEOD, DR;ROACHE, JD
通讯作者：
ROACHE, JD
影响因子：
5.7
作者：
MacLeod, David B.;Habib, Ashraf S.;Gan, Tong J.
通讯作者：
Gan, Tong J.