Acute Physiological and Behavioral Effects of Intranasal Methamphetamine in Humans

Abstract

Intranasal methamphetamine abuse has increased dramatically in the past decade, yet only one published study has investigated its acute effects under controlled laboratory conditions. Thus, the current study examined the effects of single-dose intranasal methamphetamine administration on a broad range of behavioral and physiological measures. Eleven nontreatment-seeking methamphetamine abusers (two females, nine males) completed this four-session, in-patient, within-participant, double-blind study. During each session, one of four intranasal methamphetamine doses (0, 12, 25, and 50 mg/70 kg) was administered and methamphetamine plasma concentrations, cardiovascular, subjective, and psychomotor/cognitive performance effects were assessed before drug administration and repeatedly thereafter. Following drug administration, methamphetamine plasma concentrations systematically increased for 4 h postdrug administration then declined. Methamphetamine dose dependently increased cardiovascular measures and 'positive' subjective effects, with peaks occurring approximately 5-15 min after drug administration, when plasma levels were still ascending. In addition, cognitive performance on less complicated tasks was improved by all active methamphetamine doses, whereas performance on more complicated tasks was improved only by the intermediate doses (12 and 25 mg). These results show that intranasal methamphetamine produced predictable effects on multiple behavioral and physiological measures before peak plasma levels were observed. Of interest is the dissociation between methamphetamine plasma concentrations with cardiovascular measures and positive subjective effects, which might have important implications for potential toxicity after repeated doses. INTRODUCTIONAlthough methamphetamine abuse has increased dramatically over the past decade, much of our knowledge about its acute effects in humans is anecdotal. The drug is frequently abused via the intranasal, i.v., and smoked routes (Domier et al, 2000; Community Epidemiology Work Group, 2005), but few studies have evaluated the acute effects of methamphetamine in humans using these routes of administration. The majority of studies conducted with humans have focused primarily on the cardiovascular and subjective effects produced by oral methamphetamine, a route of administration least often associated with abuse presumably due to its slow onset of effects. The onset of peak effects produced by oral methamphetamine does not occur until about 90 min after the administration (Hart et al, 2001a). By comparison, peak effects produced by intranasal, smoked, and i.v. methamphetamine occur within 15 min (Harris et al, 2003;Newton et al, 2005).Given that the rapidity of drug-related effects is a critical determinant of abuse liability (Hatsukami and Fischman, 1996), it is surprising that only a few studies have examined methamphetamine-related effects via routes of administration other than oral (eg Cook et al, 1993;Mendelson et al, 1995;Newton et al, 2006). Although inhalation by s...

Methamphetamine self-administration in humans during d-amphetamine maintenance

“…Methamphetamine administered alone dose dependently increased positive subject-rated drug-effects (e.g., Like Drug; Willing to Take Again), which is consistent with the results of previous research (e.g., [21][22][23][24]. d-Amphetamine maintenance attenuated some of the positive subject-rated drug-effects, which is consistent with a previous study that showed 45 mg/day d-amphetamine reduced the subject-rated drug-effects of methamphetamine (8).…”

“…Finally, methamphetamine dose dependently increased systolic blood pressure and d-amphetamine maintenance attenuated these increases, compared to placebo maintenance. These findings are consistent with the results of prior studies that showed intranasal methamphetamine is safe and well-tolerated in a controlled laboratory setting (8,16,17,(22)(23)(24) and that d-amphetamine maintenance reduces some of the cardiovascular effects of methamphetamine (8). The attenuation of cardiovascular effects of methamphetamine during d-amphetamine maintenance may be attributable to participants developing cross-tolerance to the cardiovascular effects of stimulants.…”

The Effects of Naltrexone on Subjective Response to Methamphetamine in a Clinical Sample: a Double-Blind, Placebo-Controlled Laboratory Study

“…Medication also moderated ratings of 'bad drug effects' following MA administration, such that ratings of 'bad drug effects' were higher on NTX than placebo at earlier time points following MA infusion. NTX did not significantly alter peak MA effects; however, although peak drug responses are important factors in stimulant abuse (Hart et al, 2008), the modulation of broader acute subjective effects, such as those observed in this study, represent equally important targets for pharmacological intervention. As would be predicted, there were elevations in heart rate and blood pressure in response to the MA cues and to the MA administration.…”

An Evaluation of the Evidence that Methamphetamine Abuse Causes Cognitive Decline in Humans

“…However, this study did not administer urinalyses to ensure that participants were drug free at the time of testing, which is important considering that acute MA can improve baseline performance (Hart et al, 2008;Mahoney et al, 2011). Further, it is unclear whether the weekly use of MA examined in this study constitutes either dependence or abuse as defined by the DSM-IV.…”