Acute Physiological and Behavioral Effects of Intranasal Methamphetamine in Humans

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.

[1]  C. Hart,et al.  Methamphetamine attenuates disruptions in performance and mood during simulated night-shift work , 2003, Psychopharmacology.

[2]  C. Hart,et al.  Effects of the NMDA antagonist memantine on human methamphetamine discrimination , 2002, Psychopharmacology.

[3]  J. Parsons,et al.  An Exploratory Study of Contextual and Situational Factors Related to Methamphetamine Use among Gay and Bisexual Men in New York City , 2003 .

[4]  S. Comer,et al.  Choice between money and intranasal heroin in morphine-maintained humans , 1997, Behavioural pharmacology.

[5]  M. Fillmore,et al.  Reinforcing effects of modafinil: influence of dose and behavioral demands following drug administration , 2005, Psychopharmacology.

[6]  D. Segal,et al.  Relevance of pharmacokinetic parameters in animal models of methamphetamine abuse , 2001, Synapse.

[7]  C. Wallace,et al.  Effects of isradipine on methamphetamine-induced changes in attentional and perceptual-motor skills of cognition , 2005, Psychopharmacology.

[8]  C. Wallace,et al.  Bupropion Reduces Methamphetamine-Induced Subjective Effects and Cue-Induced Craving , 2006, Neuropsychopharmacology.

[9]  R. Griffiths,et al.  Enhancing caffeine reinforcement by behavioral requirements following drug ingestion , 1994, Psychopharmacology.

[10]  M. Haney,et al.  Amphetamine self-administration by humans: modulation by contingencies associated with task performance , 1996, Psychopharmacology.

[11]  C. Hart,et al.  Methamphetamine self-administration by humans , 2001, Psychopharmacology.

[12]  Gawin Fh,et al.  Is craving mood-driven or self-propelled? Sensitization and "street" stimulant addiction. , 1996 .

[13]  Douglas A. Weigmann,et al.  Methamphetamine effects on cognitive processing during extended wakefulness. , 1996, The International journal of aviation psychology.

[14]  H. Jones,et al.  Reinforcing effects of oral cocaine: contextual determinants , 2001, Psychopharmacology.

[15]  S. Vosburg,et al.  Modafinil Attenuates Disruptions in Cognitive Performance During Simulated Night-Shift Work , 2006, Neuropsychopharmacology.

[16]  J. Tinklenberg,et al.  A comparison of assessment techniques measuring the effects of methylphenidate, secobarbital, diazepam and diphenhydramine in abstinent alcoholics. , 1988, Neuropsychobiology.

[17]  Bankole A Johnson,et al.  Effects of Isradipine, a Dihydropyridine-Class Calcium Channel Antagonist, on D-Methamphetamine-Induced Cognitive and Physiological Changes in Humans , 2000, Neuropsychopharmacology.

[18]  R. Griffiths,et al.  Modulation of drug reinforcement by behavioral requirements following drug ingestion , 1994, Psychopharmacology.

[19]  C. Hart,et al.  Effects of repeated oral methamphetamine administration in humans , 2001, Psychopharmacology.

[20]  K. Wesnes,et al.  Effects of smoking on rapid information processing performance. , 1983, Neuropsychobiology.

[21]  Reese T. Jones,et al.  Methamphetamine and ethanol interactions in humans , 1995, Clinical pharmacology and therapeutics.

[22]  M W Fischman,et al.  Performance-based testing for drugs of abuse: dose and time profiles of marijuana, amphetamine, alcohol, and diazepam. , 1993, Journal of analytical toxicology.

[23]  P. Bordnick,et al.  Isradipine, a dihydropyridine-class calcium channel antagonist, attenuates some of d-methamphetamine’s positive subjective effects: a preliminary study , 1999, Psychopharmacology.

[24]  W. Ling,et al.  A Comparison of Injecting and Noninjecting Methamphetamine Users , 2000, Journal of psychoactive drugs.

[25]  C. Wallace,et al.  Effects of isradipine, a dihydropyridine-class calcium-channel antagonist, on d-methamphetamine's subjective and reinforcing effects. , 2005, The international journal of neuropsychopharmacology.

[26]  Daniel R. McLeod,et al.  An automated version of the digit symbol substitution test (DSST) , 1982 .

[27]  M. Fillmore,et al.  Reinforcing effects of methylphenidate: influence of dose and behavioral demands following drug administration , 2004, Psychopharmacology.

[28]  C. Hart,et al.  Combined effects of methamphetamine and zolpidem on performance and mood during simulated night shift work , 2005, Pharmacology Biochemistry and Behavior.

[29]  G. Pearlson,et al.  Repeated intranasal cocaine administration: lack of tolerance to pressor effects. , 1988, Drug and alcohol dependence.

[30]  R. Croft,et al.  The acute effects of d-amphetamine and methamphetamine on attention and psychomotor performance , 2006, Psychopharmacology.

[31]  C. Hart,et al.  Effects of Acute Smoked Marijuana on Complex Cognitive Performance , 2001, Neuropsychopharmacology.

[32]  Reese T. Jones,et al.  The bioavailability of intranasal and smoked methamphetamine , 2003, Clinical pharmacology and therapeutics.

[33]  M W Fischman,et al.  Crack cocaine and cocaine hydrochloride. Are the differences myth or reality? , 1996, JAMA.

[34]  D. Bloch,et al.  A comprehensive assessment of the safety of intravenous methamphetamine administration during treatment with selegiline , 2005, Pharmacology Biochemistry and Behavior.

[35]  B. Sadler,et al.  Pharmacokinetics of methamphetamine self-administered to human subjects by smoking S-(+)-methamphetamine hydrochloride. , 1993, Drug metabolism and disposition: the biological fate of chemicals.

[36]  M. Haney,et al.  Intranasal cocaine in humans: acute tolerance, cardiovascular and subjective effects , 2004, Pharmacology Biochemistry and Behavior.