Acute Physiological and Behavioral Effects of Intranasal Methamphetamine in Humans

Department of Psychiatry, Division on Substance Abuse, New York State Psychiatric Institute, College of Physicians and Surgeons, Columbia University, New York, NY 10032, USA.
Neuropsychopharmacology (Impact Factor: 7.05). 08/2008; 33(8):1847-55. DOI: 10.1038/sj.npp.1301578
Source: PubMed


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.

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    • "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. "
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    ABSTRACT: Methamphetamine (MA) use disorder is a serious psychiatric condition for which there are no FDA-approved medications. Naltrexone (NTX) is an opioid receptor antagonist with demonstrated efficacy, albeit moderate, for the treatment of alcoholism and opioid dependence. Preclinical and clinical studies suggest that NTX may be useful for the treatment of MA use disorder. To inform treatment development, we conducted a double-blind, randomized, crossover, placebo-controlled human laboratory study of NTX. Non-treatment seeking individuals meeting DSM-IV criteria for MA abuse or dependence (n=30) completed two separate 5- day inpatient stays. During each admission, participants completed testing sessions comprised of MA cue-reactivity and intravenous MA administration (30 mg) after receiving oral NTX (50 mg) or placebo for 4 days. This study tested the hypotheses that NTX would (a) attenuate cue-induced MA craving, and (b) reduce subjective responses to MA administration. Results largely supported the study hypotheses such that (a) NTX significantly blunted cue-induced craving for MA and (b) attenuated several of the hedonic subjective effects of MA, including craving, during controlled MA administration and as compared to placebo. NTX decreased overall subjective ratings of "crave drug," "stimulated," and "would like drug access," decreased the the post MA administration timecourse of "anxious" and increased ratings of "bad drug effects," as compared to placebo. These findings support a potential mechanism of action by showing that NTX reduced cue-induced craving and subjective responses to MA. This is consistent with positive treatment studies of NTX for amphetamine dependence as well as ongoing clinical trials for MA.Neuropsychopharmacology accepted article preview online, 24 March 2015. doi:10.1038/npp.2015.83.
    Neuropsychopharmacology: official publication of the American College of Neuropsychopharmacology 03/2015; 40(10). DOI:10.1038/npp.2015.83 · 7.05 Impact Factor
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    • "However, a typical dose of METH that is self-administered (i.v.) by rats is 0.1–0.2 mg/kg that is equivalent to a human dose (7–14 mg/70 kg) (Cook et al., 1992; Hart et al., 2008; Kuczenski et al., 2009; Krasnova et al., 2010; Kousik et al., 2014). Also, pigeons injected i.v. and intramuscularly (i.m.) with 0.8 mg/kg of METH showed 100% of bioavailability; however , i.v. "
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    ABSTRACT: The prevalence of methamphetamine (METH) use is estimated at ~35 million people worldwide, with over 10 million users in the United States. METH use elicits a myriad of social consequences and the behavioral impact of the drug is well understood. However, new information has recently emerged detailing the devastating effects of METH on host immunity, increasing the acquisition of diverse pathogens and exacerbating the severity of disease. These outcomes manifest as modifications in protective physical and chemical defenses, pro-inflammatory responses, and the induction of oxidative stress pathways. Through these processes, significant neurotoxicities arise, and, as such, chronic abusers with these conditions are at a higher risk for heightened consequences. METH use also influences the adaptive immune response, permitting the unrestrained development of opportunistic diseases. In this review, we discuss recent literature addressing the impact of METH on infection and immunity, and identify areas ripe for future investigation.
    Frontiers in Neuroscience 01/2014; 8:445. DOI:10.3389/fnins.2014.00445 · 3.66 Impact Factor
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    • "Conclusion The only relevant twin study available found that stimulantabusing twins performed worse than non-abusing twins on a few cognitive measures, although this pattern was reversed on one test in which the stimulant-abusers performed better than the non-abusers. 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. "
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    ABSTRACT: Methamphetamine (MA) is one of the most commonly abused illicit substances worldwide. Among other problems, abuse of the drug has been associated with reduced cognitive function across several domains. However, much of the literature has not attempted to differentiate cognitive difficulties caused by MA abuse from preexisting cognitive difficulties that are likely caused by other factors. Here, we address this question, evaluating evidence for a priori hypotheses pertaining to six lines of research: (a) animal studies; (b) cross-sectional human studies; (c) a twin study; (d) studies of changes in cognition with abstinence from MA; (e) studies of changes in brain structure and function with abstinence from MA; and (f) studies of the relationship between the severity of MA abuse and the extent of cognitive deficits observed. Overall the findings were mixed, with some support for a causal relationship between MA abuse and cognitive decline, and other findings suggesting that there is no relationship. The preponderance of the data, however, does support the possibility that MA abuse causes cognitive decline, of unknown duration, in at least some users of the drug. When averaged across individuals, this decline is likely to be mild in early-to-middle adulthood. However, moderator variables are likely to contribute to the presence and/or severity of cognitive decline exhibited by a given individual.Neuropsychopharmacology advance online publication, 5 September 2012; doi:10.1038/npp.2012.179.
    Neuropsychopharmacology: official publication of the American College of Neuropsychopharmacology 09/2012; 38(2). DOI:10.1038/npp.2012.179 · 7.05 Impact Factor
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