Pharmacotherapy of Methamphetamine Addiction: An Update

Elkashef, Ahmed; Vocci, Frank; Hanson, Glen R.; White, Jason M.; Wickes, Wendy; Tiihonen, Jari

doi:10.1080/08897070802218554

Cited by 107 publications

(84 citation statements)

References 89 publications

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“…However, there currently are no approved medications for these METH problems, including drugs with direct DA actions (Elkashef et al, 2008). As a consequence, it is important to research novel systems to develop effective medications to treat METH addiction.…”

Section: Introductionmentioning

confidence: 99%

Effect of Methamphetamine Self-Administration on Neurotensin Systems of the Basal Ganglia

Frankel¹,

Hoonakker²,

Alburges³

et al. 2010

J Pharmacol Exp Ther

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Methamphetamine (METH) dependence causes alarming personal and social damage. Even though many of the problems associated with abuse of METH are related to its profound actions on dopamine (DA) basal ganglia systems, there currently are no approved medications to treat METH addiction. For this reason, we and others have examined the METHinduced responses of neurotensin (NT) systems in the basal ganglia. This neuropeptide is associated with inhibitory feedback pathways to nigrostriatal DA projections, and NT tissue levels are elevated in response to high doses of noncontingent METH because of its increased synthesis in the striatonigral pathway. The present study reports the contingent responses of NT in the basal ganglia to self-administration of METH (SAM). Intravenous infusions of METH linked to appropriate leverpressing behavior by rats significantly elevated NT content in both dorsal striatum (210%) and substantia nigra (202%). In these same structures, NT levels were also elevated in yoked METH animals (160 and 146%, respectively) but not as much as in the SAM rats. These effects were blocked by a D1, but not D2, antagonist. A NT agonist administered before the day 5 of operant behavior blocked lever-pressing behavior in responding rats, but a NT antagonist had no significant effect on this behavior. These are the first reports that NT systems associated with striatonigral pathway are significantly altered during METH self-administration, and our findings suggest that activation of NT receptors during maintenance of operant responding reduces the associated lever-pressing behavior.

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Section: Introductionmentioning

confidence: 99%

Effect of Methamphetamine Self-Administration on Neurotensin Systems of the Basal Ganglia

Frankel¹,

Hoonakker²,

Alburges³

et al. 2010

J Pharmacol Exp Ther

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“…Efficacious pharmacotherapies for MA use disorder remain elusive despite extensive research on the neurobiology of the effects of amphetamines (Brensilver et al, 2013;Elkashef et al, 2008). Naltrexone (NTX) is an opioid receptor antagonist with empirically supported efficacy and FDA approval for the treatment of alcoholism (Anton et al, 2006;O'Malley et al, 1992;Volpicelli et al, 1992) and opioid dependence (Cornish et al, 1997).…”

Section: Introductionmentioning

confidence: 99%

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

Ray

Bujarski

Courtney

et al. 2015

Neuropsychopharmacol

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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-treatmentseeking 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 with 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 with 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.

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“…The present study and previous work with lobeline [3,29] suggest that lobeline may have clinical potential as a treatment for managing narcotic abuse and dependence. Lobeline decreases heroin self-administration behavior [16], which models drug-taking behavior in humans.…”

Section: Discussionmentioning

confidence: 82%

Lobeline Attenuates the Locomotor-Activating Properties of Repeated Morphine Treatment in Rats

Miller¹,

Polston²,

Rodvelt³

et al. 2011

Trop. J. Pharm Res

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Pharmacotherapy of Methamphetamine Addiction: An Update

Cited by 107 publications

References 89 publications

Effect of Methamphetamine Self-Administration on Neurotensin Systems of the Basal Ganglia

Effect of Methamphetamine Self-Administration on Neurotensin Systems of the Basal Ganglia

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

Lobeline Attenuates the Locomotor-Activating Properties of Repeated Morphine Treatment in Rats

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