Use of stimulants to treat cocaine and methamphetamine abuse

Moeller, F. Gerard; Schmitz, Joy M.; Herin, David V.; Kjome, Kimberly L.

doi:10.1007/s11920-008-0062-x

Cited by 21 publications

(15 citation statements)

References 51 publications

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“…That is, dopamine transport blockers (e.g., methylphenidate and bupropion) may have improved efficacy for amphetamine use disorders compared to dopamine releasers (e.g., d -amphetamine and methamphetamine) (reviewed in: 34, 35). Conversely, dopamine releasers (e.g., d -amphetamine and methamphetamine) have improved efficacy for cocaine abuse compared to dopamine transport blockers (reviewed in: 5–7, 34). d -Amphetamine maintenance reduced cocaine subject-rated drug-effects and self-administration in human laboratory studies and has reduced cocaine use in clinical trials (11, 36–39).…”

Section: Discussionmentioning

confidence: 99%

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Methamphetamine Self-Administration in Humans During d-Amphetamine Maintenance

Pike¹,

Stoops²,

Hays³

et al. 2014

Journal of Clinical Psychopharmacology

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Agonist replacement may be a viable treatment approach for managing stimulant use disorders. This study sought to determine the effects of d-amphetamine maintenance on methamphetamine self-administration in stimulant using human participants. We predicted d-amphetamine maintenance would reduce methamphetamine self-administration. Eight participants completed the protocol, which tested two d-amphetamine maintenance conditions in counter-balanced order (0 and 40 mg/day). Participants completed 4 experimental sessions under each maintenance condition in which they first sampled one of four doses of intranasal methamphetamine (0, 10, 20, or 30 mg). Participants then had the opportunity to respond on a computerized progressive ratio task to earn portions of the sampled methamphetamine dose. Subject-rated drug-effect and physiological measures were completed at regular intervals prior to and after sampling methamphetamine. Methamphetamine was self-administered as an orderly function of dose regardless of the maintenance condition. Methamphetamine produced prototypical subject-rated effects on 13 items of the drug-effects questionnaires, 10 of which were attenuated by d-amphetamine maintenance (e.g., increased ratings were attenuated on items such as Any Effect, Like Drug, and Willing to Take Again on the Drug Effect Questionnaire). Methamphetamine produced significant increases in systolic blood pressure, which were attenuated by d-amphetamine maintenance compared to placebo maintenance. Methamphetamine was well tolerated during d-amphetamine maintenance and no adverse events occurred. Although d-amphetamine attenuated some subject-rated effects of methamphetamine, the self-administration results are concordant with those of clinical trials showing that d-amphetamine did not reduce methamphetamine use. Unique pharmacological approaches may be needed for treating amphetamine use disorders.

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Section: Discussionmentioning

confidence: 99%

“…Dopamine agonists have also shown promise when tested for treating cocaine dependence (reviewed in: 5–7). Few studies have tested agonist replacement for methamphetamine.…”

Section: Introductionmentioning

confidence: 99%

Methamphetamine Self-Administration in Humans During d-Amphetamine Maintenance

Pike¹,

Stoops²,

Hays³

et al. 2014

Journal of Clinical Psychopharmacology

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“…Despite these efforts, much work remains in identifying an effective pharmacotherapy. Recent review articles provide summaries of laboratory-based and outpatient trials conducted to date, and include lists of novel medications on the horizon (Elkashef et al, 2008, Haile et al, 2009, Kampman, 2008, Karila et al, 2010, Moeller et al, 2008, Rose and Grant, 2008, Vocci and Appel, 2007), as well as more recent efforts to develop a vaccine for METH dependence (Shen et al, 2012). …”

Section: Introductionmentioning

confidence: 99%

Rivastigmine reduces “likely to use methamphetamine” in methamphetamine-dependent volunteers

Garza

Newton

Haile

et al. 2012

Progress in Neuro-Psychopharmacology and Biological Psychiatry

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We previously reported that treatment with the cholinesterase inhibitor rivastigmine (3 mg, PO for 5 days) significantly attenuated “Desire for METH”. Given that higher dosages of rivastigmine produce greater increases in synaptic ACh, we predicted that 6 mg should have more pronounced effects on craving and other subjective measures. In the current study, we sought to characterize the effects of short-term exposure to rivastigmine (0, 3 or 6 mg) on the subjective and reinforcing effects produced by administration of methamphetamine (METH) in non-treatment-seeking, METH-dependent volunteers. This was a double-blind, placebo-controlled, crossover study. Participants received METH on day 1, and were then randomized to placebo or rivastigmine on day 2 in the morning and treatment continued through day 8. METH dosing was repeated on day 6. The data indicate that METH (15 and 30 mg), but not saline, increased several positive subjective effects, including “Any Drug Effect”, “High”, “Stimulated”, “Desire METH”, and “Likely to Use METH” (all p’s<0.0001). In addition, during self-administration sessions, participants were significantly more likely to choose METH over saline (p<0.0001). Evaluating outcomes as peak effects, there was a trend for rivastigmine to reduce “Desire METH” (p=0.27), and rivastigmine significantly attenuated “Likely to Use METH” (p=0.01). These effects were most prominent for rivastigmine 6 mg when participants were exposed to the low dose (15 mg, IV), but not high dose (30 mg, IV), of METH. The self-administration data reveal that rivastigmine did not alter total choices for METH (5 mg, IV/choice). Overall, the results indicate some efficacy for rivastigmine in attenuating key subjective effects produced by METH, though additional research using higher doses and longer treatment periods is likely needed. These data extend previous findings and indicate that cholinesterase inhibitors, and other drugs that target acetylcholine systems, warrant continued consideration as treatments for METH dependence.

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“…Using a stop signal task, we (and others) have demonstrated that patients with cocaine (and other stimulant) misuse display impaired inhibitory control and prefrontal activation during a stop signal task (5,(23)(24)(25)(26)(27). Whereas prior research has examined stimulants in clinical trials of therapeutic efficacy (28)(29)(30)(31)(32)(33) and neuroimaging studies of regional brain activation and connectivity in cocaine users (34)(35)(36)(37), none to our knowledge have specifically evaluated their association with the behavioral and neural aspects of inhibitory control. In the current study, we sought to address this gap in a pharmacological functional MRI (fMRI) study in which cocaine-dependent individuals received an i.v.…”

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confidence: 99%

Biological markers of the effects of intravenous methylphenidate on improving inhibitory control in cocaine-dependent patients

Morgan²,

Matuskey³

et al. 2010

Proc. Natl. Acad. Sci. U.S.A.

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Prior research points to the importance of psychostimulants in improving self-control. However, the neural substrates underlying such improvement remain unclear. Here, in a pharmacological functional MRI study of the stop signal task, we show that methylphenidate (as compared with placebo) robustly decreased stop signal reaction time (SSRT), an index of improved control, in cocaine-dependent patients (a population in which inhibitory control is impaired). Methylphenidate-induced decreases in SSRT were positively correlated with inhibition-related activation of left middle frontal cortex (MFC) and negatively with activation of the ventromedial prefrontal cortex (vmPFC) in whole brain linear regressions. Inhibition-related MFC but not vmPFC activation distinguished individuals with short and long SSRT in 36 demographically matched healthy individuals, whereas vmPFC but not MFC activation, along with improvement in SSRT, was correlated with a previously implicated biomarker of methylphenidate response (systolic blood pressure). These results implicate a specific neural (i.e., vmPFC) mechanism whereby stimulants improve inhibitory control. Altered ventromedial prefrontal activation and increased blood pressure may represent useful CNS and peripheral biomarkers in individualized treatment with methylphenidate for patients with cocaine dependence.D eficits in cognitive control have been implicated in the pathophysiology of several neuropsychiatric disorders, including attention deficit hyperactivity disorder (ADHD) and cocaine dependence (1-5), and a wide literature supports the utility of stimulants, including methylphenidate, in improving cognitive control (6-9, see ref. 10 for review). For example, studies have shown that stimulants alter cerebral activation and influence cognitive functions, including improving inhibitory control, in healthy individuals (11-21). Similarly, Overtoom et al. (22) reported that methylphenidate improved stopping performance and restored the electrophysiological potential of stopping in a stop signal task, whereas it did not affect go trial reaction time, in adult patients with ADHD. Although neuroimaging studies have examined the effects of stimulants on regional brain activation and connectivity, the neural substrates underlying stimulant-mediated improvements in inhibitory control remain unclear. A more complete understanding of the neural mechanisms whereby stimulants improve cognitive control will be critically important, not only for an improved understanding of its biological basis but also for understanding the pathophysiology and treatment of conditions associated with its impairment. Using a stop signal task, we (and others) have demonstrated that patients with cocaine (and other stimulant) misuse display impaired inhibitory control and prefrontal activation during a stop signal task (5, 23-27). Whereas prior research has examined stimulants in clinical trials of therapeutic efficacy (28-33) and neuroimaging studies of regional brain activation and connectivity in cocaine user...

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Use of stimulants to treat cocaine and methamphetamine abuse

Cited by 21 publications

References 51 publications

Methamphetamine Self-Administration in Humans During d-Amphetamine Maintenance

Methamphetamine Self-Administration in Humans During d-Amphetamine Maintenance

Rivastigmine reduces “likely to use methamphetamine” in methamphetamine-dependent volunteers

Biological markers of the effects of intravenous methylphenidate on improving inhibitory control in cocaine-dependent patients

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