Psychostimulant drugs for cocaine dependence

Castells, Xavier; Cunill, Ruth; Pérez‐Mañá, Clara; Vidal, Xavier; Capellà, Dolors

doi:10.1002/14651858.cd007380.pub4

Cited by 70 publications

(97 citation statements)

References 116 publications

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“…The overall potency of amphetamine maintenance to attenuate ICSS facilitation in this study was similar to amphetamine-maintenance potency to reduce cocaine selfadministration in rats responding in various drug selfadministration procedures, including progressive-ratio, longaccess, and cocaine-vs.-food choice procedures [16,41,42]. These effects are also consistent with amphetamine-maintenance effectiveness to decrease cocaine self-administration in monkeys and humans and to decrease metrics of cocaine use in clinical trials [9,43,44].…”

Section: Microdialysissupporting

confidence: 76%

“…Although no pharmacotherapies are approved to treat psychostimulant use disorders, amphetamine maintenance decreases cocaine use in double-blind placebo-controlled clinical trials [9][10][11][12][13] and also decreases the choice of cocaine over an alternative reinforcer in laboratory studies in humans, non-human primates, and rats [14][15][16]. In contrast, amphetamine maintenance is not effective in decreasing methamphetamine use in either clinical trials or preclinical studies [17,18], and the effects of amphetamine maintenance on abuse-related effects of other psychostimulants like MDPV are unknown.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Amphetamine maintenance differentially modulates effects of cocaine, methylenedioxypyrovalerone (MDPV), and methamphetamine on intracranial self-stimulation and nucleus accumbens dopamine in rats

Johnson

Banks

Selley

et al. 2018

Neuropsychopharmacol

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Amphetamine maintenance is effective clinically to reduce the consumption of the monoamine uptake inhibitor cocaine but not of the monoamine releaser methamphetamine, and its effectiveness in treating the abuse of other psychostimulants is not known. The mechanisms for differential amphetamine-maintenance effectiveness to treat different types of psychostimulant abuse are also not known. Accordingly, the present study compared the effects of amphetamine maintenance on abuse-related behavioral and neurochemical effects of cocaine, methamphetamine, and the "bath salts" constituent 3,4-methylenedioxypyrovalerone (MDPV) in rats. In behavioral studies, rats were trained to lever press for electrical brain stimulation in an intracranial self-stimulation (ICSS) procedure. In neurochemical studies, nucleus accumbens (NAc) levels of dopamine (DA) and serotonin (5-HT) were monitored by in vivo microdialysis. Cocaine, methamphetamine, and MDPV each produced dose-dependent ICSS facilitation and increases in NAc DA; cocaine and methamphetamine also increased NAc 5-HT. Amphetamine maintenance (0.32 mg/kg/h × 7 days) produced (1) sustained increases in basal ICSS and NAc DA with no change in NAc 5-HT, (2) blockade of cocaine but not methamphetamine effects on ICSS and NAc DA, and (3) no blockade of cocaine- or methamphetamine-induced increases in NAc 5-HT. Amphetamine maintenance blocked the increases in NAc DA produced by the selective DA uptake inhibitor MDPV, but it did not block MDPV-induced ICSS facilitation. These results show different effects of amphetamine maintenance on behavioral and neurochemical effects of different psychostimulants. The selective effectiveness of amphetamine maintenance to treat cocaine abuse may reflect attenuation of cocaine-induced increases in NAc DA while preserving cocaine-induced increases in NAc 5-HT.

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Section: Microdialysissupporting

confidence: 76%

Section: Introductionmentioning

confidence: 99%

Amphetamine maintenance differentially modulates effects of cocaine, methylenedioxypyrovalerone (MDPV), and methamphetamine on intracranial self-stimulation and nucleus accumbens dopamine in rats

Johnson

Banks

Selley

et al. 2018

Neuropsychopharmacol

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“…Strategies to upregulate striatal D2 receptors have been shown in animal models to protect against compulsive stimulant drug intake 102 and, thus, interventions that lead to D2 up-regulation, such as physical activity as recently shown in a preliminary study in methamphetamine abusers 103, merit further investigation. A number of dopaminergic treatments have been tried to treat stimulant use disorder with limited success to date 104–106. Our data suggest some potential explanations for the lack of success and identify a number of clear targets for treatment interventions.…”

Section: Discussionmentioning

confidence: 85%

Association of Stimulant Use With Dopaminergic Alterations in Users of Cocaine, Amphetamine, or Methamphetamine

et al. 2017

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Importance Stimulant use disorder is common, affecting between 0.3 to 1.1% of the population, and costs over $85 billion per year globally. There are currently no licensed treatments. Several lines of evidence implicate the dopamine system in the pathophysiology of substance use disorder. Thus understanding the nature of dopamine dysfunction seen in stimulant users has the potential to aid the development of new therapeutics. Objective To comprehensively review the in-vivo imaging evidence for dopaminergic alterations in stimulant (cocaine or amphetamine/methamphetamine) drug abuse or dependence. Data sources The entire PubMed, EMBASE and PsycINFO databases were searched for studies from inception date to May 14, 2016. Study selection A total of 31 studies were identified that compared dopaminergic measures between 519 stimulant users and 512 controls using positron emission tomography or single-photon emission computed tomography to measure striatal dopamine synthesis or release, or dopamine transporter or receptor availability. Data extraction and synthesis Demographic, clinical and imaging measures were extracted from each study and meta-analyses and sensitivity analyses were conducted for stimulants combined and cocaine and amphetamines separately where there were sufficient studies. Main Outcomes and Measures We determined the difference in dopamine release (assessed using change in the D2/3 receptor availability following administration of amphetamine or methylphenidate), transporter and receptor availability in cocaine, amphetamine and methamphetamine users and healthy controls. Results In majority of the studies the duration of abstinence varied from 5 days to 3 weeks. There was a significant decrease in striatal dopamine release (stimulants combined: Hedge’s g= −0.84; cocaine: −0.87, both p<0.001), dopamine transporter availability (stimulants combined: Hedge’s g= −0.91, p<0.01; amphetamine and methamphetamine: Hedge’s g: −1.47, p<0.001) and D2/3 availability (stimulants combined: Hedge’s g= −0.76; cocaine: −0.73; amphetamine and methamphetamine: −0.81, all p<0.001). We did not find consistent alterations in vesicular monoamine transporter, dopamine synthesis or D1 receptor studies. Conclusion and relevance Our data suggest that both pre and post-synaptic aspects of the dopamine system in the striatum are down-regulated in stimulant users. We discuss the commonality and difference between these findings and the discrepancies with the preclinical literature as well as their implications for future drug development.

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“…Current therapies focus on psychosocial approaches, including cognitive-behavioral therapies [96]. Several studies have explored the use of sustained release formulations of methylphenidate or amphetamine for this indication, thus using an “agonist-based” approach [97,98], with mixed results. A further pharmacotherapeutic strategy that has been examined for stimulant use disorders is the use of the opioid antagonist naltrexone (which acts primarily as a μ-antagonist and κ-antagonist/partial agonist) [99–101].…”

Section: Existing Treatmentsmentioning

confidence: 99%

Medications for substance use disorders (SUD): emerging approaches

Butelman

Kreek

2017

Expert Opinion on Emerging Drugs

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Introduction: Substance use disorders are a group of chronic relapsing disorders of the brain, which have massive public health and societal impact. In some disorders (e.g., heroin / prescription opioid addictions) approved medications have a major long-term benefit. For other substances (e.g., cocaine, amphetamines and cannabis) there are no approved medications, and for alcohol there are approved treatments, which are not in wide usage. Approved treatments for tobacco use disorders are available, and novel medications are also under study. Areas covered: Medication-based approaches which are in advanced preclinical stages, or which have reached proof-of concept clinical laboratory studies, as well as clinical trials. Expert opinion: Current challenges involve optimizing translation between preclinical and clinical development, and between clinical laboratory studies to therapeutic clinical trials. Comorbidities including depression or anxiety are challenges for study design and analysis. Improved pharmacogenomics, biomarker and phenotyping approaches are areas of interest. Pharmacological mechanisms currently under investigation include modulation of glutamatergic, GABA, vasopressin and κ-receptor function, as well as inhibition of monoamine re-uptake. Other factors that affect potential market size for emerging medications include stigma, availability of treatment settings, adoption by clinicians, and the prevalence of persons with SUD who are not actively treatment-seeking.

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Psychostimulant drugs for cocaine dependence

Cited by 70 publications

References 116 publications

Amphetamine maintenance differentially modulates effects of cocaine, methylenedioxypyrovalerone (MDPV), and methamphetamine on intracranial self-stimulation and nucleus accumbens dopamine in rats

Amphetamine maintenance differentially modulates effects of cocaine, methylenedioxypyrovalerone (MDPV), and methamphetamine on intracranial self-stimulation and nucleus accumbens dopamine in rats

Association of Stimulant Use With Dopaminergic Alterations in Users of Cocaine, Amphetamine, or Methamphetamine

Medications for substance use disorders (SUD): emerging approaches

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