Combination pharmacotherapies for stimulant use disorder: a review of clinical findings and recommendations for future research

Stoops, William W.; Rush, Craig R.

doi:10.1586/17512433.2014.909283

Cited by 34 publications

(24 citation statements)

References 77 publications

(215 reference statements)

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“…Anker et al (2012) demonstrated that the CocH vector blocked reinstatement of cocaine-seeking in rats given priming doses of cocaine, but it did not prevent reinstatement primed by methamphetamine. Thus, like other therapies for polydrug abusers, the best treatment would be a combination of efficacious pharmacological and behavioral measures aimed at pre-existing drug abuse vulnerabilities (Stoops and Rush, 2014). In the future, the efficacy of the present viral vector-delivered treatment could serve as a prototype for the development of novel longterm interventions against an array of abused drugs.…”

Section: Discussionmentioning

confidence: 99%

Long-Term Blockade of Cocaine Self-Administration and Locomotor Activation in Rats by an Adenoviral Vector-Delivered Cocaine Hydrolase

Smethells

Swalve

Brimijoin

et al. 2016

Journal of Pharmacology and Experimental Therapeutics

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A promising approach in treating cocaine abuse is to metabolize cocaine in the blood using a mutated butyrylcholinesterase (BChE) that functions as a cocaine hydrolase (CocH). In rats, a helper-dependent adenoviral (hdAD) vector-mediated delivery of CocH abolished ongoing cocaine use and cocaine-primed reinstatement of drug-seeking for several months. This enzyme also metabolizes ghrelin, an effect that may be beneficial in maintaining healthy weights. The effect of a single hdAD-CocH vector injection was examined in rats on measures of anxiety, body weight, cocaine self-administration, and cocaine-induced locomotor activity. To examine anxiety, periadolescent rats were tested in an elevated-plus maze. Weight gain was then examined under four rodent diets. Ten months after CocH-injection, adult rats were trained to self-administer cocaine intravenously and, subsequently, cocaine-induced locomotion was tested. Viral gene transfer produced sustained plasma levels of CocH for over 13 months of testing. CocH-treated rats did not differ from controls in measures of anxiety, and only showed a transient reduction in weight gain during the first 3 weeks postinjection. However, CocH-treated rats were insensitive to cocaine. At 10 months postinjection, none of the CocH-treated rats initiated cocaine self-administration, unlike 90% of the control rats. At 13 months postinjection, CocH-treated rats showed no cocaineinduced locomotion, whereas control rats showed a dosedependent enhancement of locomotion. CocH vector produced a long-term blockade of the rewarding and behavioral effects of cocaine in rats, emphasizing its role as a promising therapeutic intervention in cocaine abuse.

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Section: Discussionmentioning

confidence: 99%

Long-Term Blockade of Cocaine Self-Administration and Locomotor Activation in Rats by an Adenoviral Vector-Delivered Cocaine Hydrolase

Smethells

Swalve

Brimijoin

et al. 2016

Journal of Pharmacology and Experimental Therapeutics

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“…Combining medications with modest efficacy could result in greater reductions in stimulant self-administration while reducing the risk of side effects associated with higher doses of the treatment drugs. 8 For example, a series of preclinical experiments demonstrated that combining low doses of two different drugs that each modestly attenuate the abuse-related effects of methamphetamine is an effective strategy to manage stimulant use disorders. 8–9 More specifically, combining low doses of oxazepam and metyrapone that were ineffective when tested alone resulted in reduced cocaine self-administration in rats.…”

Section: Introductionmentioning

confidence: 99%

“…8 For example, a series of preclinical experiments demonstrated that combining low doses of two different drugs that each modestly attenuate the abuse-related effects of methamphetamine is an effective strategy to manage stimulant use disorders. 8–9 More specifically, combining low doses of oxazepam and metyrapone that were ineffective when tested alone resulted in reduced cocaine self-administration in rats. 9 In agreement with the preclinical data, oxazepam-metyrapone combinations were well tolerated and significantly reduced cocaine use in a small clinical trial.…”

Section: Introductionmentioning

confidence: 99%

Separate and Combined Effects of Naltrexone and Extended-Release Alprazolam on the Reinforcing, Subject-Rated, and Cardiovascular Effects of Methamphetamine

Marks

Lile

Stoops

et al. 2016

Journal of Clinical Psychopharmacology

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Opioid antagonists (e.g., naltrexone) and positive modulators of γ-aminobutyric acid type A (GABAA) receptors (e.g., alprazolam) each modestly attenuate the abuse-related effects of stimulants. A previous study demonstrated that acute pretreatment with the combination of naltrexone and alprazolam attenuated a greater number of the subject-rated effects of d-amphetamine than the constituent drugs alone. This study tested the hypothesis that maintenance on the combination of naltrexone and alprazolam XR would attenuate the reinforcing and “positive” subject-rated effects of methamphetamine to a greater extent than the constituent drugs alone. Eight non-treatment-seeking, stimulant-using individuals completed a placebo-controlled, crossover, double-blind inpatient protocol. Participants were maintained on naltrexone (0 and 50 mg), alprazolam XR (0 and 1 mg), and the combination of naltrexone and alprazolam XR (50 mg and 1 mg, respectively) for 6–7 days. Under each maintenance condition, participants sampled intranasal doses of methamphetamine (0, 10, and 30 mg), and were then offered the opportunity to work for the sampled dose on a modified progressive-ratio procedure. Subject-rated drug effect questionnaires, psychomotor, and physiology assessments were collected. Intranasal methamphetamine functioned as a reinforcer and produced prototypical stimulant-like “positive” subject-rated and physiological effects. Maintenance on naltrexone significantly decreased the reinforcing, but not subject-rated drug effects of 10 mg methamphetamine. Alprazolam XR and the combination of naltrexone and alprazolam XR did not impact methamphetamine self-administration or subject-rated drug effects. The results support the continued evaluation of naltrexone for methamphetamine dependence, as well as the identification of other drugs that enhance its ability to reduce drug-taking behavior.

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“…One such strategy is combination treatment, especially with medications that display some efficacy when administered alone (Stoops and Rush, 2014). Naltrexone, a mu opioid receptor antagonist, and bupropion, a dopamine and norepinephrine reuptake inhibitor, are two candidate medications that have been evaluated for managing amphetamine use disorder from preclinical research to clinical trials.…”

Section: Introductionmentioning

confidence: 99%

Naltrexone and bupropion, alone or combined, do not alter the reinforcing effects of intranasal methamphetamine

Stoops

Pike

Hays

et al. 2015

Pharmacology Biochemistry and Behavior

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Naltrexone and bupropion, when administered alone in clinical trials, modestly reduce amphetamine use. Whether combining these drugs would result in greater reductions in methamphetamine taking relative to either drug alone is undetermined. This study examined the influence of naltrexone, bupropion and a naltrexone-bupropion combination on methamphetamine self-administration in humans. Seven subjects reporting recent illicit stimulant use completed a placebo-controlled, crossover, double-blind study in which the reinforcing, subject-rated and physiological effects of intranasal methamphetamine (0, 10 and 30 mg) were assessed during maintenance on placebo, naltrexone (50 mg), bupropion (300 mg/day), and naltrexone combined with bupropion. Methamphetamine maintained responding and produced prototypic subjective and physiological effects (e.g., increased ratings of Good Effects, elevated systolic blood pressure). Maintenance doses were well tolerated and generally devoid of effects. No maintenance condition reduced methamphetamine self-administration or systematically altered the subject-rated effects of methamphetamine. These outcomes demonstrate the robust behavioral effects of methamphetamine that could make it resistant to pharmacological manipulation. Although these outcomes indicate that this combination may be ineffective for managing methamphetamine use disorder, future work should evaluate longer maintenance dosing, individuals with different levels of amphetamine use, adding this combination to a behavioral platform and other pharmacotherapy combinations for reducing methamphetamine use.

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Combination pharmacotherapies for stimulant use disorder: a review of clinical findings and recommendations for future research

Cited by 34 publications

References 77 publications

Long-Term Blockade of Cocaine Self-Administration and Locomotor Activation in Rats by an Adenoviral Vector-Delivered Cocaine Hydrolase

Long-Term Blockade of Cocaine Self-Administration and Locomotor Activation in Rats by an Adenoviral Vector-Delivered Cocaine Hydrolase

Separate and Combined Effects of Naltrexone and Extended-Release Alprazolam on the Reinforcing, Subject-Rated, and Cardiovascular Effects of Methamphetamine

Naltrexone and bupropion, alone or combined, do not alter the reinforcing effects of intranasal methamphetamine

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