Topiramate's effects on cocaine‐induced subjective mood, craving and preference for money over drug taking

Abstract

Topiramate, presumably through antagonism of excitatory glutaminergic pathways and facilitation of inhibitory gamma-aminobutyric acid neurons in the cortico-mesolimbic system, might reduce cocaine’s abuse liability. We tested whether topiramate (100 mg twice daily) would reduce the euphoria, subjective mood, craving, and preference for cocaine over money induced by low and high doses (0.325 and 0.650 mg/kg i.v., respectively) of experimentally administered cocaine in 24 male and female, cocaine-dependent, non-treatment-seeking research volunteers in a university inpatient laboratory. We utilized a randomized, double-blind, placebo-controlled, within-subject, Latin-square crossover design in which 3 experimental challenge doses of low-dose cocaine, high-dose cocaine, and placebo were administered in counterbalanced order after 5 days of topiramate or matching placebo pretreatments separated by a 1-week washout period (2006–2009). After placebo pretreatments, cocaine produced dose-related increases in euphoria, stimulant effects, craving for more cocaine, and monetary value of cocaine in a behavioral preference test of cocaine vs. money choice. Topiramate pretreatment reduced the cocaine-related craving and monetary value of high-dose cocaine while increasing the monetary value, euphoria, and stimulant effects of low-dose cocaine. Validated and standardized human experimental methods evaluating the potential for topiramate to alter cocaine’s abuse liability suggest that topiramate may reduce the reinforcing effects and craving induced by higher cocaine doses. Low-dose cocaine might appear to have some enhancement of its stimulant properties in the presence of topiramate’s prominent sedative effects.

Topiramate for the management of methamphetamine dependence: a pilot randomized, double‐blind, placebo‐controlled trial

“…It is possible that the anxiolytic effect of topiramate prevented cocaine withdrawal signs [21] which might be mediated by central GABAA and opioid receptors activation [22]. It is possible that the anxiolytic effect of topiramate prevented cocaine withdrawal signs [21] which might be mediated by central GABAA and opioid receptors activation [22].…”

A double-blind, placebo-controlled trial of topiramate for the treatment of comorbid cocaine and alcohol dependence

“…It is also possible that topiramate promoted cocaine abstinence by reducing the euphoric effects of cocaine. Topiramate was shown to reduce the reinforcing effects of high doses of cocaine in a human laboratory trial (Johnson et al, 2012). This effect of topiramate may be particularly useful in cocaine users with more severe cocaine withdrawal symptoms who have been shown to have higher levels of cocaine euphoria (Sofuoglu et al, 2003).…”

Pharmacotherapy for Stimulant-Related Disorders

“…Yet study retention favored topiramate and individuals with more severe cocaine withdrawal symptoms on entering the study responded better to topiramate [84]. A randomized, double-blind, within-subjects cross-over designed laboratory study by Johnson et al assessed the effects of topiramate (100mg twice daily for 5 days; N=24) compared to placebo in combination with low (0.325 mg/kg, iv) and high (0.65 mg/kg) doses of cocaine [85]. Interestingly, topiramate treatment reduced cocaine craving and monetary value of the high dose of cocaine but increased the subjective effects (e.g.…”

“…Interestingly, topiramate treatment reduced cocaine craving and monetary value of the high dose of cocaine but increased the subjective effects (e.g. euphoria) and monetary value of the low dose of cocaine [85]. Overall, evidence is not entirely convincing for the use of topiramate as a treatment for CUD.…”