Effects of cortisol administration on craving in heroin addicts

Abstract

Heroin dependence is a severe and chronically relapsing substance use disorder with limited treatment options. Stress is known to increase craving and drug-taking behavior, but it is not known whether the stress hormone cortisol mediates these stress effects or whether cortisol may rather reduce craving, for example, by interfering with addiction memory. The aim of the present study was to determine the effects of cortisol administration on craving in heroin-dependent patients and to determine whether the effects depend on the daily dose of heroin consumption. We used a double-blind, placebo-controlled, cross-over study in 29 heroin-dependent patients in a stable heroin-assisted treatment setting. A single oral dose of 20 mg of cortisol or placebo was administered 105 min before the daily heroin administration. The primary outcome measure was cortisol-induced change in craving. Secondary measures included anxiety, anger and withdrawal symptoms. For the visual analog scale for craving, we found a significant interaction (P=0.0027) between study medication and heroin-dose group (that is, daily low, medium or high dose of heroin). Cortisol administration reduced craving in patients receiving a low dose of heroin (before heroin administration: P=0.0019; after heroin administration: P=0.0074), but not in patients receiving a medium or high dose of heroin. In a picture-rating task with drug-related pictures, cortisol administration did not affect the ratings for the picture-characteristic craving in all the three heroin-dose groups. Cortisol also did not significantly affect secondary outcome measures. In conclusion, a single administration of cortisol leads to reduced craving in low-dose heroin addicts. The present findings might have important clinical implications with regard to understanding stress effects and regarding treatment of addiction.

Neural Underpinnings of Cortisol Effects on Fear Extinction

“…In men, cortisol administration or stress induction also reduced neural activation in the amygdala-hippocampal complex during fear acquisition and reward anticipation (Kinner et al, 2016;Merz et al, 2012Merz et al, , 2013. Seemingly, cortisol exerts comparable effects on negative as well as on positive emotional processing opening the adjunct treatment application of cortisol to new avenues: not only patients with phobias (de Quervain et al, 2011;Soravia et al, 2006) or PTSD (Aerni et al, 2004;Schelling et al, 2004;Yehuda et al, 2015) might profit from cortisol administration or high cortisol concentrations due to the circadian rhythm (Lass-Hennemann and Michael, 2014), but also patients with disorders related to aberrant reward processing such as addiction as recently shown in heroin addicts (Walter et al, 2015).…”

Stress and Memory: A Selective Review on Recent Developments in the Understanding of Stress Hormone Effects on Memory and Their Clinical Relevance

“…Recently, novel evidence was provided showing that GC administration can reduce craving in heroin addicts . There is growing evidence that memory and addiction partly share neural circuitries and molecular mechanisms .…”

“…Importantly, the powerful incentives associated with drug taking that produce a strong feeling of craving are stored in memory; also referred to as addiction memory . Thus, GCs may have reduced craving by interfering with the retrieval of addiction memory .…”

Substance use modulates stress reactivity: Behavioral and physiological outcomes

“…Within a small sample of addicts, Walter et al [221] found that cortisol administration led to a decrease in craving within low dose heroin addicts while not affecting heavier users. Additionally, clonidine, which decreases noradrenergic activity through presynaptic activation of alpha-2 receptors [222], is currently used in the treatment of opiate withdrawal [223], further supporting an idea that peripheral stress responsivity may be critically involved in addictive behaviors.…”