Acute Effects of Intravenous Heroin on the Hypothalamic-Pituitary-Adrenal Axis Response

Abstract

Heroin dependence is associated with a stressful environment and with dysfunction of the hypothalamic-pituitary-adrenal (HPA) axis. The present study examined the acute effects of intravenous heroin versus placebo on the HPA axis response in heroin-dependent patients. Twenty-eight heroin-dependent patients in heroin-assisted treatment and 20 age- and sex-matched healthy participants were included in a controlled trial in which patients were twice administered heroin or saline in a crossover design, and healthy controls were only administered saline. The HPA axis response was measured by adrenocorticotropic hormone (ACTH) levels and by cortisol levels in serum and saliva before and 20 and 60 minutes after substance administration. Craving, withdrawal, and anxiety levels were measured before and 60 minutes after substance application. Plasma concentrations of heroin and its main metabolites were assessed using high-performance liquid chromatography. Heroin administration reduces craving, withdrawal, and anxiety levels and leads to significant decreases in ACTH and cortisol concentrations (P < 0.01). After heroin administration, cortisol concentrations did not differ from healthy controls, and ACTH levels were significantly lower (P < 0.01). In contrast, when patients receive saline, all hormone levels were significantly higher in patients than in healthy controls (P < 0.01). Heroin-dependent patients showed a normalized HPA axis response compared to healthy controls when they receive their regular heroin dose. These findings indicate that regular opioid administration protects addicts from stress and underscore the clinical significance of heroin-assisted treatment for heroin-dependent patients.

Epigenetic Effects of Intravenous Diacetylmorphine on the Methylation of <b><i>POMC</i></b> and <b><i>NR3C1</i></b>

“…As previously reported [11], a single dose of DAM instantly reduces state-anxiety, craving scores, and stress reactivity, as measured by the secretion of ACTH and cortisol in heroin-dependent patients, and indicating a dampening effect of stress-related responses. Furthermore, we recently observed that patients even revealed increased state-anxiety and craving scores after the injection of saline [3], indicating an experimentally induced state of acute withdrawal.…”

“…Our group previously found suppressed cortisol concentrations and reduced craving scores after acute methadone administration in heroin-dependent patients [9]. We also demonstrated a normalized HPA axis response as well as a decrease in negative feelings such as anxiety and craving when heroin-dependent patients received their regular dose of DAM [10, 11]. This dampening effect on negative emotions highlights the regulatory effect of acute DAM administration and illustrates how compliance is maintained.…”

“…The procedure has been described previously in more detail [11]. The patients received DAM and saline through a permanent catheter in a randomized, double-blind, vehicle-controlled crossover design.…”

“…The ACTH and cortisol levels after DAM injection compared to saline injection have been reported in another study [11], but here they are mentioned with regard to methylation. For ethical reasons, the control group did not receive DAM.…”

Schizophrenia and Addiction

“…This compulsion is frequently driven by craving which is triggered by stress and drug-related stimuli (Sinha et al 2006, Walter et al 2013. The mesolimbic dopamine pathway-dopamine cells in the ventral tegmental area projecting into the nucleus accumbens-is considered essential for drug reward and drug-seeking behavior (Volkow et al 2011).…”