Depot Naltrexone Mechanism of Action in Heroin Dependent Patients Using fMRI and SPECT

The aim of this project is to study brain functions of 20 heroin addicts (compared to brain functions of 20 healthy controls) just before and during a three month extended release naltrexone treatment using functional MRI and dopamine transporter SPECT.

The following hypotheses are tested:

* XRNT modulates the fMRI response to drug cues in predetermined brain regions.
* The expression of striatal transporters (assessed with SPECT) will decrease after a three-month course of extended release naltrexone

Heroin dependence is a quintessential international health problem, with a significant prevalence. Drug free treatments, including pharmacologically supported interventions using oral naltrexone, have not been very successful, mainly due to low compliance. The recent introduction of Vivitrol®, consisting of monthly injections, may create new opportunities. Vivitrol® is an innovative treatment delivery method that blocks the rewarding effects of heroin.

Eligibility Criteria:
Inclusion Criteria:

* Heroin dependent patients: have a diagnosis of opioid dependence according to DSM-IV criteria, heroin as primary drug of abuse and inhalation as primary route of administration.
* Healthy controls: no diagnosis of substance dependence, no current psychotropic medication. Care will be taken to match controls for gender, age, smoking status, IQ and handedness.

Exclusion Criteria:

* Age below 18 or over 55
* Medical contraindications for XRNT or MRI (Langleben 2006; Langleben, Ruparel et al. 2008). Briefly, the former include candidates with known hypersensitivity to naltrexone,PLG (poly-lactide-coglycolide), carboxymethylcellulose, or any other components of the Vivitrol® diluent, hepatic or renal disease, chronic pain syndromes, female subjects who are pregnant or lactating, or are of child bearing potential and are not using an acceptable method of birth control. MRI contraindications include chronic medical (neurological, cardiovascular, infectious, metabolic, etc) conditions that may affect the brain morphology and/or activity and indwelling foreign metallic or magnetically sensitive objects and devices, such as shrapnel, pacemakers, orthopaedic fixation devices or vascular stents
* Presence of disorders precluding normal perception of visual and auditory stimuli, such as color blindness, deafness, severe myopia, etc.
* Patients with a history of or current psychosis or current major depressive disorder with suicidal ideation
* Patients who are being treated under forced treatment conditions
* History or evidence of disorders that may affect cerebral function or circulation, such as diabetes and other metabolic disorders, encephalopathy, cardiovascular or cerebrovascular disease, history of head trauma with depressed skull fracture or prolonged loss of consciousness and history of brain surgery
* Female subjects: women who are pregnant or breast-feeding
* Current psychotropic medication
* Use of any prescription medications that could affect alertness or the circulatory system
* IQ \< 70
* Naltrexone use within the past 6 months
* Baseline aspartate aminotransferase or alanine aminotransferase more than three times the upper limit of normal
* Patients with no intention to be opioid-free for a minimum of 7 days before starting XRNT treatment