Naltrexone implants in opioid dependence: a proof of mechanism study with pk and pd measures

Heroin addiction is a major social and health problem that results in many thousands of deaths per year, and is also a cause of many other health social and criminal problems. Current treatments are effective but they rely on keeping addicts on alternative drugs such as methadone and buprenorphine that effectively keep them ?stoned? ? sp limiting the ability to return to work and also necessitating daily attendance at clinics or pharmacies. A much better strategy would be to use a drug to block the brain sites of action of heroin so that the addict got no effect when it was taken. This is proven to work in people with high motivation to take the blocker e.g. doctors, but again daily dosing is required so that it is easy to stop and then resume heroin use. This grant uses a new blocker preparation that is implanted under the skin [like the long-acting depot contraceptive pill] and so will work for between 3-6 months. Before using this as a treatment we need to explore just how long the blockade last so that the timing of repeat implants can be made and this grant is designed to do this. From our findings we should be able to design the optimal treatment package for heroin addiction with this exciting new approach.

Heroin addiction is a major health and social problem in the UK as well as in most other countries that has been recently highlighted in the government Foresight report Brain Science Addiction and Drugs 2006. The mainstay of current treatments are methadone and buprenorphine which maintain addiction in a controlled way using substitute opioid agonist drugs. This grant will explore a potentially exciting alternative approach ? the use of a long acting preparation of the po receptor antagonist naltrexone. This has potential advantages over agonist substitution in many ways ? especially the reduction of overdose deaths, zero risk of diversion, reduction of iv drug use. Currently the limitation of naltrexone treatment is the need for once daily oral dosing which can lead to escape from treatment. The current project is designed to test a much longer acting preparation that is given as an implant and which releases the active drug over a period of about 6 months. 30 heroin addicts will be entered into an open treatment program that will allow us to monitor plasma levels of naltrexone and its active metabolite over the 6 months to determine the pharmacokinetics of the implants. In addition the plasma levels of the antagonists needed to provide effective blockade of ?on-top? heroin use will be determined by giving test doses of heroin at different times during the 6 months. These data will allow the more general use of implants in randomised controlled efficacy trials, which hopefully will result in a new treatment approach to heroin addiction ? the first in twenty years.