An open-label study of a functional opioid kappa
antagonist in the treatment of opioid dependence

Rothman RB, Gorelick DA, Heishman SJ,
Eichmiller PR, Hill BH, Norbeck J, Liberto JG
National Institute on Drug Abuse,
National Institutes of Health,
5500 Nathan Shock Drive, Baltimore, MD, USA.
J Subst Abuse Treat 2000 Apr; 18(3):277-81


Several lines of evidence, including the well-established observation that kappa opiate agonists produce dysphoria and psychotomimetic effects in humans, suggest that dysfunction of the endogenous kappa opioid system may contribute to opioid and cocaine addiction. The objective of this open-label study was to determine the effectiveness of a functional kappa antagonist as a treatment for opioid dependence. This was accomplished by combining a partial mu agonist/kappa antagonist (buprenorphine, 4 mg, sublingual) with a mu antagonist (naltrexone, 50 mg by mouth), theoretically leaving kappa antagonism as the major medication effect. Subjects were treatment-seeking heroin-dependent (as per Diagnostic and Statistical Manual of Mental Disorders, 4th ed.) men (41 +/- 7 years old; 19 +/- 8 years heroin use) eligible for methadone maintenance. After inpatient detoxification and a naloxone-challenge test to verify that they were not physically dependent on opioids, subjects received naltrexone. Starting on the fourth day, patients also received liquid buprenorphine. All patients received medication at the clinic 6 days per week and a full program of psychosocial treatment. The major endpoints of the study were: pupil diameter to determine if the &mgr; agonist effects of buprenorphine were blocked by naltrexone, urine toxicology, and retention in treatment. Five patients (33%) completed the 3-month study. Four were abstinent from opioids and cocaine for the entire study, and one was abstinent from opioids and cocaine for the last 9 weeks. Six subjects dropped out due to either minor side effects or disliking the sensation of sublingual buprenorphine. There were no significant changes in pupillary diameter. The positive response to treatment exceeds that expected from naltrexone alone (90% dropout). These promising results suggest that controlled studies of this medication combination should be conducted.
Kappa confusion
Receptor subtypes
Fentanyl and ketamine
Kappa upregulation and addiction
kappa-Opioid withdrawal in planaria
The mesolimbic kappa-opioid system
Kappa opioid agonists make rats depressed
Kappa antagonists as future antidepressants?
Nalbuphine and anti-analgesia in men and women
Depressive effects of the kappa-opioid receptor agonists
Indolomorphinan antagonists of the kappa-opioid receptor
Kappa opioid receptor gene polymorphism and opiate addiction
Kappa agonists, antagonists and partial agonists for mood disorders
The kappa receptor antagonist norbinaltorphimine as an antidepressant

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Future Opioids
BLTC Research
Utopian Surgery?
The Abolitionist Project
The Hedonistic Imperative
The Reproductive Revolution
Critique of Huxley's Brave New World

The Good Drug Guide
The Good Drug Guide

The Responsible Parent's Guide
To Healthy Mood Boosters For All The Family