Naltrexone attenuates the subjective effects of amphetamine in patients with amphetamine dependence.

Abstract

Amphetamine abuse and dependence is a global health concern with a collateral increase in medical and social problems. Although some of the neurobiological mechanisms underlying amphetamine dependence and its devastating effects in humans are known, the development of rational and evidence-based treatment is lagging. There is evidence from preclinical studies suggesting that the endogenous opioid system plays a role in mediating some of the behavioral and neurochemical effects of amphetamine in a variety of controlled settings. In the present study we assessed the effects of naltrexone, an opioid antagonist (50 mg) on the subjective physiological and biochemical response to dexamphetamine (30 mg) in 20 amphetamine-dependent patients. Patients received naltrexone/amphetamine followed by placebo/amphetamine, 1 week apart in a randomized double-blind placebo-controlled design. The primary objective of the study was to evaluate the effect of pretreatment with naltrexone on the subjective response to amphetamine, using a Visual Analog Scale. The secondary objective was to investigate the effects of naltrexone on physiological and biochemical responses to amphetamine, as measured by changes in blood pressure, heart rate, skin conductance, and cortisol. Naltrexone significantly attenuated the subjective effects produced by dexamphetamine in dependent patients (p<0.001). Pretreatment with naltrexone also significantly blocked the craving for dexamphetamine (p<0.001). There was no difference between the groups on the physiological measures. The results suggest that the subjective effects of amphetamine could be modulated via the endogenous opioid system. The potential of naltrexone as an adjunct pharmaceutical for amphetamine dependence is promising.

• Authors: Nitya Jayaram-Lindström, Maija Konstenius, Staffan Eksborg, Olof Beck, Anders Hammarberg, Johan Franck
• Journal: Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology (Neuropsychopharmacology) Vol. 33 Issue 8 Pg. 1856-63 (Jul 2008) ISSN: 0893-133X [Print] England
• PMID: 17957221 (Publication Type: Journal Article, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)

Chemical References

• Central Nervous System Stimulants
• Endorphins
• Narcotic Antagonists
• Naltrexone
• Dextroamphetamine
• Hydrocortisone

Topics

• Adult
• Aging (psychology)
• Amphetamine-Related Disorders (psychology)
• Central Nervous System Stimulants (antagonists & inhibitors, pharmacokinetics, pharmacology)
• Cross-Over Studies
• Dextroamphetamine (antagonists & inhibitors, pharmacokinetics, pharmacology)
• Double-Blind Method
• Endorphins (physiology)
• Half-Life
• Humans
• Hydrocortisone (blood)
• Male
• Naltrexone (pharmacokinetics, pharmacology)
• Narcotic Antagonists (pharmacokinetics, pharmacology)
• Psychiatric Status Rating Scales
• Psychological Tests
• Substance Withdrawal Syndrome (psychology)