Document Detail


Narcotic antagonists in drug dependence: pilot study showing enhancement of compliance with SYN-10, amino-acid precursors and enkephalinase inhibition therapy.
MedLine Citation:
PMID:  15288384     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
We decided to test the hypothesis that possibly by combining a narcotic antagonist and amino-acid therapy consisting of an enkephalinase inhibitor (D-phenylalanine) and neurotransmitter precursors (L-amino- acids) to promote neuronal dopamine release might enhance compliance in methadone patients rapidly detoxified with the narcotic antagonist Trexan (Dupont, Delaware). In this regard, Thanos et al. [J. Neurochem. 78 (2001) 1094] and associates found increases in the dopamine D2 receptors (DRD2) via adenoviral vector delivery of the DRD2 gene into the nucleus accumbens, significantly reduced both ethanol preference (43%) and alcohol intake (64%) of ethanol preferring rats, which recovered as the DRD2, returned to baseline levels. This DRD2 overexpression similarly produced significant reductions in ethanol non-preferring rats, in both alcohol preference (16%) and alcohol intake (75%). This work further suggests that high levels of DRD2 may be protective against alcohol abuse [JAMA 263 (1990) 2055; Arch, Gen. Psychiatr. 48 (1991) 648]. The DRD2 A1 allele has also been shown to associate with heroin addicts in a number of studies. In addition, other dopaminergic receptor gene polymorphisms have also associated with opioid dependence. For example, Kotler et al. [Mol. Phychiatr. 3 (1997) 251] showed that the 7 repeat allele of the DRD4 receptor is significantly overpresented in the opioid-dependent cohort and confers a relative risk of 2.46. This has been confirmed by Li et al. [Mol. Psychiatry 2 (1997) 413] for both the 5 and 7 repeat alleles in Han Chinese case control sample of heroin addicts. Similarly Duaux et al. [Mol. Psychiatry 3 (1998) 333] in French Heroin addicts, found a significant association with homozygotes alleles of the DRD3-Bal 1. A study from NIAAA, provided evidence which strongly suggests that DRD2 is a susceptibility gene for substance abusers across multiple populations (2003). Moreover, there are a number of studies utilizing amino-acid and enkephalinase inhibition therapy showing reduction of alcohol, opiate, cocaine and sugar craving behavior in human trials (see Table 1). Over the last decade, a new rapid method to detoxify either methadone or heroin addicts utilizing Trexan sparked interest in many treatment centers throughout the United States, Canada, as well as many countries on a worldwide basis. In using the combination of Trexan and amino-acids, results were dramatic in terms of significantly enhancing compliance to continue taking Trexan. The average number of days of compliance calculated on 1000 patients, without amino-acid therapy, using this rapid detoxification method is only 37 days. In contrast, the 12 subjects tested, receiving both the Trexan and amino-acid therapy was relapse-free or reported taking the combination for an average of 262 days (p < 0.0001F). Thus coupling amino-acid therapy and enkephalinase inhibition while blocking the delta-receptors with a pure narcotic antagonist may be quite promising as a novel method to induce rapid detox in chronic methadone patients. This may also have important ramifications in the treatment of both opiate and alcohol-dependent individuals, especially as a relapse prevention tool. It may also be interesting too further test this hypothesis with the sublingual combination of the partial opiate mu receptor agonist buprenorphrine.
Authors:
Thomas J H Chen; Kenneth Blum; James T Payte; John Schoolfield; David Hopper; Mathew Stanford; Eric R Braverman
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Publication Detail:
Type:  Clinical Trial; Controlled Clinical Trial; Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Medical hypotheses     Volume:  63     ISSN:  0306-9877     ISO Abbreviation:  Med. Hypotheses     Publication Date:  2004  
Date Detail:
Created Date:  2004-08-03     Completed Date:  2005-02-10     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  7505668     Medline TA:  Med Hypotheses     Country:  Scotland    
Other Details:
Languages:  eng     Pagination:  538-48     Citation Subset:  IM    
Affiliation:
Chang Jung Christian University, Tainan, Taiwan, ROC.
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MeSH Terms
Descriptor/Qualifier:
Adult
Aged
Amino Acids / administration & dosage*
Drug Combinations
Female
Humans
Male
Middle Aged
Naltrexone / administration & dosage*
Narcotic Antagonists / administration & dosage*
Neprilysin / antagonists & inhibitors*
Opioid-Related Disorders / epidemiology*,  prevention & control*
Patient Compliance / statistics & numerical data*
Phenylalanine / administration & dosage
Pilot Projects
Recurrence / prevention & control
Texas / epidemiology
Treatment Outcome
Chemical
Reg. No./Substance:
0/Amino Acids; 0/Drug Combinations; 0/Narcotic Antagonists; 16590-41-3/Naltrexone; 63-91-2/Phenylalanine; EC 3.4.24.11/Neprilysin

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