Tamea Sisco
Tamea Sisco
INTRODUCTION
The purpose of this paper is to review the clinical efficacy if using narcotic antagonism in the treatment of opiate and alcohol dependence. While there is a plethora of evidence for opiate dependence the research on alcohol dependence is more sparse. However, the method called rapid detoxification that relies upon the use of narcotic antagonism both oral and intravenous may be enhanced by amino-acid precursor and enkephalinase inhibition. Thus this paper serves two purposes: 1) a brief review of the literature 2) clinical evidence showing the synergy between narcotic antagonism and amino-acid therapy.
Alcohol
It is important to begin by reminding ourselves that we do not fully understand the major effects of alcohol on the brain. There are no easily identified, highly specific “alcohol receptors”. In addition, alcohol exerts an impact on almost all brain chemicals, making-it difficult to determine which, if any, are key to the intoxicating or subsequent craving phenomena associated with this drug (Ticku and Mehta, 1995). To make matters even more complicated, the initial administration of alcohol has different effects on brain chemicals than are seen after repeated administration of this drug and all these effects are likely to be different at different doses.
Despite these complexities, there are at least three theories about how a drug that affects opiates might have an important impact in the treatment of alcoholism.
First, alcohol, at least indirectly, does affect the brain’s natural opiate-like or endorphin system. So, even if the impact is modest, it makes sense that any drug that alters the functioning of the natural brain opiates could alter the effects that alcohol exerts on the brain itself. There are data to indicate that one brain opiate substance; leucine-enkephalin in animals and beta-endorphin in humans is decreased in amount in the presence of alcohol (Gennazanni et al., 1982). It is theorized that this could be the result of an inhibition of the production of this opiate by alcohol itself. Similarly, another study documented that if opioid peptides are administered to an animal before alcohol is given, that animal is less likely to consume alcohol (Ho et al., 1982). Consistent with these observations is an early study showing that animals with prior intake of alcohol are more likely to maintain their abstinence when given morphine. These studies, along with the ill-advised turn of the century practice of administering morphine to alcoholics to attempt to maintain abstinence from alcohol, are consistent with some level of interaction between alcohol and the opiate systems.
A second area of support for the potential interaction between alcohol and the opiate systems occurs through studies of stress. Acute stresses do increase the level of the body’s natural opiates. At least theoretically, if stress (either from the environment or from heavy drinking) occurs regularly enough, it is possible that the body becomes used to having higher levels of opiates. Thus, when stress levels decrease (either in the environment or through abstinence) the body might crave the higher levels of endogenous opiates to which it has become accustomed. This discomfort might cause symptoms that make it more likely that the individual will then go back to his or her usual drug of abuse, in this instance alcohol. Consistent with this hypothesis is the observation that animals placed in a high-stress situation are likely to increase their selection of alcoholic beverages, but also that this alcohol-seeking behavior can be blocked by fairly modest doses of naloxone (Ross, Hartmann and Geller 1976)
The third, and perhaps the most attractive, of the theories focuses on the hypothesized brain reward system. A number of investigators feel that most pleasurable experiences, including the acute effects of most drugs, are mediated through the actions of the brain chemical dopamine, especially in a part of the brain called the nucleus accumbens. This area is part of a complex of the brain called the meso-limbic system. Thus, it is possible that the pleasurable effects of alcohol occur, at least in part, through mechanisms that are similar to those that contribute to the pleasurable effects of opiates. If this is true, then a drug that blocks some of the effects of opiates could have a beneficial effect by decreasing the rewarding effects of alcohol, and this elimination of the expected reinforcements might even decrease craving (Meyers and Melclior, 1977).
However, just because a theory makes sense does not mean that it is correct. Nonetheless, there are good reasons to consider whether an opiate antagonist drug might have some beneficial effects in the treatment of alcohol dependence. After a twelve year battle the US FDA approved the use of naltrexone/Trexan® for opioid detoxification, then in the