Manipulation of catechol-O-methyl-transferase (COMT) activity to influence the attenuation of substance seeking behavior, a subtype of Reward Deficiency Syndrome (RDS), is dependent upon gene polymorphisms: A hypothesis.

@article{citeulike:1338980, abstract = {There are common genetic mechanisms responsible for both drug effects and subsequent seeking behavior. In 1996, we coined the term Reward Deficiency Syndrome (RDS). Past and current treatment of substance seeking behavior, a subtype of Reward Deficiency Syndrome (RDS), is considered by most to be inadequate. Recently, we evaluated a complex named Synaptaminetrade mark [Haveostrade mark (SG8839R)]. The main difference with an older studied variant and the latest variant is the inclusion of a proprietary form of Rhodiola rosea, a known catechol-O-methyl-transferase inhibitor (COMT) to potentially enhance the activity of presynaptic released dopamine. In this regard, based on the current literature we hypothesize that manipulation of catechol-O-methyl-transferase (COMT) activity to influence the attenuation of substance seeking behavior, is dependent upon gene polymorphisms. In this regard we hypothesize that carrying the LL genotype with low COMT activity should as theorized, increase the reward induced by substance-induced dopamine release and may indeed increase the propensity to type 1 alcoholism and possibly other drugs that activate the dopaminergic system. Thus when alcohol is present in low COMT LL genotype, increasing COMT activity, not inhibiting it should assist in the reduction of social consumption or abuse. Alternatively, under physiological conditions (no psychoactive substances present (e.g. alcohol) carrying the DRD2 A1 allele with associated low D2 receptors should, as theorized, increase craving behavior because of a low or hypodopaminergic state causing the individual to seek out substances that increase the release of dopamine for subsequent activation of unbound D2 sites in the nucleus accumbens. Thus, in the absence of alcohol or other psychoactive drugs (dopamine releasers), especially during recovery or rehabilitation, decreasing, not increasing COMT activity, should result in enhanced synaptic dopamine as physiologically released, thereby proliferating D2 receptors while reducing stress, increasing well-being, reducing craving behavior and preventing relapse. Based on this hypothesis, we believe that adding the COMT inhibitor R. rosea (as Rhodimintrade mark) to our amino-acid and chromium combination in DUI offenders and other illegal drug-related crimes, increases the potential for more targeted neurochemical rebalancing and enhanced relapse prevention. Finally, we hypothesize that these data coupled together provide evidence that the combination of enkephalinase inhibition, neurotransmitter precursor loading, brain tryptophan enhancing and COMT inhibition as well as DNA analysis of the individual's genome, may be useful as an adjunct to therapy when used in outpatient recovery, specifically to assist in reducing craving behavior and preventing relapse.}, address = {Department of Physiology and Pharmacology, Wake Forest University School of Medicine, Medical Center Boulevard, Winston-Salem, NC, United States; Salugen, Inc. San Diego, CA, United States; Genwellness, San Diego, CA, United States; Allied Nutraceutical Research, Lederach, PA, United States.}, author = {Blum, Kenneth and Chen, Thomas J H J. and Meshkin, Brian and Waite, Roger L L. and William Downs, B and Blum, Seth H H. and Mengucci, Julie F F. and Arcuri, Vanessa and Braverman, Eric R R. and Palomo, Tomas }, citeulike-article-id = {1338980}, doi = {http://dx.doi.org/10.1016/j.mehy.2006.12.062}, issn = {0306-9877}, journal = {Med Hypotheses}, keywords = {comt, dopamine, genotype, reward}, month = {April}, posted-at = {2007-05-28 18:32:35}, priority = {2}, title = {Manipulation of catechol-O-methyl-transferase (COMT) activity to influence the attenuation of substance seeking behavior, a subtype of Reward Deficiency Syndrome (RDS), is dependent upon gene polymorphisms: A hypothesis.}, url = {http://dx.doi.org/10.1016/j.mehy.2006.12.062}, year = {2007} }

TY - JOUR ID - citeulike:1338980 L3 - citeulike-article-id:1338980 TI - Manipulation of catechol-O-methyl-transferase (COMT) activity to influence the attenuation of substance seeking behavior, a subtype of Reward Deficiency Syndrome (RDS), is dependent upon gene polymorphisms: A hypothesis. JF - Med Hypotheses AD - Department of Physiology and Pharmacology, Wake Forest University School of Medicine, Medical Center Boulevard, Winston-Salem, NC, United States; Salugen, Inc. San Diego, CA, United States; Genwellness, San Diego, CA, United States; Allied Nutraceutical Research, Lederach, PA, United States. SN - 0306-9877 N2 - There are common genetic mechanisms responsible for both drug effects and subsequent seeking behavior. In 1996, we coined the term Reward Deficiency Syndrome (RDS). Past and current treatment of substance seeking behavior, a subtype of Reward Deficiency Syndrome (RDS), is considered by most to be inadequate. Recently, we evaluated a complex named Synaptaminetrade mark [Haveostrade mark (SG8839R)]. The main difference with an older studied variant and the latest variant is the inclusion of a proprietary form of Rhodiola rosea, a known catechol-O-methyl-transferase inhibitor (COMT) to potentially enhance the activity of presynaptic released dopamine. In this regard, based on the current literature we hypothesize that manipulation of catechol-O-methyl-transferase (COMT) activity to influence the attenuation of substance seeking behavior, is dependent upon gene polymorphisms. In this regard we hypothesize that carrying the LL genotype with low COMT activity should as theorized, increase the reward induced by substance-induced dopamine release and may indeed increase the propensity to type 1 alcoholism and possibly other drugs that activate the dopaminergic system. Thus when alcohol is present in low COMT LL genotype, increasing COMT activity, not inhibiting it should assist in the reduction of social consumption or abuse. Alternatively, under physiological conditions (no psychoactive substances present (e.g. alcohol) carrying the DRD2 A1 allele with associated low D2 receptors should, as theorized, increase craving behavior because of a low or hypodopaminergic state causing the individual to seek out substances that increase the release of dopamine for subsequent activation of unbound D2 sites in the nucleus accumbens. Thus, in the absence of alcohol or other psychoactive drugs (dopamine releasers), especially during recovery or rehabilitation, decreasing, not increasing COMT activity, should result in enhanced synaptic dopamine as physiologically released, thereby proliferating D2 receptors while reducing stress, increasing well-being, reducing craving behavior and preventing relapse. Based on this hypothesis, we believe that adding the COMT inhibitor R. rosea (as Rhodimintrade mark) to our amino-acid and chromium combination in DUI offenders and other illegal drug-related crimes, increases the potential for more targeted neurochemical rebalancing and enhanced relapse prevention. Finally, we hypothesize that these data coupled together provide evidence that the combination of enkephalinase inhibition, neurotransmitter precursor loading, brain tryptophan enhancing and COMT inhibition as well as DNA analysis of the individual's genome, may be useful as an adjunct to therapy when used in outpatient recovery, specifically to assist in reducing craving behavior and preventing relapse. KW - comt KW - dopamine KW - genotype KW - reward AU - Blum, Kenneth AU - Chen, Thomas J H AU - Meshkin, Brian AU - Waite, Roger L AU - William Downs, B AU - Blum, Seth H AU - Mengucci, Julie F AU - Arcuri, Vanessa AU - Braverman, Eric R AU - Palomo, Tomas PY - 2007/04/27/ UR - http://dx.doi.org/10.1016/j.mehy.2006.12.062 ER -