Dr. Weeks’ Comment: Cutting cravings – be it for alcohol, heroin, methamphetamine, tobacco or sex – is easier accomplished when the person is well-hydrated and has stable blood sugar. Medications and nutritional supplementation can help (Baclofen for alcohol, high dose oral vitamin C for heroin and opioids, resveratrol for methamphetamine, omega 6 whole crushed seeds for nicotine) but controlling hydration and blood sugar with an anti-inflammatory diet is critically important. Micronutrients like that found in Equilib are very beneficial and now we have a new drink Synaptamine which is acts as an amino-acid enkephalinase inhibitor (helps with craving) which is described below.
Synaptamine (SG8839),™ An Amino-Acid Enkephalinase Inhibition Nutraceutical Improves Recovery of Alcoholics, A Subtype of Reward Deficiency Syndrome (RDS)
Authors Kenneth Blum et al
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Despite approval by the US. FDA of two drugs for the treatment of alcoholism, the narcotic antagonist Naltrexone and the glutamate receptor agonist, Acamprosate®, the rate of recovery following these two drugs has been only moderate.
We believe that these drugs fall short because they only affect either the opioid receptor or glutamate receptor systems. While it is well established that addictive behavior, such as alcoholism, is a multi-factorial disease that has both genetic and environmental antecedents, it would be more prudent to provide treatment that couple these multiple systems. Previous literature suggested that alteration of the brain reward cascade (Blum and Kozlowski, 1990) by utilization of oral precursor amino-acids and enkephalinase inhibition therapy produced significant reductions in alcohol withdrawal symptomology and alcohol/drug/glucose craving behavior in a number of controlled studies (Blum et al., 1988a-c, 1990b, 1997; Brown et al., 1990; Defrance et al., 1997; Cold, 1996; Chen et al., 2004).
In 1996, our laboratory first described Reward Deficiency Syndrome (RDS) to define a common genetic variant involving dopamine D2 receptor gene (DRD2) polymorphisms as a putative predictor of impulsive, compulsive and addictive behaviors (Blum et al., 1996a). The D2receptor has been associated with pleasure and the DRD2 A1 allele has been referred to as the reward gene (Blum et al., 1990a, 1996a; Blum and Braverman, 2000).
The dopamine D2 (DRD2) gene and especially its allele Taq1 A1 and its receptor, also may be involved in co-morbid antisocial personality disorder symptoms (Ponce et al., 2003), high novelty seeking (Noble et al., 1998) and related traits (Hill et al., 1999). The mesocorticolimbic dopaminergic pathway system plays an especially important role in mediating reinforcement by abusable drugs and it may be a common denominator for multiple addictions and a number of psychiatric disorders (Comings et al., 1991).
When the mesocorticolimbic system dopamine reward system dysfunctions (potentially caused by certain genetic variants), the end result is Reward Deficiency Syndrome (RDS) and subsequent drug-seeking behavior (Blum et al., 1996a, b). RDS refers to the breakdown of the reward cascade (Blum and Koslowski, 1990) and resultant aberrant conduct due to specific genetic and environmental influences (Rowe, 1986).
It is well known that alcohol and other drugs of abuse, as well as most positive re-inforcers (i.e., sex, food, gambling, aggression) cause activation and neuronal release of brain dopamine, which can decrease negative feelings and satisfy abnormal cravings (Gessa et al., 1985; Dichiara and Impereto, 1988; Blum, 1991; Noble et al., 1994; Adler et al., 2000). A deficiency or absence of the D2 receptors then predisposes individuals to a high risk for multiple addictive, impulsive and compulsive behaviors (Comings and Blum, 2000). Although other neurotransmitters (e.g., glutamate, gamma-aminobutyric acid (GABA), serotonin and enkephalins) may be important in determining the rewarding and stimulating effects of ethanol, dopamine may be critical for initiating drug use and for reinstating drug use during protracted abstinence (Gardner, 1997; Connor et al., 2002).
A number of studies have observed that the Taq1 A1 allele is associated with low dopamine D2 densities in alcoholics (Noble et al., 1992; Hietala et al., 1994; Tihonen et al., 1995; Little et al., 1998; Repo et al., 1999; Kuilkka et al., 1998). Moreover, other studies have confirmed that the striatal post-synaptic D2-receptor densities are low among alcoholics (Volkow et al., 1996).
In light of these and other findings involving the role of dopaminergic activity and alcoholism (Volkow et al., 1996, 1993, 2000, 2001, 2002; Thanos et al., 2005; Noble, 2003), we decided to test the hypothesis that manipulation of the reward neural circuitry and potential NAC dopamine release by utilization of oral and intravenous amino-acid-enkephalinase therapy would improve both the emotional and behavioral symptomology of recovering alcoholics in an open trial clinical study….
The following Intensity of Feeling score means and standard deviations were observed for each parameter tested: anxiety (pre: 6.5±0.84 vs. post: 3.0±0.68) (p<0.001]); craving (pre: 5.7±0.57 vs. post: 1.35±0.16) (p<0.001); depression (pre: 5.0±0.35 vs. post: 1.95±0.31) (p<0.001]); fatigue (pre: 5.2±0.57 vs. post: 1.2±0.14) (p<0.001); concentration (pre: 4.9±0.98 vs. post: 4.18±0.54) (p<0.001); anger (pre: 4.24 vs. post: 1.9± 0.36) (p<0.001]; lack of energy (pre: 5.85±0.64 vs. post 3.5±0.47) (p<0.001); and crisis (pre: 6.5±0.65 vs. post: 3.0±0.30) (p<0.001). Further statistical testing using one-sample Student’s t-tests was done to determine if the average reduction in mean scores due to treatment exceeded 50%, suggesting clinical improvement. Mean reductions for anxiety (53.8±10.2%), craving (76.3±3.1%), depression (61.0±6.3%), fatigue (76.9±3.1%) and crisis (53.8±5.5%) were all significantly greater than 50% (p<0.001). It is noteworthy that, in the 600 alcoholics tested, the only parameters that did not result in clinical improvement after treatment were concentration (14.7±20.2%) and lack of energy (40.2±8.4%) (Fig. 1).
While we are not able to emphatically prove that the improvement in both emotional and behavioral parameters found in this clinical trial are solely due to the oral and intravenous amino-acid-enkephalinase therapy (cannot eliminate the positive affect of drug abuse counseling), these results strongly suggest the potential significant effects of this novel therapeutic modality.
The notion that the oral and intravenous amino-acid therapy actually paves the way for the patient to intellectually accept RDS as a lifelong condition she/he must face seems to be the key to successful substance abuse treatment. This dual therapeutic approach allows the brain to say No to substance abuse and provides the body with a softer, gentler way. Thus it has become apparent that positive mind-body interaction actually creates the feeling of well-being necessary for successful recovery.
We further hypothesize that SG8839, increases dopamine release at the NAC, thereby activating D2 receptors and reduces alcohol craving behavior (Thanos et al., 2001).
Based on this well-studied foundation, whereby the deficiency or absence of DRD2 receptors then leads to a high risk for multiple addictive, impulsive and compulsive behavioral propensities called Reward Deficiency Syndrome (Blum et al., 1996a, b; Gardner, 1997; Xu et al., 2004), we propose that SG8839, because of its potential induction of a slow, natural, neuronal release of dopamine may indeed be an important treatment modality. This premise warrants further investigation including a double-blinded, randomized, placebo controlled study for both the intravenous and oral forms of delivery of this novel modality.
While there are no controls in this open label study, the strength of the experiment resides in the large sample size (n = 600) and the high levels of significant differences between pre and post measurements.
We further hypothesize that coupling certain gene polymorphisms involved in dopaminergic, serotonergic, gabaergic and catecholamine catabolism enzymes (e.g., Catechol-O-Methyl-Transferase COMT) function to guide customized formulations based on solid nutrigenomic principles may indeed enhance treatment outcomes in the future (Blum et al., 2006).