Neuro-Nutrient Therapy: Clinical Ramifications and Pitfalls

By: David Miller, Kenneth Blum, Merlene Miller

Neuro-Nutrient Therapy

Addiction is the Product of Brain Reward Deficiency

It is now known that individuals who seek treatment for chemical dependency have an impairment in the reward system of the brain that leads to low levels of the neurotransmitter dopamine which plays a significant role in feelings of pleasure and wellbeing. The impairment may be due to genetic or environmental factors. The sense of pleasure and satisfaction produced when adequate dopamine is released into the reward site (nucleus accumbens) are deficient when the reward system is impaired.Impairment leads to craving and discomfort and other symptoms of what is referred to as Reward Deficiency Syndrome (RDS). When RDS is present, an individual often uses addictive substances or behaviors to relieve the pleasure deficit caused by the impairment. Because the substance or behavior works to bring relief, the individual is likely to continue to use and is in high risk of becoming addicted.

Evidenced-based medicine has revealed a well-defined interaction of certain neurotransmitters in the reward system of the brain that leads to normal dopamine release. This was first reported by Drs. Kenneth Blum and Gerald Kozlowski in 1989 and has been termed the “Brain Reward Cascade” (BRC). Any impairment, due to either genetics or environment, on this cascade will result in a reduced amount of dopamine release in the brain reward site and in symptoms such as cravings, anxiety, depression, and poor memory.

The following schematic describes the known interaction of the neurotransmitters showing how dopamine is released and regulated. Serotonin (by activating serotonin receptors in the hypothalamus) stimulates the release of enkephalins (opioid peptides). Then enkephalins (by activating mu receptors) influence the release of the inhibitory neurotransmitter GABA (in the Substantia Nigra). In turn, GABA inhibits the release of dopamine (at the Ventral Tegmental Area) via GABA receptors; and the correct amount of dopamine is released at the reward site of the brain to bring about a sense of well–being.

Neuro-Nutrient Therapy

In the schematic, the happy brain (A) is illustrated showing the normal amount of dopamine being released as explained above. However, the schematic also shows the unhappy brain (B). It is noteworthy that GABA is in a higher amount, and as such, significantly reduces the amount of dopamine released. This could be due to, for example, a genetic deficit of serotonin synthesis and or receptor function (including an increased serotonin transport resulting in not enough serotonin to stimulate the needed enkephalins to inhibit GABA). Certainly, other genetic deficits would also lead to less control of GABA. The regulation of dopamine is so important because too little leads to depression and too much leads to schizophrenia.

Neurotransmitters of the BRC include at least four known pathways: Serotonin, Opioid peptides, GABA, and dopamine. Impairments of specific neurotransmitters (serotonin, endorphins GABA, Dopamine) in the BRC can occur via genetics, stress and/or overconsumption of psychoactive substances like alcohol, drugs, nicotine, or glucose. However, due to the known interaction of these brain chemical messengers it is the net dopamine release that translates to well-being.

While it is would be beneficial to know exactly which neurotransmitter impairments are present, there is no known scientific methodology to date such as blood/urine analysis (neurotransmitter analysis) that could definitively identify or categorize neurotransmitter deficiencies. With this said, information related to drug of choice provides some basis for this categorization as well as the utilization of our “Neurotransmitter Questionnaire.” The only way to accurately determine specific neurotransmitter deficits is through genotyping an individual for risk behavior. This genetic testing known as Genetic Addiction Risk Score (GARS) is under validation and will not be commercialized until 2017. (Meanwhile, the present formula of neuro-nutrients, KB220Z, contains adequate amounts of neurotransmitter precursors and facilitators to optimize dopamine in the brain without the need to target a certain neurotransmitter.)

The GABA Paradox
The above explanation as it relates to dopamine regulation strongly suggests that GABA control is tantamount to a happy brain. The paradox is that abstinent addicts have enormous amounts of stress. Based on known pharmacological principles the benzodiazepine- GABA complex combats anxiety. Thus, the use of benzodiazepines as tranquilizers to treat all kinds of stress is widespread and abused by big pharma. While there are benefits in the short term, especially for alcohol detoxification, it is not recommended for long-term use.

Based on the initial development by Blum and associates in 1984, clinicians adopted amino-acid therapy as a tool to treat addiction and other RDS conditions. However, a number of clinicians have inappropriately utilized the amino acid L-glutamine (a GABA precursor) in high amounts to mimic benzodiazepines to reduce stress and treat certain addictions. The take home message here is that too much GABA in the brain leads to too little dopamine. Thus, even without any genetic deficits in the Brain Reward Cascade, the indiscriminate use of anything that will increase GABA, especially long–term, could compromise dopamine function, leading to anti-reward and a low dopamine state.

(We would note here that a number of respected clinicians have also erroneously prescribed the substance GABA to treat addiction which may be ineffective due to the fact that the blood-brain barrier prevents the penetration of GABA into brain).

A Natural Solution for Reward Deficiency: KB220Z Recovery from addiction requires healing the brain. It means balancing the Brain Reward Cascade to optimize the amount of dopamine to be released in the reward site in order to relieve the symptoms of RDS. How do we do that?

Utilizing precursor amino acids as building blocks for the synthesis of brain neurotransmitters has been known for many decades. Over the past 40 years, based on many studies and years of human trials it has been found that a combination of certain precursor amino acids and enkephalinase inhibitors promotes the release of dopamine at the reward site of the brain. Over the years, thousands of addicts have been able to get sober and stay sober using the patented KB220Z, developed with a combination of these ingredients.

The discovery of natural opioid peptides is relatively recent and occurred in 1975. Prior to this discovery, Pert and Snyder reported in Science on the first identification of the opiate receptor. Interestingly, at about the same time Blum and associates working on rodent models discovered that an amino acid, D-phenylalanine (DPA) reduced alcohol craving in genetically craving high alcoholpreferring mice. The mechanism for such a finding resides in the important innate property of D-amino acids to block the enzyme enkephalinase (responsible for the breakdown of opioid peptides including enkephalins) and as such significantly raise brain enkephalin levels. After a series of additional experiments, it was found that high drinking genetically bred mice had low levels of brain enkephalins. Subsequent experiments showed that the administration of direct brain injections of endorphins and or oral and IV injections of D-Phenylalanine resulted in significant reductions of alcohol drinking in these mice.

Many objective studies have verified what these recovering people have testified to. The most recent ingredients has been rigorously researched in 27 human clinical trials including double and triple randomized placebo controlled evaluation. The evidence emerging utilizing neuroimaging tools such as qEEG and fMRI is that the highly researched patented KB220Z is indeed a pro-dopamine regulator. The exciting findings (utilizing qEEG) have now revealed that in both the intravenous and oral forms, this compound regulates the dysregulated brain waves in the cingulated gyrus in abstinent alcoholics and heroin and cocaine dependent patients. In fact, it (see figure 2) has been shown in one hour to bring about calming by increasing alpha brain waves along with increasing low beta waves. This important effect, according to the past president of the American Society of Neurofeedback, would take up to 10-20 neurofeedback sessions.

Neuro-Nutrient Therapy

Moreover, utilizing fMRI in abstinent heroin addicts in China (see figure 3) one hour after administration of KB220Z compared to placebo showed profound activation of dopamine pathways of the caudate-accumbens region of the brain. This suggests that through this now known mechanism, craving behavior as well as stress will be reduced.

Neuro-Nutrient Therapy

Moreover, figure 4 also shows the KB220Z reduces the risk of leaving treatment against medical advice (AMA) as well. Certainly, if patients leave treatment they are unlikely to get into recovery. The importance here is that KB220Z reduces the need for benzodiazepines, reduces withdrawal tremors, reduces building up to drink scores (BUD), reduces the severity of reward deficiency symptoms, and increases recovery rates.

Relapse Prevention
Considering the high rates of relapse, it is clear that it is time for people leaving treatment to do something different. Sobriety is difficult because with abstinence the symptoms of low dopamine return in full force. Continuing to take KB220Z lowers the risk of relapse by reducing the severity of those symptoms. It reduces cravings, relieves stress and anxiety, lifts depression, and increases energy.

Evidence of the benefits of KB220Z for relapse prevention as reported in peer reviewed publications include:
• It regulates the brain wave dysregulation at the Pre-frontal Cortex- Cingulate Gyrus by increasing alpha and low beta bands. By doing so this relapse site will be normalized and as such reduce relapse.
• It activates the caudate-accumbens-dopaminergic pathways inducing an attenuation of aberrant craving behavior.
• A major problem with addiction is that there are poor executive function abilities, which in part are due to genetic deficits and environmental elements leading to hypodopaminergic function and poor memory and focus. As reported in a published paper, KB220Z significantly increased focus after 30 days as measured by qEEG in healthy volunteers.
• Drug abuse counselors are very familiar with the importance of stress as a relapse factor in the recovering community. In a randomized–placebo–controlled study KB220Z significantly reduced stress as measured by skin conductance in patients attending a residential treatment facility.
• In recovery it is important to also boost immunity in aftercare patients because it is well-known that stress reduces brain endorphins with concomitant reduced immunity. Published papers show the importance of endorphins as a regulator of one’s immunity. One key ingredient in KB220Z raises brain endorphins and as such should boost immunity and needed brain flow.
• Especially in the world of legal RX pain killers, patients that have detoxified from prescription opiates may still have pain. Interestingly, dopaminergic tone is tantamount to pain control along with brain endorphins, our natural pain killer system. KB220Z has a known analgesic effect.
• In support of relapse prevention, the following graph (X figure) represents a culmination of oral and IV studies showing very significant relapse reduction in alcoholics, heroin and cocaine dependent patients.

Reward Deficiency Syndrome resulting in low dopamine makes sobriety uncomfortable and even painful for many. Comfortable sobriety requires healing of the brain. Neuro-nutrient therapy prevents relapse by enabling a comfortable sobriety. There are many tasks on the road to recovery. Reduced stress, clear thinking, and the ability to experience pleasure allow the recovering person to accomplish the tasks of recovery that lead to an enriched life.

David Miller is President of NuPathways, Inc. specializing in
nutrients for addiction recovery. He has worked in the addiction
field for 40 years as a therapist, an author, and an educator.

Kenneth Blum, B.Sc. (Pharmacy), M.Sc., Ph.D. & DHL; received
his Ph.D. in Neuropharmacology from New York Medical College
and graduated from Columbia University and New Jersey College
of Medicine. He has published more than 550 abstracts; peerreviewed
articles and 14-books.

Merlene Miller has authored numerous books on addiction and
recovery, specializing in relapse prevention. She is an educator
with 16 years’ experience as director of addiction studies at Park
University and Graceland University.