Nov 2017 | By: Kenneth Blum, Ph.D., DHL, B. William Downs, B. Sc., David Siwicki, MD, John Giordano, MAC, DHL, Thomas McLaughlin, MD, Ph.D., Jennifer Neary, Ph.D.

In 1908, President Theodore (Teddy) Roosevelt worried that the national crisis of opiate addiction was weakening America and diminishing its greatness. So, he appointed an Ohio doctor, Hamilton Wright, to be the nation’s first Opium Commissioner. In the decades after the Civil War, the United States developed a deadly narcotics habit. Suffering veterans were hooked on morphine while genteel “society ladies” dosed up with Laudanum — a tincture of alcohol and opium. The wonder drug was used widely as a cough suppressant, and it proved very effective in treating diarrhea in children. In fact, in 1911, Wright told the NY Times- “Our prisons and our hospitals are full of victims of it, it has robbed ten thousand businessmen of moral sense and made them beasts who prey upon their fellows … it has become one of the most fertile causes of unhappiness and sin in the United States.”

Remarkably, more than a century later, America has relapsed. The current opioid crisis is more lethal, with record numbers of fatal overdoses, public health professionals expose. However, it is not the fi rst time in U.S. history that the lax commercialization of legal opioids led to a national epidemic. Faced with a late 19th century dope scourge, federal law enforcement offi cials, doctors, and pharmacists, eventually managed to contain the country’s first addiction epidemic.

The authors, who have numerous scientific publications on this issue, believe that FDA approved Medication Assisted Treatments (MATS), such as the acute administration of Buprenorphine, are helpful in inducing short-term dopamine release. Chronic use, however, induces a significant reduction in dopamine release at the reward site of the brain, causing an unwanted anti-reward state (see figure 1).

Figure 1.

For more than 50 years, our research has provided a signifi cant dossier of peer-reviewed and published evidence in scientific journals showing that balancing Dopamine dynamics in the brain reward circuitry is a far more desirable and useful strategy than blocking its normal physiologically required function. Fundamentally, dogmatic protocols used routinely in addiction treatment are an attempt to medicate people with substance dependence back to health. To put it more simply, we are trying to force health rather than nourish the body’s ability to repair and rebalance via optimal gene expression. This focus on medicating abstinence seems counterintuitive. Health can only be nourished not forced; this is more easily said than done.

In this multi-billion-dollar market, Big Pharma’ opted for simplicity, combating the global drug epidemic by blocking dopamine function with Naltrexone (via mu receptor antagonism) or with, for example, Acamprosate via antagonizing the NMDA– glutaminergic drive to release dopamine at the reward site (Nucleus Accumbens).

Mark Gold and associates in their “dopamine depletion hypothesis” suggested that the powerful dopamine two receptor (DRD2) agonist Bromocryptine could be used for the treatment of cocaine addiction. Fortunately, neuroscientists realized that chronic administration caused a severe reduction in the number of dopamine receptors (down-regulation). The reason for this unwanted side effect is that Bromocriptine or other powerful D2 agonists like L-Dopa overwhelm the neuro-pathways of the brain, especially the pleasure centers, and the biologically intelligent neurochemical adaptive mechanisms react to prevent too much dopamine function (hyper-dopaminergia) and possibly schizophrenic–like behaviors.

Blum and associates have been developing by trial and error a neuro adaptogen, KB220 and many variants since 1968. One recent innovation is the KB220ZBR variation. To date, 37 published clinical studies have validated this nutrient technology based on gene mapping research. This patented technology is comprised of an extraordinary list of ingredients intended to optimize gene expression and the synthesis, transport, reception, and disposal of neurotransmitters. This optimization of gene expression affects the entire brain reward cascade, from serotonin down to dopamine, achieving the functional ‘symphony of neurochemistry’ and the induction of “dopamine homeostasis.”

The first ever confirmed psychiatric genetic discovery by the Blum and Noble’s group; the association of the Dopamine D2 Receptor (DRD2) gene and severe alcoholism, was published in JAMA in 1990. The association in genetic studies of the DRD2 gene with many addictions such as alcohol, drugs, food, sex, nicotine, and other excessive reward seeking or selfmedicating behaviors led to the idea of “Reward Deficiency Syndrome” (RDS), first coined by Kenneth Blum in 1995. Reward Defi ciency Syndrome is now considered to be an established abnormal psychological disorder listed in the SAGE Encyclopedia of Abnormal Psychology (2017) and refers to a deficiency of reward; disrupted neurological dopamine function. This dysregulation of dopamine is the cause of all addictive, compulsive and impulsive behaviors.

To highlight the importance of the RDS concept, in 2013, B. William Downs and Kenneth Blum, published a paper entitled “Have We Hatched the Addiction Egg: Reward Deficiency Syndrome Solution System” dedicated to all the people who have lost loved ones to substance-abuse and “reward deficiency syndrome” related tragedies. Why are we failing at reducing the incidence of RDS behaviors? Are we aiming at the wrong treatment targets? At that time, we proposed a paradigm shift; the “Reward Deficiency Solution System,” and provided evidence for its adoption. The Reward Deficiency Syndrome Solution System” included:

1) A psychological RDS questionnaire (RDSQ);
2) Genetic Addiction Risk Score (GARS) and
3) A Pro-Dopamine Regulator (KB220ZBR).

While the RDSQ and GARS are in development and should be launched in 2018, KB220 variants, with a variety of different ingredients, have been studied in both animal (see fi gure 2) and human research (see fi gure 3). At the time of this writing, research on KB220ZBR is progressing. After 50 years of study, we now have fMRI evidence that KB220 variants can enhance resting state functional connectivity and volume (recruit neuron fi ring in the reward center of the brain) and balance the brain reward circuitry, especially in abstinent heroin-dependent people.

Figure 2.


Figure 3.


Unfortunately, the success of a useful product technology incentivizes the entrance of opportunistic knock-off marketers. After all these years, it has come to our attention that an unnamed company is attempting to copy KB220 technology and commercialize what could be a very harmful product. While the product contains some of the same ingredients as found in KB220 variants, the inclusion of the drug L-Dopa, an amino-acid precursor of dopamine approved by the FDA for Parkinsonism, with well documented side effects, is of concern. Of even more concern, is the potential of this product to cause more harmful effects, with the daily use, common to products identified as ‘dietary supplements.’ A possible harmful offense notwithstanding, this ingredient disrupts the neurochemical balance, especially of dopamine, and can induce unwanted hyperdopaminergia and dyskinesia, instead of much-needed balance. It has the same effects as bromocriptine leading to dopamine D2 receptor down-regulation and even possible heightened schizophrenia-like behaviors. The body maintains the ideal environment to optimize health via an elaborate system of ‘checks and balances’; i.e. a highly complex feed-back system to achieve homeostatic equilibrium. Examples include body temperature, pH, insulin, thyroid, and other hormone functions, neurotransmitter function and much more. So, to protect against excesses or deficiencies of such bio-substances, feed-back regulatory signals maintain balance and optimal health. Pharmacological impositions can have a shortterm benefit, but chronic administration of drugs like SSRIs (or any ‘reuptake inhibitor’) prolongs neurotransmitter presence in the synapse and blunt or inhibit the synthesis and reception of serotonin or other neurotransmitters using this pharmacological tactic.

There is evidence that chronic administration of L-Dopa increases pre-frontal cortex dopamine and serum corticosterone (the stress-related hormone). There is also evidence of a profound serotonin-dopamine imbalance following L-Dopa treatment. Some manufacturers despite FDA limitations have produced plant-based L-Dopa in the form of Velvet Bean and studies have linked this to both psychosis and homicidal behavior.

Over 100 million people in the United States carry the D2 receptor gene A1 allele, which is responsible for lower D2 receptor formation, present in Parkinson disease, and may be a precursor to the development of Drug-Induced Dyskinesia. Therefore, persons presenting for chemical dependency treatment should be warned about using any product containing L-Dopa. Moreover, low Dopamine function can be problematic especially in carriers of the Valine allele (replacement of Methionine) that causes reduced dopamine function due to the high activity of synaptic dopamine break down. This high activity could subsequently produce an unwanted potent neurotoxin metabolite from L-Dopa in the form of 3-O-methyldopa. Another associated problem with L-Dopa administration is that it is known to cause a decrease in concentrations of S-adenosyl Methionine (SAMe) in cerebrospinal fluid with an increase in 3-methoxytyrosine, especially in children. The small molecule (SAMe) is involved in a process known as methyl donation, seen as an intermediate in one pathway to epigenetic cellular maintenance.

Known side effects of the chronic administration of L-Dopa for Parkinson patients include mania, dyskinesia (rigidity in extremities, face, mouth, and tongue) and abnormal involuntary movements (AIMs). Also, psychosis, auditory hallucinations, homicidality, hypersexuality, confusion, delusions, orthostatic hypotension, sleep disruption, age-related mental disturbances, impaired gait, cognitive decline and kaliuresis (renal dysfunction; the induction of unwanted excretion of potassium) are side effects. Based on ignoring many studies, the use of L-Dopa is still considered Recognized As Safe (GRAS) but the FDA has provided limitations on the over-thecounter use of L-Dopa and even the plant extract.

Certain combinations that evoke significant caution include threonine, a GRAS listed amino acid precursor, in combination with L-Dopa, are present in products that claim benefit for anti-cravings. L-theanine increases neurotransmitter production, one of which is dopamine. Green tea has lots of threonines, although it can also be taken as a supplement. Along these lines, Acetyl-l-tyrosine (a potential supplement) is a production-ready form of tyrosine, which will make it easier for your brain to create dopamine. It is easy to understand that this combination is unwanted especially in any nutraceutical supplement with the potential to impact the over-production of dopamine both within the central nervous system and peripherally.


The well-researched pro-dopamine regulator KB220ZBR and prior variants, show increased functional connectivity, in both animal and human neuroimaging studies. Prolonged neuroplasticity (brain cell repair) has been observed in rodents. Moreover, studies have been published showing that KB220Z increased connectivity volume, enhances neuronal dopamine firing, and has eliminated lucid dreams in humans over a prolonged period. An unprecedented number of clinical studies validating the success of a patented nutrigenomic technology (KB220ZBR and prior variants) to re-balance brain chemistry and optimize dopamine sensitivity and function have been published. On another note, it is sad that unsuspecting consumers could be duped and endangered by false promises of knock-off marketers with look-and-soundalike products. Moreover, unscrupulous marketers sell products containing ingredients having potential dangers (i.e., combinations of potent D2 agonists including L-Dopa and L-Theanine) which threaten the credibility and reputation of validated, authentic, and ethical products. We encourage clinicians and neuroscientists to continue to embrace the concept of “dopamine homeostasis” and search for safe, effective, validated and authentic means to achieve a lifetime of recovery, instead of reverting to anti-dopaminergic agents disrupting feed-back sequela or promoting powerful D2 agonists compromising needed balance that are doomed to fail in the war against this devastating drug epidemic.

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 also received a doctor of humane letters from Saint
Martin’s University Lacey, WA.

Bill Downs is a nutritional biochemist. In 2008, Downs was cofounder
and CEO of LifeGen, Inc., a nutrigenomic company
In 2013, Downs founded Victory Nutrition International, Inc. to
research, develop and market evidence-based proprietary, patented
and patent-pending nutraceutical products direct to consumers.
Jennifer Neary MS, PhD serves as Chief Scientific Officer for Avagen
Health in San Antonio, Texas.

Dr. McLaughlin is the Medical Director of the Center for Psychiatric
Medicine in Lawrence Mass.

Dr. Siwicki is a Co-Founder of Dominion Diagnostics and served as
President and a Director of Dominion since its founding in 1997. He
continues to serve on Dominion’s Board of Directors and Addictions
Advisory Board.