Reward Deficiency Syndrome

Updated: Jun 21, 2020



By Drew W. Edwards, EdD, MS and Sean C. Orr, M.D.

April 5, 2020


"I could watch the sunset or see the rainbow,  but I could never experience their warmth or beauty." - Amanda 33


Reward Deficiency Syndrome, or RDS, is brain disorder characterized by a clinically significant deficiency of the essential neurotransmitter -Dopamine - in the brain's Reward Center, specifically the midbrain and prefrontal cortex. RDS is primarily acquired genetically but can also result from prolonged stress.  Dr. Edward's friend, colleague, and mentor,  Dr. Mark S Gold,  former chairman of Psychiatry and the 17th Eminent Scholar from the University of Florida  proposed the "Dopamine Deficit Hypothesis" some 30 years ago. Neuropharmacologist, neuroscientist, and colleague, Dr. Ken Blum identified important precursor enzymes and proteins necessary for dopamine synthesis and production. These giants paved the way for our current understanding of the genetic basis and manifestation of Reward Deficiency. 


Why is dopamine so essential?

Dopamine mediates the biology of reinforcement and how we experience pleasure, reward and contentment. Dopamine ascribes "salience" to behaviors directly connected to behaviors  germane to the survival of the species, such as eating, hydration, self defense, aggression, and copulation, to name a few.  Recent research shows that perhaps as many as 30% of the US population have a genetically acquired “dopamine deficiency”- and are thus at "increased "risk"  for developing Reward Deficiency (addictive disease, depression, anxiety disorder, ADHD,  stress related disorders, sexual compulsions, pathological gambling, hedonic overeating and obesity).


New research into networks of connected brain cells has shown us that there are strong ties between the dopamine-rich Salience Network (which evokes the fight-or-flight response) and three other fundamental neural networks of the brain. First, the Attention Network is what governs our focus and concentration, and it is steered by the dopamine-driven influence of the Salience Network. Next, the Default Mode Network is where we process our thoughts in our imagination, which of course is largely determined by where we place our attention. Finally, the Central Executive Network is where we take action and execute the plans that emerge from our imagination-driven processes of the Default Mode Network.


Source: Dr. Riccardo Cassini and Dr. David Bercelli. http://www.tre-webinar.com/p/tre-webinar-interview-with-dr-cassiani-about-the-nervous-system-and-tre


This new knowledge helps us to better understand the practical effects of life in the post-modern world. Today, the number of distractions that hijack our brain has increased exponentially with the introduction of smart phones and marketing strategies that set off "notifications." We are bombarded with countless distractions every day that are designed to capture our attention, our most valuable resource. For all of us, this bombardment of overstimulation produces a strain on our dopamine-producing brain salience network, literally putting the entire population into a heightened state of alert, fear, and panic, which send our Default Mode Networks into overdrive.


So it should be no surprise that for those who are particularly prone to having deficient amounts of dopamine that they would turn to activities that compensate to boost their dopamine release. Unfortunately, all too often, those activities only accelerate the damage in a vicious cycle, leading to a downward spiral of cognitive decline and, for many, homelessness and death.

"My life was just blah and boring.  But after a few drinks or smoking some weed,  life became interesting and exciting for a little while." ---Terrell, 23

How do you know if you have RDS?

If you've inherited the gene for dopamine deficiency - and are exposed to a substance or engaged in a behavior that elevates your dopamine level, particularly during a time of stress or sadness - you will feel better—at least for a little while. You may even conclude that you had found the solution to stress, boredom, bad feelings, bad days, and difficult people. Of course, the relief is only temporary, but learning how to change your mood artificially is the first stage of addiction. 


The persistent use of drugs and/or alcohol may also create reward deficits in the brain. All drugs of abuse artificially spike the brain’s dopamine level which results in a chemically induced "high" that far exceeds what one could attain naturally. But what goes up--must come down. Unlike natural rewards, after a drug-induced high (alcohol is a drug), dopamine levels become deficient. So the more someone uses a mood altering substance or engages in an addictive behavior to feel better, the worse they actually feel. Welcome to the hamster wheel.


Normally,  sustained abstinence is necessary before the individual’s brain is able to restore its normal reward biology and function properly. But a deficit in dopamine is no small thing. It creates "Anhedonia", or the inability to feel happy, content, and appreciative of natural rewards and beauty.  For many, abstinence alone may not be enough, depending their circumstances-- such as stress, poor social support, and numerous concurrent social and environmental stressors. For these folks, additional treatment often indicated. 


 I have been sober for 3 months and today I awoke to the sounds of birds chirping and singing outside my window. Those birds have been there for years, but I never noticed them until today. It was awesome! --Kalisha, 27

Being able to characterize RDS as a syndrome has been an important advance in how we conceptualize and treat Substance Use Disorders , Depression, Anxiety, Stress disorders, Problems with Attention and Focus, Overeating, Obesity.  RDS has also opened the door for new and novel treatments by reframing the question. Simply stated: What do all the aforementioned disorders have in common? The answer is a depleted reward biology, primarily, but not exclusively, dopamine deficit, in critical areas of the brain.  Serotonin, norepinephrine, GABA (Gamma Amino Butyric Acid) and others form a "cascade" of biological wellbeing  to maintain homeostasis, or natural balance. Understanding this from a scientific perspective has made us rethink how to help patients suffering from addiction.


The traditional treatment modalities for Substance Abuse Disorder include medication for concurrent depression or anxiety, psychotherapy, 12-Step Recovery Programs, and social support. These remain the mainstay for most people and are, by design, symptom-reduction strategies. However, RDS has illuminated the need for new and novel treatment approaches, such as neuronutrient-neurotransmitter agonist therapy.


Clinical trials over the past decade have produced statistically significant reduction of RDS-associated symptoms through the use of neuronutrient-agonist-therapy. The genetic profile of the individual is paramount to understanding who will benefit from specific pharmacological treatment, and potentially achieve reward stability. Our genes determine how our brain processes dopamine and other neurotransmitters. Some people are "fast metabolizers" and naturally run through their own dopamine stockpiles very quickly. Others are "slow metabolizers" and build up more than ample amounts of dopamine.


Understanding this has helped us to unlock a whole new level of thinking about how certain people behave in times of peace and times of stress. It also has helped us to realize why people who are fast metabolizers gravitate more towards addictive behaviors as part of the syndrome of RDS. This is an exciting time for that reason, as we realize that there is an entirely new set of diagnostic and therapeutic options that are opening up for people who suffer with RDS.


A double-blind cross-over study in abstinent heroin-dependent participants of KB220Z, a DA precursor complex one hour following delivery of neurotransmitter precursors, functional connectivity between regions of the accumbens and the medial orbital cortex is enhanced. Arrow and blue circle are shown to emphasize increases in functional connectivity in NAc with oral KB220Z. Reproduced with permission from (6). Marcelo Febo, Kenneth Blum, Rajendra D. Badgaiyan, David Baron, Panayotis K. Thanos, Luis M. Colon-Perez, Zsolt Demotrovics, Mark S. Gold. (2017). Dopamine homeostasis: brain functional connectivity in reward deficiency syndrome. Frontiers in Bioscience, 22, 669-691.


Diagnosing RDS


In July 2018, Dr. Blum received a U.S. patent for his GENETIC ADDICTION RISK SCORE (GARS) test. Backed by nearly 40 years of research, development, Geneus Health has created the GARS™ test (a simple saliva swab) to help people understand their specific genetic profile and risk for RDS.  

"restoreGen™ is not your usual infomercial driven miracle supplement made from a jelly fish or some other exotic sounding source."  - Dr. Drew Edwards

Do Not Misunderstand the word "ADDICTION" in the GARS name. All the disorders under the RDS umbrella share common etiology and psychopathology. The GARS test can identify thousands of Single Nucleotide Polymorphisms (SNPs) found on our chromosomes, which have been shown to increase genetic risk and expression of DIS-EASE.  Learn More about GARS.


restoreGen™ (research codes KB220Z and  KB220PAM) is not your basic infomercial driven miracle supplement made from a jelly fish - restoreGen™ has undergone rigorous, peer reviewed scientific scrutiny and has proved to be both safe and effective to help patients suffering from RDS.


Due to the recent opioid epidemic, Dr. Blum and Dr. Gold have worked with the National Human Genome Center to advance this research through a clinical grant awarded by the National Institute of Health (NIH) in hopes of developing additional tools to stem the deadly tide of addiction, depression, stress disorders, and suicide... what we now recognize to be an epidemic of despair. Their work has exposed the failures of the health care system to properly care for patients suffering from addictions, but it also gives hope for millions around the world that there is a newer, better way of handling their cravings and addictive drives.


More importantly now in the face of unprecedented worldwide stress and despair, their trailblazing work into RDS could not have been more perfectly timed. The world's overall sense of reward is on track to reach an historic low with the global meltdown in the face of the COVID-19 pandemic. Fortunately, with the proper nutritional supplementation, an opportunity exists to help our population not only make it through this health crisis but also flourish as we exit it. The bottom is: There has never been a better time to feel bad.


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