Fifty Years in the Development of a Glutaminergic- Dopaminergic Optimization Complex (KB220) to Balance Brain Reward Circuitry in Reward Deficiency Syndrome: A Pictorial

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Dopaminealong with other chemical messengers like serotonin, cannabinoids, endorphins and glutamine, play significant roles in brain reward processing. There is a devastating opiate/opioid epidemic in the United States. According to the Centers for Disease Control and Prevention (CDC), at least 127 people, young and old, are dying every day due to narcotic overdose and alarmingly heroin overdose is on the rise. The Food and Drug Administration (FDA) has approved some Medication-Assisted Treatments (MATs) for alcoholism, opiate and nicotine dependence, but nothing for psychostimulant and cannabis abuse. While these pharmaceuticals are essential for the shortterm induction of “psychological extinction,” in the long-term caution is necessary because their use favors blocking dopaminergic function indispensable for achieving normal satisfaction in life. The two institutions devoted to alcoholism and drug dependence (NIAAA & NIDA) realize that MATs are not optimal and continue to seek better treatment options. We review, herein, the history of the development of a glutaminergic-dopaminergic optimization complex called KB220 to provide for the possible eventual balancing of the brain reward system and the induction of “dopamine homeostasis.” This complex may provide substantial clinical benefit to the victims of Reward Deficiency Syndrome (RDS) and assist in recovery from iatrogenically induced addiction to unwanted opiates/ opioids and other addictive behaviors.

The bigquestion is - “what is the best way, based on scientific evidence, to provide a balanced brain in people involved in addiction treatment and recovery”? While the answer may not be simple, because of the enormous efforts made by our national institutes (NIAAA and NIDA) we are making progress. The fifty-year journey began in the late 60’s and 70’s with the investigation of neurotransmitters in 1969 [1,2] that revealed that dopamine could control tremors in the periphery of cats.

In 1968,Blum and Geller received a grant from the National Institute on Alcohol Abuse and Alcoholism (NIAAA) to do animal research into the role of neurotransmitters in stress and aberrant alcohol drinking. Funded by this grant, their laboratory was the first to look into darkness induced drinking based on the effect of pineal gland melatonin. They discovered that drinking was increased because there was an increase in the synthesis of melatonin in darkness which is inversely proportional to a reduction in serotonin. In fact, injecting melatonin during the light phase also induced high alcohol intake. From 1968-1972, the research focused on the role of stress-induced changes in brain neurochemistry. One finding that influenced the development of KB220 was the discovery that reduced serotonin in the brain of rodents resulted in intense stress-related behavior.