We are about to publish this study in the Journal of Personalized Medicine. I am a co-author. A sample press release is attached.
Dr. Modestino
Title: A comprehensive 4-layered in silico pharmacogenomics analysis on the Genetic Addiction Risk Severity (GARS) Test: Predominance of genetic evidence support GARS as a novel personalized Pre-addiction assessment tool in the opioid crisis era
Authors: Alireza Sharafshah *, Kai-Uwe Lewandrowski, Igor Elman, David Baron, Panayotis K Thanos, Colin Hanna, Mark S Gold, Rajendra D Badgaiyan, Jean Lud Cadet, Edward J Modestino, Eric R Braverman, Catherine A Dennen, Keerthy Sunder, Kevin Murphy, Abdalla Bowirrat, Albert Pinhasov, Marjorie Gondre-Lewis, Eliot Gardner, Daniel Sipple, Nicole Jafari, Foojan Zeine, Jag Khalsa, Rossano Kepler Alvim Fiorelli, Sergio Schmidt, Kenneth Blum *
A new study sheds light on understanding the pre-addiction phenotype and early genetic identification testing.
A data-driven pharmacogenomic computational analyses, involving millions of large data bank annotations, provides scientific evidence supporting the incorporation of Genetic Addiction Risk Severity (GARS) as a predictive test to identify an incipient phase of addiction, namely preaddiction. This test introduces unique therapeutic targets, aiding in the early identification of addiction risk.
These new findings offer hope for the billions of people worldwide caught in addiction’s grasp. The recent study published in the Journal of Personalized Medicine and presented at the NIDA Genetics and Epigenetics Cross-Cutting Research team meeting in 2024 was led by Dr. Kenneth Blum, a Research Professor at Western University Health Sciences. The study included twenty-six authors from various countries such as the USA, Iran, and Israel. This study comes on heels of findings recently published in the New England Journal of Medicine concerning an NIH-funded (~ 400 million) intervention that did not impact opioid-related overdose death rates over the evaluation period that was launched in 2019.
The HEALing Communities Study is the largest addiction prevention and treatment implementation study ever conducted and took place in 67 communities in Kentucky, Massachusetts, New York, and Ohio – four states that have been hard hit by the opioid crisis. The HEALing Communities Study successfully engaged communities to select and implement hundreds of evidence-based strategies over the course of the intervention. Nora Volkow, the director of NIDA, stated, “ Yet, particularly in the era of fentanyl and its increased mixture with psychostimulant drugs, it’s clear we need to continue developing new tools and approaches for addressing the overdose crisis. Ongoing analyses of the rich data from this study will be critical to guiding our efforts in the future.”
Certainly, with over 100,000 people now dying annually of a drug overdose in the US; over 75% of those deaths involving an opioid, there is real need to find better “out of the box” solutions. The term “preaddiction” first introduced in the 1970s and reintroduced by Drs. Thomas McLellan, George Koob, and Nora Volkow in 2022. They propose that ‘preaddiction’ is a crucial concept for addressing addictive behaviors that was previously overlooked.
In response to this suggestion, the lead author, Alireza Sharafshah, a PhD candidate from Cellular and Molecular Research Center, School of Medicine, Guilan University of Medical Sciences, Rasht, Iran, found via PGX analyses that the GARS test is indeed an accurate predictor of pre-addiction including 59 refined genes which represented highly significant associations of dopamine pathways in the brain reward circuitry. In essence, Sharafshah pointed out that ” pre-addiction can be referred to as “reward dysregulation”. Based on our findings, the hypothesis is that the true phenotype is Reward Deficiency Syndrome(RDS), or dopamine dysregulation, and other behavioral disorders are endophenotypes where the genetic variants play important roles specifically in the brain reward circuitry”.
As noted by Dr. Albert Pinhasov, an esteemed molecular biologist and Rector, Ariel University, Israel, and a co-author: “This paper provides molecular scientific evidence for the importance of incorporating GARS as a predictive test to identify preaddiction” an important achievement in identifying this unwanted condition early in life as a preventive tool in our vulnerable youth”.
In addition, Dr. David Baron, full professor and psychiatrist of Western University, stated in an interview that “ While the NIH HEAL Initiative facilitated the implementation of 615 evidence-based practice strategies, with the potential to yield lifesaving results in coming years, unfortunately it recognizes there is no quick fix to reduce opioid overdose deaths.”
However, based on the results of the PGX analyses, Dr. Kai Lewandowski, a co-author and highly recognized spine physician at the University of Arizonia School of Medicine, and a member of the Brazilian National Academy of Medicne suggested “ The importance of our findings introduces unique therapeutic targets assisting in the treatment of pain, drug dosing of prescription pharmaceuticals, and identify the risk for subsequent addiction early in -life.
While the use of a candidate gene approach is controversial especially in the era of GWAS, Dr. Panayotis Thanos, a co-author and an associate professor at the University of Buffalo Jacob School of Medicine, pointed out that the GARS test in humans seemed to be highly predictive with patients undergoing bariatric surgery in terms of eating expectation and post one-year outcomes.
Finally, Igor Elman, a Board-Certified Psychiatrist and Addiction Psychiatrist from Harvard Medical School, also a co-author commented: “While our study provides important translational utilization of genetic testing as a preventive tool, the real importance is to now encourage both the scientific and especially the clinical field to perform high level studies to further confirm these intriguing results."
In 2022, almost 49 million people in the United States had at least one substance use disorder. Consequently, innovations like early identification of preaddiction in youth via GARS testing is important. This current study provides some hope for the people born with addiction liability, highlighting the potential of the role of genes as well as of course epigenetic insults (environmental) requiring all hands on deck.
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