For years, the molecular mechanisms that underlie the toxic actions of cocaine on neural pathways have eluded scientists. As one of the most abused substances in the nation with more and more lethal overdoses occurring, finding solutions for people in cocaine addiction has become paramount for researchers. However, a recent study published in the Journal Proceedings of the National Academy of Sciences have heightened concerns for the progressive use of cocaine as well as provide hope for a treatment intervention that promise to help curb cravings for this drug.
According to Solomon Synder, professor of neuroscience at John Hopkins and his team of researchers, they now have real evidence that high doses of cocaine not only kill brain cells but also cause cells to consume their own insides. This finding culminated after over twenty years of study by Synder who in 1978 received the Lasker Award for identifying the brain’s opiate receptors. Since discovering the coordinated activity between nitric oxide gas and the brain’s complex signaling network, Synder and his team have been working tirelessly to unravel the interaction between a number of proteins in the network and GAPDH in particular, which is a protein known for regulating sugar storage and use.
In this recent study, these John Hopkins scientists has confirmed that high volumes of cocaine trigger a cascade of effects in the brain that utilizes nitric oxide and leads to cell death otherwise known as autophagy. According to Snyder, studies included performing multiple autopsies to determine the reason for this outcome. The result of this information, he said, provided vital information and evidence that cocaine abuse at high doses cause autophagy. It also offered an exciting and significant insight into a treatment intervention that could make a major difference in preventing cocaine abuse and rehabilitating those trapped in the addiction cycle.
While conducting research, Synder stumbled on a 1998 scientific research on the CGP34668B compound that had been conducted by Novartis scientist. The compound had been tested unsuccessfully as a treatment for patients with Parkinson’s disease and amyotrophic lateral sclerosis. However, thanks to continued research by Novartis scientists of CGP34668B interaction with molecules in the brain, they discovered the GAPDH enzyme that help to break down glucose in the body for energy. During tests, the CGP3466B compound disrupted interaction between nitric oxide and GAPDH that has been shown in studies to halt the destruction and cannibalizing effects on cells by cocaine in the brain.
Referring to the discovery, Synder stated that it was remarkably serendipitous after identifying the brain’s pathway that cocaine act on that they were already cognizant of the CGP3466B compound that had been proven to block that specific pathway and was safe for use by humans. He further commented that the CGP3466B compound not only helped to confirm the details of cocaine’s action, but it now holds the promise of becoming the first drug to be approved by the Food and Drug Administration to treat cocaine addiction. Once approved, this pharmacological intervention will require very low doses to effect results. It also appears to only impact the specific pathway necessary to achieve the desired results with limited side effects.
Although some members of the research team, caution that further research should be conducted to determine the CGP3466B compound’s ability to fulfill its promises so far as curbing the insatiable appetite for cocaine, Snyder has already brokered a deal between the company that owns the CGP3466B compound and the National Institute on Drug Abuse. As such, the NIDA will conduct clinical trials in preparation for CGP3466B approval as a treatment for cocaine addiction.
Based on recent data from the Centers for Disease Control and Prevention between 2001 and 2014 overdose deaths for cocaine abusers increased by 42%. As such, this recent discovery by Synder and the John Hopkins team of scientists represent a significant breakthrough and hope for millions of current and potential cocaine suffers.
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