Epigenetics is the "software" that tells the "hardware" of DNA how to execute the program of life.
Epigenetics also provides a platform for the interaction between the environment and the genetic code. As one progresses through life, interactions with the environment including diet, exercise, exposure to chemicals, etc. are translated into epigenetic marks that control gene activity. A simple example is seen when consuming alcohol over a long period time as this leads to epigenetic marks that increase expression of alcohol dehydrogenase (the enzyme that breaks on alcohol) which leads to increase alcohol tolerance.
THE DISRUPTIVE DIFFERENCE...
There is a growing body of research that has established epigenetic memory as the facilitator of pathogenic addictive behaviors. In order for a behavior pattern to become fixed, Epigenetic bookmarks are erased, re-arranged and re-written to support the new behavior. These Epigenetic marks fix the pathogenic gene expression program and facilitate higher-order structural changes in the brain. Despite this fact, nearly all current treatments for substance abuse target the signaling chemicals neurons use to communicate, rather than the underlying epigenetic causes. In a search of 240 active or recently-active pharmaceutical programs in the addiction space, nearly all were focused on molecules that directly alter brain signaling molecules like dopamine, opiate receptors, etc.
Only 10 out of 240 programs focused on a drug target which isn’t directly involved in the neurochemical pathways, and none of these 10 focused on epigenetic or gene regulation as a mechanism to treat the disease [data from Citeline database].
Despite some limited success, targeting neurochemicals is akin to targeting the symptoms of the disease. If pathogenic epigenetic states underlie pathogenic neurochemical patterns, then targeting the root epigenetic cause will not only be innovative approach, but could provide a deeper impact on these patients than the therapeutic options currently in the clinic and in the pipeline.
OUR SCIENTIFIC THEORY
Vulnerability to addiction emerges through approximately equal parts (50-50) of genetic predisposition and environmental risk, strongly suggesting an important role for epigenetic mechanisms. All abused drugs target the mesolimbic dopamine circuitry, which serves the evolutionary purpose of reinforcing activities important for an individual's survival and reproduction, such as seeking palatable food and sex.
All natural rewards and abused drugs share the property of acutely increasing dopaminergic neuro-transmission in NAc. Chronic drug use includes long-lasting structural, electrophysiological, and transcriptional changes in this region, which are considered the sustained biological substrate of addiction
Addiction is a significant public health problem, with over 50% of Americans having reported illicit substance use. There is a critical need to develop treatment strategies that may mitigate the abuse-related effects of stimulants (such as methamphetamine). A growing body of literature suggests cannabinoid type 2 (CB2) receptor agonists may be able to modulate the reward pathway, thereby decreasing the reinforcing effects of drugs of abuse. Furthermore, these agents may also have utility for healing the brains of individuals suffering from stimulant use disorder, improving cognitive function, protecting the dopamine system, and reducing brain inflammation in the methamphetamine exposed individual.
In our research, we have found a compound that decreased the reinforcing effects of methamphetamine, reduced place conditioning induced by methamphetamine, and attenuated both methamphetamine-induced dopamine neurotoxicity and its associated cognitive dysfunction. We have found similar promising results with the compound for cocaine, oxycodone, and alcohol. As such, we are planning to hire a CRO lab (Contract Research Organization) to conduct early proof of concept research to assess novel CB2 receptor agonists, chosen by ACT SCIENCES pharmaceutical for testing.