Posted on May 3, 2013 in Alcohol and Drug News

New Enzymes May Be the Key to Treatment for Cocaine Addiction, Overdose

Enzymes are specialized proteins that power a vast array of chemical reactions that keep us alive and functioning properly. One of the chief responsibilities of these proteins is the molecular breakdown of various substances such as drugs and medications; without the actions of enzymes, these substances would stay in the body indefinitely. In recent years, researchers have begun developing enzyme-based therapies designed to address issues surrounding the use of cocaine, including a therapy that could potentially prevent cocaine addiction and another that could potentially reverse the effects of a cocaine overdose.

Call Them Instigators

Enzymes are created from instructions encoded by our DNA. They play their essential role by acting as catalysts or instigators for all sorts of chemical reactions; scientists refer to these reactions as the process of metabolism. Some metabolic reactions powered by enzymes involve anabolism, a process that joins relatively small chemical/biological molecules together and forms larger molecules. Other metabolic reactions powered by enzymes involve catabolism, a process that breaks down larger chemical/biological molecules into smaller molecules.

Enzymes are critical for the breakdown of potentially toxic substances such as medications, legal or illegal drugs and alcohol. Without enzyme activity, these substances would remain in the body. By breaking down (i.e., catabolizing) medications, drugs and alcohol, enzymes produce two critical benefits. First, they limit the peak levels of the effects of any substance in question, whether those effects center on a therapeutic treatment goal or a non-therapeutic form of mind/body alteration. Enzymes also limit the potential for an overdose, a situation that occurs when enough of a given substance accumulates in the body to overwhelm the normal function of the nervous system and create damaging or life-threatening changes in that system.

Enzymes for Cocaine Addiction

In order to set the preconditions for abuse and addiction, cocaine molecules must achieve their mind-altering effects before being broken apart by the process of enzyme catabolism. Under normal circumstances, they manage this goal rather easily by passing rapidly into the brain through a network of blood vessels called the blood-brain barrier, which acts as a filter between the main circulatory system and the structures of the brain and spinal cord. Once inside the brain, molecules of the drug make abuse- and addiction-supporting changes in nervous system function by altering the levels of several chemicals known collectively as neurotransmitters.

According to the results of a study published in 2012 in the journal PLOS Computational Biology, researchers from the University of Kentucky have both identified and custom-designed enzymes that can dramatically speed up the pace of cocaine catabolism. In fact, the study’s authors report that just one copy of one of their customized enzymes can break down thousands of individual cocaine molecules in the space of a single minute; when large numbers of these enzymes are introduced into the body, they can potentially break down cocaine fast enough and in amounts large enough to negate the drug’s ability to cross the blood-brain barrier and trigger its mind-altering effects.

Enzymes for Cocaine Overdose

A cocaine overdose occurs when a given individual takes too much of the drug and overloads his or her central nervous system. When compared to users of methamphetamine and a variety of other common drugs of abuse, cocaine users have an ongoing heightened risk for an overdose, regardless of their previous tolerance for the drug’s effects or the amount they take at any given time. This is true because of the unpredictable nature of cocaine’s impact on central nervous system function.

In 2010, researchers from Columbia University, the University of Michigan and the University of Kentucky reported the preliminary results of their attempts to modify an existing enzyme, called cocaine esterase or CocE, and create a new enzyme capable of rapidly breaking down cocaine and reversing the ongoing effects of a cocaine overdose. In its natural form, this enzyme—which comes from soil bacteria that breed in the root structure of the coca plant—breaks down cocaine much more quickly than the enzyme in the human body responsible for catabolizing cocaine. However, natural CocE is highly heat-sensitive and doesn’t live for long inside the body. The multi-university research team, which presented its findings to the American Society for Pharmacology and Experimental Therapeutics, managed to modify CocE enough to make it stable inside the body, and therefore useful for overdose treatment.

Future Trials

These promising results, in combination with previous studies, that show CocE can reverse cocaine-induced cardiovascular changes, seizures, convulsions and lethality in rodents suggest that CocE may be a good candidate for clinical treatment of cocaine toxicity in humans.

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