Diltiazem Reduces Cocaine Craving in Rats

A seemingly unlikely candidate in the battle against cocaine addiction has emerged from work being done by researchers at Boston University School of Medicine and Harvard Medical School. The group administered diltiazem, a drug commonly used to treat hypertension, to cocaine-addicted rats, and found that it significantly reduced their cravings for cocaine.

Diltiazem is a type of drug known as a calcium (Ca2+) channel blocker. Ca2+ channels are voltage-gated ion channels, which when activated allow an influx of Ca2+ into a cell. This inflow of Ca2+ can exert any number of effects, depending on the cell. In neurons, it is often the trigger for the release of neurotransmitter-filled synaptic vesicles, which is the basis of communication between the nerve cells. Ca2+ channels also can be involved in hormone and gene expression. In the heart, they contribute to muscle contraction. Diltiazem limits the activity of Ca2+ channels, and reduces contraction of the heart muscle. This lowers the amount of oxygen the heart needs, which can alleviate symptoms of hypertension.

So what does this have to do with cocaine? Current models indicate drug addiction occurs due to neural reconfigurations caused by the memory-encoding activity of two neurotransmitters: glutamate and dopamine. Glutamate, the main excitatory neurotransmitter in the brain, is thought to encode specific sensory and motor information in cortical and thalamocortical areas, while dopamine seems to react in a more general sense to rewarding stimuli. The interaction of these two chemicals is believed to be responsible for intensifying the memory of drug use and all the stimuli related to it, leading to craving, repeated use of the drug, and addiction.

Ca2+ channels play an integral role in these neurotransmitters working together harmoniously. When they are blocked and brain Ca2+ decreased, the process is disrupted. This is what may account for the reduction of cocaine cravings in the rats.

This study is a promising one for the addiction field, as there are no effective drug therapies currently available for cocaine dependency. It also speaks volumes about how far our understanding of addiction has come. Once it was regarded simply as a choice made by degenerates who had no motivation to live a normal life. Eventually scientists found there are biological mechanisms underlying it that seem to, for the most part, preclude consciously choosing it as a lifestyle. As we come to understand those mechanisms more, the concept of addiction becomes at the same time more tangible and complex.

For example, dopamine was originally thought to be the substrate of pleasure in the brain. It now has a better understood, but more complicated role, of helping us to identify rewarding stimuli in our environment. This is a skill that is evolutionarily adaptive for obvious reasons. Fairly recently it was learned that glutamate is involved in the addiction process as well. Now that our understanding of the interaction between dopamine and glutamate is growing, we are beginning to understand addiction involves a series of synaptic changes made through associative learning, which result in an almost indelible imprinting of an addictive memory. And this expanding knowledge of the neuroscience of addiction all must be viewed against a backdrop of identified genetic patterns, which predispose certain people toward the disorder.

Although this view of addiction as having a neurobiological and genetic basis is commonly accepted science, it has yet to be embraced by a large portion of society, including governments who continue to use incarceration of addicts as their preferred method of dealing with the issue of drug use. Most of us have an addiction of some sort. It may be food, or cigarettes, shopping, or heroin. It’s important to remember, though, that all addictions, from the most minor to the most severe, are probably due to a similar process in the brain that has caused too much importance to be placed on the pursuit of a once-rewarding stimulus. So a crack addict is victim to the evolution and organization of the human brain’s reward system in the same way a shopoholic is. And for those who are lucky enough to not have an addiction, or at least a very damaging one, you might want to hesitate before you credit yourself too much or denigrate someone with an addiction. If the addict were born with your genes and your brain, chances are they wouldn’t be an addict either. It’s time we begin, as a society, recognizing addiction as a disorder instead of a reprehensible and prosecutable offense, in and of itself.