An 'Off' Switch for Addiction Is a Nice Idea, But It's No Cure

Researchers get close enough to the neurological root of being hooked to make big statements, but an addiction "cure" isn't so simple.

Jul 2 2014, 10:10am

Addiction isn't vaguely defined, not really. There is a distinct line that must be crossed for chemical dependence to take over the brain's reward centers, past which the continued use of some or another drug (or behavior) becomes rooted in avoidance. 

No longer is a user hunting for a dopamine kick; instead, they begin running from a lack of dopamine. The neuro-hunter becomes the hunted; desire for good feelings becomes an intense fear of bad feelings. If it's possible to know more about that line, what it is and how it's drawn, then it could be possible to "beat" addiction, and treat it at its root.

In less abstract terms, after a chemically-induced, unnaturally-large flood of dopamine, mechanisms in addiction sufferers begin to withhold the chemical from their brains, leaving neurons "dry." The result is pain of every sort: panic attacks, nausea, anxiety, sickness—​just collect all the things you might consider "bad feelings" and imagine them packaged together and shoved up your spinal column. It's a model that views addiction and withdrawal as much the same thing, two sides intertwined on a neurochemical strange loop.

It's been known for some time that the root of withdrawal misery is a lack of dopamine in the brain, which researchers have been able to demonstrate occurs as a defensive posture. Too much dopamine is actually damaging to synapses, encouraging oxidation.

This is the specific sort of neurotoxicity served by methamphetamine and its relatives (albeit at very high, sustained doses). Dopamine goes from being a feel-good friend to a thing literally tearing neurons apart. The neurotoxic effects of meth are so severe that a group of researchers is proposing its use in animals to model Parkinson's disease.

The brain is good at stuff, however, and in order to prevent further damage, it turns off the dopamine tap by producing a protein called BDNF (brain derived neurotrophic factor), which arrests dopamine production. The problem, however, is that it overcompensates, according to a study out this week from researchers at Brigham Young University. Rather than turn the switch back on after the dopamine flood recedes, the brain leaves it off, potentially for a very long time (so: withdrawal). 

“I wouldn’t be as motivated to do this research, or as passionate about the work, if I didn’t think a cure was possible.”

The relationship of BDNF to dopamine isn't a new revelation, and the researchers have already successfully used the protein to turn drug-dependent behaviors "on" and "off" in rats. The experiment behind BYU's new contribution again took rats and switched off their receptors for BDNF, and then got them hooked on opiates.

What they found is that, over time, the rats developed new receptors for the protein via the processes of neural plasticity, essentially recreating the structures "necessary for both the establishment of an opiate-dependent state and aversive withdrawal motivation," the researchers wrote in the Journal of Neuroscience. The upshot is that the brain is remodels itself in response to substance abuse. This is addiction.

As such, BDNF and the processes that create it are powerful targets for an addiction "cure." This is what the research team's lead investigator, Scott Steffensen, sees in the discovery: "Addiction is a brain disease that could be treated like any other disease,” he said in a BYU statement. “I wouldn’t be as motivated to do this research, or as passionate about the work, if I didn’t think a cure was possible.”

The catch, however, is that addiction isn't limited to the mechanisms and chemicals in the brain that we call "addiction." We know well enough that it's closely related to mental illness, as well as all kinds of socioeconomic factors. Addiction is, in some ways, a symptom in itself. Roughly half of diagnosed schizophrenics drink or use drugs to excess, while nearly 60 percent of patients with bipolar disorder have some substance abuse in their history.

In this light, we might look at an addiction "cure" as actually just another method of treating the symptoms. No doubt the existence of such a method would be an overall good, but a reasonable concern is some future in which substance abuse is treated in an even less holistic manner that it is now.

If you've spent even a small amount of time in the trenches of substance abuse treatment, you know what goes into it. It's not a matter of treating just the drug or even the drug-specific behaviors; addiction is like a hydra, with different snarling heads burrowing into every aspect of a patient's existence. In essence, drug treatment becomes a matter of treating someone's life: work, family, living conditions, diet, and so on.

An on/off switch doesn't change the nature of addiction from a self-reinforcing, all-encompassing monster to a wound in need of stitches. The ability to turn off withdrawal symptoms would be a marvelous addition to the intervention of drug treatment. But a cure? It's not so easy.