Magazine article Addiction Professional

From Drugs to Food: A Career in Research

Magazine article Addiction Professional

From Drugs to Food: A Career in Research

Article excerpt

My career as an addiction researcher started with memory research. In the 1970s I was studying the effects of amphetamines on memory', and this early work led to an exploration of drug-related new learning and recall. It appeared that memory was not the problem in amphetamines' "on during learning" and "off during recall" condition. State dependency of memory helps explain why one slip can re-ignite a long-quiet drug personality and memory. Addicts become like their old selves so fast that a slip quickly becomes a relapse. State dependency of learning means that all the things addicts learn in order to survive on the street and interact with others can be locked away once they are clean and sober for a sufficient length of time. They can learn new ways of living and coping and interacting with otherswhat we call "recovery."

Neuroscience was an emerging discipline at this time, and we had a limited understanding of what the brain looked like. The neurotransmitter anatomy of the day included only norepinephrine, dopamine, serotonin and acetylcholine. We knew that certain cell groupings could clearly be seen in the brain in the gross anatomical lab. Most notable were the substantia nigra and the nucleus locus coeruleus.2,3 The substantia nigra was a dopamine-rich area with an important role in Parkinsons disease, but the noradrenergic nucleus locus coeruleus (LC) did not have a clear function at the time. I had the good fortune to work in a translational neuroscience lab and tried to stimulate and also lesion the LC. I also did some work on human LC during neurosurgery rotations, and heard stories of functional studies done at Washington University.

For most of the next decade, I worked on the LC's connection to opiate action, opiate withdrawal and relief of withdrawal symptoms. This work began with a theory for where and how opiate withdrawal symptoms and signs occur. We tested and ultimately translated this theory into a new therapy and therapeutic approach.^ With the LC inhibited by opiates, repeated inhibition would be thought to be the state of the LC in the opiate addict. Chronic inhibition would reverse itself when the opiates were removed slowly, abruptly or after administration of naloxone (Narcan). Withdrawal signs and symptoms would follow the rebound hyperactivity and they would be correlated. Morphine or methadone would reverse the signs and symptoms of withdrawal and return the LC to the chronic inhibition state. This early hypothesis and subsequent tests clearly showed the LCs connection to opiate action, opiate withdrawal and relief of withdrawal symptoms.

This theory remains how opiate withdrawal is understood today. In 1978, it allowed us for the first time to try nonaddicting antihypertensive agents that had LC inhibitory actions through a parallel system to the opiate system that inhibited the LC: the alpha-2 receptor system. Production of opiate withdrawalrelated LC hyperactivity could be turned off by opiates and reversed by naloxone. Similarly, opiate withdrawal-related LC hyperactivity could be turned off by clonidine, and that inhibition reversed by yohimbine or piperoxane.6 Once a dose was found in the translation from rodents to non-human primates to man, we gave human addicts in withdrawal either clonidine or placebo. Clonidine effectively reversed opiate withdrawal and could help detoxify human addicts without giving them an opiate taper. Clonidine could be given as part of a rapid detox protocol, and patients could switch from methadone or opiate maintenance to naltrexone or opiate antagonist maintenance.

Cure remained elusive

At this point (1978-1980), we thought we had a cure for opiate addicts. Unfortunately, we only had a cure in the lab model for addiction. Adherence to long-term naltrexone treatment was low; relapse after clonidine detoxification became the rule rather than the exception. Clearly, we confirmed what many had thought before-that detoxification is not recovery. …

Search by... Author
Show... All Results Primary Sources Peer-reviewed


An unknown error has occurred. Please click the button below to reload the page. If the problem persists, please try again in a little while.