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First, there was opium

The first in a series on opioid addiction

 

How do opioids relieve pain, cause euphoria and lead to an addiction that refuses to take “no” for an answer? How is it that in 2017, 72,000 Americans died of opioid drug overdose? What is the chemistry behind this catastrophe? Is there any hope of controlling it?

Scratch the seed bulb of a poppy plant with a knife and a milky white latex secretion oozes out. This raw opium contains morphine, codeine and thebaine. The first two are pain-relievers of the first order; thebaine is the molecule from which chemists (or criminals) make oxycodone, fentanyl and other semi-synthetic opiates. Laudenum is an alcohol extract (or tincture) of opium and was widely used as a sedative and painkiller in Europe and the United States in the 19th and early 20th centuries, until physicians and users realized how addictive it was.  Codeine, the second component of opium, is an effective pain reliever and cough suppressant and is still widely used. 

Morphine was purified from opium and sold by Merck in 1827.  Heroin, a chemical variation, is more potent than morphine, partly because it can cross the blood-brain barrier and has greater access to the central nervous system. Created by Bayer in 1874, it was sold for pain relief. Heroin was also used to control diarrhea because it affects the gut, which has its own dedicated branch of the nervous system. 

Cocaine, from the coca plant, is in a separate chemical family. Heroin mixed with cocaine is particularly potent at blocking the nerve impulses that control breathing. Many of the drug-associated deaths in the United States are the result of this or other drug mixtures, according to the National Institute of Drug Abuse (NIDA).

Opioids can be smoked, snorted or swallowed as pills or tinctures, but the invention of the syringe (about 1857) provided another way to get drugs into the bloodstream in a sudden way and to induce rapid pain relief and euphoria. In our current epidemic, contaminated syringes increase the risk of infection — notably for hepatitis, HIV and bacterial infections of the heart valves. At great expense and effort, modern medicine can deal with these conditions, but only for patients who remain drug free and participate in their treatment. 

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Pain is an overriding medical problem and always has been. Consider this statement from a physician in 1915 on the entire collection of drugs then available: If the entire materia medica at our disposal were limited to the choice and use of only one drug, I am sure that a great many, if not the majority, of us would choose opium…” A hundred years later we have many synthetic opioids (hundreds, at least) from oxycodone to fentanyl. The number of surgical procedures — tens of thousands of hip and knee replacements and other procedures each year — would be impossible without pain suppression that currently depends on opioids.

Since chronic pain is central to the addiction crisis, I was surprised to learn how little we know about the neuronal mechanisms that are responsible for it. According to one recent review I read by Dr. Christophe Stein in The Annual Review of Medicine (2016): “The central integration of signals from excitatory and inhibitory neurotransmitters and from cognitive, emotional, and environmental factors results in the perception of ‘pain.’” I offer this statement as proof of complexity. Unlike the acute pain of a stubbed toe, chronic pain, when established, takes up residence in the nervous system and is hard to treat. 

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Chronic pain is also hard to study. First, pain is subjective: reported severity varies from one person to the next. Second, to study pain relief, one has to cause chronic pain and that we cannot do with human beings. Pain is even hard to study in mice. A mouse can’t rate its discomfort on a scale of 1 to 10. Humans are not so reliable either. Third, the nervous system is unique: if pain is inflicted on it or morphine is given to relieve that pain, the nervous system learns. It builds new connections (synapses) between neurons, removes others, and activates new genes. It is no longer the same brain as before addiction. Even when the source of pain is removed, parts of the brain may still signal that pain exists and that it needs that heroin, desperately. We’ll examine the basis of this need in the next column.

For later columns, I will be joined by former Executive Director of Emergency Medical Services in New York City James T. Kerr, who after that post was a senior civil servant in the U.S. Department of Health and Human Services. He will help us understand the spread and cost of the opioid epidemic. 

 

Richard Kessin, PhD, is Professor Emeritus of Pathology and Cell Biology at Columbia University. He lives in Norfolk, Conn., and can be reached at Richard.Kessin@gmail.com. Contact him for original references.

 

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