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 or
other drug overdoses? What is the chemistry behind this catastrophe and is there a
hope for 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 cocoa plant, is in a separate chemical family. Heroin mixed with
cocaine, is particularly potent at blocking the nerve impulses that control breathing
and 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.
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 he nervous system and it hard to treat.
Chronic pain is 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.