Let me take you back to the world of 4000 years BCE, between two great rivers- the Tigris and the Euphrates. This is within the land we now call the Middle East. Once, the Ancient Sumerians there ruled, and the area was called Mesopotamia.
This was the land where seeds of the poppy were first used to deliver pleasure to the mind. This is the beginning of a thousand-year tradition of using for medicinal reasons what we now call opioids.
Historically, what has happened is that the drug derived from this plant, eventually known as opium, has been used and abused worldwide. In a famous sequence of events, English colonials carted the drug into China and the Orient throughout the 1800s. Eventually the drug was more efficiently synthesized and given. Within the early 20th century, most doctors stayed away from the prescription of opium for medical reasons, even though it was considered to have value in relieving pain (analgesia). This was because the analgesic effect was known to diminish over time, and there was concern about the development of addiction.
An aside: let’s define the drugs we’re discussing, as it’s branched out to become much more than the first seed. These drugs are similar in activity to opium, which is the famous derivative of the aforementioned plant. They are not necessarily derived from opium though. Drugs which are directly derived from the opium are known as opiates, and these include codeine and morphine. Opioids, which include opiates, are substances that act on the body’s opioid receptors to produce morphine-like effects. Fentanyl, buprenorphine and oxycodone are examples.
The US and the Opioid Crisis
What changed, and why did opioids become so deeply embedded in the land of pain medicine? Since the final decade of that century, the rates of medical use have been rising, and they show no signs of diminution. An excellent article in Nature by Sarah deWeert examines the cause of this historical change. What happened was that in the early 80s there emerged a school of thought in North America that this great analgesic tool was underused and many were suffering needlessly. A seminal article in this respect was Ronald Melzack’s “The Tragedy of Needless Pain”. For example, there were a couple of studies which suggested but a small fraction of users will become addicted, especially when opioids are prescribed and not within a recreational context. This, combined with what many speculate to be a concerted effort by pharma companies to lobby lawmakers and medical courses, led to the establishment of opioids as a main course of treatment for chronic pain. (They had been used for acute pain, and the range of scenarios of their use will be discussed below.) This started with the release of OxyContin in the mid-80s, a slow-release form of a well-known opioid with the name oxycodone. The rest is history, and many journalists and medical commentators these days bemoan the “opioid crisis”. Many have gone as far to say that they are the cause of lowered life expectancy in the US! The CDC’s National Center for Health Statistics in 2021 reported 75,673 opioid overdose related deaths in the US in a 12 month period. Synthetic opioids were the biggest culprit!
Defining addiction
Let’s consider the main concern, which is addiction. Since those decades, “addiction” has become better defined, although there is still much confusion. The essence is that addiction as defined is a rare consequence of prescribing opioids to patients, and what is more common is a whole set of behaviours which are undesirable, known as “aberrant drug-related behaviours”. This term acknowledges that many behaviours, such as unsanctioned use of the drug or overuse, are multifactorial: they may follow from criminal intent, or from an external issue such as family conflict, for example. As a result they do not belong to the term “addiction”. Tolerance and physical dependence are still well-understood effects of the drug. These are limited by time and there are many guidelines in place for eroding these effects by “tapering down” the drug use. This is generally effective. It is accepted that at some point all people will develop a tolerance and physical dependence to opioids. Addiction is not a certainty.
The side effects of opioids
For 75 years, the British Pharmacological Society have searched for a drug with the analgesic effects of morphine, yet without the side effects, a quest which has been considered “in vain”. What are these other side effects that are so difficult to bear? Nausea, constipation, and fatigue were well-established effects of the drug in many users, yet there were effects such as myoclonus, a term for “spasmodic jerking of the muscles”, which have been underestimated. Immune system and hormonal dysfunction, which can lead to an increased risk of infections, osteoporosis and lowered sex hormones. There even may be some types of pain which are resistant to opioids. And then there is the dreaded opioid induced hyperalgesia, or OIH, the paradoxical response to opioids whereby people become more sensitive to painful stimuli. In essence opioids can cause rather than treat pain!
When should opioids be used to treat pain
There are yet no established guidelines addressing the appropriate range of use for opioids in every setting. What is believed so far? When are opioids good and when are they not? The evidence is that opioids are good for dealing with acute pain, palliating someone who is dying, and helping someone recover from an addiction. There is some debate though about cancer and chronic non-cancer pain. This is of course pain that lasts beyond the expected period, generally 3-6 months, and this is when it becomes hazy whether opioids are the best treatment. The common belief, as stated in many medical guides used in Australia, is that opioids are a good treatment for cancer pain, but they are not a good treatment for chronic non-cancer pain. The acronym for this final category is CNCP. Of course, they can be used effectively for this disorder, and they are used nationwide. Yet there are various conditions recommended for the way they are used.
Chronic pain is now regarded as an event which must reach into many areas of care, if it is to be dealt with. These are known as non-drug methods and include everything from regular exercise, to therapy, interventional pain strategies, to the betterment of the social and family environment. This comes with the emerging understanding that pain is more than an organic event which is deeply influenced by psychosocial and psychiatric factors, as well as cultural and historical forces. Reading the world of commentary on chronic pain out there suggests whether people will respond well to the prescription of opioids, or whether they will display those unwanted, “aberrant” behaviours, will follow from how well the drug fits into their life as well as their diagnosis. This calls for an experienced physician to sit at the center of care, research the history of the patient, and monitor the use of these drugs, which has been shown to be effective. Opioids are a legendary tool, but they are not enough; we need guidance.
Footnotes
- For example, the NSW Therapeutic Advisory Group.
References
- From Exp Clin Pharmacol, “Opioids and the Treatment of Chronic Pain”, by several authors, Rosenthal et al., made available in 2009
- nature.com/articles/d41586-019-02686-2
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