The administration of opioids is commonplace in hospitals. They are the go to drug for the treatment of serious pain. Back in the 1990s pharmaceutical companies were quoted to have said that opioid pain relievers would not becoming addictive in patients. Since then the USA has entered what can only be described as an opioid epidemic. It is obvious to us now that opioids are addictive. This addictive nature of opioids has led many patients to seek out and transition to the far more dangerous heroin. In 2017 there were 47000+ deaths due to opioid overdose in the United States. Along with these deaths were an estimated 1.7 million people who suffered with substance abuse due to prescription opioids. This has cost the US over $70 billion a year.
Many pharmaceutical companies have been taken to court in the US over the promotion of opioid drugs while also downplaying their addictive nature. Many settled pre-trial, however major company Johnson & Johnson went to court in Oklahoma. They were ordered to pay $572m for their role in promoting opioid drugs to consumers. Therefore contributing to the opioid crisis within the US. An attorney for Johnson & Johnson stated that you cannot sue your way out of this crisis. In truth there are many issues at play here. The pharmaceutical companies failing to deliver the required warnings about the drugs they were promoting. Along with this is a major issue in the way drugs are so easily prescribed to patients.
Current Pain Options
To understand the problems with opioids we need to look at the pain treatment options currently available. Treatments can be divided into several categories each with their own specific function. Perhaps the most common are the non-steroidal anti-inflammatory drugs (NSAIDs) these include your aspirin, paracetamol, ibuprofen etc. These drugs act to reduce the action of the immune system in triggering pain, effective over the counter options for those day to day ailments.
There are the steroidal drugs, made up of the corticosteroids these tend to be applied to the skin in a cream. They enter through the skin and reduce inflammation by also inhibiting the activity of the immune system. Often used to treat the pain associated with arthritis or tendonitis. Steroidal treatments come with several side effects, such as the degeneration of skin layers, so can’t be used for long periods of time.
Another group I’ll mention are the local anaesthetics these work to prevent all sensation in a region, numbing the area. They do this by blocking the nerve fibres directly removing not only pain, but the sense of touch and in some cases the use of the muscle. Along with their relatively short duration local anaesthetics don’t work as the best choice for pain treatments.
Opioids
That brings us to the opioid family and the gold stand pain drug morphine. The opium poppy gave us one of the most addictive drugs in history as well as the best pain drug we have. Sadly that’s the problem, morphine can’t be beaten, its effectiveness at treating extreme pain is unparalleled. So what does morphine actually do? You first need to understand that there exist controls or fail-safes to prevent extreme pain events. The brain understands that too much pain is a bad thing and can try to override it. Morphine aids in this process basically telling the spinal cord to ignore the pain signals it is receiving. However due to its similarity to drugs like heroin there exist many associated risks with it.
The dangers of morphine and other opioid-like drugs like codiene and fentanyl are that they possess the addictive qualities of their more sinister cousin heroin. Once these drugs enter the body they will generate a reduction in the sensation of pain almost immediately. However they are able to reach other areas of the body most importantly the brain. Once in the brain their sadistic nature comes into fruition. They are able to activate the pleasure centres of the brain leading to the sensation of reward. Chemicals including dopamine and serotonin are released producing a sense of euphoria. It is this that leads to the drugs becoming addictive. The brain craves more of that feeling and instant satisfaction leading to addiction. This is a simplistic explanation of addiction there are many other mechanisms at play. However the take away message is that opioids trigger addiction.
There is also the problem of tolerance, the effectiveness of these drugs to treat pain get lower the longer you use them. Your body basically adapts to the presence of these compounds in your body, for example increasing the mechanisms needed to dispose of them. You will need more and more of the drug to achieve the same amount of pain relief. The more you take the more the brain begins to crave it this then leads to potential overdoses, causing breathing problems and nausea. There is also the side effect of having your pharyngeal reflex (also known as your gag reflex) with a rather unpleasant chance of death via drowning in your own vomit.
The problems facing the healthcare system is a lack of alternatives and the ease in which morphine is administered. This along with no follow up to prevent potential addiction. I would like to state that morphine is an incredibly effective drug and its use has made lives better. So please don’t come away from this with a fear of it. With better precautions in place these problems should not arise. Should there be a risk of addiction there need to be alternative treatments along with better post-treatment options.
What’s the Problem
That brings up the question as to why there hasn’t been another drug developed to compete with morphine. The reality is that there are many obstacles to get over for a pain drug to be successful. Firstly the pain system is spread throughout the body and is important for defence. Removing pain completely is not really a solution as I mentioned in my post on pain. There are many different systems that contribute to pain and selectively blocking them in the region that is injured is difficult. Then there is the fact that a majority of the pain system is located within the spinal cord and the brain (the central nervous system; CNS). From a drug standpoint this makes life very difficult. The CNS is incredibly well protected, obviously there is the skull and the spinal column. These are dense bones that prevent as much damage as possible from occurring to these crucial sensitive regions. However for drugs there is something far more important to consider, and that is referred to as the blood-brain barrier (BBB). Blood does not freely flow around the brain it is carefully filtered to prevent contaminants from getting to this vital organ easily. This means for a drug to get into the brain or spinal cord it needs to get through the BBB. Morphine is one of these drugs that can penetrate the barrier and get access to the brain and spinal cord to work its magic. If you look at the other opioids they too can easily traverse into the brain. Heroin is so good at it that it can enter the brain within seconds, and as discussed this unlimited access to the brain also leads to the major problem of addiction.
Alternative Choices
This means we need a drug that can easily gain access to the brain or spinal cord while also providing strong pain relief without the risks of addiction. A few years ago there was this potential with drugs derived from the venom of cone snails. These conotoxins were almost 100x as potent as morphine with none of the risks of addiction. The problem was that they couldn’t get through the BBB. The only way to get them to the site they needed to be was via direct injection into the spinal. This is an uncomfortable and tricky procedure that can’t really be conducted over and over again. Morphine is just more convenient. Another potential area for investigation are the chemicals found in cannabis called cannabinoids. There already exist cannabinoid-like compounds naturally within the body called endocannabinoids. The endocannabinoids have been shown to possess analgesic properties. This led pharmaceutical companies to develop drugs derived from the cannabis plant that perform the same function. Drugs that utilise the chemicals THC and cannabidiol have found success in the treatment of neuropathic (nerve pain) and cancer pain.
After the disastrous outcome of this opioid crisis the need to replacements is crucial. However as I said we cannot just dismiss morphine and other opioids. We instead need to monitor its usage and conduct careful follow up on those who were on them. Along with this it is necessary to have countermeasures in place. Methods to help those with addiction while also providing drugs that reverse overdose. All these need to be common practice while researchers are incentivized to investigate newer drug options. The opioid crisis will take time and money to eventually solve, but it is the job of the government working with pharmaceutical companies to set out better regulations. The hope for the future is to eventually replace opioid drugs as the preferred pain treatment.
Reading Sources
- US Department of Health; National Vital Statistics System.
- The Economic Burden of Prescription Opioid Overdose, Abuse, and Dependence in the United States.
- Descending control of pain. Millan M.J
- Conotoxins That Could Provide Analgesia through Voltage Gated Sodium Channel Inhibition. Munasinghe & Christie
- Cannabinoids in the management of difficult to treat pain.
NociSci 