why is it so hard to develop an analgesic that isn’t opiate-based?
In: Chemistry
Pain is caused by neural signals in response to different forms of damage to the body.
There are three main ways to treat it:
1. Fix the pain at the source of the signals
2. Stop the pain signals in the brain
3. Make the patient not care by feeling good
Opioids work through both 2 and 3: by stimulating opioid receptor proteins, they both reduce pain signals and induce euphoria. This is really good for most forms of pain, making opioids excellent general analgesics for all types of severe pain.
Opioids were easy to discover because of the historical use of opium, containing morphine and other chemicals. However, not all opioids are based on opium chemicals. Fentanyl for instance is structurally very distinct as a molecule, but it works on these same receptor proteins.
To replace opioids, a new pathway responsible for global pain perception would need to be identified and targeted. In addition, it may not actually be beneficial to do so over using opioids. The replacement may be just as addictive, have a similar OD risk, etc. Global brain pathways are often overlapping with many essential processes. So messing with them is inherently dangerous when not done with proper medical oversight.
Instead, it is likely better to provide proper medical therapy to pain patients using opioids. Help them manage their dose. Help them taper off. Provide therapy. Work to develop better drugs to treat withdraw. Make them controlled but available to discourage the reliance on unregulated black market drugs.
Now, we do have many non-opioid analgesics. But they do not really have the same uses as opioids.
Many other drugs work through strategy #1, which means they only are effective for certain forms of pain or targeted relief. And because severe pain often has multiple sources, they may not work as well.
For example, ibuprofen/aspirin/naproxen works by inhibiting COX proteins, which produce chemicals that create inflammation in damaged tissue and induce pain signals. This makes them great for things like muscle aches or fevers, but not for deeper severe pain or traumatic injury.
Cocaine/lidocaine works by locally blocking neuron signals at the site of application. This is great for short term relief from small traumatic injuries, or during invasive medical procedures. but it produces numbing effects that also stop normal sensations such as touch, which can be undesirable. These are also unsafe for frequent use or in high doses to treat larger areas of pain.
Cannabis can relieve some pain, nausea, and induce euphoria to help manage remaining pain. It may also help in opioid withdraw. But it does not really replace opioids. It’s effect is different, as the cannabinoid receptors are more involved in general mood regulation and inflammation rather than pain perception.
There is also dextromethorphan, which is structurally related to opioids but does not strongly bind opioids receptors as it is the mirror image of the backbone structure. It can help with pain at high doses, but is not used for this as the effective doses for pain can induce dissociation, disorientation, and hallucination. Long term use is also addictive and can cause psychological damage.
And lots of others. But the general gist is that opioids are still used because they are really good at what they do, and there are no known safer alternatives that really have the same uses. Drugs that work differently also inherently have different applications.
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