why is it so hard to develop an analgesic that isn’t opiate-based?
In: Chemistry
Because the purpose of senses is to keep youall alive. Shutting that down isn’t easy, because you don’t want some random plant to kill you.
They exist, Methoxyflurane is fairly effective (mostly commonly seen as a green whistle), nitrous oxide isn’t uncommon.
Methoxyflurane inconveniently kills your kidney at high dosages and in a user friendly form (Penthrox Inhaler/Green whistle) only lasts for 30min.
Nitrous oxide isn’t exactly user friendly, causes neuro toxicity and B12 deficiency with excessive use.
Opioids also have the advantage of being able to extract them from poppy seeds instead of a complex synthesis.
Because discovering new chemicals that have an effect on pain is almost a random process.
The problem is when we do find such a chemical, the side effects of new drugs can be worse than opiates, or straight up lethal. So even when we do find such a chemical it may not be practical.
We take Acetaminophen (Tylenol) for granted but it is kind of a miracle drug in that its side effects are very very mild while being an extremely effective, albeit mild, pain killer. It was discovered totally by accident. The only flaw with it is that larger doses are toxic and kill your liver preventing it from being useful for large amounts of pain.
Ibuprofen (Advil) was developed after decades of painstaking research.
Nitrous Oxide is well known as a pain reliever and anesthetic but its anesthetic qualities make it no good for dealing with day to day pain. It’s also an oxidizer making it extremely dangerous for fire.
Opiates and Aspirin are both derived from plants (Opium Poppies and Willow) that we have known have pain killing properties for millennia.
Cocaine similarly has been turned into a variety of analgesics like novacane, but have potentially nasty side effects if used daily.
The reason so many pain killers are derived from these plants is that researchers keep going back to the well as it were. Since the mechanisms that these drugs operate on are well understood it makes sense to research and develop chemicals that are similar but slightly different in the hopes that they will give favorable results.
We actually already have a potentially great alternative to Opiates that is being researched right now… cannabis.
The next major developments in pain relief will very likely come from the Marijuana plant.
Now that it is finally being decriminalized after more than a century doctors and researchers are discovering that individual compounds within the plant are actually incredibly good pain relievers with minimal side effects. It is possible to take these chemicals for pain relief without the unwanted side effects (ie getting high).
Cannaboids could become a very effective way to treat chronic pain and act as an alternative to highly addictive Opiods.
Unfortunately research into this is a century behind because of stigma associated with it, and the US Federal government in particular is very set against decriminalizing the plant because of its political use as a tool to arrest undesirables. (Thanks Nixon!)
It would be pretty ironic if the cure for the Opioid epidemic (addictive prescription medication) turns out to be the decriminalization of certain narcotics.
I think what the OP wants to know is, since physical pain is our number one fear, and the number one cause of human unhappiness, why aren’t the world’s wealthy nations sponsoring moon-shot scale initiatives to speed up the discovery of new pain killing compounds? Why isn’t the discovery of safe pain killers our civilization’s primary mission right now? The discovery of safe, long lasting, multi-use pain killers would be the greatest and most profitable invention of all time.
The main receptors in the central nervous system that mediate pain are called opioid receptors.
Drugs that act on those pain receptors are called opioids.
Thus any non opioid drug doesn’t just need to invent a new drug, they need to find a whole new way the body can deal with pain. They need to first move our understanding of pain forward.
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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