Breakthrough Alternatives to Opioids for Pain Treatment

Breakthrough Alternatives to Opioids for Pain Treatment

Speaking of pain treatment, opioids seem to have reached a point when they start producing more harm than we are willing to accept and alternatives to opioids are more than necessary. Opioids crisis does not come just from pain relief, but it plays a part and addiction is even more difficult to escape having in mind that people suffering from chronic pain take painkillers on a daily basis to be able to cope way before any trace of addiction appears.

The issues with overuse of opioids greatly surpass addiction problems alone, as detrimental as they are. They cause other social, financial, medical, business and political issues and, as we have seen in the past few years in the USA, they develop into a nation-wide emergency.

This put the spotlight on something that has always been clear, but often neglected because of the immediate need to relieve pain – we have to find better pain treatment alternatives to opioids.

These need to be safer, good for long-term use and efficient enough to replace opioids.

Moreover, painkilling opioids have another downside, aside from the fact that they are not safe. They are not curative, but palliative. This means that they do not treat the cause, but only mask pain. As important as this is for people who suffer from pain on a daily basis, opioids offer no hope of complete recovery.

Many experts have jumped on the bandwagon of trying to find better solutions. One of them is Lynn Webster, MD Vice President of Scientific Affairs at PRA Health Sciences, who compiled a very nice list of non-opioid pain treatment solutions.


Advancements in pain treatment

The main problem with universal pain treatment solutions is that they are very difficult to develop. There are many different kinds of pain, different triggers and causes, sensations, severity levels, mechanisms… In short, in order to treat some kinds of pain, treatment methods need to be targeted, developed to be efficient for that particular kind of pain. Basically, it is not clear that pain is not only a symptom, but can also be a disease in its own right. A disease that sometimes needs dedicated treatment.

Being consistent with the idea of safe treatment, I will present you with some non-opioid, but scientifically confirmed solutions that have been emerging. However, it is fair to say that opioids pain treatment solutions are also being developed in order to reduce the negative effects and emphasize the positive ones.


Non-opioid pain treatment options/potential


Palmitoylethanolamide (PEA)

Anyone who has been on this website before should be well familiar with palmitoylethanolamide, or PEA as it is often called – mind you, there is another substance with the same acronym, so make sure you know what you are looking for.

Aside from pain, PEA deals with inflammation and immune system issues. It is naturally present in the body and released locally in order to exert its benefits. The main issue with endogenous PEA is that it is quickly metabolized by two very efficient enzymes. This is why adding more PEA through diet or supplementation makes it far more efficient.

It is very efficient, thoroughly tested over more than half a century and completely safe. Although it has been familiar for more than 60 years and researched by some of the biggest name of the science world, only recent findings began to explain the mechanisms and a very wide scope of positive effects PEA exerts. This brought a whole new set of interest of the scientific community and we are currently on the verge of the golden era of PEA, with many studies being dedicated to it at the moment.

Recent advancements also brought us liposomal PEA which greatly improves bioavailability of PEA through advanced liposomal delivery system.

A major benefit of PEA is that it is efficient in several different ways and, depending on the underlying condition, it also treats several causes of pain, addressing the underlying condition and not only masking pain.


Opiod-biased ligands

Mind you – ‘biased’, not ‘based’. This is a whole new approach to treating pain sensation which is supposed to keep the efficacy of opioids but eliminate side effects. Opioids usually work by activating the membrane of opioid receptors and this activation then causes numerous different effects, including positive and negative ones through a number of different pathways. The level of activation of these pathways actually determines the strength of particular positive and negative effects and the differences lie within the particular ligand and receptor relationship.

This means that choosing to activate some pathways and not activate others can actually produce the positive effects without the negative ones.

This sounds like a very good solution, but these opioid-biased ligands are still in development. Even if they do not manage to exclude the side effects completely, this kind of selective activation could lead to a whole new set of painkillers.



Another new analgesic that uses selective activation tactics. It is similar to endomorphins but exerts selective activation that makes it safer, but equally or more efficient. Being a completely new option, it is still in development and not certain, but some early tests show that it might be very efficient against inflammatory pain.


Calcitonin Gene-Related Peptide (CGRP)

CGRP is a peptide that is released from sensory nerves and works through calcitonin-like receptor. Its antagonists produce pain relieving effects for migraines as well as pruritus. CGRP is found in C and A delta sensory neurons whose job is to mediate sensation of pain.


CARA 845

I know, CARA 845 is an opioid officially, but it does not breach into the central nervous system, so it cannot cause opioids-related issues, such as addiction. It is actually a great example of advancement in the opioids treatment development. It is still in development, so we’ll keep our reserves, but there is great potential in treating pain not within the central nervous system. The final verdict regarding its benefits is yet to come.


Nektar 181

This is another example of an opioid receptor stimulant which is safe, as it has no rewarding effects, so abuse is very unlikely. Aside from this addiction-removing solution, it enters the brain very slowly, which means that other side effects caused by opioid receptor stimulants, such as sedation, are also reduced.

Nektar 181 is a chemical drug currently being developed and tested and if it turns out to be efficient and safe, it could be a major benefit for people suffering from chronic pain.


Vitamin D

Two different sets of research showed that Vitamin D can play a big role in management of chronic pain. The first one showed that many people suffering from chronic pain also have insufficient amounts of Vitamin D.

Secondly, it was shown that bringing Vitamin D to its optimal levels reduces pain. It is not completely clear what the connection is at this point, but if there is a causal connection between these, it could prove to be an easy treatment for some kinds of chronic pain.


It seems that there is a large set of new research behind safer alternatives to opioids and many solutions bear a lot of potential. It is actually sad that we had to reach this point to push us towards safer alternatives. However, it seems that better days are ahead…