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And a potential solution to it: https://arstechnica.com/science/2017/03/tweaking-fentanyls-chemical-structure-may-create-safer-opioid/ https://arstechnica.com/

And a potential solution to it: https://arstechnica.com/science/2017/03/tweaking-fentanyls-chemical-structure-may-create-safer-opioid/ https://arstechnica.com/science/2017/03/tweaking-fentanyls-c... For their chemical makeover, the researchers noted that when tissue is damaged and hurting, it becomes inflamed and more acidic. The pH drops from approximately 7.4—what’s seen in normal, healthy tissue—to between 5 and 7. Fentanyl can work regardless of the pH, so it’s active throughout the nervous system no matter what. But, if it was altered to only work at the lower pH, then it could target just the pain source at the peripheral nerves, the researchers hypothesized. And with no activity in the central nervous system, it would dodge opioid’s serious side-effects, including addiction and systemic responses that can be lethal during overdoses. They're testing a modified version of fentanyl that only works in lower pH, restricting its activity to injured areas of the body, eliminating the risk of overdose and dependence: In further experiments, the researchers noted that, unlike fentanyl, high doses of NFEPP weren’t lethal to the rats. And rats on the NFEPP didn’t display impaired motor activity or reward-seeking behavior linked to addiction.

M_Grey 10y ago
That's great, and there are other painkillers on the horizon too, but that's "maybe" and "later". Today we could take concrete steps to alleviate this crisis which we created in the first place. Cannabis is a good choice for people addicted to opiates, along with medical detox. You also have to manage underlying mental health, social, and medical issues. No amount of throwing new molecules at these problems will solve them.
- ucaetano 10y ago
  Agreed, and cannabis is a good choice not only for the addicted, but to those suffering chronic pain what would eventually use opioids.
refurb 10y ago
But, if it was altered to only work at the lower pH, then it could target just the pain source at the peripheral nerves, the researchers hypothesized. It's been a while since I took a pharmacology class, but opioids work centrally - that is, the pain relief is due to their action in the brain. That's why an opioid like loperamide (can't cross the CNS barrier) doesn't have an analgesic effect, only constipating. If fentanyl only worked peripherally, it wouldn't have a painkilling effect.
- ucaetano 10y ago
  It seems opioids work centrally and peripherally. From WP: Opioids act by binding to opioid receptors, which are found principally in the central and peripheral nervous system and the gastrointestinal tract. Recent investigations discovered opioid receptors on peripheral sensory neurons.A significant fraction (up to 60%) of opioid analgesia can be mediated by such peripheral opioid receptors, particularly in inflammatory conditions such as arthritis, traumatic or surgical pain. Inflammatory pain is also blunted by endogenous opioid peptides activating peripheral opioid receptors. Here are some of the studies mentioned: * https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4565585/ https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4565585/ * https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4173362/ https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4173362/ * http://www.nature.com/nm/journal/v9/n8/full/nm908.html http://www.nature.com/nm/journal/v9/n8/full/nm908.html PS: I have no idea of what I'm talking about, just doing some basic research, so take it all with a lot of salt.
  - refurb 10y ago
    Thanks for digging up the references. My only thought is there is evidence that the peripheral effect is either weak or non-existent. Loperamide is a great example. mu-opioid agonist that doesn't penetrate the brain-blood barrier. Will constipate you (by acting on GI opioid receptors), but has no analgesic effect.
stagbeetle 10y ago
> But, if it was altered to only work at the lower pH, then it could target just the pain source at the peripheral nerves, the researchers hypothesized. Do you know how this interacts with anti-inflammatory drugs?
- ucaetano 10y ago
  No idea! I'm by no means an expert in the subject.

M_Grey 10y ago

That's great, and there are other painkillers on the horizon too, but that's "maybe" and "later". Today we could take concrete steps to alleviate this crisis which we created in the first place. Cannabis is a good choice for people addicted to opiates, along with medical detox. You also have to manage underlying mental health, social, and medical issues. No amount of throwing new molecules at these problems will solve them.

ucaetano 10y ago
Agreed, and cannabis is a good choice not only for the addicted, but to those suffering chronic pain what would eventually use opioids.

refurb 10y ago

But, if it was altered to only work at the lower pH, then it could target just the pain source at the peripheral nerves, the researchers hypothesized. It's been a while since I took a pharmacology class, but opioids work centrally - that is, the pain relief is due to their action in the brain. That's why an opioid like loperamide (can't cross the CNS barrier) doesn't have an analgesic effect, only constipating. If fentanyl only worked peripherally, it wouldn't have a painkilling effect.

ucaetano 10y ago
It seems opioids work centrally and peripherally. From WP: Opioids act by binding to opioid receptors, which are found principally in the central and peripheral nervous system and the gastrointestinal tract. Recent investigations discovered opioid receptors on peripheral sensory neurons.A significant fraction (up to 60%) of opioid analgesia can be mediated by such peripheral opioid receptors, particularly in inflammatory conditions such as arthritis, traumatic or surgical pain. Inflammatory pain is also blunted by endogenous opioid peptides activating peripheral opioid receptors. Here are some of the studies mentioned: * https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4565585/ https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4565585/ * https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4173362/ https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4173362/ * http://www.nature.com/nm/journal/v9/n8/full/nm908.html http://www.nature.com/nm/journal/v9/n8/full/nm908.html PS: I have no idea of what I'm talking about, just doing some basic research, so take it all with a lot of salt.
- refurb 10y ago
  Thanks for digging up the references. My only thought is there is evidence that the peripheral effect is either weak or non-existent. Loperamide is a great example. mu-opioid agonist that doesn't penetrate the brain-blood barrier. Will constipate you (by acting on GI opioid receptors), but has no analgesic effect.

stagbeetle 10y ago

> But, if it was altered to only work at the lower pH, then it could target just the pain source at the peripheral nerves, the researchers hypothesized. Do you know how this interacts with anti-inflammatory drugs?

ucaetano 10y ago
No idea! I'm by no means an expert in the subject.