Existing drug found to limit some side effects of opioids in mice

We have all heard about America's addiction to opioids (heroin and prescription drug abuse) I have been prescribed huge doses of opioid medication for more than a quarter century, so I have first-hand experience with both the benefits and side-effects. Without them, I was unable to function due to chronic pain, as well as post-operative pain from multiple extensive surgeries. But, without going into too much detail, I have also had to deal with some pretty lousy aspects of long-term use, too.

So, when I read this article about an existing drug that (apparently) reduces or eliminates a couple of the problems with these types of prescription pain treatments, I decided to share the article in case it might be of interest to other members that may have had experiences similar to my own.

In an article from Stanford Medicine's Website, Tracie Wright wrote:

David Clark, MD, PhD, believes that opioid painkillers are not only a safety concern for patients — with risks of addiction and possible overdose — they also just don’t work very well. “They don’t in general provide substantial pain relief for a long period of time,” said Clark, who leads the pain service at VA Palo Alto Health Care System. He said his patients regularly return to ask for increased doses of prescription painkillers such as oxycodone and hydrocodone because their pain returns.

Regarding David Clark, MD, PHD:

He is co-author of a new study published in Nature Medicine that shows in mouse models that the use of a commercially available drug can almost eliminate two common side effects of opioids — a growing tolerance and a paradoxical increased sensitivity to pain — without reducing its painkilling properties. If the results can be replicated in humans, it could mean a world of difference for the veterans he treats, Clark said.

What causes the unwanted side-effects?:

Based on previous research, the authors of the study postulated that at the molecular level, painkillers binding to neurons on the periphery of the body cause these two unwanted side effects, while the pain relief occurred at sites in the brain and spinal cord.

As a fellow who loves rodents, this is the part I have trouble reading:

To test their theory, they injected morphine into both normal mice and a group of mice in which the receptors on these peripheral neurons had been knocked out. They found that when they injected the drugs chronically, pain relief actually lasted much longer in the knock-out mice compared with the normal mice. Their conclusion: the action of morphine on the periphery was causing the growing tolerance to the drug in the normal mice.

Possible breakthrough?:

They then found a drug that worked to block these peripheral binding sites. As Gregory Scherrer, PhD, Pharm.D, senior author for the study, explains in our release: We demonstrate that these two side effects can be drastically reduced with co-administration of an already used compound, methylnaltrexone bromide, currently used to combat constipation, which is another unwanted side effect of opioids, while still maintaining pain relief.

I find this amazing, and hopeful. Not everyone benefits from opioid medication for pain, but for some, it is a miracle and the only thing currently available that gives them any quality of life. If this constipation medication can help reduce even one or two of the harmful side-effects in humans, it will be beneficial to a large number of patients. And, they didn't even have to create another drug, it already exists!

As I always do when posting anything related to testing on mice, rats, or other non-human entities, I will finish by saying:
I hate that we test on animals.

SOURCE
Related Stories:
Stanford Study: Battle the Opioid Epidemic One Surgery at a Time
Drug Dealer, MD: A Look at the Opioid Epidemic
Shifting the Focus from Opioids to Life Beyond Pain

a reply to: seattlerat

I can see how big pharma (and/or others) would be motivated enough to quiet such breakthroughs since it could hurt their profits.

But I hope that doesn't happen. Spread the word!

originally posted by: FamCore
a reply to: seattlerat

I can see how big pharma (and/or others) would be motivated enough to quiet such breakthroughs since it could hurt their profits.

But I hope that doesn't happen. Spread the word!

???

How is repurposing an existing drug (all expenses already paid for) going to hurt profits?

a reply to: GetHyped

if this drug allows opiate-addicted "consumers" to no longer need those pain pills, the stakeholders for the opiate med companies lose a potentially lifelong buyer and all of the money that person would have spent on their opiate-containing meds.

I'm sure there is some overlap because there are pharm-giants who make/sell many different meds, but I know the pain pills are biggg money makers

a reply to: FamCore

One of the side-effects that the researchers in the source article are trying to reduce/eliminate is "Tolerance"- the need for a patient to take more of the drug just to maintain a steady level of efficacy. I think what FamCore may be suggesting is that it really isn't in the pharmaceutical manufacturer's best interest to come up with ways that allow a patient to stay on a particular dosage, as opposed to being forced to take more and more and more and more and more as time goes on.

Big Pharma is not angelic, and they (apparently) don't care much about anything other than their bottom-line.
Check out this article (dated but still informative and interesting): How the American Opioid Epidemic was Started by One Pharmaceutical Company

Great. More drugs to treat the side-effects of the drugs we're already taking.

Look into the eyes of that mouse. It is not on drugs. It is not an addicted mouse, it is a normal mouse

It isn't even drinking a beer.

I am all for something along these lines. Having been shot, broke back and hip I have also been on massive amounts of opiates for 26 years now. Tolerance makes it much worse. I have been on so much during one time in the hospital an intern shot 10 grams of morphine in my IV at once. The chief immediately revoked his prescribing rights because it would have killed the normal person. My tolerance was so high it didn't have a bad effect.

I am taking very low doses today. I was taking 2400 MME (Morphine Milligram Equivalents) for about a decade. I am down to 80 today. If there wasn't tolerance I would never had gone up so high. I do disagree that higher doses don't give more pain relief though. The largest side effects I ever had were from benzodiazepines. There is also the issue that when you use opiates for pain you have more pain (increased sensitivity) when you are coming off the previous dose than if you didn't take them at all. I feel it causes joint swelling and is a way to keep people on them. If you stay off long enough your pain will actually be less.

For me, defeating tolerance would be a blessing. I don't like taking all the meds. I actually went from 5 meds to 2 and hardly take much at all any more. My pain is still there, but the other side effects are negligible now.

I don't think this will work in humans.

If I am not mistaken, naltrexone is similar to naloxone, which kicks other opiods off the receptors, and binds so tightly no other opiates can have an effect for a long time.

This will cause severe precipitated withdrawal in the opiate dependant, and render opiods completely ineffective.

I don't think this will work in humans.

If I am not mistaken, naltrexone is similar to naloxone, an opioid antagonist, which means it kicks other opioid off the receptors, and binds so tightly no other opiates can have an effect for a long time.

This will cause severe precipitated withdrawal in the opiate dependant, and render opioid completely ineffective.

Naloxone is used in instances of opiate and alcohol overdose. The also have Naloxone centers where people can do to detox.

There are signs all over my town advertising a naloxone clinic as a pain free way to kick heroin. It has been FDA approved for the purpose of blocking withdrawal symptoms for quite a while now.

Zubsolv is a long term variant that is implanted in a person with addiction which and lasts about 6 months. It prevents them from getting the opiate high.

Is cannabis a good substitute? Maybe not for all patients, but i think that it is the option that do the least damage/harm as compared to opioids

a reply to: calstorm
Naloxone is used in opiate overdose, but not alcohol. It would do nothing for alcohol poisoning.

Naloxone is an opiate antagonist, so it targets receptors in the brain occupied by opiates and knocks them off. This reverses the effect of opioids and puts the person in immediate withdrawal.

I think you may mean suboxone clinic for painless heroin detox. Naloxone would cause an extremely painful heroin detox.

Suboxone does contain Naloxone as a means to deter addict from using their medication intravenously, but it has zero effect when taken sublingually as intended.

The main ingredient in suboxone is bupenorphine, a partial opiate agonist that binds to the receptors tighter than anything else but doesn't get you high. I am pretty sure the medication you mentioned at the end is bupe as well.

It is absolutely correct that bupe can make heroin detox nearly painless, and that it blocks other opioids.

Thanks for the thread and agree with you about animal testing.

originally posted by: JD163
Is cannabis a good substitute? Maybe not for all patients, but i think that it is the option that do the least damage/harm as compared to opioids

It is such as CBDs. Problem is this with Big Pharma:
"Opioid use decreases in US states that legalize medical marijuana - study "

New research shows a decline in the use of opioid painkillers in US states that allow people to treat pain with medical marijuana, affirming the fears of Big Pharma who have been vigorously seeking to frustrate efforts to legalize the herb.

Columbia University researchers examined data from 1999 to 2013 and found an association between a state legalizing medical marijuana and a reduction in testing positive for opioids after dying in a car accident, particularly among drivers aged 21 to 40.

Source

originally posted by: dreamingawake
Thanks for the thread and agree with you about animal testing.

originally posted by: JD163
Is cannabis a good substitute? Maybe not for all patients, but i think that it is the option that do the least damage/harm as compared to opioids

It is such as CBDs. Problem is this with Big Pharma:
"Opioid use decreases in US states that legalize medical marijuana - study "

New research shows a decline in the use of opioid painkillers in US states that allow people to treat pain with medical marijuana, affirming the fears of Big Pharma who have been vigorously seeking to frustrate efforts to legalize the herb.

Columbia University researchers examined data from 1999 to 2013 and found an association between a state legalizing medical marijuana and a reduction in testing positive for opioids after dying in a car accident, particularly among drivers aged 21 to 40.

Source

Ahh, as usual....and even if big Pharma gets into the game,....its pretty hard to stop someone from growing a few plants in their backyard or wardrobe.

a reply to: GoShredAK

The billboards say naloxone, but the website for the clinic it does say suboxone.

On the topic of alcohol

One of the strongest effects of using naltrexone in the treatment of alcoholism is the progressive decrease in the craving for alcohol.

It is being offered intranasaly. I will have to do some more research on it later.

I

originally posted by: FamCore
a reply to: GetHyped

if this drug allows opiate-addicted "consumers" to no longer need those pain pills, the stakeholders for the opiate med companies lose a potentially lifelong buyer and all of the money that person would have spent on their opiate-containing meds.

I'm sure there is some overlap because there are pharm-giants who make/sell many different meds, but I know the pain pills are biggg money makers

You must've been under a rock for the last 100 years or so of medical advances (and their subsequent products).

Sorry, but this lazy conspiratorial thinking just doesn't hold u