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New composite antidepressant targets opioid receptors

Marco

Grrrrrrr!
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Near Cognac, France

Hip

Senior Member
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To quote that article:
Buprenorphine reduces the patient's response to stress by blocking a receptor in the brain called the kappa opioid.

However it also stimulates a related receptor called the mu opioid, which could cause addictive effects if taken long term or used by depressed patients.

To counter this, the researchers used the anti-addiction drug naltrexone, which blocks the mu receptor. They found for the first time that in mice this combination gave an antidepressant effect.

Dr Bailey added: "Our study shows that using a combination of naltrexone and buprenorphine gives an antidepressant effect in mice, but without the problems of addiction that could be caused by using buprenorphine alone.

This is an interesting approach. It seems that to get the antidepressant effects, the goal is to block the kappa opioid receptor, but without agonizing the mu opioid receptor.


Though there is already a similar combination drug on the market called suboxone (a combination of buprenorphine and naloxone), which is taken as a sublingual tablet, and sued by some ME/CFS patients on this forum. Naloxone and naltrexone have very similar effects.


Another possible approach might be to take the supplement amentoflavone, which is a kappa opioid antagonist. Amentoflavone is found in ginkgo biloba, but can also be bought separately. Hesperidin (found in orange juice) is also a kappa opioid antagonist with apparent antidepressant effects. 1


I found this forum post about the anti-anhedonia effects of kappa opioid antagonists interesting. To quote this post:
Kappa opioids are THE cure.

Key areas are kappa opioid involvement in fear response, notable fear memory recall and storage. They opose the reward "mu" opioid, they are the other side of the medal.

A few highlights:

1. Kappa opioid agonists at higher doses cause fear, anxiety, depression and anhedonia - directly and rapidly without any other effects. No other chemical does anything remotely similar.

2. Kappa opioid antagonists stop fear anxiet and depression and restore hedonia directly and rapidly without any other effects(such as sedation or euphoria). No other chemical does anything remotely similar.

3. Kappa opioid antagonists RESTORE normal mood. You can not get high off them. Mu opioids are for getting high. Kappa opioids are the oposition - the inhibition of reward. They can only go so far as to disinhibit.

4. Kappa agonists are the only known chemicals that REVERSE drug tolerance. To ALL drugs. Tolerance is infact the kappa opioid network tone. When consuming drugs the high dopaminergic state causes kappa opioid network upregulation to compensate and reduce all this dopamine - this is development of drug tolerance. To counter it you need to hit the kappa opioid receptors instead of mu opioid. The body will not restore this balance back any time soon as drugs users painfully know.

Here's a very throrough study that is pretty much scientific but there are some animal examples that are easy to understand.

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2787673/

There is a cure but it has been hidden for years by the fact that Mu opioid receptors are the pleasure ones and cause addicitions and thus the kappa opioids were ignored as well.... thruth is, even natural substances that agonize mu receptors usually antagonize kappa... it's the fear/reward -approach/avoid system. And all these years they only thought of it as rewarding and painkilling. While infact pushing kappa receptors causes bad feelings and fear.
 
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Marco

Grrrrrrr!
Messages
2,386
Location
Near Cognac, France
This is a beyond obvious treatment approach. The only reason it's taken many decades of torture of depressed patients with serotonergic mind-numbing drugs to arrive at this trivial conclusion is puritanistic concerns about the opioid system and drugs.

Yep - it's like high dose Baclofen for alcoholism or e-cigarettes for tobacco. It seems that some people aren't satisfied unless the people with the problem suffer or have to undergo some sort of 'moral rehabilitation' to cure them of their 'habit'.
 

Marco

Grrrrrrr!
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Location
Near Cognac, France
Let's be clear. I'm in no way in favour of illegal drug use but high dose Baclofen has been licensed to treat alcoholism in France and e-cigarettes are currently legal but various lobby groups in various countries are seeking to severely restrict or ban them. Ketamine has an almost instant anti-depressant effect in treatment resistant depression yet is unlikely to be approved due its previous misuse as a 'recreational' drug.
 

helios

Senior Member
Messages
136
Location
Brisbane
Let's be clear. I'm in no way in favour of illegal drug use but high dose Baclofen has been licensed to treat alcoholism in France and e-cigarettes are currently legal but various lobby groups in various countries are seeking to severely restrict or ban them. Ketamine has an almost instant anti-depressant effect in treatment resistant depression yet is unlikely to be approved due its previous misuse as a 'recreational' drug.
You can add GHB on to that...though its back out now in very restricted circumstances by a pharama company at 10 times the previous cost. . Where I live Kava and tryptophan were off the market for years unnecessarily. Kraton sounds like a very interesting medicinal plant yet its outlaws where I live even though there has been zero issues/bad cases.
 

Ema

Senior Member
Messages
4,729
Location
Midwest USA
Doesn't suboxone have a pretty nasty withdrawal though?

Amentoflavone hits the GABAa receptor like benzos so it might further dysregulate glutamate as well. I'm wary of anything to do with GABA after my Valium debacle.

But other than that, it sounds great!
 
Messages
79
Location
Seattle
I've tried buprenorphrine to good effect. Had anyone else tried any of this stuff?
maybe no one replied due to the stigma around opiates? perhaps things have changed?

i take it. i find it helps a great deal with depression, agitation, ptsd, and pain. it may cause some additional neurological issues - i find all opiates do, but, here they seem to be much lower in frequency and intensity than with a traditional full agonist opiate like oxy or hydrocodone. i would think that something like the butrans low-dose patch would be of great interest to me/cfs researchers. a low-dose buprenorphine is actually functioning as a kappa receptor antagonist rather than as a mu receptor partial agonist - which is what it does at normal doses.