# Has anyone tried hesperidin? Might block the kappa receptor and have anti-depressant effect.



## 35467 (Dec 31, 2010)

I have looked for natural drugs that might have the properties of affecting the kappa-opioid receptor.

Amentoflavone that is at some levels in Ginkgo Biloba, St. Johns Worth should affect the kappa-receptor but I don't know the concentration of amentoflavone in these substances. There should be some more refined sources to get amentoflavone.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2265593/

Another natural source that might affect the kappa receptor is hesperidin. Hesperidin is found in citrus fruit peel and is a part of the fruit defence system of citrus plants. Some studies in animals shows that is has anti-depressant activity and it comes from blocking the kappa receptor:https://www.ncbi.nlm.nih.gov/pubmed/23178563

Other studies have shown that is can reverse stress induced immobilisation in mice: https://www.ncbi.nlm.nih.gov/pubmed/22550596

other studies shows it have anti-depressant activities and anti-inflammatory effect in various CNS disorders; https://www.ncbi.nlm.nih.gov/pubmed/30759833

Hesperidin is most used as a natural supplement in inflammatory disorder and little can be found in humans who have tried it for mental disorders. There is a overview article here on hesperidin; http://www.drrathresearch.org/attachments/education/Phytobiology/Hesperidin.pdf

Hesperidin as a supplement is available in capsules at 500.mg from several providers.


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## Broken (Jan 1, 2017)

Hello there, from Denmark? Amazing English if you are... we may have spoken before in threads actually OI recognise the name

I have been down this path with Apigenin. This is found in Chamomile tea & is a Kappa antagonist. The problem is these agonist/antagonists found naturally are pretty weak, so wouldn't have much affect. I got salvia divornum in the end which is a super strong natural agonist (causes dissociation and is a weird drug). The theory is that if you microdose this it can downregulate receptors and have the same effect as an anatagonist

Just had a little search of Hesperidin and it is found in high amounts in peppermint tea... as is menthol which is a weak kappa agonist. So peppermint would be a weak version of the drug that gets spoken about here that is being researched (forget its name but it has both a kappa agonist & antagonist in which could help DP).

The study said "In addition, a sub-effective dose of hesperidin (0.01 mg/kg) produced a synergistic antidepressant-like effect in the forced swimming test when combined with a sub-effective dose of morphine (1 mg/kg)". That makes me question whether it was the hespiridin or the morphine really. Time will tell but I don't imagine it is a very strong antagonist and cant find any research on that yet


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## 35467 (Dec 31, 2010)

Bronken

Yes, i am from Denmark. It reads that;"The antidepressant-like effect of hesperidin in the forced swimming test on mice was dependent on its interaction with the κ-opioid receptor, but not with the δ-opioid, μ-opioid or adenosinergic receptors. Taken together, these results suggest that hesperidin possesses antidepressant-like properties and may be of interest as a therapeutic agent for the treatment of depressive disorders." One properly has to read the whole text to understand the trial.

So, the presence of morphnie shouldn't be relevant. There are some other studies that indicate that it is also effective in anxiety, stress and depressive like states. It can normalise a stress induced inflammation. I will try to get it and give it a try. I don't use time on substance where there itn´t sufficient publications. Here there are some publications but it is all on animals and can't find any who has tried it for mental disorders. Many uses it for inflammations with some succes. I am trying some other substances right now Gingko has just been started up.


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## Broken (Jan 1, 2017)

I wish you all the best I really do. I hope it works. All I am saying is that some of these natural agonists/antagonists are too weak, and if they were strong they would already be medicines, such as opioids.

I think the interesting thing will be once scientists start to modify these natural molecules and they become stronger antagonists/agonists. I think you are in the right area as I have been on the kappa opioid quest recently. Honestly try peppermint tea and mix it with chamomile. Tastes ok and has natural antagonists and agonists in. I did this but it had no effect. I also tried like you did multiple sources to aim at kappa but they are too weak. Amentoflavone was one I looked for in Ginkgo, and I also took Lion's mane mushroom coffee which has a natural kappa agonist in.

https://en.wikipedia.org/wiki/%CE%9A-opioid_receptor#Agonists

This is the list I used. Ibogaine is on there, I would be interested to perhaps microdose this if I could get my hands on it. Some people with addictions/severe depression etc are cured as if by magic by an ibogaine trip (not a recommendation though, it is a risky process)

Good luck to you. I hope you find it helps more than I did


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## Phantasm (Jul 16, 2017)

I'm interested in trying hesperidin if only for the anti-inflammatory properties, as inflammation can become more of an issue as you get older and it's known to affect mood and well-being. I've ordered some.


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