Antihistamines can treat anxiety-based disorders like PTSD

Scientific studies related to Ray Peat and his work.
haidut
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Antihistamines can treat anxiety-based disorders like PTSD

Unread postby haidut » Fri Oct 25, 2013 12:37 am

The specific drug studied was diphenhydramine (Benadryl), which Ray Peat recommends for several problems including endotoxin protection and liver support.
http://psychcentral.com/news/2013/10/23 ... 61082.html
http://www.pnas.org/content/early/2013/ ... l.pdf+html

However, I have seen pretty similar results for cyproheptadine, which is also antihistamine in action.
http://www.ncbi.nlm.nih.gov/pubmed/9606583
http://www.ncbi.nlm.nih.gov/pubmed/10964879

So, it seems that this may be a general property of the antihistamines. I wonder what the mechanism of action is. Based on Peat's ideas anxiety/PTSD/panic are probably caused by serotonin so that explains why cyproheptadine is effective since it's a general serotonin inverse agonist. But if Benadryl is working as well, then does that imply Benadryl has anti-serotonin action as well???
Maybe somebody already exchanged emails with Peat on Benadryl and how he thinks the drug achieves its effects. So, please share what you know.
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Re: Antihistamines can treat anxiety-based disorders like PT

Unread postby pranarupa » Fri Oct 25, 2013 3:34 am

Not sure if other things are involved, but I'd guess that anything that inhibits the phase transition that releases histamine from platelets and mast cells also inhibits serotonin release.

Not familiar with benadryl, my quack answer to everything is check your breathing, if you're losing co2 then everything's going to start going wonky.
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Re: Antihistamines can treat anxiety-based disorders like PT

Unread postby Peata » Fri Oct 25, 2013 7:57 am

You might be interested in this discussion on Benadryl and serotonin: viewtopic.php?f=11&t=2248

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Re: Antihistamines can treat anxiety-based disorders like PT

Unread postby pboy » Fri Oct 25, 2013 10:40 am

hmm...I think it can help, but its probably not due to a special healing property, but rather due to pure quieting of certain parts of the mind...I've drinking very strong antihistamine herbs, such as nettle leaf and others, and it does I guess reduce anxiety, but pretty much makes you want to pass out and stay out...until a really good nap is taken. I suppose that's how bendryl works, a deep rejuvanative, but mroeso due to the fact that allows, and almost requires, a good nap

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Re: Antihistamines can treat anxiety-based disorders like PT

Unread postby lindsay » Fri Oct 25, 2013 11:19 am

if only benadryl didn't make me so drowsy :? what about loratadine? I find it helps my histamine problems without making me sleepy.
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Re: Antihistamines can treat anxiety-based disorders like PT

Unread postby SAFarmer » Sat Oct 26, 2013 2:05 am

lindsay wrote:if only benadryl didn't make me so drowsy :? what about loratadine? I find it helps my histamine problems without making me sleepy.


Hi Lindsay

My son uses Loratadine too with good results. Here is a post I made about it in another thread,
viewtopic.php?f=3&t=2508&p=31355#p31355

Cyproheptadine is a 1st generation anti-histamine drug. Second generation variants include cetirizine and loratadine with fewer side effects like drowsiness, etc. My son uses the last 2 and have very good response for hayfever and general better feeling when stressed because of the hayfever allergic reactions.

Ray Peat has said that it is anti estrogenic and thats probably why he responds so well on it.

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Re: Antihistamines can treat anxiety-based disorders like PT

Unread postby haidut » Sat Oct 26, 2013 6:33 pm

Hi SAFarmer,

I saw your earlier post about loratadine and how it is anti-estrogenic. Are you sure Peat was talking about loratadine or cyproheptadine? I have some references that loratadine is actually quite estrogenic. If you are in contact with Peat I'd like to hear his opinion on this study:
http://www.ncbi.nlm.nih.gov/pubmed/16407038

Not trying to be contrarian here, just saying that I did some research on the anti-histamines several years ago and they pretty much all have a warning that side effects may include low libido and even erectile dysfunction. As you can see, the study above found out a lot more than just dysfunction.
Notably, drugs without such warning are Benadryl and cyproheptadine, which is why Peat probably has less issue suggesting them for use.
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Re: Antihistamines can treat anxiety-based disorders like PT

Unread postby SAFarmer » Sun Oct 27, 2013 6:06 am

Hi Haidut

You are perfectly in your right to question. I don't have an issue with it and just want to learn and know the truth as well.

I did read it somewhere, and remember discussing it with my wife as well, because I am generally very sceptical of pharmaceutical drugs, and she said my son reacts well to Loratadine. I should have posted the source, but don't know why I didn't. I tried again to find the quote, but can't remeber where it was, or it was maybe a radio interview.

Anyway, the closest I could find again, was this quote,

http://raypeat.com/articles/hormones/h1.shtml
Histamine mimics estrogen's effects on the uterus, and antihistamines block estrogen's effects (Szego, 1965, Szego and Davis, 1967).

So I stand corrected, but it could also possibly have been my interpretation of all antihistamines being anti estrogen like. Cyproheptadine generally causes side effects like drowsiness and Loratadine do not do this to my son, which is why my wife gives it to him when needed.

As to your quoted study, I cannot comment, as there is too little information available regarding dosage and also rats vs humans. (even if it were true, luckily my son is not in the uterus anymore ! :D )

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Re: Antihistamines can treat anxiety-based disorders like PT

Unread postby Mittir » Sun Oct 27, 2013 8:24 am

Here is a RP email advice to Charlie on use of Cetirizine. I believe it is also applicable to
Loratadine , because there is chlorine attached to carbon molecule of Loratadine

Ray Peat wrote: I avoid drugs that contain chlorine or fluorine, because of the risk to the liver.
(and gave me the research)

When I asked him about Benadryl containing chloride, and even salt does, he clarified:

Ray Peat wrote: Our enzymes aren't designed for the combination of chlorine with carbon molecules.

He gave me this research:.


Full response with studies at
viewtopic.php?f=68&t=1035&p=13904&hilit=benadryl#p13904

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Re: Antihistamines can treat anxiety-based disorders like PT

Unread postby aquaman » Sun Oct 27, 2013 11:27 am

INteresting - I took a cetirizine 2 hours ago (often get nasal drip after a coffee, was really bad today, i'm sure coffee doesn't agree with me!), and I feel very calm and focused now - doing some work on my business, boring accounts, but actually way more focused than normal.

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Re: Antihistamines can treat anxiety-based disorders like PT

Unread postby SAFarmer » Sun Oct 27, 2013 2:45 pm

Mittir wrote:Here is a RP email advice to Charlie on use of Cetirizine. I believe it is also applicable to
Loratadine , because there is chlorine attached to carbon molecule of Loratadine

Ray Peat wrote: I avoid drugs that contain chlorine or fluorine, because of the risk to the liver.
(and gave me the research)

When I asked him about Benadryl containing chloride, and even salt does, he clarified:

Ray Peat wrote: Our enzymes aren't designed for the combination of chlorine with carbon molecules.

He gave me this research:.


Full response with studies at
viewtopic.php?f=68&t=1035&p=13904&hilit=benadryl#p13904


I guess everyone must take his own chances. Ray Peat has said it's anti estrogen, so you have to weigh it against the possible side effects. Even the literature you mention states very rare occurances, 2 cases ! , and one does not know the possible effects of other drugs, which is also mentioned. As I said, and others, if it works for you, why not ?

Ons can make the case for anything being negative in the wrong dose or with certain other substances. Life is complicated.

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Re: Antihistamines can treat anxiety-based disorders like PT

Unread postby Charlie » Tue Nov 26, 2013 2:04 pm

Ray Peat sent me the studies below regarding Cetirizine. I will not be taking it anymore and will be trying to source pure Diphenhydramine (Benadryl) or Cyproheptadine.

Ray Peat wrote:Ann Hepatol. 2011 Apr-Jun;10(2):237-8.
Levocetirizine induced hepatotoxicity in a patient with chronic urticaria.
Ekiz F, Yüksel I, Ekiz O, Coban S, Basar O, Yüksel O.

2. Med Clin (Barc). 2011 Sep 10;137(6):283-4.
[Cetirizine hepatotoxicity].
[Article in Spanish]
Prieto de Paula JM, Franco Hidalgo S, Nalotto L, Ginés Santiago A.

3. N Z Med J. 2010 Feb 19;123(1309):106-7.
Severe hepatitis in a primary sclerosing cholangitis patient receiving recent
cetirizine therapy.
Jurawan R, Smith A.

4. Gastroenterol Hepatol. 2010 Jan;33(1):68-9. Epub 2009 Sep 3.
[Benign recurrent intrahepatic cholestasis simulating cetirizine-induced toxic
hepatitis].
[Article in Spanish]
Díaz-Sánchez A, Marín-Jiménez I, Aldeguer M.

5. Ann Pharmacother. 2004 Nov;38(11):1844-7. Epub 2004 Sep 21.
Recurrent acute hepatitis associated with use of cetirizine.
Pompili M, Basso M, Grieco A, Vecchio FM, Gasbarrini G, Rapaccini GL.
Department of Internal Medicine, Università Cattolica del Sacro Cuore, Rome,
Italy. mpompilii@rm.unicatt.it
OBJECTIVE: To describe a case of recurrent acute hepatitis related to the use of
cetirizine, a selective histamine(1)-receptor antagonist approved for the
treatment of common allergic diseases.
CASE SUMMARY: A 26-year-old man was hospitalized with a week-long history of
weakness, nausea, anorexia, and hyperchromic urine, which had developed after 6
days of therapy with oral cetirizine 10 mg/day for allergic rhinitis. Admission
laboratory testing revealed evidence of acute hepatitis and seropositivity for
liver-kidney microsome antibodies. Liver biopsy findings of diffuse portal tract
and lobular inflammation with a prominent eosinophilic infiltrate were consistent
with drug-related hepatitis. The patient was discharged after one week of
treatment with tocopherol and glutathione. Three months after discharge,
transaminase levels were normal. At 6 months, seropositivity for liver-kidney
microsome antibodies was still present, but considerably less intense. The
patient had suffered 2 previous episodes of "acute hepatitis of unknown origin,"
and both had occurred after cetirizine use.
DISCUSSION: Use of the Naranjo probability scale indicated cetirizine as the
probable cause of acute hepatitis, and the positivity for liver-kidney microsome
antibodies is suggestive of an autoimmune mechanism for liver damage. As of
September 13, 2004, ours is the fourth reported case of acute hepatitis
associated with cetirizine and the second in which liver-kidney microsome
antibodies have been documented.
CONCLUSIONS: Although cetirizine is considered to have low potential for severe
hepatic toxicity, the possibility that it can provoke autoimmune-mediated
hepatotoxicity should be considered.

6. Clin Allergy Immunol. 2002;17:389-419.
Potential cardiac toxicity of H1-antihistamines.
Yap YG, Camm AJ.
St. George's Hospital Medical School, London, England.
Nonsedating H1-antihistamines are widely prescribed for the treatment of allergic
disorders because of their lack of sedative and anticholinergic effects; however,
certain nonsedating antihistamines such as terfenadine and astemizole are now
known to cause QT prolongation and TdP, particularly in overdosage or with
concomitant ingestion of imidazole antifungals or macrolide antibiotics.
Mechanistic studies showed that the cardiotoxic effects of some nonsedating
antihistamines are due to the inhibition of repolarization potassium channels,
particularly IKr, which leads to prolongation of the action potential and QT
interval, and the development of early after-depolarization, which triggers TdP.
Patients at risk of developing TdP, such as those with congenital long QT
syndrome, cardiac disease, liver disease, electrolyte disturbance, or those
taking drugs that can prolong QT interval, should avoid nonsedating
antihistamines that are also capable of prolonging the QT interval. Many
questions still need to be answered, such as the role of other potassium channels
(IKs, ITo, and Iped) and the relative expression of various potassium channels in
different individuals, which may be important in the pathogenesis of TdP with
nonsedating antihistamines. There is also a lack of information on the cardiac
actions of newer nonsedating antihistamines. The evidence so far indicates that
the potential to cause ventricular arrhythmias is not a class effect and that
loratadine, cetirizine, and fexofenadine are not associated with QT prolongation,
TdP, or other ventricular arrhythmias. It is hoped that with a better
understanding of the arrhythmogenic mechanism of nonsedating antihistamines, we
will be able to identify patients at risk and prevent any cardiac toxicity
associated with H1-antihistamines, and ultimately, death.

7. J Clin Gastroenterol. 2002 Apr;34(4):493-5.
Acute hepatitis associated with cetirizine intake.
Sánchez-Lombraña JL, Alvarez RP, Sáez LR, Oliva NP, Martínez RM.

8. Ann Intern Med. 2001 Jul 17;135(2):142-3.
Severe hepatitis in a patient taking cetirizine.
Watanabe M, Kohge N, Kaji T.

9. J Clin Gastroenterol. 2000 Oct;31(3):250-3.
Cetirizine-induce cholestasis.
Fong DG, Angulo P, Burgart LJ, Lindor KD.
Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota
55905, USA.
Cetirizine, a human metabolite of hydroxyzine, is a selective H1-receptor
antagonist currently approved for the treatment of seasonal allergic rhinitis,
perennial allergic rhinitis, and chronic urticaria. In U.S. clinical trials,
transient reversible hepatic transaminase elevations were observed in <2% of
patients during cetirizine therapy. We report a case of cetirizine-induced
cholestasis in a 28-year-old man with no previous hepatobiliary disease after a
2-year period of taking cetirizine on a daily basis. The treatment of this
patient included the use of ursodeoxycholic acid, as well as hydroxyzine, for
symptomatic relief of pruritus. In light of the patient's clinical and
biochemical improvement while using hydroxyzine, it appears that the hepatic
metabolism of hydroxyzine to metabolites, including cetirizine, is not involved
in the pathogenesis of this particular case of drug-induced hepatotoxicity.
Cetirizine should be considered as a potential cause of drug-induced cholestasis.

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Re: Antihistamines can treat anxiety-based disorders like PT

Unread postby SAFarmer » Tue Nov 26, 2013 2:27 pm

Thanks Charlie . I 'll surely reconsider Citirizine use for my son as well. It seems keeping blood sugar levels up works better anyway .


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