Reducing opiate tolerance with Doxepin?

pizzystrizzy

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Apr 4, 2013
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So I'm not an opiate guy and have no immediate interest in this, but I came across this article in the process of doing some entirely unrelated research, and I thought it was interesting, particularly b/c I can't find any reference on bluelight of anyone ever mentioning it before (the article is rather old):

Macenski MJ, Cleary J, Thompson T. Effects on opioid-induced rate reductions by doxepin and bupropion. Pharmacology Biochemistry and Behavior. 1990;37(2):247–252. doi:10.1016/0091-3057(90)90329-G. I uploaded it here: http://db.tt/cjb8GjEg

Relevant parts of the article:

Chronic daily doxepin administration significantly attenuated methadone-induced response rate reductions. Bupropion reduced the effect of the highest methadone dose, but this effect was mitigated by the development of opioid tolerance. Unlike bupropion, doxepin interfered with the development of opioid tolerance.... The effects of methadone during chronic daily doxepin or bupropion administration are shown in Fig. 2. The methadone dose-effect curve was shifted to the right during chronic doxepin under both VI parameters (top panels). No tolerance to methadone was apparent when the dose-effect relationship was reestablished following discontinuation of doxepin.... This attenuation of the rate-reducing effects of methadone cannot be accounted for by opioid tolerance, in fact, tolerance to methadone is diminished following doxepin treatment (see Figs. 2 and 3).
I thought this might be of interest to someone here.
 

fairnymph

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I downloaded the study but my tablet shows the pdf as blank. :\

Offhand, I would guess that doxepin potentiates opioids in the same manner as some other TCAs like amitriptyline, i.e. via liver enzyme inhibition & possibly additional mechanisms. I highly doubt it actually affects tolerance.
 

pizzystrizzy

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Apr 4, 2013
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Hmm, I'm not sure what the problem is with the PDF, I tried it on a different computer and it works fine for me.
 

Wizzle

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Doxepin is a very strong H1 antagonist. The sedative effect of antihistamines have a synergistic effect with opioids. Same goes for amitryptyline.
 

Toz

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Oct 2, 2012
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The only successfull way to prevent tolerance to opioids that I've found is to not take any opioids. Other than that maybe low dose naltrexone would be worth a try if you can measure your dose accordingly.

Now, I can not read the study but find it highly unlikely that this will prevent tolerance. It may potentiate the methadone but I doubt it will do anything to actually prevent tolerance.

I'm skeptic to everything that's supposed to prevent tolerance, mainly because from my experience nothing really works in practice.
 
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