Morphine treatment increases 5AR activity (in rat)

Therapeutic Efforts Pharmaceutical
#1

Interesting… although it says it reduces T levels.

sciencedirect.com/science?_o … c6604c676d

In vivo evidence for an increase in 5alpha-reductase activity in the rat central nervous system following morphine exposure

Hossein Amini and Abolhassan Ahmadiani,
Department of Pharmacology, Neuroscience Research Center, Shaheed Beheshti University of Medical Sciences, P.O. Box 19835-355, Tehran, Iran
Received 27 April 2005; revised 5 July 2005; accepted 6 July 2005. Available online 6 September 2005.

Abstract
In the present study, the effects of acute and chronic morphine exposure on testosterone concentrations in the central nervous system (CNS) and serum were investigated in rats. Acute morphine administration (5 mg/kg, sc) reduced significantly testosterone levels in serum and spinal cord but not in the brain.

Following chronic morphine administration (orally for 21 days), the brain testosterone was also significantly reduced as well as serum and spinal cord.

Since, the decrease in testosterone levels following morphine exposure was more obvious in the CNS than serum, we suggested that it cannot be caused by only a direct decline in testosterone levels in periphery, and an increased local metabolism of testosterone in the CNS might be attributed in these effects.

This hypothesis was supported with the findings that pretreatment with finasteride, a 5alpha-reductase inhibitor (5 mg/kg, sc) blocked testosterone elimination from the CNS following morphine exposure.

Moreover, the serum concentration of 5alpha-reduced metabolites of testosterone, dihydrotestosterone and 3alpha-diol glucuronide was increased significantly following chronic morphine exposure, but not after co-treatment with finasteride.

These results suggest that morphine exposure increase the CNS activity of 5alpha-reductase, which is an important metabolizing enzyme for testosterone.

1 Like
#2

Another study…

Finasteride, a 5alpha-reductase inhibitor, potentiates antinociceptive effects of morphine, prevents the development of morphine tolerance and attenuates abstinence behavior in the rat.

ncbi.nlm.nih.gov/pubmed/17428486

It has been shown that morphine increases 5alpha-reductase enzyme activity in the rat central nervous system; however importance of this finding on morphine analgesia, tolerance and dependence has not been reported.

In the present study, we investigated inhibition of 5alpha-reductase enzyme on morphine effects using finasteride. To determine whether the 5alpha-reductase enzyme interact with morphine analgesia, finasteride (5 mg/kg, i.p.) was administrated with morphine (5 and 7 mg/kg, i.p.).

The tail-flick test was used to assess the nociceptive threshold, before and 15, 30, 45, 60 and 90 min after drug administration. In tolerance experiments, morphine 20 mg/kg was injected i.p., twice daily for 4 days. The development and expression of dependence were assessed in the naloxone precipitation test 5 days after the morphine (20-30 mg/kg, i.p.) administration.

We found that finasteride could potentiate the antinociceptive effect of morphine. In addition, chronic finasteride administration effectively blocked development of tolerance and dependence to morphine.

Following chronic morphine administration, single dose injection of finasteride failed to reverse tolerance but prevented naloxone precipitate withdrawal syndrome.

Therefore, it was concluded that there is a functional relationship between 5alpha-reductase enzyme and morphine.

#3

In addition to increasing 5AR activity, Morphine is an opiate and dopamine agonist.

thebrain.mcgill.ca/flash/i/i_03/ … roine.html

epa.gov/endo/pubs/edmvac/chem_lab_list.pdf

jneurosci.org/cgi/content/ab … 2/10/RC224

Though, as with anything, it has its risks.
sciencedaily.com/releases/20 … 142116.htm

#4

hi there…

In both CCI and sham rats, there was a significant increase in nociceptive … Upper panel, 10 days after once daily i.t. treatment with morphine (10 μg) but not … On the contrary, cannabinoids reduce NMDA receptor-mediated activity

#5

Why are we not pursuing this further? Is it just me or does this seem incredibly promising? There is already a post on this forum by a member saying that opiates were the only thing that improved his symptoms.

I know alot of people would be scared at the idea of taking morphine and i would be too, but what about codiene? it’s OTC and only differs from morhine by i think one carbon atom. couldn’t we try something like this to reactivate 5AR2?

(Wikipedia Article)

Roughly 5-10% of codeine will be converted to morphine, with the remainder either free, conjugated to form codeine-6-glucuronide (~70%), or converted to norcodeine (~10%) and hydromorphone (~1%). It is less potent than morphine and has a correspondingly lower dependence-liability than morphine.[4]

#6

Tylenol 2, 3 and 4 with Codeine is available OTC, if you feel so inclined. But you’ll probably get knocked out like a zombie!

en.wikipedia.org/wiki/Tylenol
Tylenol 1 (available in Canada without a prescription) contains 325 mg acetaminophen, 15 mg caffeine and 8 mg codeine; Tylenol 2 contains 300 mg acetaminophen and 15 mg codeine, Tylenol 3 (300 mg/30 mg), and Tylenol 4 (300 mg/60 mg

#7

Hmmm… i guess the real question is would it raise 5AR2 and keep it there, or whether it would just fall back to sub optimal levels once you stopped taking it.

#8

well if the heroin guys symptoms never came back then that means that 5ar2 stays at the normal levels after.heroin is an opiate isn’t it

#9

The guy who was shooting H became addicted to it. When he stopped his body was desperately trying to get dopamine back into it so it went in stages of flux, one was was sexual release. I’m not sure if it was permanent or the guy just ODed.

Don’t you think this is akin to us stopping finasteride and our hormone levels fluxuating all over? I mean I went 2 weeks with an erection after I stopped…then i crashed.

#10

I have sent him a PM asking him these questions to see if his symptoms came back or not, but he has not answered me.

Yes, heroin is an opiate…

#11

I’ve been wondering why opiates work so much better while on fin. In very slow doses and rarely any nausea. While not on fin I often get just endless hours of horror dizziness with an occasional vomit and with no euphoria. 30mg of codeine, 30-50mg of tramadol or tea of just 0.5-1 poppy while on fin is enough to stabilize mood to happiness and reverse any negative side effects of finasteride. It’s a no-go road to permanent solution of course, so never took it more than one day at a time.

#12

If fin could perminantly down regulate its action why couldnt something perminantly up regulate its action.
Im about a year away from trying this if nothing happens in the mean time.

#13

I used Buprenorphine, 10, .2 mg doses over the course of about two weeks. (.2 mg = 40 mg Morphine)

It did seem to help with spontaneous erections and libido considerably the day after taking a dose (it has a long half life for an opiate) But unfortunately, it didn’t last after I came off and I went through a mild withdrawl.

#14

Any experiences with morphine please share. Morphine increases 5AR in the brain increasing brain DHT and progesterone metabolites.

#15

hi all

I know I only crashed just over a week ago, but just though I’d let you know that I took 100mg of tramadol (a synethic opioid) yesterday for this intermetant back pain I have been having and earlier today i started feeling this warmth all over the body and minor brain shivers. now i can pretty easily sustain an erection, flacid penis looks much more normal and girth has increased, slight increase in libido, brain fox is at maybe 75% or at least to the point where I can attempt to have a discussion with someone, also twitching muscles are much less frequent

now obviously these effects are going to wear off again tomorrow or the day after, but surely there would be a way to treat this more permanently? like would 50mg of trammadol every second day over a significant period time be able to up regulate 5arII to a point whrere we reach a homeostatis? even better - what about some kind of morphine pill that was combined with something that would target the removal of the high and focus purely on the up-regulation of 5arII? surely that’s possible with the existence of subutex etc

i dunno, seems promising. apologies with regards to my science knowledge as I am still trying to learn about all this stuff

#16

This might be useful but bear in mind those drugs can be addictive.

#17

Hmm, I actually have some morphine but I’m not so sure I should risk it…what do we all think?

#18

If your like me and you dont find drugs addictive then I would try it, but again dont take it if you have any addiction problems.

#19

No addiction issues but I am worried that taking more drugs could make things worse.

Taking morphine seems kinda extreme too- I am just scared after the mess that propecia has left me in.

#20

i wouldn’t risk it. the stuff i was taking was at such a low dose and i was taking it so infrequently that i wasn’t really worried about addiction. i also feel like it is in no way a permanent fix and would probably only over complicate things in the long run.

ps: for the record, just re-read that post of mine up there. cannot believe the amount of typos in it, haha, i guess that’s what extreme brainfog does to you…