Wondering about a particular effect of THC on the MU1 receptor-agonist mechanisms

[Gandalf_The_Grey]

Last night I was in a significantly extra large amount pain so I took an extra dose of tramadol (a morphine receptor agonist), and now I've woken up at 3:00am with seratonin blasting through my brain. I'm unable to sleep because my brain is utterly excited, eccentric and wildly creative in thought, enthusiastic and possitive in outlook (as opposed to the usual as of late), and overal very clear thinking. I attribute this to the increase and reuptake-inhibition of seratonin triggered by tramadol and probably other MU receptor agonists.

What's interesting is that this possitive outcome only happens when I take the extra tramadol and smoke weed, after the effects of the THC have worn off. When I don't smoke any weed and double-up on the tramadol by itself, it just muddles up my brain, makes me tired and grouchy, and significantly hinderes my mental capacity.

So, does anybody have a theory as to why smoking weed with a morphine-receptor agonist would have such an opposite effect to the usual fatique, grouchiness, and mental hinderance?

Gandalf_The_Grey Reviewed by Gandalf_The_Grey on 10-12-2007. Wondering about a particular effect of THC on the MU1 receptor-agonist mechanisms Last night I was in a significantly extra large amount pain so I took an extra dose of tramadol (a morphine receptor agonist), and now I've woken up at 3:00am with seratonin blasting through my brain. I'm unable to sleep because my brain is utterly excited, eccentric and wildly creative in thought, enthusiastic and possitive in outlook (as opposed to the usual as of late), and overal very clear thinking. I attribute this to the increase and reuptake-inhibition of seratonin triggered by tramadol Rating: 5

[Chronisseur]

I wonder if it's possible the THC is bonding with an element in the Tramadal, delivering this slightly altered compound to the rest of your body via fat cells?

...ya got me?

[beachguy in thongs]

The effect of naloxonazine, a selective mu(1)-opioid receptor antagonist, on oxycodone-induced antinociception was examined in streptozotocin-induced diabetic mice. Oxycodone (5 mg/kg, s.c.) induced significant antinociception in both non-diabetic and diabetic mice. This antinociceptive effect of oxycodone was completely antagonized by pretreatment with naloxonazine (35 mg/kg, s.c.) in both non-diabetic and diabetic mice. The selective kappa-opioid receptor antagonist nor-binaltorphimine (20 mg/kg, s.c.) also antagonized oxycodone-induced antinociception in diabetic mice, but only had a partial effect in non-diabetic mice. These results suggest that although primarily interacts with mu(1)-opioid receptor, kappa-opioid receptors are also strongly involved in oxycodone-induced antinociception.

Eur J Pharmacol. 2007 Apr 10;560(2-3):160-2. Epub 2007 Jan 19.

O-4394 and O-4395 exhibit similar in vitro potencies to eDelta(9)-THCV as CB(1) receptor ligands and as antagonists of cannabinoid receptor agonists and can antagonize Delta(9)-tetrahydrocannabinol in vivo.

Br J Pharmacol. 2007 Mar;150(5):586-94. Epub 2007 Jan 22.

Gotta take the dog out!!!

[Gandalf_The_Grey]

Um.... Beachguy, the article's appreciated and all, but what did that have to do with anything relating to this thread?:wtf:

[partcleguy]

He says "O-4394 and O-4395 exhibit similar in vitro potencies to eDelta(9)-THCV as CB(1) receptor ligands and as antagonists of cannabinoid receptor agonists and can antagonize Delta(9)-tetrahydrocannabinol in vivo."

But what I get from that is these opioids act as THC agonists and block the action of other cannabinoid agonists. This does not answer his question.

I would think that the opposite would occur in that having both THC and tramadal would increase the rate and production of MAO and COMT, enzymes which break down many types of neurotransmitters. This would in fact decrease the amount of neurotransmitters making it to receptors after your blood THC/Tramadal levels are low enough.

This suggests that enzymes are not at work. Perhaps the down regulation of cannabinoid receptors, which has been shown to happen after being exposed to large(ish) amounts of cannabinoids, causes an increase in sensitivity to Tramadal?

[Chronisseur]

I know nothing about biochemistry, but it sounds like maybe the compounds are going through some form of Glucuronidation.

I've been on TONS of meds in my day, and have experienced a countless number of times where I felt the medications have been affected on a molecular level, as a result of the chemical compounds I choose to inhale!

...are ALL my posts today so abstract...lol

[beachguy in thongs]

Um.... Beachguy, the article's appreciated and all, but what did that have to do with anything relating to this thread?:wtf:

I was seeing what the receptor does, in the first one. In the second, I think, I looked at the wrong study.

[beachguy in thongs]

:yeahright:

The effects of the active ingredient of Cannabis, Delta9-tetrahydrocannabinol (Delta9-THC), and of the highly addictive drug heroin on in vivo dopamine transmission in the nucleus accumbens were compared in Sprague-Dawley rats by brain microdialysis. Delta9-THC and heroin increased extracellular dopamine concentrations selectively in the shell of the nucleus accumbens; these effects were mimicked by the synthetic cannabinoid agonist WIN55212-2. SR141716A, an antagonist of central cannabinoid receptors, prevented the effects of Delta9-THC but not those of heroin. Naloxone, a generic opioid antagonist, administered systemically, or naloxonazine, an antagonist of micro1 opioid receptors, infused into the ventral tegmentum, prevented the action of cannabinoids and heroin on dopamine transmission. Thus, Delta9-THC and heroin exert similar effects on mesolimbic dopamine transmission through a common mu1 opioid receptor mechanism located in the ventral mesencephalic tegmentum.

Science. 1997 Jun 27;276(5321):2048-50.

[Gandalf_The_Grey]

So if I'm reading that right (I'm familiar with most but not all of the terminology in the report), the THC increasing dopamine levels has a sort of neuro-stimulatory effect to counter the cognitive inhibition and sedation? Although this would counter my previous theory that rapid dopamine reuptake is why cannabis exacerbates mine and some other people's pain.

[beachguy in thongs]

Maybe, it isn't the Cannabis that's exacerbating the pain.