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DARI=blockade of opioid euphoria?

Limpet_Chicken

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Does the administration of a DARI prior to administration of an opioid (or the kicking in of a slower acting opioid, such as the prodrug codeine, or dihydrocodeine (in fact the opioid I am most curious about in this respect is dihydrocodeine, as I am prescribed this, but occasionally enjoy getting high instead of merely just using it for analgesia) directly block the euphorigenic action of the opioid?

I have twice had an experience with DHC that is quite atypical, a dose was taken on both occasions that would normally have me high as a kite, about
3/4th to half a gram of the tartrate salt, I am somewhat tolerant but not hugely so, my rx is for 30mg qds, sometimes I do use more, not enough to get high, but on occasion my knee pain is of sufficient severity to need it, but more often than not I use less, sometimes as little as 30mg/d average of 2x30mg/d, and of late I have been tapering down to lessen my tolerance, so this is NOT a tolerance issue, and the amount I took today, and the time previous this happened should most certainly have come on pretty strong.

Both times, desoxypipradrol was used, today at 2.5mg with an initial dose of
2mg plugged, and then a couple of hours later, a further 0.5mg was dosed orally (as a 1mg/ml solution in 40% EtOH) at the same time as the DHC was taken. Opioid was calming, did, and is providing analgesia although not as much so in the latter case as per usual at the recreational dose range used, and certainly prevented any autie-related sensory irritation, BUT, bugger all to very little euphoria that I can attribute to the DHC.

I'm guessing blockade at DAT is inhibiting DA release by the opioid?

You ADD guys agree with that theory?

Other question: if I were to take the same dose of DHC, or thereabouts, I.E enough to properly get off on it, and THEN take the desoxy after the opiate feels as though it has kicked in as strongly as it is going to, is it likely that it would cut short the high by shutting off further, ongoing DA release, OR, is it more likely that once the desoxy started acting, that it would enhance the euphorigenic properties of the DHC due to inhibiting reuptake of the released DA? or is a mixture of both effects more likely? inhibiting further release, but prolonging the high?

And if the latter of the three, which is likely to predominate, and is it more likely that the total euphoria/enhancement of cognitive processing and attention span would be greater than that of solely the opiate, or less?

Note: I do not find desoxypipradrol to be euphoric much, very, very little in fact, although I choose to use it at a dose no higher than 2-3.5mg or so, I did once try it at 5mg, but I found that rather too much for me, not overstimulating, the stuff is nearly imperceptible to me as far as peripheral stimulation goes, just the way I like stimulants (normally I HATE stimulants, but my cognitive, executive function, and attention focussing ability now are utter shit so finally I chose to resort to a stimulant). I'm not seeking recreational effects from the desoxy, but I don't want it interfering with any recreational use of opioids.
 
Are you sure it won't do? the effect in vivo from experience seems to point to a distinct lack of the feeling that opioids usually produce, selective for the euphorigenic activity.

And anecdotally, those people who have taken an SSRI, and then MDxx (potentially dangerous as that is) have said on BL that serotonergic effects were diminished or absent.

Question regarding monoamine transporters: Whilst they of course reuptake their target neurotransmitter and remove it from the synaptic cleft once released, does DAT in particular also work in reverse naturally to release DA? aside from the obvious mode of release via VMAT? and if not, why has it been reported that SERT inhibition diminishes or abolishes the serotonergic effects of MDx?

And the question remains, why on this combination, is opioid-mediated euphoria markedly absent? it isn't a slight lessening, but a very, very pronounced effect, and I believe it will remain so regardless of the dosage of opiate used, given there is little change comparitively between a DHC dose of a little over 100mg or upwards of 300-400mg (or as close to, given the fact 30mg tablets are my rx'd dosage unit)

I would be curious to see if this is repeatable with much, much larger doses, but I don't intend to try for 2 practical reasons, one being I am currently physically dependent and am tapering, as I said, and two-whilst due to my tapering, and the last time I saw my doc, he ended up giving me my months supply only a little over a week after the script just previous to that I have 'spare' boxes, I don't want to waste them, or to drive up my tolerance, and make any withdrawal more severe when I start cutting down again.

What IS going on here?
 
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I dont think this is the case that dopamine or NE reuptake inhibitors would block opiate euphoria through blocking dopamine release.


Focalin and coke both work fine with opiates and actually increase the euphoria alot.

I think DRI's can still force the release of dopamine and NE they just cant reverse the transporter like amps and force cytoplasmic release from the pool.
 
Don't have time to answer in full. DHC is kind of a bitchy opioid but no time for that....

Point is this should in practice occur. Sure a "DARI" may reduce they sedative-hypnotic effect of an opioid, particular one with such little potency. Essentially you are taking an ultra-low potency opioid with a high potency stimulant....the second is likely to dominate in subjective effects. Combine it with fentanyl......you may see things differently.....Oh and 2-DPMP is by no means a selective DARI......its inhibition of NE is very strong, and this cannot be overlooked........
 
IIRC Ki for NAT is roughly twice that for DAT.

I do not notice any adrenergic peripheral stuff, or central sympathomimetic activity at all, subjectively, and I am oversensitive to adrenergic anything, always causes akathisia, many stimulants do, most in fact, for me, desoxy does not.
 
If dopamine reuptake inhibition killed opiate euphoria would speedballs ever have become popular?
 
Actually it would substancitate the auphoria of opioids by supplementing it with dopamine euphoric properties.

Certainly if you are trying to sedate sombedy and them give him a quite heavy dopse of Methylphenidate then..we would likely have problems staying still and falling asleep.
 
Is there any data assaying effects on opioid receptors? I'm not confident on that theory being correct though, as I am currently physically dependent, been taking pain meds for years thanks to chronic joint pain in my knee, although I have been lowering my tolerance with a slow taper so it can once again be more effective. Taking an antagonist would put me in withdrawal, indeed, taking meptazinol, a mu1 selective partial agonist makes me feel like utter shit.

I know opioids don't depend on DAT, I was thinking more of an interaction between the two, just how DO opioids release DA? I have never looked into it, always sort of taken it for granted that they do as it is well known.

Does desoxy target VMAT at all?

It is just...odd, considering that the lessening of opioid action seems to be totally selective for the euphoric aspects whilst sparing analgesia. Of course I have no way to tell if it actually pharmacologically antagonises the sedation specifically via an opioid receptor class/subtype-dependent pathway, and indeed sedation in general isn't going to show itself whilst on a sodding potent stimulant.

Again wierd, but desoxypipradrol seems in me to cause zero euphoria at doses up to 5mg (and I wish to go no higher with it, 5mg was too much, 1-2mg works really well as a functional drug for my purposes), yes it puts me in a good mood, but not euphoric, not in the slightest.
 
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