Endogenous Opioid Release in the Human Brain Reward System Induced by Acute Amphetami

[AlphaMethylPhenyl]

Kent Berridge, University of Michigan, MI, USA. F1000 Prime Neuroscience
20 Apr 2012 | Confirmation, New Finding
DOI: 10.3410/f.14267051.15779178
If dopamine is not a pleasure neurotransmitter, then why is amphetamine so pleasantly euphoric? This important study reports that amphetamine elicited elevations of human endogenous opioid neurotransmitters in brain structures such as nucleus accumbens striatum and limbic regions of prefrontal cortex. Release of natural brain opioids might therefore explain why amphetamine and related dopaminergic drugs can be so pleasurable.

Colasanti and colleagues here gave ordinary men an oral dose of amphetamine before measuring subjective ratings of euphoria, and using positron emission tomography (PET) neuroimaging to measure synaptic levels of endogenous opioid neurotransmitters (via displacement by the natural ligands of bound radioactive [11C]carfentanil from mu opioid receptors). The authors report that amphetamine produced increases in endogenous opioid release (reflected in reduced drug binding) in subcortical ventral striatum (nucleus accumbens), dorsal striatum (caudate and putamen) and thalamus, as well as increased cortical release in orbitofrontal cortex, anterior cingulate cortex and insula cortex. Of special interest, subjective ratings of euphoria produced by amphetamine were positively correlated, significantly and specifically, with ventral striatum displacement, implying that nucleus accumbens opioids might mediate subjective pleasure of the drug.

Given that dopamine is no longer regarded by many neuroscientists to be a pleasure neurotransmitter after all, the intense pleasure of drugs that specifically elevate synaptic dopamine (e.g. amphetamine and cocaine) has presented something of a puzzle. Colasanti et al.'s results suggest a possible resolution: amphetamine's dopamine stimulation of opioid levels might cause the pleasure via endogenous opioid stimulation of mu receptors in hedonic circuits involving nucleus accumbens.
Acknowledgments
This evaluation was prepared with Professor Marco Leyton (McGill University, Montreal, Canada), who found this paper.
Disclosures
None declared
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http://f1000.com/prime/14267051


Cool...

 

[sekio]

via displacement by the natural ligands of bound radioactive [11C]carfentanil from mu opioid receptors

so they give you radioactive super opioids AND amphetamine?? party time

 

[AlphaMethylPhenyl]

Is it basically saying that Amphetamine increases endogenous opiate release?

 

[endotropic]

Is it basically saying that Amphetamine increases endogenous opiate release?

Bingo. This fits in pretty well with the finding that Naltrexone can attenuate the subjective effects of amphetamine (and pretty much every other drug of abuse).

Effects of naltrexone on the subjective response to amphetamine in healthy volunteers.
http://www.ncbi.nlm.nih.gov/pubmed/15538132

 

[sekio]

The authors report that amphetamine produced increases in endogenous opioid release

I don't know, does it? </sarcasm>

This has long been a suspicion of many people. Maybe it plays some part in why the rewarding effects of amphs are so easily tolerated

 

[Jakeperson]

^^ Helps explain why the Amphetamine addiction>Opiate Addiction is such a common pattern and why Heroin feels so fucking good, or is that normal?

 

[Epsilon Alpha]

So damn happy this study is finally out... :')

 

[sekio]

Can someone post the full text?

 

[pofacedhoe]

^^ Helps explain why the Amphetamine addiction>Opiate Addiction is such a common pattern and why Heroin feels so fucking good, or is that normal?

this is exactly what happened to me.

also i think its because a drug that is physically and mentally destructive in a big obvious way leads you towards one with a lower toxicity and more manageable side effects that fits in neatly with eating and sleeping at moderate dosing levels.

also after a speed habit a lot of people find themselves with bad anxiety, which funny enough opiates work quite well for.

also people get a taste for downers when the need to come down is pressing i.e. benzo addiction coming after a cocaine addiction: beginning at the end of coke binges but quickly becoming a way of life long after the coke is off the radar

 

[MeDieViL]

also i think its because a drug that is physically and mentally destructive in a big obvious way leads you towards one with a lower toxicity and more manageable side effects that fits in neatly with eating and sleeping at moderate dosing levels.

Going for that to things like heroin seems rather stupid imo (in the way how destructive of a drug it is), im not familiar with opiates but it seems heroin users dont do much when high and just have their life passing by while on stims i fully live my life, am outgoing etc, those side effects you talk about are easily counteracted with benzo's.

Im satisfied with highs i get with my drugs, dont care that opiates may be better, perhaps for others that arent satisfied and want to experience better highs.

 

[JimRaynor]

If AMP gives pleasure through opiate release then why doesn't AMP give an opiate-like withdrawal upon cessation?

 

[sekio]

You have obviously never seen someone who is withdrawing from heavy amphetamine use.

 

[JimRaynor]

You have obviously never seen someone who is withdrawing from heavy amphetamine use.

My question goes deeper than that. The concensus (in the medical community) seems to be that AMP addiction don't result in physical addiction, nor that OST (opiate substitution therapy) is effective among stimulant abusers. This study suggest otherwise?

 

[Jakeperson]

Going for that to things like heroin seems rather stupid imo (in the way how destructive of a drug it is), im not familiar with opiates but it seems heroin users dont do much when high and just have their life passing by while on stims i fully live my life, am outgoing etc, those side effects you talk about are easily counteracted with benzo's.

Im satisfied with highs i get with my drugs, dont care that opiates may be better, perhaps for others that arent satisfied and want to experience better highs.

Heroin may be destructive but can be a lot more functional for some. On Meth I never leave the house, on opiates I am bulletproof.

 

[sekio]

This study suggest otherwise?

Not neccesarily, all this suggests is that amphetamine releases opioid peptides in parts of the brain responsible for reward and reinforcement, not neccesarily systemwide

 

[MeDieViL]

If AMP gives pleasure through opiate release then why doesn't AMP give an opiate-like withdrawal upon cessation?

Because it wont downregulate mu as much, it indirectly activates it like endorphines do and a drop in release of those never causes withdrawals. Amp doesnt release morphine and heroin, atleast for most it would be cool tough

On Meth I never leave the house

I wont either unless combined with downers, its like wearing a bulletproof jacked when on amp, wich makes taking bulletproof stuff not of much use, unless you dont like the style of the jacket. Still better then wearing clothes with holes in when they are destructed by something destructive but that may be me.

 

[fatstep]

Goes along with something i read on here sorry i cant post the article though, saying that analgesia post-amphetamine administration was about equal to post-morphine administration very interesting

 

[PerekurPro]

Amphetamine analgesic actions is due to increased amounts of Noradrenaline and Adrenaline, it is called fight-or-flight response, and i think it covers different type of pain, like decreased touch sensitivity, more endurance, while opioids may "cover" pain in the inner organs.

 

[MyDoorsAreOpen]

^ Yeah, I always chalked the analgesia up to a catecholamine effect, and as much a peripheral one as a central one.

 

[Tussmann]

I kinda have the inclination that any strong psychoactive chemical is going to have a host of unknown downstream effects on several neurotransmitters/receptors.