#d-amphetamine

[impetuousvampire]

Julian Casablancas is building future ruins?? Going Shopping with a NIN reference!!! omg omg omg omg!!! The two are definitely not related!!!!

[committedpsychonaut]

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

Finally found the full text of this paper. I've been looking for it for about a year, full paper can be found here.

Objective: demonstrate pharmacologicallystimulated endogenous opioid release in living human brain by elevating effects of amphetamine administration on 11C carfentanil binding with positron emission tomography (PET)

Methods: 12 healthy male volunteers underwent [ 11 C]carfentanil PET before and 3 hours after a single oral dose of d-amphetamine (either a “high” dose, .5 mg/kg, or a sub-pharmacological “ultra-low” dose, 1.25 mg total dose or approximately .017 mg/kg). Reductions in [ 11 C]carfentanil binding from baseline to post-amphetamine scans (?BP ND ) after the “high” and “ultra-low” amphetamine doses were assessed in 10 regions of interest.

[ 11 C]carfentanil binding was reduced after the “high” but not the “ultra-low” amphetamine dose in the frontal cortex, putamen, caudate, thalamus, anterior cingulate, and insula

Conclusions: Findings indicate oral amphetamine administration induces endogenous opioid release in human brain, including basal ganglia, frontal cortex areas, and thalamus. The combination of an amphetamine challenge and [ 11 C]carfentanil PET is a practical and robust method to probe the opioid system in the living human brain.

Endogenous opioid system consists of three distinct opioid receptors and four families of endogenous peptides (endorphin, enkephalins, dynorphins, endomorphins).

-          Reward system, pain response, eating, negative emotions, social behaviors

-          Pathophysiology: chronic pain, depression, anxiety, borderline personality disorder

-          Mediates impulsivity and effects of multiple drugs

-          Opioid receptors and peptides high expression in areas of reward and motivation

o   ventral striatum, putamen, caudate, frontal and cingulate cortex, hypothalamus, amygdala, and ventral tegmental area

o   Other brain areas with high OR expression are those involved in pain regulation such as thalamus, insula, and periaqueductal grey (PAG)

-          Suggest dopamine is primarily responsible for reward behavior, opioid is second

-          Acute administration of amphetamine, a monoamine-releasing agent, induces the release of

-endorphin in the rodent ventral striatum and increases striatal enkephalin and dynorphin precursor messenger RNA levels

-          PET can detect endogenous neurotransmitter release on the basis of the competition between synaptic neurotransmitters and PET radiotracers at receptor level [11C]carfentanil is a PET agonist radioligand with high and selective affinity for receptors (MOR)

-          Investigate interactions between monoamines and endogenous opioids by looking at effect of amphetamine administration on binding of carfentanil

o   Compare amphetamine dosage with inactive dosage

-          The examined areas were: the ventral striatum, caudate, putamen, amygdala, thalamus, hypothalamus, frontal cortex (including up to the primary motor cortex), insula, anterior cingulate cortex, and PAG. The brain areas where changes were predicted include those involved in reward and motivation processes, such as ventral striatum, putamen, caudate, frontal and cingulate cortex, hypothalamus, and amygdala.

Results + Discussion

-          Found reduction in the binding of [11C]carfentanil to the MOR in the human basal ganglia, thalamus, and frontal cortex after an administration of a pharmacologically relevant dose of d-amphetamine

o   The availability of the MOR to bind [11C]carfentanil can be reduced by the release of a variety of opioid peptides that have relatively high affinity for MOR, including

-endorphin, endomorphins 1 and 2, met- and leu-enkephalins, and dynorphin B

o   Fibers rich in beta-endorphin are in the arcuate nucleus of the hypothalamus, are abundant in all diencephalic structures and the whole striatum.

-          Direct occupancy of the MOR by amphetamine is very unlikely to lead to the changes in [11C]carfentanil BPND we observed.

-          Amphetamine administration is not believed to directly induce opioid release. Amphetamine administration leads to release of a variety of monoamines, including DA, norepinephrine (NE), and serotonin . Finally, DA and DA-agonists but not NE enhance the efflux of met-enkephalin from striatal slices. Our data therefore support the notion that the brain dopaminergic system modulates opioid neurotransmission.

-          The distribution of the observed amphetamine-induced changes in [11C]carfentanil BPND overlaps partially with the known distribution of the DAT and dopaminergic tracts. The DAT is highly expressed in the putamen, caudate, and ventral striatum and to a lesser extent in the frontal cortex, cingulate cortex, insula, and thalamus.

-          However, the relationship between monoamine release and endogenous opioid release might not be straightforward. Opioid release might occur in close proximity to the release of monoamines, such as DA

-          injected mass of carfentanil is not a significant factor in the interpretation of our data. Thus, we are confident that the effects reported here are mediated through the action of monoamines

Conclusion:

In conclusion, we have characterized an amphetamine challenge in the context of a [11C]carfentanil PET study as a practical and robust method to probe the opioid system in the living human brain. This represents the first direct demonstration of pharmacologically stimulated endogenous opioid release in the living human brain. The application of this methodology to patient populations has the potential to elucidate the role of opioid peptides in neuropsychiatric disease more broadly.

Colasanti, A, Searle, G.E, Long, C.J, Hill, S.P, Reiley, D.Q, Erritzoe, D, Tziortzi, A.C, Reed, L.J, Lingford-Hughes, A.R, Walkman, A.D, Schruers, K, Matthews, P.M, Gunn, R.N, Nutt, D.J, Rabiner, E.A. Endogenous Opioid Release in the Human Brain Reward System Induced by Acute Amphetamine Administration. Biol Psychiatry. 2012 Sept 1;72(5):371-7. Epub 2012 Mar 3.

[committedpsychonaut]

1.5g Dextroamphetamine

A friend recently acquired a total of 150x 10mg dextroamphetamine tablets! That's 1.5 grams of pure dextroamphetamine! Took a total of about 40mg over the course of the morning. Completed all of my psychopharmacology and neuroscience capstone work for the week. Working my way through insect biology and abnormal mental psychology right now. Still 1500mg of d-amphetamine? Absolutely crazy.