Low dose D-Amphetamine suppr. Norepinephrine

[stoneinfocus]

I always thought that there´s a great deal of receptro dowregulation and doses for a medical regime are usually thought to produce proper figuers on paper and rarteyl take into account the effects of very low doese or acute and lo dose drug-actions, often by educated medics reffered to as placebo or subjective bullshit of placobo-induced wishful thinking of the reporting individual (when swim first used cortisone his 400mcg, which weren´t even oraly bioavailable to a great deal, though swims metabolism is/was a fuckin´ 2% bodyfat, pure muscle and extreme metabolic speed-machine without using any drugs, he felt an effect that was very consitently reproducable over the first, well spaced acute administrations, and included the feeling, that at the exact same time ~18-22min. the pill liberated a great deal of its drug or the drug being absorbed at a suitable place, maybe duodenum, maybe stomach, which was always like a booster that was fired, a speed-like mental sensitivation and higly elevated energy levesl, from an already highly trained ground-state).

But these effects wore off even when paused a month or so, or maybe beacuse of the poor oral bioavailability of the drug.

To cut a long story short, swim always felt, that a low dose of speed rahter had a tranquilizingf effect, than a speeding effect and since swim was told that noradrenaline was a main-concern in psyxhotic behaviour, he suggested at least to himself, that those patients might profit from a desensitivation of
firing ability, like an exacerbation would lead to a subsequent desenzitation and equilivrium of the desired mental state.

So maybe this theory might proof wrong, a low dose regime seems to do well, in this aspect:[http://www.ncbi.nlm.nih.gov/entrez/q...=pubmed_docsum

<H2>D-Amphetamine at low doses suppresses noradrenergic functions.

• Huang YH,
• Maas JW.

This study examined the effects of d-amphetamine on the firing rate of hippocampal cells which had been shown to have an inhibitory, noradrenergic input from the nucleus locus coeruleus (LC). d-Amphetamine at low doses of 0.1 mg/kg i.v. or 0.5 mg/kg i.p. increased the firing rates of these cells. With higher doses of d-amphetamine, both increases and decreases in the firing rates of hippocampal cells were observed. These differential effects on the firing rate of hippocampal cells were statistically significant (x2 = 13.32, d.f. = 3, P less than 0.01). The increased firing rate of hippocampal cells produced by the low doses of d-amphetamine was blocked by a prior destruction of the LC indicating that the drug effect was mediated by LC neurons. d-Amphetamine also significantly attenuated the decrement in the firing rates of hippocampal cells produced by LC stimulation (P less than 0.01). These results suggest that low doses of d-amphetamine suppress rather than enhance the actions os norepinephrine.
PMID: 7318907 [PubMed - indexed for MEDLINE]

</H2>

[lulz]

I found this research so bizarre, I've been trying to figure out how it makes sense.

You might be interested in this research:

Amphetamine's effects on terminal excitability of noradrenergic locus coeruleus neurons are impulse-dependent at low but not high doses.

Ryan LJ, Tepper JM, Young SJ, Groves PM.

The actions of amphetamine in the locus coeruleus and its terminal fields in the frontal cortex were studied using extracellular recording to measure terminal excitability, firing rate and the probability of antidromic action potential invasion of the somatodendritic region in urethane anesthetized rats. At low dose (0.25 mg/kg), amphetamine increased terminal excitability. In comparison, subsequent administration of the highest dose (5.0 mg/kg, i.v.) of amphetamine tested suppressed neuronal firing and blocked antidromic action potential invasion of the somatodendritic region. Despite the absence of impulse traffic, high dose amphetamine reversed the effect of low dose amphetamine in the terminal field and decreased terminal excitability. The alpha 2 antagonist, yohimbine (0.5 mg/kg, i.v.), reversed the effects of high dose amphetamine on terminal excitability and somatodendritic invasion without reinstating neuronal firing. Noradrenergic autoreceptor agonists are known to decrease terminal excitability, whereas antagonists are known to increase terminal excitability. Thus, since low dose amphetamine produces the same effect on terminal excitability that antagonists do, it appears that low dose amphetamine may reduce autoreceptor activation by reducing norepinephrine release in frontal cortex as a consequence of inhibiting locus coeruleus neuronal firing. In contrast, high dose amphetamine acts like autoreceptor agonists do and decreased terminal excitability. Hence high dose amphetamine may increase norepinephrine release, even in the absence of impulse traffic.

Like the research you posted, this confirms that low doses of amphetamine increase the activity of the hippocampus, which has an overall calming effect on the brain.

But what should interst you in particular was this sentence:

The alpha 2 antagonist, yohimbine (0.5 mg/kg, i.v.), reversed the effects of high dose amphetamine on terminal excitability and somatodendritic invasion without reinstating neuronal firing.

As I understand it, the main problem of high dose amphetamines is that the high levels of noradrenaline/norepinephrine reach levels where autoreceptor stimulation become significant.

If autoreceptor activity is a problem, then a norepi autoreceptor antagonist such as yohimbine would be beneficial, as the cited study supports.

Have you ever taken yohimbine? If low doses of amphetamine are causing such benefit for you, it definitely warrants experimentation with yohimbine, as this may achieve the same effect you're looking for.

I've read that BZP might be as effective on this autoreceptor as yohimbine, despite being about ten thousand times less potent in terms of affinity. If you've had positive results from BZP I seriously encourage experiments with yohimbine!

[stoneinfocus]

Intresting, I´m a kind of buzzed rigth now and most of my brain terminals are
busy with processing reactions, pain, anger and manging roidrage and sexual overstimulation as well as some nice, transcedent, hyper-empathetic feelings caused by the action of these drugs and some tropinone alkaloids.

I have to research on the treminology of the neurological language, especially autoreceptor effects of norepi et al. and their psychological and physiological effects in man, even if these actions will cause any realizable effects at , in combination with amphetamine.

Yes, swim experimented with yohimbine and he felt very dangerous serotonergic effects in combination with caffeine and tramadol, soemtimes he thinks with his bulk caffein poweder has been messed.

caffein and yohimbine*hcl gave tremndous endurance in highly trained athletes,
and a strange jittery excitation, not quite a true aggression, but a kind of aggression, that was more a CNS stimulation, with a huge energy facilitation in the fat-metabolism

If swim will get some amphetamine next time he will experimant with it and yohimbine, to see the effects in man.

[stoneinfocus]

Swim just tried it a little yoimbine and a few (~1,5-3) mg of perv., a bit coke and it is def. very cool, all very low dose, exept yohimbine, being about 7mg.

The opposite of stress even in stress-situations, very cool and stable, yet, fantastic endurance, seemingly resulting of an enhanced fat-metabolism,
lighter breathing, also.

[Micklemouse]

Originally Posted by co-incidence

Swim just tried ... a few (~1,5-3) mg of perv.,

What is "perv."?

[stoneinfocus]

methamphetamine = pervitin

[stoneinfocus]

Ahh, autoreceptor is this stuff, that especially with exitatory amines produces the almost unique negative feedback loop, that´s caused by norepinephrine itself... ususally it´s a whole lot of other mechanisms and effector drugs,. that will cause a casced, that then will cause an inhibition of the "starting" compound, but with norepi it´s norepi itself.