Difference between Methamp and amp

[Binding_Affinity]

Hi, all

So I've been taking Desoxyn for several months now after switching from Adderall (for those of you who may not know, Desoxyn is methamphetamine salt, whereas Adderall is a blend of dextro and levoamphetamine salts). The differences are quite amazing for me. I notice that with only a third of the dose, I can get much longer, cleaner effects from Desoxyn; much more subtle, though (although, not in a bad way). I understand that a metabolite of methamphetamine is amphetamine. Since Desoxyn is purely psychoactive, I'm assuming all the amphetamine metabolites are also psychoactive (as in, no nasty levoamphetamine)?

So my question is this, can parallels be drawn with tryptamine substances in the sense that x-aco-xxt is comparable to Desoxyn and x-HO-xxt is comparable to Adderall? I ask because I notice much calmer but still focused effects from Desoxyn with a longer comeup than Adderall, much like peoples' experiences when comparing Aco molecules to HO, since from my understanding, HO is a metabolite of Aco. I'm simply curious if conceptually speaking, I am correct in my thinking

Cheers!

 

[sekio]

nasty levoamphetamine

That's a long standing rumor, looking at the binding affinity for l-amphetamine, it is more correct to call it "inactive" than "nasty" - it is less than 1/10 the potency per milligram of d-amphetamine.

Since Desoxyn is purely psychoactive, I'm assuming all the amphetamine metabolites are also psychoactive (as in, no nasty levoamphetamine)?

Because Desoxyn is 100% d-methamphetamine it produces d-amphetamine as a metabolite. However the conversion to amphetamine is not really important in the drug's effect - that is to say, d-methamphetamine is not really a prodrug, and when someone takes it most of the activity will be from d-meth, not the amphetamine produced by hepatic demethylation.

So my question is this, can parallels be drawn with tryptamine substances in the sense that x-aco-xxt is comparable to Desoxyn and x-HO-xxt is comparable to Adderall? I ask because I notice much calmer but still focused effects from Desoxyn with a longer comeup than Adderall, much like peoples' experiences when comparing Aco molecules to HO, since from my understanding, HO is a metabolite of Aco.

Not really, see the above paragraph. As far as I know the 4-AcO tryptamines are effectively just prodrugs for the parent psilocin-type drugs, they are very rapidly metabolised by esterases in the blood and don't produce any effects themselves.

 

[Binding_Affinity]

That's a long standing rumor, looking at the binding affinity for l-amphetamine, it is more correct to call it "inactive" than "nasty" - it is less than 1/10 the potency per milligram of d-amphetamine.

From my understanding, l-amp works on the PNS as opposed to CNS like d-amp. I experienced a heavy body load at the dose that I needed for the d-amp to work effectively and I attributed that to the l-amp, hence why I said it was nasty. I understand it's not psychoactive but it still causes stimulation on the PNS, correct?

Because Desoxyn is 100% d-methamphetamine it produces d-amphetamine as a metabolite. However the conversion to amphetamine is not really important in the drug's effect - that is to say, d-methamphetamine is not really a prodrug, and when someone takes it most of the activity will be from d-meth, not the amphetamine produced by hepatic demethylation.

So the majority of psychoactive properties are due to the d-methamp alone? I guess I was under the impression d-amp was still the chief driving factor due to its very long and subtle comeup. I would have assumed d-methamp would "hit" faster because it has an easier time passing the BBB. I'll keep that in mind next time I take my meds.

Not really, see the above paragraph. As far as I know the 4-AcO tryptamines are effectively just prodrugs for the parent psilocin-type drugs, they are very rapidly metabolised by esterases in the blood and don't produce any effects themselves.

So I guess based on what you said before, it's not a good parallel because methamp is psychoactive in and of itself and 4-Aco are more just precursors? So they're more similar to 5-HTP and serotonin? That makes more sense. Thank you for clearing all of that up for me!

 

[sekio]

I understand it's not psychoactive but it still causes stimulation on the PNS, correct?

I don't see any evidence that it would be, at least not at doses typically found in Adderall. If it can't bind to the DAT/NET it won't have any stimulating effects. I'm not sure about its affinity at adrenergic receptors but I'd expect it would be minor if anything.

Fun fact, L-methamphetamine used to be used as a decongestant at much higher does than d-meth so it obviously can't be that nasty.

So the majority of psychoactive properties are due to the d-methamp alone? I guess I was under the impression d-amp was still the chief driving factor due to its very long and subtle comeup. I would have assumed d-methamp would "hit" faster because it has an easier time passing the BBB.

Orally administered d-meth still has to pass through the stomach, liver and blood before it reaches the brain, and if you are taking a much lower dose of d-meth than you'd take of amphetamine salts then of course the experience will seem milder.

 

[Hodor]

Fun fact, L-methamphetamine used to be used as a decongestant at much higher does than d-meth so it obviously can't be that nasty.

I think it still is used for this purpose, perhaps even more so than it used to be - levo-methamphetamine has effects similar to pseudoephedrine, except unlike pseudoephedrine, you can't just easily convert it to d-methamphetamine.
On the bottle, pharmaceutical levo-methamphetamine (e.g. on Vick's OTC cold remedies) is usually labelled "L-desoxyephedrine" (hence also the brand name "Desoxyn" for pharmaceutical d-methamphetamine), since the conversion of ephedrine to methamphetamine only requires the removal of an oxygen atom.

So I guess based on what you said before, it's not a good parallel because methamp is psychoactive in and of itself and 4-Aco are more just precursors? So they're more similar to 5-HTP and serotonin? That makes more sense. Thank you for clearing all of that up for me!

The best comparison for 4-AcO-trypts would probably be... heroin (3,6 Di-Acetyl-morphine), I guess? In both cases, the ester is cleaved rapidly, and most of the activity comes from the active metabolites, psilocin/morphine. If and how active 4-AcO-tryptamines are before the ester cleavage is still a matter of debate. Looking at the structure it would be a reasonable hypothesis that the 4-AcO version enters the brain more rapidly, but is weaker at activating the receptor than the 4-HO metabolite, so maybe the come-up might be ever-so-slightly different. At any rate, I seriously doubt many people would be able to tell apart 4-AcO-DMT, 4-HO-DMT (Psilocin) and 4-PO-DMT (Psilocybin) in a blind test.

In methamphetamine, the unmetabolized form is clearly much more active, and the de-methylation to amphetamine takes place at a much slower rate. People should be able to easily tell apart meth and regular amp in a blind test.

So 4-AcO-DMT can justifiably be called a pro-drug, while methamphetamine is a very powerful, long-lasting drug that just happens to have powerful, moderately long-lasting metabolites.

 

[Binding_Affinity]

Sekio, from my understanding, many doctors prefer prescribing Adderall over Dexedrine because it's harder to abuse due to the l-amp effects on the PNS. There are studies done on its effect on the PNS as well as many people who feel uncomfortable bodyloads with Adderall as opposed to little to no bodyload on Dexedrine. Although, that isn't the primary reason (if a reason at all) pharmaceutical companies put l-amp, though. Research has concluded that the 1:3 ratio can potentiate d-amp for some people so that's why it's there.

Hodor, thanks for throwing in a little biochem. I love that stuff haha. That all makes sense. I definitely can tell the difference between methamp and just amp.

 

[sekio]

There are studies done on its effect on the PNS

Any references to these? At least for binding at the dopamine transporters, L-amph is about 1/4 as potent.(ref)

Research has concluded that the 1:3 ratio can potentiate d-amp for some people so that's why it's there.

I thought it was because the mix of amphetamines was pre-FDA safety approved for weight loss (back before amphetamines were banned for this purpose) but was repurposed for ADD/ADHD after the expiry of Dexedrine patents...

 

[Tubbs]

They still prescribe amphetamines for weight loss, albeit extremely rarely. It's still listed as an approved use for desoxyn.

 

[Seppi]

They still prescribe amphetamines for weight loss, albeit extremely rarely.

That "albeit extremely rarely" clause isn't quite right:

Racemic amphetamine → FDA-approved for obesity
Lisdexamfetamine → currently the only FDA-approved drug for binge-eating disorder

 

[Seppi]

@OP: I don't feel like restating something I mentioned in a previous thread, so I'll just give you the incredibly brief summary version.
The main distinction between amphetamine's and methamphetamine's pharmacodynamics is between the EAAT subtype that they inhibit uptake at and methamphetamine's agonist activity at human sigma receptors. Amphetamine isn't a human sigma receptor ligand.