“Stacking” Amphetamines

[Jabberwocky]

Someone recently claimed in a post that they enjoyed mixing Adderall and Meth which surprised me as I thought it would probably be wasteful of the Adderall as it would just be overpowered by the Meth or, alternatively, that the Adderall (or d-amph or whatever other amp) would already 'occupy' (?) the receptors 'antagonised' (?) by the Meth, thus reducing the subjective effects of the meth? Sorry, I'm unfamiliar with exact terminology to describe what I'm talking about. However, I get that each amphetamine interacts slightly differently with different types of receptors so that some might be more dopaminergic (e.g Meth) and some might be more serotonergic (e.g. MDMA) and others more norepinephrine activating (e.g Meth) possibly leading to interesting compound effects.

So I am interested in understanding what happens when you take different kinds of amphetamines at the same time or one after the other. In my own case I am interested in what happens in terms of receptor activity and subjective effects when one takes recreational doses of methamphetamine on top of Rx doses of Dexamfetamine or vice versa. As above, my assumption is that the meth would simply overwhelm the dex making it pointless to combine the two. Or that the dex first would reduce the rush of the Meth but then be overpowered by it. But I would like to understand the mechanism of action better as to how this works in the brain.

I’d also be interested in understanding other combinations of amphetamines: eg. Meth + MDMA or Dex + MDMA in terms of how the combination adds to or reduces the effect of one or the other of the two drugs.

Anecdotal stories welcome but bonus points for explaining the science of it.

 

[Jabberwocky]

Mods: could you please shift this to neuroscience and pharmacology? @falsifiedhypothesi /@F.U.B.A.R./@negrogesic ??

 

[clubcard]

Amphetamine and methamphetamine have slightly different action. If memory serves, their VMAT transport site is different as well. I have to agree with F&B when he stated that fencamfamine (and camfentamine) are vastly better. The latter has more pronounced opiod effects than the former. If an ester moiety is added to the beta position, the product overlays nortilidine perfectly (well, the aromatic ring, N lone-pair & ester function overlay perfectly. Not a practical target, but interesting.
On the whole, medicines are what theysay in the dose they say which is in their favour.

 

[Gaffy]

I liked mixing speed (amphétamine sulfate) with Ephylone which is a much more pronounced stimulant and has an action ressembling meth more than MDMA. You'd think the Ephylone would totally overpower thé speed but nah, they play together liké pups and balls. I think the greater neurotransmetteurs release potential of speed Plays a rôle in this.

 

[Gaffy]

Amphetamine is a strong MAOI whereas Meth isn't. Meth has a higher molecular weight, therefor it must be more "electrified" by ionic bonding to be active at receptors, thus reducing the amount of possible bonding with the protein compared to amphetamine, althoug the methyl might play a role in this (lighter electrophilic part of the molecule?). Also, formaldehyde or methanol is formed in the brain by N-Demethylation which occurs upon hydrolisis and probably upon reuptake of the drug into the neuron (Maybe even the methanol blocks the channel of entry maintaining the formed amphetamine at the channel port resulting in lingering un-euphoric stimulation ( tweaking?). I know this for a fact as I've experienced what happens when you break open that overloaded closed gate. But that's another story. Maybe the methyl enters the channel or a part of the protein, who knows. On the other side, amphetamine is less active as a serotonine agonist,instead being serotonergic by being an MAOI and upping serotonin levels via dopamine release, as it releases way more than Mehhth does. Added to mehth, which plays a bigger role in trapping the serotonin intersynaptically is a bonus, it would be almost sedating, just as with big shots of meth, where you feel like energized but without the ability to move.
Just to say that amphetamine is taken up into the neuron faster than meth and has a faster onset of action that is shorter but more spread in its way of action. So mixing amphetamine to meth will give you a more rolly meth high that feels more energetic. If there's not too much meth. Because otherwise the synaptic charge of serotonin will be too high and it can create major brainzaps and coma

 

[clubcard]

I was impressed by fencamfamine, methylphenidate and G-130 although I have never had the chance to try phenmetrazine. The fact that 60 years of development lead to significantly better stimulants suggests that there are still places to go. If only nomifenside wasn't flawed. Anybody else noticed how desoxypipradrol overlays nomifensine? I strongly suggest that the thiomorpholine homologue of desoxypipradrol would be a winner. In that I am presuming that the S is oxidised thus giving the body a much easier metabolic fate.

 

[Gaffy]

I can't seem to explain why methylphendate added to an amphetamine is pretty much dulled entirely. Also on the comedown of MPH Jexen felt especilly toxic and panic inducing. Tweaked neurons?