Amphetamine is actually a very effective weight loss drug. And it's sort of orthogonal to the fact that it's a stimulant. Stimulants in general can cause an acute reduction in appetite and temporary weight loss. This tends to stabilise with tolerance, however. As someone with obesity and ADHD, thus was my experience with methylphenidate treatment. And I used to think the weight loss effects of amphetamine were analogous until recently.
Amphetamine and methyphenidate(MPH) have very different ways of acting as stimulants. MPH is an inhibitor of the dopamine transporter(DAT) and the norepinehrine transporter(NET). These cross-membrane proteins essentially "suck up" the dopamine or norepinehrine after neurotransmission, thus regulating the effect. MPH inhibits this process, increasing the effect. This is called a norepinephrine/dopamine reuptake inhibitor(NDRI). Cocaine also works like this, as well as the antidepressant wellbutrin(bupropion).
Amphetamine on the other hand, is a bit more complicated. It interacts with DAT/NET as well, as a substrate, actually passing through them into the neuron. Inside the neuron, it has a complex series of interactions with TAAR1, VMAT2, and ion concentrations, causing signaling cascades that lead to DAT reversal. Essentially, enzymes are activated that modify DAT in such a way that it pumps dopamine out of the neuron instead of sucking it up. How that happens is very complicated and beyond the scope of this comment, but amphetamine's activity at TAAR1 is an important contributor. As such, amphetamine is a norepinephrine-dopamine releasing agent(NDRA). Methamphetamine, MDMA, and cathinone(from khat) also work like this.
Anyway, recently I was reading about TAAR1 and learned something new, namely that TAAR1, besides being and internal receptor in monoaminergic neurons, is also expressed in the pancreas, the duodenum, the stomach, and intestines and in these tissues, TAAR1 activation will increase release of GLP-1, PYY, and insulin, as well as slow gastric emptying.
So in essence, there may be some pharmacological overlap between ozempic and amphetamine(I'm still looking for data on how significantly amphetamine reaches TAAR1 in these tissues, so unclear what the relevance is. But amohetamine is known to diffuse across cellular membranes, so it's likely there is an effect).
Also interesting, amphetamine was recently approved as a treatment for binge eating disorder. Not only because it causes weight loss, but because it improves functioning in the prefrontal cortex(crucial to its efficacy in ADHD), which is apparently implicated in the neuropsychological aspects of BED as well.
There is a mixed picture on this. I see a lot reports of reports of it causing binging in the evenings despite no prior issues.
The issue is that therapeutic doses are not the multi-day bender of a speed-freak that forgoes sleep to keep their blood-concentration permanently high. Instead it's a medicated window of 6-12 hours with a third or more of their waking hours remaining for rebound effects to unleash stimulation-seeking demons that run wilder than ever.
Amphetamine and methyphenidate(MPH) have very different ways of acting as stimulants. MPH is an inhibitor of the dopamine transporter(DAT) and the norepinehrine transporter(NET). These cross-membrane proteins essentially "suck up" the dopamine or norepinehrine after neurotransmission, thus regulating the effect. MPH inhibits this process, increasing the effect. This is called a norepinephrine/dopamine reuptake inhibitor(NDRI). Cocaine also works like this, as well as the antidepressant wellbutrin(bupropion).
Amphetamine on the other hand, is a bit more complicated. It interacts with DAT/NET as well, as a substrate, actually passing through them into the neuron. Inside the neuron, it has a complex series of interactions with TAAR1, VMAT2, and ion concentrations, causing signaling cascades that lead to DAT reversal. Essentially, enzymes are activated that modify DAT in such a way that it pumps dopamine out of the neuron instead of sucking it up. How that happens is very complicated and beyond the scope of this comment, but amphetamine's activity at TAAR1 is an important contributor. As such, amphetamine is a norepinephrine-dopamine releasing agent(NDRA). Methamphetamine, MDMA, and cathinone(from khat) also work like this.
Anyway, recently I was reading about TAAR1 and learned something new, namely that TAAR1, besides being and internal receptor in monoaminergic neurons, is also expressed in the pancreas, the duodenum, the stomach, and intestines and in these tissues, TAAR1 activation will increase release of GLP-1, PYY, and insulin, as well as slow gastric emptying.
So in essence, there may be some pharmacological overlap between ozempic and amphetamine(I'm still looking for data on how significantly amphetamine reaches TAAR1 in these tissues, so unclear what the relevance is. But amohetamine is known to diffuse across cellular membranes, so it's likely there is an effect).
Also interesting, amphetamine was recently approved as a treatment for binge eating disorder. Not only because it causes weight loss, but because it improves functioning in the prefrontal cortex(crucial to its efficacy in ADHD), which is apparently implicated in the neuropsychological aspects of BED as well.