←back to thread

946 points giuliomagnifico | 1 comments | | HN request time: 0.22s | source
1. kortex ◴[] No.25607616[source]
Wow, this whole thread has prompted me to get off mobile and onto a keyboard, because I have many thoughts on this matter. I have ADHD, delayed phase sleep disorder, a dual BS in chemistry and psychology, I have studied addiction and drug reform, and even worked on synthesizing phenethylamine derivatives. I have many thoughts.

First, methamphetamine is not amphetamine. Meth belongs to the broad class of molecules properly known as "substituted amphetamines" or "phenethylamines." No one in-the-know refers to meth as "amphetamine" by itself, though some do broadly refer to assorted substituted amphetamines as "amphetamines" but this is pretty sloppy and if you want to refer to the class and "substituted amphetamines" is a mouthful, just use "phenethylamine" (PEA).

The name, of course, one of the most clever elisions in chemistry, Alpha-Methyl-PHenyl-ETthylAMINE, refers to the methyl group alpha to (the 1st substituent on the carbon backbone) the amine. This makes PEAs structural analogs of dopamine (DA, aka 3,4-OH-PEA) and norepinephrine (NE, aka 3,4,β-OH-PEA), and their the ability to modulate DA/NE receptors is what gives PEAs their general stimulating properties.

Meth-amphetamine has a methyl group on the amine. This seemingly small structural change makes a big difference pharmacologically. Methylation of amines makes drugs more fat-soluble, which makes them better at penetrating the blood-brain barrier and cellular membranes, while inhibiting its breakdown and clearance. This makes METH harder hitting, better at receptor binding, faster acting, and with far stronger effects than AMPH. Modelling addiction is tricky, but we can loosely approximate how strongly habit-forming a drug can be by multiplying the blood plasma curve by an exponential decay. The faster and higher a drug peaks, the more likely it will be addicting.

METH's lipophilicity also means it tends to cause DA to leak into places it shouldn't, resulting in unwanted chemical side-reactions which can damage neurons and glia, making it more toxic than AMPH. (this is a huuuge oversimplification; there are reams of studies on the mechanism of METH toxicity, and yes the literature uses METH as the abbreviation, I'm not being dramatic by all-capsing it)

Together, this makes METH much more dangerous than AMPH, and hence why AMPH and prodrugs such as Vyvanse (lysine-dexamphetamine) are commonly prescribed for ADHD, sleep disorders and eating disorders, while METH (under the name Desoxyn) is much more obscure medicinally (but still used! In fact another comment in this post mentions it).

Both are DEA Schedule II. Scheduling has basically no correlation to actual addictive potential or harm in any way. Psilocybin is SchI, has virtually no risk of addiction or overdose, Zolpidem is SchIV but is notoriously prone to abuse, and tobacco isn't even scheduled but is exceptionally addictive, causes easily >$100B in costs in USA alone. Yeah, the DEA schedule is kinda useless IMHO, but I digress.

AMPH can be abused and sold on the street, but that's true of literally any drug that humans find interesting to consume, including weak PEAs like bupropion, and OTC drugs like diphenhydramine and dextromethorphan.

Bottom line is - amphetamine is safe and effective when used as prescribed for improving focus and wakefulness. Lumping it in with METH or other street drugs is chemically imprecise, and does a disservice to those struggling with executive disorders. Apple makes it seem like just the name Amphetamine implies inappropriate drug consumption, which adds to the stigma those who benefit from amphetamine treatment already experience.

Thanks for coming to my TEDHN talk.