Things I like to Blog About: Amphetamine

Apr 13 2009 Published by under Neuroscience

Man, that series of depression posts back there was intense, huh? And Sci will admit that she's not done. I've still got to cover the BDNF theory, not the mention the coolness that is all the possibilities in Brodmann's area 25.
But Sci is currently in the process of getting sick. While I attempt to preemptively strike this cold with copious amounts of sleep, zinc, and fluids, it's best to blog on a topic that I feel pretty comfortable blogging about. It also helps to blog while high on LOTS of on-sale Easter candy. Peeps are like blogging CRACK.

And speaking of things that give you excessive energy...
Amphetamine: speed, crank, Adderall, Dexedrine, or Vyvanse.

Amphetamines: A history of speed
Unlike other psychostimulants, like cocaine, amphetamine is a lab drug and has to be synthesized. The chemical name is actually (±)-alpha-Methylbenzeneethanamine, but for obviously reasons, amphetamine is a much better name for everyday use. It was originally synthesized in 1887 by Lazăr Edeleanu, a chemist in Germany. He was looking for compounds related to ephedrine, a drug found in a Chinese herb. If that drug name sounds familiar, it's because ephedrine, and its cousin pseudoephedrine, are still used today, as nasal decongestants found in things like Sudafed. Ephedrine was also used as a diet pill once upon a time. Possibly more about that when I get around to it.

Side note: Unfortunately, they're taking things containing pseudoephedrine in particular and putting them behind the counter and allowing you to only buy so much per month in many states, as pseudoephedrine is one of the necessary ingredients in the synthesis of crystal meth. So to stop people from buying tons of Sudafed and making it in to meth, they're not recording how much Sudafed you buy. For those of us who love Sudafed for it's decongestant purposes, this sux. So meth guys, STOP IT. You are ruining my groove, and causing my sinuses much pain. Don't buy meth, it causes Sci pain.)

So anyway, amphetamine was synthesized in 1887. It was studied in a very limited way until WWII, when it made its major debut as a stimulant, allowing soldiers to work longer and harder, and allowing pilots to stay awake. Since then, it's because incredibly obvious that this is a Bad Idea, because of course, amphetamine is...a bit addictive. It has since been made illegal for anything but prescription use. It's now a schedule 2 drug under the controlled substances act, which means that, though it has valid medical usage, it is also known to be an addictive substance. Not that this stops us from prescribing the HELL out of it. Because we do. Boy, we do.

The uses of speed

The biggest use of amphetamine is the drug known as Adderall. Adderall and its generics are one of the biggest prescriptions used right now for treatment of ADHD, attention-deficit hyperactivity disorder (the other is Ritalin, or methylphenidate, and its generics, which I will also have to blog about sometime). Amphetamine is especially used in cases of adult ADHD.

But ADHD isn't the only possible use. For a long time, amphetamine were marketed as stimulants to increase alertness, and they are prescribed in many cases for treatment of narcolepsy, or excessive daytime sleepiness. Amphetamine also has anorectic properties (stops you from eating), and so is sometimes used in cases of weight loss (though not half as much anymore as in the past).
In therapeutic doses like those used in the clinic, amphetamine is really pretty safe and effective. The long-term release of many of the formulations, coupled with the fact that it's taken as a pill, make the onset very long, and prevent the rush associated with a high. On the other hand, ground up and snorted, or mixed with saline and injected, it's very capable of being abused.
And it is abused. Quite a bit. Abuse of amphetamine runs the gamut from people who take the drug without a prescription of increase alertness and concentration for studying, to those who inject it straight into the vein for a high.
If you've read this blog in the past, you're probably aware that there are certain neurotransmitters that have a lot to do with the initial rewarding and reinforcing properties of drugs like cocaine, and in this case, amphetamine. And if you think that the abuse potential for amphetamine comes down to dopamine, serotonin, and norepinephrine, well, you would be CORRECT, SIR! (Well, at least, as far as science knows right now, you are correct.)
Amphetamine modes of action
It's believed that most of the effects of amphetamine on things like ADHD and narcolepsy arise from its effects on dopamine. Going back to basics, let's start with our dopamine synapse.
dopamine synapse.jpg
(Via NIDA)
So there you can see the top neuron (the presynaptic), and the bottom neuron (the postsynaptic) sommunicating with each other across the synapse, or space between them. The orange things represent dopamine, being released from vesicles in the presynaptic neuron into the synapse, where they can bind with receptor sites on the postsynaptic neurons (the receptors are blue). But what you want to look at here is the presynaptic neuron, at the vesicles, and at the fuschia thing. The fuschia thing is the dopamine transporter (DAT), which prevents dopamine from hanging around the synapse and continuing to stimulate receptors. Instead, the signal needs to be terminated, and while some of this happens with stopping of release, and some from diffusion and breakdown of dopamine in the synapse, the rest is the dopamine transporter. It takes dopamine and whips it back up into the presynaptic neuron, where it can then be repackaged and used again, or broken down into parts.
In the case of some psychostimulants, like cocaine, the DAT gets blocked, causing dopamine to build up in the synapse. In the case of amphetamine, something different happens.
Amphetamine is shaped a LOT like dopamine, and so, instead of blocking the DAT, is taken up by it, acting as a "false neurotransmitter" (damn faker). Then, as far as we know, two possible things happen.
1) The DAT is REVERSED, dumping dopamine out into the synapse.
2) Vesicles containing dopamine dump their dopamine into the cytosol, buidling up dopamine in the presynaptic neuron, and making a lot more availible to be dumped into the synapse by the reversed DAT.
So far, it appears that both of these mechanisms occur. Amphetamine appears to act both at the DAT (and norepinephrine and serotonin transporters as well), and at the vesicular monoamine transporter, a protein found on the membranes of vesicles, that controls the uptake of monoamines into the vesicles for vesicular release. It is taken up by both of these transporters, and may reverse them, dumping dopamine from the vesicles into the terminal, which is then dumped into the synapse. I wish I could find some good pics of this, or make one myself, but Sci is tried, so ya'll are going to have to use your imaginations.

Of course, dumping all of that dopamine out into the synapse is going to make for a major increase, and this increase happens FAST. Not surprisingly, this makes for one hell of a high. Right now, when we use these drugs in the clinic, we make them in long release formulations and give them in very low doses, so that increases in dopamine are both smaller and slower, taking away the effects of the high, while still causing wakefulness and increases in focus.
And that's all I've got for amphetamine right now. It's something (along with all stimulants, really) I really like to blog about, so there may be lots of details in the future. For now, Sci is nursing her cold, and also her tummy, which is very sore from an excess of Peeps. They might be some blogging crack, but the withdrawal is AWFUL.

12 responses so far

  • Larry Ayers says:

    Good overview, Sci, and I hope you are feeling better soon!
    It's been thirty years since I have recreationally used an amphetamine-based drug. Just a couple of times, and I realized that it just felt "too good to be true", and that the addictive potential was high. I had some friends crash and burn from meth abuse.
    I live in a neighborhood where meth and crack are pretty common, and I've learned to recognize the users. They tend to be amoral and desperate characters and in general can't be trusted.
    These days caffeine is the strongest stimulant I indulge in...

  • CRhu says:

    I have been on (Rx'd) d-Amphetamine for a few years now. Adderall was too harsh on me givin that I have GAD (Generalized Anxiety Disorder) and PAD (Panic Attacks w/ Agorophobia); comorbid with ADD (Adult). Dexedrine is and has been a life saver for me along with the xanax and klonipan. Given the fact that I was a very scared and fairly usleless human being scared of my shadow... now I am married and have finished school, and held down a job for a couple of years.
    In short until I found Dexedrine I didn't think I would ever be much of anything, now I know that to be false. I am still kinda all over the place, be that as it may... I found that this is the lesser of the evils that be since it makes me a more self-actualized human who is more or less productive and whatnot!
    Good post!
    PS: CRANK USERS (STOP) speed kills!

  • D. C. Sessions says:

    Another characteristic of the amphetamines is that they clear rapidly. From an ADHD standpoint, this is a Bad Thing: it makes for attention roller-coaster effects, including having to schedule the day around dosage schedules.
    Of course, from a "marketing" standpoint this is a very Good Thing since having "customers" yo-yoing makes for high demand.

  • Scicurious says:

    Larry: "They tend to be amoral and desperate characters and in general can't be trusted." I would be careful about making this generalization. After all, most of the amph users I know are overachieving students trying to study for their LSATs. And amoral is not a judgment I would want to make about addicts. Addiction is a disease, and once it has its hold, it's not a matter of "moral" or "amoral" anymore. You wouldn't want to cast judgment on someone who has lung cancer from smoking. Sure, they smoked, but does anyone deserve lung cancer? I would say that no one deserves addiction (or lung cancer, for that matter).
    CRhu: interestingly, you are still ON amphetamine. Dexadrine is just a different formulation, and you may also be on a lower dose (along with the Xanax) so you can avoid some of the anxiety-related side effects.

  • D. C. Sessions says:

    And amoral is not a judgment I would want to make about addicts.

    Not judging one way or another, but frankly I don't read it that way. "Morality" is a motivation, and when a higher-priority motivation is in charge it's hardly surprising that "morality" might lose out.
    Calling people with a major addiction problem "amoral" is just another way of saying that the addiction has taken over their lives -- it's no different from observing the deterioration of their livers.

  • dora says:

    Why do amphetamines like Adderall seem to have a slowing, or dulling effect on people who have something like ADD, but a highly stimulating effect, closer in spirit to coke, when used by poeple who don't have ADD?

  • Scicurious says:

    dora: good question. Short answer: we don't really know.
    Long answer: There are some theories out there that the effects of therapeutic doses of ADHD drugs are due to the primary effects occurring on norepinephrine in the prefrontal cortex. Unfortunately, that data is in methylphenidate rather than amphetamine. But it appears that effects of ADHD drugs on those with ADHD are localized to the prefrontal cortex, and that those effects primarily improve focus. It actually doesn't matter whether you have ADHD or not, the drugs will improve your focus. As for the slowing effect, people aren't really sure, but we think right now that children (and possibly adults) who have ADHD have changes in their dopamine and norepinephrine systems that may contribute to the effect.
    DC: I realize that "morality" in the sense of motivation does lose out in those who are addicted. The problem is that most people don't see the words "moral" or "amoral" in a motivation light. They see them as judgments as to whether or not someone is a good person. Thus, to call abusers and addicts "amoral" would imply to many people that they are bad people because of their drug problems, or that they became drug abusers because they are bad people, and this is simply not the case. I do agree with you that the direct definition of "moral" or "amoral" is different, but most people don't think of it the same way you do.

  • Tom Michael says:

    Curiously, pseudoephedrine really helps me to feel better when I'm feeling depressed. If I can get my head together enough to write the psychology of depression post, I'll email it to you...

  • Austin says:

    Despite common usage, "amoral" is not the antonym for "moral", "immoral" is. "Amoral" should mean that something is outside the realm of moral judgement. However, I cannot agree that addiction is a disease per se, as the pathologization of consciousness by ignoring fundamental problems of mind seems invalid, from a philosophy of science perspective. That being said, medication can be the most efficacious therapeutic tool for many situations.

  • Pete the angry mushroom says:

    Fuchsia, goddamit. Not fuschia!

  • [...] mostly studied for the way dopamine signals within it change in response to drugs like cocaine or amphetamine. But dopamine in the ventral striatum is important for more than just drugs, it’s also [...]

  • Dina says:

    I am 44 I have been taking Adderall for almost 2 years I try cutting myself off, but my ADHD is too bad. Therapy does not help believe me.

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