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.
(This entry brought to you by Peeps. Also by Cadbury creme eggs. Post-Ester candy may have dangerous side effects, such as excessive energy, liver failure, and death. Please use Easter candy wisely, and only under then influence of an adult.)
And speaking of things that give you excessive energy...
Amphetamine: speed, crank, Adderall, Dexedrine, or Vyvanse.
(From erowid, where all the good pics of drugs are to be found. Also a good source of information, though it's less than reliable. But hey, it's the internet.)
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.
(Adderall, again courtesy of erowid)
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.
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.
EDIT: Leigh sent Sci an awesome diagram of amphetamine action! I submit it for your perusal.
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.