2-Minute Neuroscience: Amphetamine

Amphetamine is a stimulant drug that is used primarily in the treatment of ADHD. In this video, I discuss some of the proposed mechanisms by which amphetamine acts on the brain to produce its stimulant effects.

TRANSCRIPT:

Welcome to 2 minute neuroscience, where I explain neuroscience topics in 2 minutes or less. In this installment I will discuss amphetamine.

Amphetamine is a stimulant drug used mainly in the treatment of ADHD. Several popular drugs, like Adderall, primarily contain amphetamine.

Although we don’t have a full understanding of the effects of amphetamine on the brain, there are some aspects of its pharmacology that are well established. Amphetamine binds to the transporter proteins for monoamines like dopamine, norepinephrine, and serotonin and then can be taken up into neurons via these transporter proteins. Once inside the neuron, amphetamine disrupts the storage of monoamines in synaptic vesicles. One way it does this is by inhibiting
a protein called vesicular monoamine transporter 2, or VMAT2, whose normal role is to transport monoamines into vesicles. Inhibition of VMAT2 leads to higher levels of these neurotransmitters in the neuron.

Through a mechanism or mechanisms that are still not fully understood, amphetamine is then able to cause the monoamine transporter proteins to run in reverse, leading to the increased release of monoamines---especially dopamine and norepinephrine---and increased levels of these neurotransmitters in the synaptic cleft. These elevated monoamine levels can have various effects on different parts of the central nervous system. Increased dopamine levels in the reward system, for example, may contribute to the reinforcing effects of amphetamine use.

Although the primary action of amphetamine is to cause the increased release of monoamines, there are various other mechanisms that may contribute to the effects of the drug. For example, amphetamine also competes with monoamines for reuptake into the neuron, in effect inhibiting reuptake. And it may inhibit the activity of monoamine oxidase, an enzyme that metabolizes monoamines. The effect of both of these actions is to additionally increase levels of monoamines in the neuron and the synaptic cleft.

Reference:

David J Heal, Sharon L Smith, Jane Gosden, and David J Nutt. Amphetamine, past and present – a pharmacological and clinical perspective. J Psychopharmacol. 2013 Jun; 27(6): 479–496. doi: 10.1177/0269881113482532

Photo credit for image of Adderall: Benjamin Vincent Kasapoglu

[danib]

Trying to learn this with ADHD and no Adderall is like death.

[shady]

lmao my favorite thing about pharmacology: how does it work? well we don't really know it just does.

Good vid tho

[eliaskivenmaa]

Recovering addict, redirecting my intrest in drugs to chemistry and biochemistry. Just learned how penissiline works and inspired to come find out how actually does my true love work. And the answer is "we don't really know" damn you pharmacology.

[SilverWolfHowling]

Short and sweet, exactly what i needed to know. Thank you!

[hacker]

Amphetamine presumes the existence of sufficient monoamine molecules in vesicles and merely transports them into the synapse. So after taking 2 doses of adderall, your neurons have their monoamine stores depleted by the evening. This is what leads to extreme fatigue, tiredness, and poor concentration after the adderall wears off. When I used L-Tyrosine to ramp up dopamine production, I felt way better taking adderall. Probably should do the same for L-Tryptophan, as serotonin is also affected.

[khaoticgrumpy]

For me I sometimes realise I don't feel as much pain as much than without it. Another cool perk of being on it imo

[gabrielthagr]

💡You should do a video on how amphetamines and caffeine interact with each other because from my research I have found some very interesting info❕

[rastkokomnenic]

actually on it right now, gotta adore that last line before sleeping

[venom]

most of us here have ADHD and we here because we decided after taking it what are the negative effects or you re working on something for school that relates to the nervous system or neurophysiology so got curious

[bredenis]

Is there a significant difference between amphetamine and methamphetamine other than the half-life? Are there differences between them in terms of their affinity for the DAT transporter?

[juhua]

wtf this is such a good video. so concise.

[mattclay]

My doctor that lives beside me prescribed me somethin called methamphetamine I really like it.

[CharLotus-]

I find this video very confusing because it suggests that the neurotransmitters are actually entering the receiving cell after being released by the sending cell, rather than received by the receptor proteins.

[Real_Iron_Smith]

Thank you! I Used to take ADHD meds when I was young and always wondered how they worked. Admittedly very glad I stopped it before adulthood.

[joshm]

I used to love prescription amphetamines like Adderall and Vyvanse, but ultimately, I found that I couldn’t really enjoy life as much when their effects wore off. Now I just use caffeine to help myself concentrate and feel alert, because I’m able to feel just fine even after it wears off.

[narayan..]

Coming down, can’t sleep. It doesn’t make you happy or sad. Just felt vey content and focused. Wrote 3 new songs, read a book. Appetite is zero, have work tomorrow morning it’s 4AM here and I’m up like an owl. Slight chills running down the body but otherwise I feel good

[giuliocasalis]

I guess the mechanism that makes DAT, SERT and NET work in the opposite direction is the generation of a positive gradient inside the cell, due to the inhibition of VMAT2 mediated by amphetamine. Monoamines starts concentrating in the cytoplasm until the concentration inside the cell is higher then outside, at that point there should be enough potential to get the monoamines outside

[devin]

Wow... You know a lot. You work as a neurologist? Love your videos btw

[jaredwkirkwood]

Can Amphetamine deplete these storage bins? how is the natural dopamine restored? If you are taking medication for adhd every day surely this would end up depleting this dopamine storage? or does one sleep give the brain enough time to restore these little dopamine storage bins? This sound like a tremendous stress to put the body under emptying the storage and rushing to refill it every day? Compared to a non adhd brain which has a healthy amount of dopamine floating around and a healthy amount stored? Or does and adhd brain simply not release enough of this stored dopamine and infact the non adhd brain acts like the adhd brain on stimulants releasing more of its stored dopamine and then refilling it during sleep? I'm just trying to understand what the long term effects of stimulant use is.

[hardcorestymie]

Another fairly strong action is the excitation of NMDA and AMPA receptors and causing increased glutamate release and therefore increasing cell signalling.
Would also be a cool video to explain ADHD drug tolerance. I'm sure many people would be helped from awareness of potential downregulation and damage. Acute tolerance from synaptic receptor internalization that may accumulate tolerance from not upregulating receptors overnight between doses, excitotoxicity of NMDA receptors leading to cell damage and possible apoptosis and apoptosis from excess glutamate release. autoxidation of neurotransmitters outside the synapse, in the synapse, and especially with amphetamine in the cytosol causing oxidative stress. Amphetamine can cause damage to mitochondria, not sure about the others. Downregulation of tyrosine hydroxylase, especially from amphetamine. Believe there are many others. Also the relationship between tolerance and potential dependence (not addiction, that is another topic and rare with prescribed doses of ADHD meds).. If I was familiar with these things years ago, I would not be damaged and dependent now from it. Instead of the psychiatrists saying I'll get used to the dose when I started and it was too high. Or that I may need to just titrate up to a higher dose after a while. etc.Not trying to scare people. Many people are stable on low or moderate doses. But it is good to know.