I have heard a layman’s description* of a model how ADHD/ADD medication works but I have never heard an explanation of the biochemistry. Did we just stumble onto it without knowing how it works (like lithium for bipolar disorder), or did we analyze the biochemical causes of ADHD and drugs were developed to address them?
*I am told that part of the person’s brain is racing ahead of everything else and taking a stimulant allows everything else to catch up so things get back in sync.
PET scans have shown methylphenidate makes a deficient prefrontal cortex behave more like a normal one…
Biochemically the stuff acts much like any other dopamine reuptake inhibitor (amphetamine, cocaine)
Know idea who first had the idea to give speed to such people. But the most common drugs have been around forever and certainly were not designed for the purpose.
I recall learning that adhd was caused by excessive production of the enzymes that return neurotransmitters back to the transmitter in synapses. This results part of a “message” being cleaned up before it’s been received. *
Amphetamines either increase the amount of chemicals released or slow the reuptake of them.
It’s not so much that the brain is racing too fast for some parts or that neurotransmitters are taken up too quickly, but that there seems to be a deficit in connectivity (either by fewer neurons, fewer pre-synaptic axon terminals, fewer post-synaptic dendrites, or some combo of any of those three, to name a few possibilities) between the areas of the brain responsible for controlling attention, goal-direction, perception/estimation of the passage of time, and the perception of changes in one’s internal and/or external environments which might require a change in behavior, and the parts of the brain they are controlling, in individuals with ADHD compared with controls.
Stimulant drugs, like Amphetamine and Methylphenidate, both block the synaptic reuptake of norepinephrine and dopamine at clinically relevant doses (serotonin plays more of a role as doses get higher, particularly in the doses individuals tend to use when abusing, but isn’t believed to be relevant at the doses we use to treat ADHD symptoms), as well as amphetamine derivatives also trigger the release of additional neurotransmitter by reversing a pump called VMAT (Vesicular Monoamine Transporter) which normally pulls neurotransmitter into vesicles inside the neuron and by hitting a G-protein coupled receptor called TAAR1 (Trace Amine Associated Receptor 1) which results in increased cytosolic neurotransmitter which can diffuse back out of the neuron. Since norepinephrine and dopamine are two of the principle neurotransmitters involved in attention, learning, and goal-directed behavior, in effect, the previously mentioned mechanisms results in stronger, longer lasting signalling to make up for the background deficit.
Why do some brains develop this functional connectivity deficit and others don’t? The literature seems to still be unsure, at least based on what I’ve read. If we still don’t know what the underlying cause of ADHD is, how did we determine that the stimulants were a good choice (gold standard, actually) to try? Probably, like with a large chunk of medications, we stumbled onto it at some point in the past.
The use of stimulants to treat ADHD probably originated with an anecdotal observation that caffeine seems to help. Once that was studied and confirmed, scientists would then have moved on to study other stimulants, and to look for the underlying mechanism.
My grandma tells me that my uncle, who has severe ADHD and bipolar disorder, discovered it for himself in high school when he started using cocaine and amphetamines, and all of a sudden he was actually behaving like a normal person. (That sure didn’t last.)