Stimulants.. how exactly do they work?

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Some of the most commonly prescribed medications in the world are stimulants. Understanding how they exert their effects beyond “well they increase the availability of dopamine” is the goal of this post today.

Stimulant medications like methylphenidate (e.g., Ritalin, Concerta) and amphetamines (e.g., Adderall, Vyvanse) are the most commonly prescribed treatments for ADHD. They primarily target two key neurotransmitters in our brain: dopamine and norepinephrine.

1. Dopamine and Norepinephrine Transporter Blockade:

The primary way stimulants work is by inhibiting the dopamine transporter (DAT) and the norepinephrine transporter (NET), proteins responsible for removing these neurotransmitters from the synaptic cleft (the tiny gap between neurons where chemical signals are exchanged).

• Dopamine Transporter (DAT): When DAT is blocked, the reuptake of dopamine is reduced, effectively increasing the amount of dopamine available in the synaptic cleft. This allows dopamine to act longer and stronger on postsynaptic dopamine receptors, leading to enhanced focus, attention, and impulse control.

• Norepinephrine Transporter (NET): Much like DAT, NET's job is to mop up norepinephrine from the synaptic cleft. When NET is inhibited, there's more norepinephrine available to stimulate postsynaptic neurons, which contributes to increased alertness and energy.

2. Dopamine Release:

But amphetamines take things a step further. Apart from blocking DAT, they also induce the release of more dopamine into the synaptic cleft. This is done by a fascinating reversal of the DAT, causing it to eject dopamine out of the neuron and into the synaptic cleft.

3. Action on Dopamine Receptors:

Increased dopamine in the synaptic cleft indirectly stimulates its receptors, which come in several types. The therapeutic action of stimulants primarily involves the D1 and D2 receptors:

• D1 receptors: Stimulation of these receptors in certain brain areas has been linked to cognitive enhancement and improved attention.

• D2 receptors: These receptors are part of the reward pathways in the brain, which are tied to the reinforcing effects of stimulants. But they're also involved in other brain functions such as motor control.

In essence, by increasing the levels and enhancing the activity of dopamine and norepinephrine, stimulant medications mitigate the core symptoms of ADHD: inattention, hyperactivity, and impulsivity.

Understanding the science behind ADHD and its treatment can help us appreciate the importance of these medications and the relief they provide for those dealing with the disorder. It truly is an intricate and fascinating dance of neurochemicals that brings about transformative changes in cognition and behavior.

However… the effects of stimulant medications aren't limited to alleviating the symptoms of ADHD. They are also associated with a variety of side effects. These side effects can vary from mild to severe, depending on the individual and the dose of the medication. Some of these side effects include: