How Come After Re-Dosing, Amphetamines Lose the Euphoric Effect?

Question by Ryan: How come after re-dosing, amphetamines lose the euphoric effect?
So lets say some one takes some adderal and feel really good, after a few hours the euphoria fades so you take more. But the second dose really does not stimulate the mind, causing euphoria, only the body.

Best answer:

Answer by Censure 455
The euphoria comes from the release of dopamine in the brain which binds to dopaminergic receptors causing the feeling of euphoria. However as more dopamine is released into the brain the dopaminergic receptors begin to be either binded already or gain resistance to the dopamine and the resulting pathway is not activated. This means that even if you take larger doses of dopamine (adderall) you won’t feel its effects as greatly because the brain requires time to decrease the tolerance levels of the receptors for the effects to be felt.

Answer by Mathieu
Amphetamines like those in Adderall will increase the amount of serotonin, norepinephrine, and dopamine. With the significant increase of these neurotransmitters stimulation and euphoria result. Most of the euphoria comes from the dopamine often called the “master molecule of addiction.” Dopamine provides reinforcement for a positive experiences and is released at up to 12 times normal levels with amphetamines.

To be simplistic, after the dopamine and other neurotransmitters are increased the body acts to reinstate a balance. Even when medications are correcting a problem the brain perceives the extra neurotransmitter as too much and the natural production of the neurotransmitters will be reduced. The receptors which are activated by the neurotransmitters will become less sensitive (receptor down regulation). As a result, more of a drug (this applies nearly all abused substances) will be required to achieve a “high.” This is known as tolerance. If people abuse stimulants like amphetamines and cocaine daily on a long term basis they can begin to become profoundly depressed and even anhedonic (the inability to experience pleasure). Once this occurs it can be impossible to obtain any euphoria. And even before this level of damage, tolerance can increase so that the drug is required for normal functioning due to the brains changes.

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