Prescription amphetamines can be safe for some people to use as instructed by a medical professional, but using them outside of a doctor’s recommendation can lead to tolerance, dependence and abuse. Long-term abuse of amphetamines can damage the brain’s dopamine system. This can cause schizophrenia-like psychosis, characterized by paranoid delusions, erratic or violent behavior, and visual and auditory hallucinations. If the abuse goes on long enough, the damage can also include symptoms similar to Parkinson’s disease from the dopamine depletion.
Scientific findings have established that dextroamphetamine administration increases the activity of the phosphoinositol cycle via an indirect release of dopamine and noradrenaline. These results are the first time that this has been confirmed in humans. [ 43 ] Because dextroamphetamine is a substrate analog at monoamine transporters, at all doses, dextroamphetamine prevents the re-uptake of these neurotransmitters by competing with endogenous monoamines for uptake. [ 44 ] Transporter inhibition causes monoamines to remain in the synaptic cleft for a prolonged period (amphetamine inhibits monoamine reuptake in rats with a norepinephrine to dopamine ratio (NE:DA) of 1:1 and a norepinephrine to 5-hydroxytryptamine ratio (NE:5-HT) of about 100:1). [ 45 ]