Medication and drugs - the difference
Dopaminergic drugs (THC, cocaine, amphetamine drugs, alcohol, nicotine) work by a very fast rising, very high and very fast falling dopamine level in the striatum.1 The rapid high rise of dopamine triggers the intoxicating effect. With prolonged drug use (even regular smoking of tobacco or alcohol consumption), the prolonged excessive dopamine level leads to downregulation of dopamine receptors and upregulation of dopamine transporters. When the dopamine-increasing drug is discontinued, the then normalized dopamine level does not have sufficient effect to maintain dopaminergically regulated brain functions due to the insufficient number of receptors and excessive number of transporters. The result is withdrawal symptoms that end within a few days or weeks after the dopamine receptors and transporters have regenerated.
Dopaminergic ADHD drugs, on the other hand, do not act as intoxicants because they cause dopamine levels to rise very slowly, remain constant for a long time, and fall slowly. Medications merely compensate for the existing dopamine deficit; they do not result in a dopamine surplus. Since there is no dopamine excess, neither a state of intoxication nor a dysregulation of the dopamine receptors or transporters can occur.
Oral ingestion of methylphenidate produces a slow increase in dopamine levels that does not result in intoxication. In contrast, intravenous application of MPH causes a more rapid increase in dopamine levels, which is associated with intoxication.2
Whereas drugs can cause a state of intoxication due to the rapid rise to a far excessive dopamine level and the subsequent rapid fall, this possibility is precisely not given with medicinal intake of stimulants (methylphenidate and amphetamine drugs) due to the oral (slow-acting) intake.
Bossong, van Berckel, Boellaard, Zuurman, Schuit, Windhorst, van Gerven, Ramsey, Lammertsma, Kahn (2009): Delta 9-tetrahydrocannabinol induces dopamine release in the human striatum.; Neuropsychopharmacology. 2009 Feb;34(3):759-66. doi: 10.1038/npp.2008.138. mwNw; 47 ↥
Tomasi D, Manza P, Logan J, Shokri-Kojori E, Yonga MV, Kroll D, Feldman D, McPherson K, Biesecker C, Dennis E, Johnson A, Yuan K, Wang WT, Butman JA, Wang GJ, Volkow ND (2023): Time-varying SUVr reflects the dynamics of dopamine increases during methylphenidate challenges in humans. Commun Biol. 2023 Feb 10;6(1):166. doi: 10.1038/s42003-023-04545-3. PMID: 36765261; PMCID: PMC9918528. ↥