Possible Interaction: Ethanol and Methylphenidate

“ Ethanol elevates methylphenidate (1) plasma concentrations and yields the metabolite ethylphenidate (2).”

“Background/Purpose Ethanol coadministered with immediate-release dl-methylphenidate ( dl-MPH ) or dexmethylphenidate (d-MPH) significantly increases the geomean maximum plasma concentration (Cmax) of d-MPH 22% and 15%, respectively, and elevates overall drug exposure and psychostimulant effects.”

“Findings/Results Ethanol increased the second pulse of d-MPH Cmax for dl-MPH by 35% (P < 0.01) and the partial area under the plasma concentration curve from 4 to 8 hours by 25% (P < 0.05).”

“Implications/Conclusions These findings support drug dispositional interactions between ethanol and MPH as dominant over potential biopharmaceutical considerations.”

“Interestingly it is also produced as a metabolite from the co-ingestion of methylphenidate and alcohol (ethanol).”

“A pharmacokinetic interaction between the l-isomer of dl-MPH and ethanol has previously been shown to increase early exposure to d-MPH.”

“The dl-MPH– ethanol combination significantly (P < 0.05) increased these AUCs with the exception of like (P = 0.08).”

“This study explores the … that: (1) ethanol will interact with dl‐Methylphenidate (MPH) to enantioselectively elevate plasma d‐MPH, and primarily yield l‐ethylphenidate as a transesterification metabolite; (2) women will exhibit lower relative bioavailability of MPH than men; and (3) sex‐dependent differences in subjective effects will exist.”

“Chi‐squared tests revealed that when alcohol was used in combination with any of cannabis, psilocybin, MDMA, cocaine, amphetamine, methylphenidate (ps < 0.01) or LSD (p < 0.05) its initial use preceded the administration of the other substance.”

“Paired samples t‐tests revealed that when alcohol was used with cocaine (p < 0.01) or methylphenidate (p < 0.05) it was ingested in greater quantities than when used in their absence.”

“Nonetheless, given the high likelihood that methylphenidate and ethanol coingestion frequently occurs, the detection of ethylphenidate in humans warrants further investigation into the extent of its formation as well as into any associated toxicity in nonoverdose situations.”

“ MPD also counteracted the effect of ethanol on the amplitude of P2 and N3.”

“Rearings were eliminated by ethanol in the open field but increased by MPD, and MPD counteracted the effect of ethanol on rearings.”

“Some of these results might help explain why users take MPD and ethanol in combination in order to enable consuming larger amounts of alcohol.”

“By understanding how the combination of methylphenidate and alcohol affects memory, we can better assess the risks of taking both substances simultaneously.”

“Recent epidemiological studies report the co‐abuse of MPH and ethanol in adolescents and young adults.”