Figure 21.

Proposed mechanisms underlying alcohol’s interaction with co-abused drugs. Alcohol (referred as alcohol in this article) is rapidly absorbed and distributed. It is metabolized to acetaldehyde by ADH and CYP enzymes, then to acetate by ALDH. In this process, alcohol competes with the co-administered drugs and suppresses their elimination, thus increasing the drug’s plasma concentration and altering its pharmacokinetics (increase in C_max and AUC, decrease in CL). Chronic alcohol exposure activates the liver CYP enzymes, resulting in a decrease in the drug’s plasma concentrations, with a decrease in its efficacy. Alcohol, in addition to altering pharmacokinetics of a drug, also alter its pharmacodynamics by activating GABA_ergic and OP_ergic presynaptic neurons (A₍₊₎, but inhibiting Glu_ergic presynaptic neurons (A_(-)). Post-synoptically, alcohol activates GABA_AR mediated influx of Cl⁻ ions, but inhibits AMPAR-mediated Na⁺ ions and NMDAR-mediated Ca²⁺ ions, resulting in reduced excitability via IPSP. Therefore, alcohol may augment the effects of inhibitory drugs (opioids, cannabis and GHB) but suppress the effects of excitatory drugs (cocaine, METH or nicotine). Chronic alcohol exposure may have opposite effects not shown in this figure. Abbreviations: A_(+): positive alcohol effects, A_(−): negative alcohol effects, VGSE: voltage-gated sodium ion (Na⁺) channels that may be attenuated by alcohol’s IPSP, VGCC: voltage-gated calcium ion (Ca²⁺) channels that may be attenuated by alcohol’s IPSP, GABA_AR mediated Cl⁻ channels that may be additively/synergistically activated by alcohol’s IPSP, inhibitory neurotransmitters, excitatory. neurotransmitters, action potential.