The Interaction of Alcohol and Cocaine: a Review

Psychobiology /992, 20 (3), /79-/84 The interaction of alcohol and cocaine: A review JACKIE DIAL Colorado State University, Fort Collins, Colorado Alcohol and cocaine are often ingested simultaneously, as recreational drugs. What is their combined effect on humans? Because cocaine is a stimulant and alcohol a depressant, one might expect that concurrent use of cocaine and alcohol would attenuate certain attributes of both; how ever, each drug achieves its effects through an assortment of mechanisms. The effects of these combined mechanisms are routinely discounted by the user and often by professionals as well. Recent information on the mechanisms and psychopharmacology of their interaction is reviewed. Alcohol is a central nervous system depressant that has tion typical of chronic alcoholism. Because cocaine is a long been a popular substance in society. In certain so stimulant and alcohol a depressant, one might expect that cial circles the use of cocaine, a central nervous system concurrent use of cocaine and alcohol would attenuate cer stimulant, has become more prevalent. How does their tain attributes of both; however, each drug achieves its combined ingestion affect the human body and mind? particular effects through assorted mechanisms and, in ad Among exogenous substances, shared mechanisms and dition, ethanol is known to potentiate the effects of many metabolic routes greatly increase the likelihood of addi drugs (Church, Dintcheff, & Gessner, 1988). Despite tive or synergistic effects (Jones, 1987). For obvious ethi their differences, both cocaine and ethanol are hepato cal reasons, research on the physiological effects of these toxins, and results thus far accumulated on their combined drugs has been confined primarily to animal models, and effects are included in this paper. Future research may pharmaceutical literature often is confined primarily to show even more explicitly how their combination impacts descriptions and forensics. Because of differences in drug systems in ways of which neither is capable when acting metabolism among and within species, and even between alone. sexes, generalizing must be limited. Nevertheless, within this constraint and with the human data available, knowl ALCOHOL EFFECTS edge has accrued. This paper reviews existing literature pertaining to effects of the interaction of alcohol and Ethanol, or ethyl alcohol, is a social drug of the cocaine. sedative-hypnotic class (Lee & Becker, 1989). Although it affects a multiplicity of systems, alcohol displays its MECHANISMS OF DRUG INTERACTIONS most remarkable activity within the central nervous sys tem, particularly cell membranes and brain enzymes. Al Drug interactions are considered to occur through one cohol may also affect receptor and transport molecules of three mechanisms: pharmacokinetic, the movement of and sodium-dependent calcium uptake. Hardly a neuro drugs within a system; pharmacodynamic, the system's transmitter is not implicated. Its effects on cells and tis responses to exogenous substances; or synergic (Hansten, sues, especially in the central nervous system, can vary 1989). The use of more than one drug that has an adverse as a function of dose and site, low doses initially impair effect on a structure can damage that structure, even if ing inhibitory pathways and progressively affecting higher the amount of each drug administered falls short of the centers with increased concentrations (Seixas, 1975). toxic range. Particular drugs can enhance the toxic ef Ethanol is metabolized in the body to acetaldehyde by fects of other drugs, even in the absence of inherent tox means of one of two pathways, determined in part by al icity of the enhancing drug. cohol concentration (Correia & Castagnoli, 1989; Lee & Certain attributes of drugs affect the probability of their Becker, 1989). It is thought that at low alcohol concen interacting with other drugs (Hansten, 1989). Attributes trations the main oxidizing system is alcohol dehydroge increasing the likelihood of drug interaction with alcohol nase, whereas at higher concentrations of alcohol the include the inhibited drug metabolism that occurs with mixed-function oxidase system (also called the microsomal acute alcohol intoxication (regardless of intoxication fre ethanol oxidizing system, or MEOS) becomes predomi quency) and the enzyme induction and hepatic dysfunc- nant. In this event, increases in smooth endoplasmic retic ula are of long duration. Induction of enzymes can be a mixed blessing. By accelerating metabolism, enzyme in Correspondence should be addressed to J. Dial, Department of Anat omy and Neurobiology, Colorado State University, Fort Collins, duction decreases the pharmacologic effect of the induc CO 80521 (e-mail: [email protected]). ing agent and also of coadministered drugs. However, 179 Copyright 1992 Psychonomic Society, Inc. 180 DIAL metabolism of drugs into reactive intermediates can ag been self-administered to every vertebrate species tested gravate their toxicity. As will be discussed below, this (Johanson, 1988). It is a reinforcing substance regardless may bear upon alcohol's recognized propensity to inter of the route of administration, be it intravenous, gastric, act with other drugs metabolized by MEOS. intramuscular, oral, or inhaled. It is at once anorectic and The central nervous system appears to contain no spe psychostimulant, local anesthetic and convulsant (Bates, cific receptor sites for alcohol (Seixas, 1975); alcohol, 1988; Koob & Hubnet, 1988). It produces profound sym as well as barbituates and sedatives, has a general action pathetic stimulation, both centrally and peripherally involving cell membranes, or neurotransmitter metabo (DiGregorio, 1990). The central stimulation appears lism, or both. Ethanol molecules dissolve in the lipid responsible for behavioral sensitization and kindling bilayer of cells, affecting receptors and ion channels in (Koob & Hubnet, 1988; Post & Weiss, 1988). Centrally, a process known as fluidization (Lee & Becker, 1989). cocaine affects monoamine metabolism, particularly that Although there appears to be a relationship between lipid of dopamine. Cocaine appears to assist in the transmis solubility and membrane-disordering effects (yY allace, sion of catecholamines by reducing their reuptake, and 1988), research in this area has been inconclusive. There possibly by facilitating their release (Hollister, 1973; Kat are correlations concerning alcohol and brain neurotrans zung, 1989; Porrino & Kornetsky, 1988). The euphoria mitters. Decreased serotonin is associated with alcohol reported by humans is thought to be mediated by activa craving in rats, and increasing the amount of brain seroto tion of these dopamine circuits in the brain (Dackis & nin decreases alcohol consumption in animals and humans Gold, 1990). The intensity of its euphoria both reinforces (yYallace, 1988). Decreased levels of norepinephrine cor continuing use and depletes dopaminergic reserves, thus relate as well with alcohol craving in alcoholics abstinent inducing craving and intense psychologic dependence for lengthy periods of time, while dopamine transmission (Cregler & Mark, 1986; Dackis & Gold, 1990). How appears to be biphasically affected by alcohol adminis ever, because dopamine blockers do not always preclude tration. Some evidence indicates that transmitter dispari cocaine effects, its ability to reinforce probably involves ties may antecede abuse. Two of the esteemed effects of other neurochemical systems as well (Balstar, 1988). alcohol, decreased anxiety and increased composure, can Cocaine appears to decrease synthesis of 5-hydroxy be linked to alcohol's enhancement of gamma amino bu typtamine (Woolverton & Kleven, 1988) and to inhibit tyric acid transmission. acetylcholine (Dackis & Gold, 1990). Membrane-bound receptors with a high specific affinity for cocaine have Alcohol's Interactions with Other Drugs not thus far been identified, although cocaine receptors In its interactions, alcohol achieves its effects through appear to be associated with the dopamine transport sys changes involving absorption, metabolism, synergy with tem (Jones, 1986; Kuhar, Ritz, & Sharkey, 1988; Madras the coadministered drug, self-contained congeners, and et al., 1990). secondary consequences of alcohol metabolism (Seixas, Cocaine is a lipid-soluble, low-molecular-weight alka 1975). The absorption of alcohol is delayed by epine loid (benzoylmethylecgonine, C17H21N04) capable of phrine, amphetamines, antimuscurinic drugs such as atro penetrating both the blood-brain and placental barriers pine, and similar drugs. Because of its solvent effect, on (Church et aI., 1988; Cregler & Mark, 1986). In the hu the other hand, alcohol can accelerate the absorption of man body, cocaine is metabolized either by hydrolytic less soluble agents such as nitroglycerine and toxic heavy splitting of ester bonds or by the oxidation-reduction pro metals. The primary hepatic metabolizer of alcohol, al cess described above (Correia & Castagnoli, 1989; Kloss, cohol dehydrogenase (ADH), also metabolizes other Rosen, & Rauckman, 1984; Smolen & Smolen, 1990; drugs, the by-products of which are sometimes toxic. Al Stewart, Inaba, Tang, & Kalow, 1977). In the former, cohol's most notable synergy occurs with sedatives and normally the major pathway, plasma and liver cholinester anesthetics. This is probably associated with alcohol's in ases rapidly reduce cocaine to inactive, water-soluble duction of the MEOS

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