Table 1.

Aspects and effects of alcohol and psychostimulants interactions.

Drug of Abuse	Aspect of interaction	Effects of interactions
METH	METH metabolism	Alcohol decreased p-hydroxylated metabolites of METH in the urine of METH abusers [33].
		Alcohol increased the levels of METH and its active metabolite, amphetamine, in rats and rabbits [34,35].
	Performance and sleep	Lower detrimental effects on performance and sleep compared to each drug alone [36].
	Euphoria	Increased euphoria in alcohol and methamphetamine co-abuse [36].
	Cardiac effects	Increased myocardial oxygen consumption and cardiac rate [37].
	Prenatal exposure	Damage to striatal region of the brain [41].
	Oxidative stress	Combination caused more impairment of antioxidant enzymes in rats hippocampus and oxidative stress than either drug alone [39].
Cocaine	Cocaine metabolism	Alcohol decreased metabolism of cocaine [68]. Alcohol decreased benzoylecgonine renal excretion, and increased in cocaine and cocaethylene blood concentrations [69].
	Cardiovascular and endocrine systems	Exposure to cocaine and alcohol increased heart rate, systolic blood pressure, cortisol, and prolactin levels [64,69].
	Cerebral blood perfusion	Cerebral hypo-perfusion occurred more in individuals taking cocaine and alcohol than in individuals taking cocaine or alcohol alone [72,73]
	Neurobehavioral performances	Negatively affected by concurrent intake of cocaine and alcohol compared to either drug alone [74,75].
	Mesocorticolimbic dopamine system	Increased extracellular dopamine concentration than either drug alone in nucleus accumbens in rats [90]
		Sense of pleasure and euphoria were found to be improved [71].
Nicotine	Drug reinforcement	Rats have established self-administration and place preference to combination of alcohol and cocaine in concentrations that did not provoke reinforcement to either drug alone [56,78]. Cocaine potentiated alcohol seeking [59,79]
	Mesocorticolimbic dopamine system	Increased in dopaminergic neuron firings and dopamine release in an additive mechanism [111–116].
	Pleasure and drug seeking	Increased in the pleasurable effects of each drug [119]. Rats self-administered nicotine more than rats received chronic exposure to either drug alone [108].
	Cardiovascular system	Additive effect on heart rate and blood pressure was found in healthy human volunteers [130,131]. Synergistic increase in left ventricular pressure in dogs [132].
	Cancer	Increase in the risk of developing esophageal cancer [120–123].
	Prenatal exposure	Showed a multiplicative effect in increasing the risk of head and neck cancer in human [124].
		Increased the risk of fetal growth restrictions in human [133–135]. Offspring developed rapid nicotine self-administration and at a higher level in rats [136].
MDMA	Cardiovascular system	Exacerbated cardiac cellular stress and toxicity through augmented activation of cardiac sympathetic system in adolescent mice [139].
	Blood level	MDMA plasma concentration increased following alcohol intake [149].
	Drug reinforcement	MDMA and alcohol induce a longer duration of euphoria [149].
		Exposure to alcohol during adolescent age in mice increased the reinforcing effects of MDMA [156].
	Sedation	MDMA reversed the sedative effect induced by alcohol consumption [149].
	Learning and memory	Administration of alcohol and MDMA exhibited learning and memory impairments [159]
	Dopamine reward effect	MDMA impaired dopaminergic reward pathway, leading to increase alcohol consumption [154].
	Psychopathological effect	Long term consumption of MDMA and alcohol can lead to serotonin depletion and cause psychopathological changes [155].
	Prenatal exposure	Impaired working memory, exploratory activity, and neurogenesis in rats offspring [163].