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Caffeine is a common active adulterant found in illicit drugs of abuse, including coca paste (CP). CP is a smokable form of cocaine mainly consumed in South America, produced during the cocaine-extraction process. CP has high abuse liability and its chronic consumption induces severe sleep–wake alterations. However, the effect of CP on the sleep–wake cycle and the effect of the presence of caffeine as an adulterant remain unknown. We studied the effect of an acute intraperitoneal injection of 2.5 and 5 mg/kg of a representative CP sample adulterated with caffeine (CP1) on the rat sleep–wake cycle. Compared with saline, administration of CP1 induced an increase in wakefulness and a decrease in light (light sleep) and slow wave sleep that was larger than the effects produced by equivalent doses of cocaine. Compared with CP1, combined treatment with cocaine (5 mg/kg) and caffeine (2.5 mg/kg), a surrogate of CP1, elicited similar effects. In contrast, a nonadulterated CP sample (CP2) produced an effect that was not different from cocaine. Our data indicate that caffeine produces a significant potentiation of the wakefulness-promoting effect of cocaine, suggesting that caffeine should be explored as a causal agent of clinical symptoms observed in CP users.