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.