The study of the neuropsychological deficits associated with substance abuse has become highly relevant in recent years due to the serious impact they have on the physical and mental health of users. The possible memory deficits and deterioration of executive functions were studied in a sample of 54 subjects undergoing drug detoxification and rehabilitation. Several neuropsychological tests were applied (Wechsler Memory Scale, Wisconsin Card Sorting Test, Stroop Test, Verbal Fluency Test and the Trail-Making Test). Subjects with a more prolonged history of alcohol and/or cannabis use had a greater deficit in working memory. Subjects with prolonged cannabis use also showed greater deficiencies in immediate, or short-term, memory and better conserved long-term memory, as well as less interference capacity, i.e., less inhibition of automatic responses. They also had impaired alternating attention and needed more time to execute activities that required logical and sequential thought. The study also reflected the importance of duration of use as a significant variable in the increase in memory deficits. The duration and type of substance abuse are determinants in drug-induced cerebral deterioration.