Increasingly, children and adolescents are being treated for underlying psychopathology commonly associated with the psychoactive substance use disorders. Despite this apparent increase in using medication, little is known about the interaction of drugs of abuse with the psychotropic medications. The authors describe four cases of male adolescents aged 15 to 18 years being treated with a tricyclic antidepressant for attention-deficit hyperactivity disorder who manifested transient cognitive changes, delirium, and tachycardia after smoking marijuana.