cocaine and tetrahydrocannabinol (THC)-containing drugs (marijuana/hashish) are the most frequently used recreational drugs. Both these molecules exert their main function in the central nervous system (CNS), due to their capability to trespass the blood-brain barrier [1] [2]. Once in the CNS, cocaine acts by inhibiting the re-uptake of serotonin, norepinephrine and dopamine, while tetrahydrocannabinol act as partial agonist of the cannabinoid receptor CB1 [1] [2]. Aside the action on CNS little is known about the effects of these recreational drugs on the immune system. [3] [4] We describe herein a case of a 31-year old man, non-drug addict, that abused for the first time of both cocaine and THC and was admitted in the Emergency room for acute confusional state and increase in heartbeat. We stabilized the patient’s clinical condition and analyzed the changes in the immune compartment.