Drs. Brady and Sinha Reply

To the Editor:

We thank Dr. Kudler and Drs. Monterrubio and Solowij for their insightful comments about the connection between α7-nAChRs and impaired stress regulation in individuals with schizophrenia. The hypothesized role of the endogenous cannabinoid system in the link between schizophrenia, nicotine dependence, and stress is intriguing and, as the authors point out, provides new and exciting avenues for therapeutic development.

On a related topic, the data presented by the authors have interesting implications for the role of marijuana use in schizophrenia, which we did not address in detail in our review. Although it is not as common as nicotine dependence, marijuana abuse is more common in schizophrenic individuals than might be expected by chance alone (1). In particular, the role of marijuana in adolescents and young adults and the onset of schizophrenia is an interesting area that has not been well explored. This may be of particular relevance in adolescents with a genetic vulnerability to the development of schizophrenia. Following up on the hypothesis of Drs. Monterrubio and Solowij concerning the mediation of nicotinic receptor effects in schizophrenia by endogenous cannabinoids and the role of endogenous cannabinoids in stress reactivity, cannabis abuse and withdrawal may increase susceptibility to the development of the sensory gating deficits seen in schizophrenia through disruption of the endogenous cannabinoid system. The interesting and provocative work of Drs. Monterrubio and Solowij suggests new directions in investigating the etiology and treatment of schizophrenia.