Peter R. Martin: Historical Vocabulary of Addiction.



Jose de Leon’s comment


        I found the history of coffee use very helpful and I learned a lot from it. The section on the interactions of caffeine use with tobacco and alcohol use may be strengthened by focusing on the pharmacokinetic and pharmacodynamic mechanisms as they appear to be important, according to our caffeine studies in schizophrenia. 

        The polycyclic aromatic hydrocarbon (PAH) compounds from tobacco smoke induce caffeine metabolism by increasing the expression of cytochrome P450 1A2 (CYP1A2).  This induction is probably mediated by the aryl hydrocarbon receptor (AhR) (de Leon 2015). Heavy smokers need two to three times higher caffeine intake to get the same serum caffeine concentrations as non-smokers (de Leon, Diaz, Rogers et al., 2003).  The inductive effects of smoking can confound the association studies; we first thought that caffeine use may be greater in outpatients with schizophrenia (Gurpegui, Aguilar, Martínez-Ortega et al. 2004; Gurpegui, Aguilar, Martínez-Ortega et al. 2006). However, in further studies including inpatients (Arrojo-Romero, Armas Barbazán, López-Moriñigo et al. 2015), we found that schizophrenia does not appear to be consistently associated with increased prevalence of caffeine use and the increased prevalence of high caffeine intake in caffeine users does not stand up when controlling for confounders. Future epidemiological studies, preferably using serum concentrations, will need to establish whether caffeinism (defined as >700 mg/day of caffeine) is particularly prevalent in schizophrenia or not and determine the contribution of inducers in caffeinism (Arrojo-Romero, Armas Barbazán, López-Moriñigo et al. 2015).

        Our schizophrenia outpatients had access to alcohol and demonstrated that alcohol and caffeine use were significantly associated. In caffeine users, alcohol was associated with less frequent high caffeine consumption among non-smokers, probably because alcohol may potentiate caffeine brain pharmacodynamic effects (Gurpegui, Aguilar, Martínez-Ortega et al., 2006). Chronic alcohol intake decreases adenosine tone (Ferré and O'Brien 2011), suggesting that alcohol users may have decreased need for higher caffeine intake since lower caffeine intake may have the same effects in the brain for a chronic alcohol user as high caffeine intake has for a non-alcohol user. As our inpatients had no access to alcohol (Arrojo-Romero, Armas Barbazán, López-Moriñigo et al. 2015), we could not replicate the possibility of this pharmacodynamic interaction between alcohol and caffeine in non-smokers (Gurpegui, Aguilar, Martínez-Ortega et al., 2006).



Arrojo-Romero M, Armas Barbazán C, López-Moriñigo JD, Ramos-Ríos R, Gurpegui M, Martínez-Ortega JM, Jurado D, Diaz FJ, de Leon J. Caffeine consumption in a long-term psychiatric hospital: Tobacco smoking may explain in large part the apparent association between schizophrenia and caffeine use. Schizophrenia Research 2015;164:234-41.

de Leon J. The effects of antiepileptic inducers in neuropsychopharmacology, a neglected issue. Part II: Pharmacological issues and further understanding. Revista de Psiquiatría y Salud Mental 2015;8:167-88. 

de Leon J, Diaz FJ, Rogers T, Browne D, Dinsmore L, Ghosheh OH, Dwoskin LP, Crooks PA. A pilot study of plasma caffeine concentrations in a US sample of smoker and nonsmoker volunteers. Progress in Neuropsychopharmacology & Biological Psychiatry 2003;27:165-71. 

Ferré S, O'Brien MC. Alcohol and caffeine: the perfect storm. J. Caffeine Research 2011;1:153-62. 

Gurpegui M, Aguilar MC, Martínez-Ortega JM, Diaz FJ, de Leon J. Caffeine intake in outpatients with schizophrenia. Schizophrenia Bulletin 2004;30:935-45.  

Gurpegui M, Aguilar MC, Martínez-Ortega JM, Jurado D, Diaz FJ, Quintana HM, de Leon J. Fewer but heavier caffeine consumers in schizophrenia: a case-control study. Schizophrenia Research 2006;86:276-83. 


January 13, 2022