Peter Martin: Historical vocabulary of Addiction. Coffee


Peter R. Martin’s reply to Jose de Leon’s comment



        I thank Jose de Leon for his thoughtful comments. He raises some very interesting issues about the pharmacokinetic (smoking and caffeine consumption) and pharmacodynamic (alcohol and caffeine) interactions among these widely available psychoactive substances that tend to be used together. He examined these interactions in inpatient, outpatient and controls to better understand pathogenesis and clinical features of schizophrenia. 

        Caffeine biotransformation has been used for decades to probe cytochrome P450 activity in vivo and it is now well accepted that smoking induces the microsomal metabolism of many compounds including caffeine (Axelrod and Reichenthal 1953; Conney 1967; Parsons and Neims 1978).  Nevertheless, as summarized by Nehlig (2018) in her recent review on caffeine metabolism and coffee consumption: “it appears that consumption of coffee/caffeine would rather be driven by the functional consequences of caffeine than by the rate at which the methylxanthine is metabolized.”  Moreover, tolerance to the behavioral effects of caffeine/coffee is of relatively low magnitude and incomplete compared to other drugs of abuse (Fredholm, Bättig, Holmén et al. 1999). This suggests that the pharmacodynamic interactions between alcohol and caffeine that Jose de Leon describes in his comments are theoretically possible but in fact the opposite typically occurs in life - alcohol consumption, smoking  and coffee drinking have seemed to go hand in hand in the history of the western world, acquired developmentally in the individual and culturally in society (Reich, Dietrich and Martin  2011; Fischer, Victor, Robinson et al. 2019).

        One of the major issues I wanted to raise in my contribution is that coffee is not only caffeine, although these two words are often confused and used interchangeably in common parlance as they were by Jose de Leon.  The very widely consumed beverage coffee contains a myriad of biologically active molecules which account for many of its health benefits (Farah, de Paulis, Moreira et al. 2006; Freedman, Park, Abnet et al. 2012; van Dam, Hu and Willett  2020).   In fact, the interactions between coffee and alcohol consumption alluded to by Jose de Leon are even more compelling because coffee consumption seems to be protective against development of alcoholic cirrhosis, cancer, obesity and even suicide/depression that are major causes of morbidity and mortality in alcoholism.  Additionally, most of these and other health benefits associated with coffee consumption are related to non-caffeine components of coffee rather than caffeine.  Therefore, unravelling the mechanisms involved are challenging and distinct from the pharmacology of caffeine per se and have become an emerging area of ongoing research.



Axelrod J, Reichenthal J. The fate of caffeine in man and a method for its estimation in biological material. J Pharmacol Exp Ther 1953;107(4):519.

Conney AH. Pharmacological implications of microsomal enzyme induction. Pharmacol Rev 1967;19(3):317.

Farah A, de Paulis T, Moreira DP, Trugo LC, Martin PR. Chlorogenic acids and lactones in regular and water-decaffeinated Arabica coffees. J Agric Food Chem 2006;54(2):374–81.

Fischer EF, Victor B, Robinson D, Farah A, Martin PR. Coffee consumption and health impacts: a brief history of changing conceptions. Coffee: Consumption and Health Implications. The Royal Society of Chemistry; 2019. pp. 1–19.

Fredholm BB, Bättig K, Holmén J, Nehlig A, Zvartau EE. Actions of caffeine in the brain with special reference to factors that contribute to its widespread use. Pharmacol Rev 1999;51(1):83.

Freedman ND, Park Y, Abnet CC, Hollenbeck AR, Sinha R. Association of coffee drinking with total and cause-specific mortality. N Engl J Med 2012;366(20):1891–904.

Nehlig A. Interindividual differences in caffeine metabolism and factors driving caffeine consumption. Alexander SPH, editor. Pharmacol Rev 2018;70(2):384.

Parsons WD, Neims AH. Effect of smoking on caffeine clearance. Clinical Pharmacology & Therapeutics 1978;24(1):40–5.

Reich MS, Dietrich MS, Martin PR. Temporal sequence of incident cigarette, coffee, and alcohol use among AA participants. The American Journal of Drug and Alcohol Abuse 2011;37(1):27–36.

van Dam RM, Hu FB, Willett WC. Coffee, caffeine, and health. N Engl J Med 2020;383(4):369–78.


May 19, 2022