Can Bupropion contribute to Caffeine Cessation?

Recently a reader of Psychiatry On-Line contacted me to share that he had read a case report in this very electronic journal describing a possible bupropion-alcohol interaction (1). He went on to describe that while taking bupropion he quickly lost interest in drinking coffee noting an almost repulsive taste similar to what my patients described about the taste of alcohol while taking bupropion. Was it due to nausea, which is a possible side effect associated with bupropion or due to an alteration in neurochemistry?

            Caffeine, not a drug of abuse, but certainly a substance which can cause a physical dependence is consumed by at least 80% of adults in the United States on a daily basis (2). The mechanism by which caffeine seems to exert its effects is by a number of methods including increasing norepinephrine secretion, inhibiting breakdown of cyclic 3,5 adenosine monophosphate in high concentrations, sensitizing central catecholamine postsynaptic receptors, enhancing guanosine 3,5, monophosphate, modulating acetylcholine and serotonin activity and antagonizing central nervous system adenosine receptors (2). This last mechanism appears to be the key mechanism. The adenosinergic pathways form a diffuse system, which is considered depressant within the CNS (2). Caffeine is an adenosine antagonist and can produce increased dopaminergic transmission within the brain (3). Due to the increased dopaminergic activity due to its competitive action with adenosine caffeine could possibly produce behavioral effects similar to other dopaminergic mediated stimulants (4). Bupropion, which is commonly utilized as a pharmacologic agent in tobacco cessation, is felt to exert its effects through dopaminergic release from the nucleus accumbens traveling along the mesolimbic pathway to the prefrontal cortex (5). This is the pathway proposed to be the reward pathway of other substances including nicotine, cocaine, amphetamines, marijuana and alcohol (6). Could caffeine be added to that list? Further studies will be needed to say definitively but it certainly looks promising.




1.      Berigan TR, Harazin JS. Bupropion Related Alcohol Cessation. Psychiatry On-Line

2.      Greden JF, Walters A. Caffeine. In: Substance Abuse A Comprehensive Textbook 3rd Edition. Edited by Lowinson JH, Ruiz P, Millman RB, Langrod JG. Baltimore, Williams and Wilkins, 1997 PP 297-8

3.      Ferre S. Adenosine-dopamine interactions in the ventral striatum. Implications for the treatment of schizophrenia. Psychopharmacology (Berl) 1997 Sep; 133(2):107-20

4.      Garrett BE, Griffiths RR. The role of dopamine in the behavioral effects of caffeine in animals and humans. Pharmacol Biochem Behav 1997 Jul;57(3):533-41

5.      Valenzuela CF, Harris RA. Alcohol: Neurobiology. In: Substance Abuse A Comprehensive Textbook 3rd Edition. Edited by Lowinson JH, Ruiz P, Millman RB, Langrod JG. Baltimore, Williams and Wilkins, 1997 pg. 130

6.      Lesher AI. Understanding Drug Addiction: Implications for Treatment. Hospital Practice 1996 Oct:47-59