Several limitations of the original AACTS make it difficult to determine whether the study results show a direct interaction between smoking and alcohol use or common underlying genetic mechanisms. Participants in the study were allowed to smoke if they so wished, but their smoking during the experimental session was not documented. Consequently, we were unable to separate the effects of smoking histories from smoking during the challenge session. Furthermore, because the study used a quasi-random sampling scheme and because monozygotic twin pairs exhibit a high concordance for regular smoking, few smoking discordant pairs (i.e., where only one twin smoked) participated in the protocol. Researchers are currently addressing these issues more directly in ongoing challenge studies using separate and joint administration of nicotine and alcohol to adult nonsmokers and smokers.
