In light of the widespread use of ayahuasca in a context of a changing world, there are important clinical considerations in terms of the potential adverse effects of ayahuasca use in combination with antidepressants, hypnotics and sedatives, and/or alcohol. It has been cautioned that the use of ayahuasca in conjunction with SSRI type antidepressants may result in “serotonin syndrome”due to the mechanistic action of both DMT as a 5-HT agonists and the inhibition of metabolic breakdown of serotonin transporters by MAOI [15, 39]. Further, it has been noted that the potential adverse effects from active metabolites may persist up to 5 weeks after discontinued use of SSRIs [39]; therefore, individuals employing the use of ayahuasca as a complementary approach to conventional psychotherapy and/or personal development should take the necessary precautions. In addition, in order to maximize harm reduction it is important for ayahuasca users to consider other potentially adverse interactions with the combination of ayahuasca and other drugs such as alcohol and certain foods. This said, there is perhaps wisdom in traditional dietary proscriptions employed by cultural practitioners (i.e., vegetalistas) who have long been aware of the potential adverse effects of the combination of ayahuasca and these substances – an area also in need of further investigation.