This paper aims to explore and compare the metaphysical entailments of the conventional psychopharmacological approach in the treatment of depression to those of a psychedelic approach. We will examine the thesis by which knowledge of how drugs act upon us shapes our self-image and our understanding of psychopathology and defend that this process can only take place in a supportive environment. It is commonly claimed that the nature of depression was shaped after the therapeutic success of antidepressants; nevertheless, psychedelic drugs were at least as successful as antidepressants, and they didn’t end up having the same power to influence our views. It was possible for first and second-generation antidepressants to influence our views because of a supportive environment, where social, political, economic and even metaphysical issues were at play to create that result. We will compare the unfolding of the two paradigms elicited by these two kinds of drugs, one where pills are seen as magic bullets aimed to restore biochemical balance, and another where drugs are seen as therapeutic tools capable of inducing a life-changing experience, provided there is an adequate context. We will review different factors that contributed to the establishment of a reductionist paradigm, such as the aspirations of psychiatry and the assumed objectivity of biologically oriented explanations. Finally, we will reflect on the new paradigm that unfolds with contemporary research. Keywords: Monoamine hypothesis; Therapeutic tool; Experience; Context