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According to the 2018 book ''[[How to Change Your Mind]]'' by [[Michael Pollan]], the concept of set and setting was observed by the "Johnny Appleseed" of LSD, [[Alfred Matthew Hubbard|Al Hubbard]], visiting mushroom ceremonies in Mexico. The terms were used at least as early as 1958 by [[Ludwig von Bertalanffy]] and popularized by [[Timothy Leary]] in 1961, and became widely accepted by researchers in [[psychedelic therapy]].<ref name=":0" /><ref>{{Cite journal |date=1958 |title=Ataractic and Hallucinogenic Drugs in Psychiatry: Report of a Study Group |url=https://apps.who.int/iris/bitstream/handle/10665/40410/WHO_TRS_152.pdf |journal=World Health Organization Technical Report Series |number=152}}</ref> [[Norman Zinberg]] also extensively discussed this in ''Drug, Set, and Setting: The Basis for Controlled Intoxicant Use'' (1984).
Due to the importance of setting in early [[psychedelic therapy]], Hubbard introduced a "treatment space decorated to feel more like a home than a hospital", which came to be known as a "Hubbard Room".<ref>{{Cite book |title=How to Change Your Mind |first=Michael |last=Pollan |date=15 May 2018 |authorlink=Michael Pollan |isbn=9780525558941 |page=164 |publisher=Penguin |url=https://books.google.com/books?id=3vk5DwAAQBAJ&pg=PA164 |quote=But though this mode of therapy would become closely identified with Osmond and Hoffer, they themselves credited someone else for critical elements of its design, a man of considerable mystery with no formal training as a scientist or therapist: Al Hubbard. A treatment space decorated to feel more like a home than a hospital came to be known as a Hubbard Room, and at least one early psychedelic researcher told me that this whole therapeutic regime, which is now the norm, should by all rights be known as "the Hubbard method." Yet Al Hubbard, a.k.a. "Captain Trips" and "the Johnny Appleseed of LSD," is not the kind of intellectual forebear anyone doing serious psychedelic science today is eager to acknowledge, much less celebrate.}}</ref>
In 1966, Timothy Leary conducted a series of experiments with [[dimethyltryptamine]] (DMT) with controlled set and setting. The aim was to see whether DMT, which had then been mostly thought of as a terror-inducing drug, could produce pleasant experiences under a supportive set and setting. It was found that it could.<ref>{{Cite journal |last1= Leary |first1= T. |date= 1966 |url= http://deoxy.org/h_leary.htm |title= Programmed Communication During Experiences With DMT |journal= The Psychedelic Review |volume= 1 |issue= 8 |pages= 83–95 |url-status= dead |archiveurl= https://web.archive.org/web/20170107010902/http://deoxy.org/h_leary.htm |archivedate= 2017-01-07 }}</ref>
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