Universal Set and Setting

During the 1960s and 70s Timothy Leary did more to spread psychedelic usage in America than almost any other person in the country.

For his liberal use of compounds like psilocybin and LSD, Leary became a pariah and eventually was dubbed “the most dangerous man in America”.[1]

Hyperbole aside, Leary was a controversial figure who altered the course of psychedelic research and proliferation.

One of his greatest contributions was popularizing and emphasizing the importance of “set and setting” in the use of psychedelic compounds.

This piece will breakdown the meaning of set and setting, the historical usage from cultures around the world, and how you can apply it to improve supplementation in your life.

What is Set and Setting?

The term set and setting refers to the context for taking psychoactive substances (and psychedelics in particular). It is broken up into two parts:

  • One’s mindset (set)
  • Physical and social environment (setting)

After years of experimentation with LSD, scientists started wondering whether negative reactions to the drug were related to sterile hospital environments and emotionally cold, scientific clinicians.

Far more soothing to participants was an empathetic therapist and a relatively comfortable room.

While Timothy Leary was still involved with Harvard University, he helped develop the term “set and setting” from the collective work of numerous psychedelic scientists.

One phrase from Leary’s work stands out:

…the drug dose does not produce the transcendent experience. It merely acts as a chemical key – it opens the mind, frees the nervous system of its ordinary patterns and structures. The nature of the experience depends almost entirely on set and setting.”[2]

This would explain countless anecdotal experiences (mine included) where the presence of a shaman or caretaker during psychedelic retreats greatly amplifies the experience.

Perhaps this is something our ancestors were doing rightly.

Ceremony and Psychoactive Substances

Humans develop distinct cultures across the globe, but universally alter brain chemistry through the use of plant or fungal substances [3].

The substances that have the most profound impact on human neurochemistry are often institutionalized in some form of ceremony.

In Mesoamerica (modern day Mexico and Guatemala), psilocybin mushrooms were called “teonanacatl” or “God’s flesh” by the Aztec cultures.

These psilocybin ceremonies looked much different then to the modern incarnation, but this mind-altering fungus was of paramount importance within the context of ceremony.

In the jungles of Peru, Ecuador, and Brazil, indigenous people also consumed ayahuasca in a ceremonial fashion.

People like the Yawanawa celebrated with specific rituals and rites that developed alongside the psychedelic brew as did peyote in the Huichol communities.

The ceremonial aspect of psychedelic usage often created a set and setting that proved valuable for the recipient [4].

The application is not for psychedelics compounds alone, however.

Substances like caffeine and theobromine were highly ritualized in some parts of the world. Matcha green tea is the center of the highly ritualized Japanese tea ceremony, for example.

The Maya considered cacao to be “food of the gods”. This bitter bean is the modern source of chocolate, but hundreds of years ago was used in cacao ceremonies for the elite.

Cacao has naturally occurring theobromine, which is a type of stimulant and vasodilator (opens blood vessels) often considered “heart opening”.

While largely created by modern culture, the growing popularity of ceremonial drinking cacao suggests that set and setting can still be used to influence how we interact with any substance.

Humans have lived in community and used psychoactive compounds ceremonially for thousands of years. The increased psychoactive effect that comes from set and setting is not exclusive to psychedelics alone.

How to Use Set and Setting

Ceremonies used by people across the globe provide historical context for how valuable set and setting can be in using mind altering substances of any kind.

Modern scientific inquiry provides even more examples. According to Dr. Andrew Weil:

…the combined effects of set and setting can actually reverse the pharmacological effect of drugs, that you can give a stimulant to a person in conditions of set and setting that cause the person to fall asleep. And you can give a sedative drug to somebody under conditions of set and setting that cause a person to become alert and stimulated.”[5].

The environment and our set of beliefs around a psychoactive compound matter as much or more than the drug itself.

This is clearly seen in the placebo effect. Often chastised as a confounding variable in academic journals, the placebo effect yields great opportunity for performance enhancement.

As a society (and certainly as individuals) we would be better served relinquishing the mindset that the placebo is in some way “bad” when it really suggests the power of the human mind and our healing, regenerative powers.

This doesn’t mean science should be discarded. There is use in controlling for the placebo effect and understanding statistically significant changes in physiology and neurochemistry.

The approach I advocate is to use both sparingly as they serve you. There are things we thought modern science could teach us 50 years ago that are no longer true.

This suggests there are “unknowns” today that we will only learn in the future.

If you find yourself wondering “does this nootropic work?” and you’re not sure, but you trust the source, perhaps it’s worthwhile to give the substance the benefit of the doubt.

You might find that having an affirming relationship with psychoactive substances makes them more beneficial.


  1. https://www.texasobserver.org/the-most-dangerous-man-in-america/
  2. The Psychedelic Experience by Timothy Leary, Ralph Metzner, and Richard Alpert. 1964.
  3. Every culture besides the Inuit alter brain chemistry with some form of mind-altering substance.
  4. Ceremonial human sacrifice of victims who consumed psilocybin aside. Though, there is no knowing whether the victims of human sacrifice in Aztec culture considered this a horror or an honor.
  5. https://tim.blog/2018/12/10/the-tim-ferriss-show-transcripts-dr-andrew-weil/