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Predicting Psychedelic Outcomes

The article Predicting Psychedelic Outcomes was originally published on Microdose.

One of the hardest parts about taking psychedelics is entering the…



This article was originally published by

The article Predicting Psychedelic Outcomes was originally published on Microdose.

One of the hardest parts about taking psychedelics is entering the unknown. As powerful “mind manifesting” compounds, the anxiety of new perspectives, old memories, and the potential of a difficult experience make not only patients but researchers and clinicians tread carefully.

Modern psychedelic study and treatment include screening processes for contraindicated mental or physical health conditions, but this only lowers risks and hardly guarantees outcomes. As “amplifiers” of experience, psychedelics interact with “set and setting” by making experiences of our inner and outer worlds more vivid, intense, and meaningful.

The therapeutic potential of this is perhaps obvious, but the variety of individual experiences, life stories, beliefs, biases, and expectations come together to comprise mindset. This internal program then interacts with the surrounding environment — people, the atmosphere, music, art, and a long list of other variables.

Cataloging and assigning value to all these interactions is tricky and unique across individuals. The task of understanding how they all interact is dauntingly large, yet, the payoffs would be significant — imagine psychedelic settings curated to the individual, the right therapist, music, and even substance.


Predicting Responses to Psychedelics

The idea of set and setting were first explored in the 60s by researchers Tim Leary and Ralph Metzner. They found that apprehension before taking a psychedelic was correlated with unpleasant experiences and less desire to repeat the experience. Despite set and setting being a longstanding guiding principle for psychonauts and clinicians alike, what exactly the terms mean isn’t well-defined.

In the recent renaissance, much study has been directed inside the brain, with hard, technical neuroscience. Yet a scientific exploration of human consciousness or ideas about the Default Mode Network doesn’t necessarily tell us how to navigate the psychedelic experience or what an individual’s response will be.

One paper, Predicting Reactions to Psychedelic Drugs, does summarize biological predictors like the binding potentials of 5-HT2A receptors leading to mystical experiences, the dynamics of networks in the brain predicting ego dissolution, and the thickness of the right anterior cingulate cortex predicting emotional experiences. Genetics has also been suggested to influence sensitivity to psychedelics.

Biological indicators are no doubt valuable insights, yet for the average practitioner understanding the intricacies of a client’s cortical thickness or genetics isn’t possible. Mental states and traits like absorption, openness, and acceptance have been highlighted in predicting mystical experiences of psychedelics which are tied to positive outcomes and are more accessible tools. Along with dosage and type of substance, it seems that set and setting remain the consistent elements a facilitator can work with.



Thematic Analysis of Psychedelic Predictors

Yet, despite set and setting being one the most well-established pillars of psychedelic use, specifics are poorly understood.

The concept has also been referred to as “extra-pharmacological factors” by Ido Hartogshon, and the list of potential “factors” is a long one. Nonetheless, Annie McCartney at The Royal Melbourne Institute of Technology, Hugh McGovern at The University of Queensland, and Alexander De Foe at Monash University have begun the steps to finding patterns in the interaction of people’s mindsets and their environments on psychedelics. By mapping these patterns with their paper Predictors of Psychedelic Experience: a Thematic Analysis, McGovern says a kind of taxonomy could inform clinical practice with psychedelics.

When asked about the complexity and range of states and environments a person can find themselves in before, after and during a psychedelic experience, McGovern acknowledges that “we just have to start somewhere.”, and acknowledges the wisdom derived from ancient cultures that have utilized their therapeutic potential for millennia. He emphasizes too, that when building a usable model for predicting psychedelic experience, “the overarching goal is to keep it as simple as possible, but also to be able to cater to as many individuals as possible.”

To start creating such a taxonomy, McCartney and McGovern analyzed real-life trip reports from to break set and setting into internal and external factors, with each category having emergent themes influencing the outcome of the experience.



External Factors of Psychedelics

The external factors chosen were nature, music, and preparation of one’s environment. As other studies and thousands of years of history have evidenced, both nature and music were helpful and catalyzing forces during the psychedelic experience.

Music and nature were shown to both amplify the psychedelic experience, thought of as having greater meaning or significance. A sense of connection with nature-inspired internal processes while music’s sonic and lyrical elements amplified the symbolism and meaning that participants perceived.

Both were able to shift the trajectory of a psychedelic experience. For example, nature allows one to focus externally, to momentarily leave internal processes, and to “ground.” Music also shifted experiences, with lyrics acting as “circuit breakers” for negative emotions, at times providing guidance.

Preparation of a physical environment also helped trippers exist in an atmosphere that felt safe. The right spot, dim lights, and blankets all contributed to the atmosphere, while safety might be logistical plans like transportation or the support of a loved one. Neglecting to organize and create a comfortable and familiar space to trip in led to more difficult experiences for some.


Internal Factors of Psychedelic Experience

Internal predictors or “mindset” were understanding, mindset, and motivation. Throughout the trip reports, patterns around the understanding of the effects of a drug — both physical and psychological — helped put certain experiences in context. Knowing, for example, that ketamine couldn’t affect parts of the brain controlling one’s ability to keep breathing helped one person navigate anxiety during their trip. Others who were more casual with use reported difficulties.

Mindset related to emotional states and beliefs influencing a psychedelic experience. Some found they could easily surrender to the intensity of an experience, as opposed to those who have anxiety were unable to do so and have more challenging experiences. Mindset was one’s general state of being during a trip but can be cultivated, which may be helpful for those displaying what the researchers deemed “resistance,” who had anxiety, fear, or hesitation, often leading to difficult situations.

Finally, the motivation behind why a substance was taken also affected psychedelic use, echoing the concept of “intentions.” The subjects with high degrees of curiosity and a desire to explore themselves had more positive experiences, while others exhibited what the study designers dubbed “escapism,” which predicted difficulties.



Creating a Roadmap for Psychedelic Journeys

With the flowchart one can at least see some possibilities for a psychedelic journey, but it might not be as black and white as it seems on paper. McGovern explains that the goal is not necessarily avoiding challenging experiences completely but about creating a container where difficult material can be explored with a skilled facilitator.

Elements like music and nature may be able to shift or even soften difficult aspects of a psychedelic therapy session. Instead, these can be comforting tools, like a kid bringing a stuffed toy to the dentist.

Ultimately, even with solid preparation, a person with anxiety seeking treatment from psychedelics cannot completely remove their anxiety before a psychedelic session. “There’s no point in curing someone and then giving them psychedelics,” Mcgovern points out. He says psychedelics “are a facilitator for amplifying the importance of the current experience, but that doesn’t really say much about whether it’s positive or negative.”

But he also believes that it’s possible to create what he calls a taxonomy of psychedelic effects. While it’s clear a lot more data is needed to be gathered from a wide range of people, substances, and environmental considerations. He explains that by creating variables with binary outcomes for different factors of the psychedelic experience a kind of “if this, then that” circuitry could be created, which he likens to how computer programming works.


Psychedelic Outcomes and Harm Reduction

To the experienced psychonaut, these variables might seem intuitive. Indeed, set and setting is something that many have learned by experience — from indigenous cultures, festival goers, or established psychedelic therapists. While this knowledge is readily available, it’s also clear from the clinical use of psychedelics the knowledge is not standardized, likely highly individual, and that recreational use shows how frequently ignored set and setting are.

What is also clear is that for psychedelics to gain wider acceptance, safety around navigating the experience and its outcomes is paramount. The current psychedelic landscape is full of researchers and startups looking for formulas that will scale, yet humans are still highly individual.

Exactly how psychedelics can integrate into the typical models of medicine and therapy is uncertain. In these early days, accumulating the data required is both a daunting but promising avenue, hopefully allowing safe and far more widespread access to psychedelic treatments.



Interested in more like this? Check out How Interdisciplinary Research Could Reveal Psychedelics’ Blind Spots

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