The Psychedelic Brain
Garnet > Blog article for Biohacker Center
July 1, 2023
Introduction
Is the Psychedelic Experience fundamentally created by a psychedelic compound, or is it a basic and innate capacity of the brain that can be triggered by a compound? Could other non-compound approaches trigger this same innate brain capacity?
More formally, two questions emerge:
- What is the causal relationship between the psychedelic drug and brain activity?
- What is the causal relationship between brain activity and the psychedelic experience?
Exploring these questions may reveal different ways of understanding the relationship between psychedelic compounds, brain activity, and subjective experience.
The Term “Psychedelic”
Before considering the Psychedelic Brain, it is important to examine the meaning of the term itself. A name is a designation, and designations can change over time. Understanding the concept therefore requires looking beyond the label.
The term psychedelic, derived from the Greek for “mind-manifesting,” was coined by British psychiatrist Humphry Osmond in 1957. The term was intended to describe experiences associated with compounds capable of producing profound changes in consciousness.
Other terms have also been used for these compounds, including phantastica, hallucinogen, psychotomimetic, phanerothyme, and more recently entheogen, which adds a spiritual or divine connotation.
The classical psychedelics with the greatest scientific and cultural influence include mescaline, LSD, psilocybin, and DMT. Most psychedelic drugs fall into three major chemical families: tryptamines, phenethylamines, and lysergamides.
From a pharmacological perspective, classic serotonergic psychedelics can be characterized by their 5-HT2A partial agonism. This includes psilocybin, LSD, mescaline, and DMT, distinguishing them pharmacologically from cannabinoids, dissociatives such as ketamine and salvinorin A, and entactogens such as MDMA.
Broader terms such as Altered States of Consciousness (ASC) and Non-Ordinary Conscious States (NOCS) encompass a much wider range of experiences, including meditation, hypnosis, and trance.
An altered state of consciousness can be understood as a temporary shift in ordinary wakefulness, attention, or awareness. The term ASC was coined by transpersonal psychologist Charles Tart in 1972, who described it as a temporary change in the overall pattern of subjective experience.
However, the designation “altered” also assumes that ordinary waking consciousness is a singular or “normal” state. In reality, waking consciousness can be understood as a fluid, multifaceted spectrum of conscious and unconscious psycho-emotional perspectives.
Different Perspectives
The concept of a “Psychedelic Brain” is studied from different perspectives depending on the scientific discipline and intended application.
- Pharmaceutical research approaches psychedelics primarily through pharmacology, focusing on biochemical mechanisms and therapeutic effects.
- Neuroscience investigates the neurobiological mechanisms associated with psychedelic experiences.
- Medical and therapeutic research focuses on psychological features of psychedelic experiences that may predict therapeutic outcomes.
These perspectives have contributed to new therapeutic approaches, particularly psychedelic-assisted therapy (PAT) and psychedelic-assisted psychotherapy (PAP).
A shift from assessing only “drug efficacy” toward assessing “experiential efficacy” suggests that innate brain dynamics and subjective experience may play an important role in therapeutic outcomes.
The terminology becomes particularly important in PAT/PAP. Three active approaches commonly involve ketamine, MDMA, and psilocybin. While all three are psychoactive, only psilocybin is categorized as a psychedelic in the classical pharmacological sense. Ketamine is classified as a dissociative, while MDMA is an entactogen. These distinctions reflect different biochemical characteristics rather than simply different terminology.
Current Psychedelic Theories
Two broad theoretical perspectives are presented as dominant approaches: the Integration view and the Pluralistic view.
1. The Integration View
The Integration view proposes a relatively linear causal cascade:
Psychedelic molecule → changes in brain activity → psychedelic experience
This can be described as a two-step “agent/action” process. Importantly, this model opens the possibility that different “agents” could potentially trigger the second-stage “action”—the psychedelic experience—which would represent an innate capacity of the brain itself.
The REBUS model is presented as an important example of the Integration view.
2. The Pluralistic View
The Pluralistic view argues that psychedelic experiences cannot be reduced to a single causal pathway. Instead, they emerge through the interplay of multiple causal pathways.
This perspective does not necessarily exclude the Integration view. Rather, it expands the model by considering additional forms of “agency” that may contribute to the resulting “action” of the psychedelic experience.
R.E.B.U.S. & The Integration View
The relative simplicity and popularity of the REBUS model make it a useful framework for investigating the Psychedelic Brain. Like other scientific models, however, it has also attracted criticism while continuing to offer a way of examining complex and sometimes dramatic subjective states.
The REBUS Model combines the entropic brain hypothesis with the free-energy principle. REBUS stands for:
Relaxing Existing Beliefs Under pSychedelics
The model proposes that, through their entropic effect on spontaneous cortical activity, psychedelics reduce the precision of high-level priors or beliefs. This may liberate bottom-up information flow, particularly from intrinsic sources such as the limbic system.
The related concept of the “Anarchic Brain” describes the possibility that the brain can temporarily relinquish some of its more familiar controlling processes, particularly those associated with top-down neurological integration, and enter a less constrained and information-rich state.
Here, “anarchy” refers to a condition of disorder arising from the absence or non-recognition of authority or controlling systems. Within the REBUS framework, it describes a temporary loosening of the brain’s usual higher-level constraints.
References
- Meling, D., & Scheidegger, M. (2023). Not in the drug, not in the brain: Causality in psychedelic experiences from an enactive perspective. Frontiers in Psychology, 14. doi:10.3389/fpsyg.2023.1100058
- Nichols, D. E. (2016). Psychedelics. Pharmacological Reviews, 68, 264–355. doi:10.1124/pr.115.011478
- Zhou, L. Altered States of Consciousness: 4 Non-Psychedelic Approaches. The Third Wave.
- Vollenweider, F. X., & Preller, K. H. (2020). Psychedelic drugs: neurobiology and potential for treatment of psychiatric disorders. Nature Reviews Neuroscience, 21, 611–624. doi:10.1038/s41583-020-0367-2
- Yaden, D. B., & Griffiths, R. R. (2021). The subjective effects of psychedelics are necessary for their enduring therapeutic effects. ACS Pharmacology & Translational Science, 4, 568–572. doi:10.1021/acsptsci.0c00194
- Roseman, L., Nutt, D. J., & Carhart-Harris, R. L. (2018). Quality of Acute Psychedelic Experience Predicts Therapeutic Efficacy of Psilocybin for Treatment-Resistant Depression. Frontiers in Pharmacology, 8, 974. doi:10.3389/fphar.2017.00974
- Carhart-Harris, R. L., & Friston, K. J. (2019). REBUS and the anarchic brain: toward a unified model of the brain action of psychedelics. Pharmacological Reviews, 71, 316–344. doi:10.1124/pr.118.017160