Pyschoactive Siestas: Rethinking the Role of Consciousness in Psychedelic Therapy

Written by Reece Jones

Illustration by Sydnie Lim

Ask anyone about psychedelics, and they'll tell you that the trip is what changes you. The altered perception, the visions, the mystical experience. But what if the traditional psychedelic experience isn't what actually heals you? What if the fundamental changes happen behind the scenes, independent of consciousness?

With a surge in interest in recent years, the potential of psychedelic-assisted therapy has captured the imagination of physicians and psychologists alike. Clinical trials administering psychedelics such as MDMA or psilocybin have shown promising results in the treatment of psychological conditions that were once considered nearly untreatable, including treatment-resistant depression and PTSD. This burgeoning field offers a glimmer of hope for the future of mental health treatments. 

Despite such promising results, psychedelic research has reached a roadblock. In August of 2024, the FDA overwhelmingly rejected the approval of MDMA-assisted therapy for the treatment of PTSD, the first application of its kind. Although questions were raised about the risks of psychedelic administration, one concern stood chiefly among them–"functional unblinding," or the lack of a comparable placebo/control group. Most participants in a clinical trial can tell if they have ingested a powerful psychoactive substance, biasing results and restricting researchers from attributing therapeutic benefits to the drug itself. Such concerns can typically be supplemented with experimental evidence from animal models. However, a more significant disconnect remains in psychedelic studies between current animal models and human clinical trials, a gap that scientists across the nation are seeking to bridge, including one team at Stanford. 

Dr. Boris Heifets is an associate professor and practicing anesthesiologist at Stanford School of Medicine. Focused on elucidating the mechanisms that allow psychedelics to trigger lasting transformations in one's brain, the Heifets lab conducts parallel human and animal experiments to compensate for the weakness of each model. For example, in 2018, Dr. Heifets, along with two other Stanford associates, Dr. Nolan Williams and Dr. Alan Schatzberg, published a study on ketamine in humans, where the antidepressant effects were blocked by naltrexone, an opioid receptor antagonist. "Surprisingly, this was one of the only examples where someone had done a behavioral pharmacology experiment in humans–which is usually step one in a mouse model," says Heifets. "But the fact that this result was so marked in humans suggests that interaction is important, which changes how you judge an animal model. Instead of trying to mimic depression in a mouse, we're moving towards something more physiological that would directly resemble what we see in humans." Bridging the gap between animal and human models, the Heifets lab is now applying parallel animal and human experiments to address the FDA's concern about a well-blended psychedelic trial.

Three primary components of the psychedelic therapy experience have been identified: The biochemical effects of the drug, the experiential effects during the trip, and non-drug factors, which include the expectations, aftermath, and all other psychological elements that contribute to the overall therapeutic effect. "Isolating each of these components in humans is not trivial," says Heifets. "But one approach we've taken is to suppress the conscious experience, which should isolate the biochemical effects of the drug and non-drug factors." To achieve this, the Heifets lab is co-administering a psychedelic to anesthetized individuals, the results of which may change what we deem as essential for therapeutic outcomes. 

"It's the weirdest implication, but pre-clinical data in mice suggests that your conscious awareness is interfering with your ability to experience the trip," says Heifets. Psychedelics such as psilocybin produce an identifiable increased diversity of electroencephalographic (EEG) signals, which are measures of electrical activity in the brain. Additionally, an immediate-early gene known as c-fos has been observed to upregulate upon psychedelic administration. Under anesthesia, EEG and c-fos have better "signal to noise" than awake individuals. That is, EEG and c-fos recordings are less affected by random brain activity or gene expression and appear more pronounced. "Looking at the EEG data, it's like they're not normally anesthetized," says Heifets. "The question then becomes: are they experiencing disconnected consciousness? Are they conscious but unable to move? Is it some intense dreamlike experience? It's an empirical question; you can't ask a mouse this." But you can ask a person, which is why the Heifets lab is moving to emulate these experiments in humans. 

While the immediate impact on therapeutic outcomes may be limited, the potential of the Heifets lab's research to influence future psychedelic treatments is intriguing. These extreme manipulations, while carrying unexplored risks, could open new doors in the exploration of non-ordinary states of consciousness. As Dr. Heifets puts it, ”Everything we've tried to date typically suppresses your consciousness. There isn't much depth measurement past the threshold of being unconscious." 

Differentiating between altered states of consciousness–such as being intoxicated–becomes complex when considering the subjective nature of these experiences. Although an individual can often articulate how they feel while intoxicated, that articulation tends to focus on experiential aspects, such as the euphoria or distortions associated with a psychedelic experience. However, what remains elusive is the underlying, non-conscious processes and neurobiological changes that occur at a more subtle level. “We currently lack a clear lexicon to adequately capture these processes,” reports Heifets. Thus, individuals may find it challenging to verbally report everything they experience, leaving a gap in our understanding of the full scope of a treatment like psychedelic therapy.

This distinction highlights an important aspect of the Heifets lab’s research: by manipulating conscious awareness, the lab aims to illuminate these previously obscure facets of psychedelic therapy. In understanding what occurs in the brain during these altered states, the group may provide compelling insights that go beyond mere subjective reports, allowing us to appreciate the complexities of consciousness and its impact on healing in a more nuanced way. Precisely as psychedelic-buffs of the 60s believed, this line of research could be the key to enhancing our comprehension of consciousness and the human experience, just with a little more scientific rigor.

CITATIONS

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