Psychedelics and Mental Health: A Therapeutic Breakthrough?

Audrey Herrald 23′

Robin Carhart-Harris is the Head of the Centre for Psychedelic Research, Division of Brain Sciences, and Faculty of Medicine at Imperial College London. Last week, however, Dr. Carhart-Harris was a long way from home; in Dartmouth College’s very own Filene Auditorium, he delivered a talk entitled “Psychedelics: Therapeutic Mechanisms.”

As it turns out, the term “psychedelic” refers to a revelation (from the Greek “deloun”) within the brain (“psyche.”) Such a psychological breakthrough is often the goal of therapeutic sessions, and Dr. Carhart-Harris explained that this connection between the two has long made for anecdotal evidence of psychedelics offering therapeutic value. However, in recent years, the potential for these drugs to decrease the duration of therapeutic treatment courses, thus helping to combat therapy’s substantial cost barrier, has encouraged increased scientific investigation on the subject.

Dr. Carhart-Harris’ presentation addressed this investigation, outlining the future of psychedelics in therapy through the lens of recently published scientific literature—including research performed in his own London lab. The talk began with a review of the structure and function of serotonergic psychedelic drugs, followed by an explanation of both the theory behind psychedelics as a therapeutic mechanism and of the therapeutic applications that have been examined in recent studies.

In essence, a serotonergic psychedelic functions by imitating the neurotransmitter serotonin and binding to its receptors in the brain. There are 14 different types of serotonin receptors, but it is the serotonin 2A receptor that was of particular interest to Dr. Carhart-Harris. This 2A receptor, he explained, plays an important role in brain plasticity, learning, and psychological development. When a high proportion of these receptors are activated, the brain enters a state that is electrochemically comparable to that of early psychosis; subjects enter what Dr. Carhart-Harris refers to as a “pivotal mental state,” during which they are particularly well-equipped to successfully rearrange psychological predispositions. This plasticity can be key in improving the efficiency and effectiveness of therapeutic treatment courses.

How has such a conjecture been scientifically demonstrated, and what does this “pivotal mental state” have to do with successful therapy? Dr. Carhart-Harris flashed an innocent-looking paragraph up on the projector screen as he began to address these points. Within a few seconds, a murmur arose among the audience; almost every word in the completely comprehensible paragraph was spelled with out-of-order letters. This visual trick, along with the popular face-and-vase illusion, was one of many images presented to research subjects under the influence of psychedelic drugs in a recent study. The researchers found that the type of top-down shortcut processing (predictive processing) that enables humans to unconsciously interpret misspelled words as if they were spelled correctly, is significantly inhibited by the serotonergic action of many psychedelic drugs. When it comes to cheeky optical illusions, such inhibition is relatively unhelpful. However, for people whose top-down processing has become a maladaptive driver of negative behavioral loops (e.g., feelings of loneliness that become automatic cognitive precursors for derogatory self-talk, loss of motivation, and/or increasingly negative self-talk), separation from predictive processing could be the key to psychological improvement.

During psychedelic therapy, serotonergic psychedelics are administered twice over the course of three sessions. All sessions are carefully moderated by two “sober sitters,” trained to both monitor and guide the mental and emotional states of the person receiving treatment. The first session is an introductory session; the therapist meets the patient, and a small dose of psychedelic drug is administered in preparation for the large dose to come. The second session is the main “breakthrough session,” during which a carefully determined dose of psychedelic is administered under meticulous watch. The third session is essentially a wrap-up and debrief session during which functional elements of the psychedelic experience are discussed and explored.

Following this form, Dr. Carhart-Harris explained, the actual interval of time spent in the psychedelically-influenced state that inhibits top-down processing is relatively brief. It was here, however, that he reminded audience members about the serotonin 2A receptors. These receptors, important in learning and neural plasticity, can affect processing patterns long after the psychedelic state has dissipated. The theory behind effective psychedelic therapy revolves around this receptor behavior. If, through the combined inhibition of maladaptive top-down processing and the guiding prompts of “sober sitters,” a patient is able to harness heightened neural plasticity to rearrange their patterns of predictive thought, they might achieve that breakthrough therapy session that so many patients seek. Thus far, Dr. Carhart-Harris’s own research is among a growing body of scientific evidence that offers support for this theory.

The presentation concluded with a tidbit of exciting science news: Dr. Carhart-Harris himself is currently conducting one of the most comprehensive clinical trials of psychedelic drugs in therapy ever performed. This two-arm, double-blind study with randomized controls is taking place over the course of 12 weeks. Dr. Carhart-Harris reports that the blind will be broken in late winter and that the preliminary data look quite promising. While it might be difficult to envision psychedelic drugs as a mainstream method of therapeutic treatment, legalization of such treatment is on its way to the ballot in Oregon and in preliminary stages across the U.S. Dr. Carhart-Harris predicted that psychedelic therapy could take between five and ten years to become relatively mainstream, but positive results in a study such as this could help pave the way towards a new—and more accessible—option of care for patients seeking therapy.

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