On March 14th I had the privilege of attending a talk by Roland Griffiths, Ph.D., as part of the CNS Public Talk Series at the University of Pennsylvania. As a psychopharmacologist and a researcher at Johns Hopkins, Griffiths has spent nearly twenty years “investigating the effects of the classic hallucinogen psilocybin” and has been at the forefront of modern research into this class of chemicals.
The title of his presentation was, “Psilocybin: Implications for healthy psychological functioning and therapeutics.”
Griffiths opened his talk with a brief overview of the chemical compound, which, like other psychedelics, is primarily mediated by the activation of serotonin 5-HT2A receptor sites. Quoting from one of his co-authored paper’s, the result is “a unique profile of subjective effects including robust changes in perception, cognition, affect, volition, and somaesthesia.” To demonstrate the drug's effect on the brain, Griffiths referenced a study published in 2014 which used fMRI to capture resting-state functional brain activity in a group of healthy volunteers after either a placebo or a dose of psilocybin.
The graphical representation of the results shown above was featured in his talk. On the left, you see the placebo control and, on the right, the effects of psilocybin. Griffiths’ take away was that, at a normal resting-state, you see activity within networks and relatively little across networks. Whereas under the influence of psilocybin, these across network connections suddenly become strong and ubiquitous.
He described this as a “cascade of cellular events,” and suggested it could be a mechanism in which “damaged networks can reconnect in healthy ways.”
The researchers for this study argue that their result, “supports [the] idea that psilocybin disrupts the normal organization of the brain with the emergence of strong, topologically long-range functional connections that are not present in a normal state.” Other studies on psilocybin and similar psychedelics have shown a decrease in the default mode network, a large scale brain network generally activated by thoughts of oneself or others and thoughts of the past and future, which may explain disruptions to perceptual qualities like ego and sense of time.
The Johns Hopkins Psilocybin Research Project started in 1999 and to date has involved 290 patients in 580 psilocybin sessions. These studies have targeted various populations from healthy participants, addicted cigarette smokers, psychologically distressed cancer patients, and to meditators and religious professionals.
Griffiths highlighted for us two studies of medically- and psychiatrically-healthy participants, most without any history of psychedelic use. These were “rigorous double-blind cross-over designs” and either controlled by placebo or a comparative group dosed with a central nervous system stimulant. The participants sampled were broadly representative in age and gender but skewed highly towards those with college and post-graduate degrees.
Whether assigned to psilocybin or one of the control groups, participants completed their session in a comforting living room environment, accented with dim lighting and tasteful decor.
During the study sessions, participants were encouraged to lay on the couch, listen to music on headphones, wear eyeshades, and direct their thoughts on their inner experiences. Beyond that, the session was largely unguided. Researchers remained in the room and largely to reassure any doubts that could foreseeably arise from the participants.
As expected, the doses of psilocybin produced a range of perceptual changes, visual illusions, greater emotionality, and cognitive change—and these were found to be robust dose-related effects. But the element of the experience that Griffiths zeros in on was that most volunteers reported large increases in mystical and insightful-type experiences.
Griffiths noted that the word “mystical” had certain connotations antithetical to scientific research, but in this case, the term was “defined by empirically-measured phenomenological dimensions without implying supernatural or non-rational levels of explanation.” The dimensions of a mystical experience he listed are as follows:
Unity (interconnectedness of all people and things, all is one, pure consciousness), sacredness or reverence, noetic quality (a sense of encountering ultimate reality), deeply felt positive mood (universal love, joy, peace), transcendence of time and space (past and present collapse into present moment), and ineffability.
While in many ways an elusive experience, it has nonetheless been variously described across cultures and across human history, thus making it a unique phenomenological condition to study. This research into psilocybin points to these mystical-type experiences as being a biologically natural response.
Griffiths then spoke to the long-term effects of these psilocybin sessions. When following up one month after treatment, researchers found an overwhelming majority of volunteers reported increases in various personal and behavioral qualities such as “positive attitudes about life and self, positive mood changes, spirituality,” and “altruism/positive social effects,” which had a dose-related correlation to their psilocybin session. To highlight this, he used the following statistics:
78% — among the top five most personally meaningful experiences of their life
83% — among the top five most spiritually significant experiences of their life
94% — increased sense of well-being or life satisfaction moderately or very much
89% — endorsed positive behavior change
The participants reported more self-confidence, inner authority, authenticity, playfulness, open-mindedness, self-honesty, appreciation, gratitude, enthusiasm, love, positive relationships, concern, spirituality, and more. As Griffiths listed off these behavioral changes, I struggled to jot them down in time. Eventually, I just scribbled into my notebook, “Practically every positive facet of the human experience.”
In Griffiths’ team’s research, it was found that these self-reported effects were sustained in the second follow-up 14 months post-session. Griffiths added anecdotally, that from the participants he’s communicated with, these changes continued to last far beyond that time point
As part of this fourteen-month survey, the research team also reached out to community observers, “three adults who were expected to have continuing contact with the participant,” and found their ratings to be generally consistent with the participants’ self-reports.
As a medical practitioner, Griffiths spoke to the wide range of psychoactive drugs that he has prescribed and studied in research during his long career in psychiatry and psychopharmacology, and said that psilocybin stood out as having “remarkable enduring value.” He posited that part of this enduring value may be directly related to the occurrence of the aforementioned mystical-type experiences associated with psilocybin use.
The researchers found that some of these lasting impacts were positively-correlated with the “Mysticism Score” taken after the psilocybin session, but not positively-correlated with the dose of psilocybin nor the intensity of the drug effect.
To compare these mystical experiences induced by psilocybin to naturally-occurring mystical experiences, the researchers conducted a survey among the general public where they elicited responses on the most spiritually-significant events in each individual’s life. Interestingly, most naturally-occurring mystical experiences were described as being an act of God or God’s emissary, while most psilocybin-induced mystical experiences were described as insights into the ultimate nature of reality.
But when comparing the qualitative attributions to what was encountered in either scenario, there is remarkable consistency.
In both cases, whether psilocybin-induced or without drugs, the “truth” encountered by the majority of respondents was described as “intelligent, sacred, benevolent, eternal, conscious” and not “malicious or negatively judgemental.”
In the comment section of the research paper detailing these results, the authors write, “Descriptive research suggests that naturally occurring instances of dramatic positive behavioral change are sometimes associated with spontaneously occurring, transformative psychological experiences, frequently of a mystical-type variety.” To demonstrate the personal impact of these mystical experiences under the influence of psilocybin, the reproduced comments verbatim from the volunteers.
“The sense that all is One, that I experienced the essence of the Universe and the knowing that God asks nothing of us except to receive love.”
“Freedom from every conceivable thing including time, space, relationships, self, etc… It was as if the embodied ‘me’ experienced ultimate transcendence— even of myself.”
“A reality that was clear, beautiful, bright and joyful…”
Demonstrating the potential therapeutic applications of psilocybin, Griffiths quickly covered studies that he’s been involved in concerning psychologically distressed cancer patients and cigarette cessation programs. In the former case, a study of those with life-threatening illnesses found that, “a single dose of psilocybin produced substantial and enduring decreases in depressed mood and anxiety along with increases in quality of life and decreases in death anxiety,” while a pilot study of the treatment of tobacco addiction reported that, “80% of participants were abstinent at 6-month follow-up.” The sample sizes of these populations are small and nonrepresentative but, compared to similar interventions, the prospect of therapeutic value is very promising.
The possible mechanism for these positive changes requires further research, but Griffiths speculated that, under the influence of psilocybin, “there’s this profound shift in sense of self and worldview that may result in a reconstruction of life’s story and a loosening of self-focused narratives.” His research suggests that we are all bound by inner thoughts that both shape and limit our worldview and that by unleashing our mind to what else is possible—temporarily untethering us from the past, the future, and the self—we may gain a greater awareness of our own agency to make these positive changes.
Griffiths’ parting words were both practical and existential. He urged his colleagues in the room take up research involving psilocybin in their own respective fields, while also speaking to how close these experiences of oneness and unity are to the human condition. “With that insight comes the realization that we’re all in this together,” quoth Griffiths. “This is the experience of what it is to be human.”