The Scientist Before the Turn
Roland Ray Griffiths (1946–2023) spent the first three decades of his research career as one of the most productive and conventionally respected psychopharmacologists in the United States. He joined the faculty of the Johns Hopkins University School of Medicine in 1972, shortly after completing his doctorate, and remained there for the rest of his working life. His early research addressed the reinforcing properties of drugs in animal and human models — the quantification of how substances produce and sustain dependence, the measurement of subjective effects, and the development of methodology for distinguishing genuine pharmacological reinforcement from placebo and expectation effects. The work was rigorous, technically competent, and strictly within the mainstream of behavioral pharmacology. He published several hundred peer-reviewed papers on caffeine, nicotine, benzodiazepines, opioids, and other standard pharmacological targets, and by the late 1990s he was widely regarded as one of the field’s senior figures. Nothing in the first thirty years of his career predicted that he would become the single most consequential figure in the twenty-first-century revival of psychedelic research.
The turn began with a personal meditation practice. Griffiths had taken up Siddha Yoga in 1994, following what he later described as a period of questioning about what his research career was actually for and whether the narrow quantification of drug effects was contributing to anything he regarded as important. The meditation practice produced experiences that his pharmacological training had no framework for — states of profound peace, experiences of unity, moments that felt ontologically distinct from the ordinary running of consciousness and that the materialist framework he had operated within professionally could not accommodate. He did not immediately translate these experiences into a research direction. For several years he continued his conventional work while maintaining the practice and progressively questioning whether the framework he had been trained in was actually adequate to the phenomena he was now regularly encountering in his own life.
The translation came when Griffiths read, around 1999–2000, the earlier literature on psilocybin research that had been conducted before the 1970 Controlled Substances Act shut the field down. The pre-prohibition literature included several studies — particularly Walter Pahnke’s 1962 Good Friday Experiment at Marsh Chapel, conducted as Pahnke’s Harvard dissertation research at Harvard Divinity School with psilocybin supplied by Leary’s Harvard Psilocybin Project — that had used controlled-administration protocols and structured questionnaires to study whether psilocybin could produce experiences phenomenologically comparable to the mystical states described in the spiritual literature. The early findings were affirmative: Pahnke’s divinity students, given psilocybin in a chapel setting, reported experiences that scored high on measures of mystical consciousness and that subjects described as among the most significant spiritual events of their lives. The methodology was crude by modern standards, and the political situation had prevented the follow-up work the findings required. The research program had been interrupted before it could produce definitive results.
Griffiths recognized that the thirty-year gap in the literature represented both a scientific opportunity and an institutional risk. The opportunity was that the questions Pahnke’s work had raised could be addressed with modern methodology, sample sizes, and outcome measures, potentially producing the definitive evidence the earlier work had lacked. The institutional risk was that psilocybin remained a Schedule I controlled substance in the United States, that no researcher had conducted a psilocybin administration study in the country for nearly three decades, and that reviving the research would require navigating a regulatory, ethical, and funding environment specifically designed to prevent the kind of research he was proposing. The decision to attempt the navigation — the decision to use his senior career capital and his Johns Hopkins institutional base to push a research program his earlier work had not predicted — is the moment the twenty-first-century psychedelic renaissance structurally began.
The 2006 Paper
Griffiths’s team published the founding paper of the modern psychedelic research era in Psychopharmacology in July 2006: “Psilocybin Can Occasion Mystical-Type Experiences Having Substantial and Sustained Personal Meaning and Spiritual Significance.” The study enrolled thirty-six healthy volunteers who had no prior psychedelic experience and who met criteria suggesting stable personalities and active involvement in religious or spiritual activities of their choice. Each subject received two sessions — one with thirty milligrams of psilocybin per seventy kilograms of body weight, one with methylphenidate as an active placebo — in a double-blind crossover design. The sessions were conducted in a comfortable, living-room-style environment with two trained “monitors” present to provide support. The subjects were instructed to lie on a couch, wear eyeshades, and listen to classical music through headphones while turning their attention inward.
The findings were the first institutionally rigorous demonstration of what the mystical literature had been describing for centuries. Twenty-two of the thirty-six subjects — sixty-one percent — met criteria on the Pahnke-Richards Mystical Experience Questionnaire for having had a “complete” mystical experience under psilocybin. The complete-mystical threshold on this instrument requires high scores across multiple subscales measuring unity (dissolution of the distinction between self and environment), transcendence of time and space, sense of sacredness, noetic quality (the sense that the experience reveals genuine knowledge), deeply-felt positive mood, and ineffability. Two-thirds of the subjects rated the psilocybin session among the five most personally meaningful experiences of their lives, comparable to the birth of a first child or the death of a parent. One-third rated it the single most personally meaningful experience they had ever had. And the follow-up measurements at two months after the session demonstrated that the experience had produced measurable lasting changes in attitudes toward self, life, and spirituality — changes that the methylphenidate placebo sessions had not produced.
The paper’s significance was not that the findings were unexpected. The findings were essentially what the mystical literature had been saying would happen for two millennia, what Huxley had reported after mescaline in 1953, what the pre-prohibition research had preliminarily confirmed, and what anyone familiar with psychedelic experience would have predicted. The significance was that the findings had been demonstrated through the methodology the institutional biomedical establishment recognized as legitimate: a controlled clinical trial with an active placebo, standardized administration, validated outcome measures, and peer-reviewed publication in a reputable journal. The orthodoxy that had dismissed the phenomenology as subjective confabulation or drug-induced delusion had to now contend with quantified evidence produced by one of its own senior members using its own preferred methods. The paper did not prove anything the tradition had not already known, but it made the knowledge institutionally admissible, which in the bureaucratic structure of contemporary science is the difference between a finding that exists and a finding that matters.
The Subsequent Program
The Johns Hopkins Center for Psychedelic and Consciousness Research — established in September 2019, with Griffiths as founding director — became the institutional center of gravity for the psychedelic research revival. Subsequent studies addressed specific clinical applications — psilocybin for tobacco addiction, psilocybin for depression, psilocybin for end-of-life anxiety in cancer patients — and in each case the findings were unusually strong by the standards of psychiatric clinical trials. The tobacco addiction study reported eighty percent smoking cessation at six months, a rate exceeding any pharmacological or behavioral intervention in the literature. The depression study reported sustained improvement in treatment-resistant patients who had failed multiple previous therapies. The end-of-life anxiety study reported dramatic reductions in death-related fear and existential distress in patients facing terminal diagnoses, with the effects persisting through the time of death itself in those patients who did not survive the follow-up period.
The clinical findings were accompanied by a larger research program on the phenomenology of the experience itself. Griffiths’s team developed and validated new versions of the Mystical Experience Questionnaire, conducted dose-response studies to identify the thresholds at which mystical experiences reliably emerge, and produced long-term follow-up data on the fourteen-month and longer persistence of the attitudinal and behavioral changes the experiences produced. The work went beyond the standard pharmaceutical clinical trial architecture to engage seriously with what the experiences actually contained — the transpersonal content, the sense of encounter with entities or intelligences, the post-experience integration process, the factors that predicted whether an experience would produce lasting benefit or psychological difficulty. The methodology was cautious and the conclusions were conservatively phrased, but the cumulative effect was the institutional recognition that high-dose psilocybin administration under therapeutic support produces experiences that cannot be adequately described as symptoms and that have measurable, lasting, and generally positive consequences for the people who have them.
The clinical findings attracted the most concrete form of institutional validation available short of full approval: FDA Breakthrough Therapy Designations for psilocybin. Compass Pathways received the designation for its COMP360 formulation in treatment-resistant depression in 2018; Usona Institute received it for psilocybin in major depressive disorder in November 2019. Both designations flowed directly from the evidentiary foundation Griffiths’s program had built, and both placed psilocybin on a regulatory fast-track that had not existed for any classic psychedelic since the scheduling era. The designations did not guarantee approval, but they represented the FDA’s formal acknowledgment that the research program warranted priority engagement — the highest institutional signal the regulatory apparatus had produced for psychedelic medicine.
The God Encounter Studies
Griffiths’s later research included a specific investigation of what subjects reported as encounters with God or with a divine being during psilocybin and related experiences. The 2019 paper “Survey of Subjective ‘God Encounter Experiences’: Comparisons Among Naturally Occurring Experiences and Those Occasioned by the Classic Psychedelics Psilocybin, LSD, Ayahuasca, or DMT” analyzed responses from approximately four thousand participants. The findings were directly relevant to questions the perennial philosophy had been raising for centuries and that the institutional science had refused to engage. Subjects who reported God encounter experiences — whether occurring naturally through meditation, prayer, or spontaneous mystical event, or occurring under the influence of classical psychedelics — described the encounter using similar language across categories. The psychedelic-occasioned encounters were rated as producing more dramatic and more enduring changes in existential orientation, but the phenomenological core was continuous with the naturally occurring mystical literature. Subjects who had identified as atheist before the experience frequently no longer did afterward. Subjects who had held conventional religious beliefs often reported that the experience had shifted those beliefs toward something more experiential and less propositional.
The God encounter study is significant not for what it proved — it is a survey study, not a controlled trial, and its methodological weight is limited — but for what it represented institutionally. A senior Johns Hopkins psychopharmacologist had directed his team to conduct research whose explicit subject matter was the encounter with God, had published the findings in a peer-reviewed journal, and had presented the data in terms that treated the phenomenological reports as evidence about an actual experience rather than as symptoms of a drug-induced confusion. The framing alone represented a departure from the standard biomedical approach and opened methodological territory that had been institutionally forbidden since the prohibition era. Whether the research program Griffiths initiated will continue to occupy this territory after his death, or whether it will be absorbed into the more conventional framework the contemporary medicalization prefers, is one of the open questions of the current moment.
The Death
Griffiths was diagnosed with stage IV colon cancer in November 2021. He continued to conduct research and to publish actively through the remainder of his life, and the diagnosis became itself part of his research program: he participated as a subject in end-of-life studies of the kind his team had been conducting with other patients, reported on the experience from the inside, and discussed the process publicly in interviews that are now part of the tradition’s canonical death-and-dying literature. He died on October 16, 2023, at the age of 77. In a December 2022 interview with Tim Ferriss (episode #641), Griffiths spoke at length about confronting his diagnosis, his relationship to his own research, and his spiritual evolution — disclosing his personal engagement with the experiences his team had spent two decades studying, and expressing a directness about the meaning of that engagement that his published papers had necessarily bracketed. The testimony he left — in that interview, in subsequent research papers, and in late-career public reflection — expressed what he described as a deepening confidence in the reality of the phenomena his research had addressed and in the fundamental adequacy of the mystical framework as an account of them.
The death echoes the death of Huxley sixty years earlier in ways that the tradition has not failed to notice. Both men used the recovered pharmakon at the end of their lives for the purpose the tradition had always understood it to serve. Both men approached death with a preparation that their secular education had not provided and that the recovered tradition had made available. Both men documented the process in terms that were available to readers who would never have the same preparation and who would need something to read when their own moment arrived. The generation-spanning pattern — Huxley’s preparation in the 1940s, his LSD death in 1963, Griffiths’s encounter with the research literature around 1999–2000, his own engagement with the pharmakon at the end of his life — whether or not the specific echo of Huxley’s deathbed rite is exact — suggests a continuity the institutional history of the field has not adequately recognized. The pharmakon tradition was preserved through the written record Huxley left, transmitted to Griffiths through that record, extended by Griffiths through the research program his institutional position made possible, and handed forward to the generation that will inherit what the two of them together built.
The Risk of Success
Griffiths was aware throughout his career that institutional legitimization carried its own risks. The program he built at Johns Hopkins was the most credible institutional platform the psychedelic research movement had ever possessed, and the credibility came at the cost of methodological choices that narrowed the research’s scope in ways the tradition might come to regret. The Johns Hopkins protocol treats psilocybin administration as a therapeutic intervention for clinically diagnosable conditions, conducted within a biomedical research framework, with subjects drawn from carefully screened populations under the supervision of credentialed therapists in institutional settings. The approach is the one that the FDA, the NIH, the insurance industry, and the academic medical centers will recognize as legitimate. It is also the approach that the pharmakon tradition has historically regarded as insufficient for what the substance actually does.
The risk is institutional capture: the possibility that the research Griffiths legitimized will produce FDA-approved psilocybin-assisted psychotherapy for narrowly defined indications, administered within the pharmaceutical orthodoxy‘s existing architecture, while the broader cultural and spiritual significance of the substance is systematically bracketed out of the institutional framework. On this trajectory, the substance becomes another patented commercial product, prescribed by doctors for depression the way SSRIs are currently prescribed, with the mystical experience treated as an incidental side effect whose reliable occurrence is a feature of the drug rather than the point of the administration. The traditional use, the lineage-based teacher-student relationship, the ceremonial and cultural context, and the fundamental reorientation the experience can produce in a well-prepared instrument — all of these would be excluded from the institutional framework and therefore from the access most people will have.
Griffiths was explicit in his later interviews that he saw this risk and had no simple answer to it. The choice he had faced when beginning the research program was between pursuing institutional legitimization, with its attendant risks, and allowing the research to remain marginalized, in which case the substance would continue to be inaccessible to most people who might benefit from it. He chose the legitimization strategy while remaining aware that the strategy could produce the outcome he was trying to prevent. His later work — particularly the God encounter studies, the emphasis on phenomenological content, the refusal to reduce the experience to a list of therapeutic indications — represented his attempt to keep the broader framework alive within the institutional architecture even as the architecture was being built around the narrower application.
The post-2023 regulatory record has given these concerns material form. In August 2024, the FDA issued a Complete Response Letter rejecting Lykos Therapeutics’ application for MDMA-assisted psychotherapy for PTSD — the first psychedelic-assisted therapy to complete full regulatory review, and the first to be turned back. The rejection cited deficiencies in trial design, concerns about functional unblinding, and questions about therapist conduct in the trials that had produced the efficacy data. In October 2024, Compass Pathways — holding its own Breakthrough Therapy Designation for psilocybin in treatment-resistant depression — announced delays to its Phase 3 trial readout and a thirty-percent workforce reduction, citing the Lykos rejection as a signal of increased regulatory difficulty for the sector. Oregon’s licensed psilocybin program, which launched in 2023 as the first state-level legal access pathway, had by late 2025 encountered structural problems of its own: high costs, restricted facilitator capacity, and significant attrition among licensed service centers. The institutional beachhead Griffiths’s research built is real; the path from beachhead to normalized access has proven far more contested than the 2019 moment implied.
The intramural record has simultaneously grown more complicated. Matthew Johnson — Griffiths’s longtime collaborator, co-author on the smoking cessation paper, and for years the most credible insider voice confirming the program’s methodological rigor — publicly raised concerns in 2024 about the soundness of the research in Griffiths’s lab. Johnson’s criticism, reported in a March 2024 New York Times article by Brendan Borrell, constitutes the most significant challenge from within the program itself to the evidentiary claims the psychedelic renaissance had been building. The specific concerns place the question of what the Johns Hopkins trials actually demonstrated in a different register than the managed-awakening risk the program had theorized from the outside: this is not a concern about institutional capture but about whether the foundational data fully supports the edifice constructed on it.
The Rendering-Model Reading
On the rendering-model reading, Griffiths performed the specific function that institutional science requires before the orthodoxy will admit a phenomenon into its frame of reference: he translated a traditional practice into the language and methodology the orthodoxy recognizes, without substantially distorting what the traditional practice actually was. The translation is always imperfect — the orthodoxy’s language cannot fully carry what the traditional practice knew — but the translation is also necessary, because the orthodoxy is the current gatekeeper of cultural legitimacy and anything the orthodoxy has not recognized remains inaccessible to most of the population. Griffiths’s achievement was that he translated enough of the tradition to open a door without translating so much that the door led to something the tradition would not recognize.
The longer pattern in which Griffiths’s work participates is the pattern of recovery. Eleusis was destroyed in 396 CE. Hofmann recovered the chemistry in 1943. Huxley recovered the framework in 1954. The counterculture produced a premature dissemination in the 1960s that the orthodoxy suppressed in 1970. The underground tradition preserved fragments through the prohibition era. Griffiths reopened the institutional channel in 2006. The contemporary renaissance is the current phase of a recovery whose completion — if it is completed — will be measured in generations rather than years. Griffiths’s role in that recovery was to establish the institutional beachhead from which the tradition can be progressively reintroduced into mainstream access. Whether the reintroduction will preserve what the tradition was for, or will substitute for the tradition a medicalized approximation that the orthodoxy can metabolize, is the question the current generation of researchers, clinicians, traditional practitioners, and subjects will collectively answer.
Open Questions
- Will FDA approval of psilocybin-assisted psychotherapy preserve the phenomenological fidelity the Griffiths protocols maintained, or will the regulatory process narrow the administration toward something the original research did not demonstrate was what produced the benefit?
- Is the mystical experience produced under the Johns Hopkins protocols identical to, continuous with, or distinct from the mystical experiences reported in the historical mystical literature, and what methodology could answer this question definitively?
- What proportion of the clinical benefit observed in the Johns Hopkins trials depends on the mystical experience itself as distinct from the pharmacological effect, and how should protocols be structured to maximize the former without treating it as an incidental side effect?
- Can the traditional teacher-student lineage model be integrated into institutional psychedelic therapy, or is the integration structurally incompatible with the institutional framework?
- Did Griffiths leave a specific succession plan for the program he built, and who currently holds the institutional authority to continue the research direction he established?
References
Griffiths, Roland R., et al. “Psilocybin Can Occasion Mystical-Type Experiences Having Substantial and Sustained Personal Meaning and Spiritual Significance.” Psychopharmacology 187, no. 3 (2006): 268–283.
Griffiths, Roland R., et al. “Mystical-type Experiences Occasioned by Psilocybin Mediate the Attribution of Personal Meaning and Spiritual Significance 14 Months Later.” Journal of Psychopharmacology 22, no. 6 (2008): 621–632.
Griffiths, Roland R., et al. “Psilocybin Produces Substantial and Sustained Decreases in Depression and Anxiety in Patients with Life-Threatening Cancer.” Journal of Psychopharmacology 30, no. 12 (2016): 1181–1197.
Griffiths, Roland R., et al. “Survey of Subjective ‘God Encounter Experiences’: Comparisons Among Naturally Occurring Experiences and Those Occasioned by the Classic Psychedelics Psilocybin, LSD, Ayahuasca, or DMT.” PLOS ONE 14, no. 4 (2019).
Johnson, Matthew W., et al. “Pilot Study of the 5-HT2AR Agonist Psilocybin in the Treatment of Tobacco Addiction.” Journal of Psychopharmacology 28, no. 11 (2014): 983–992.
MacLean, Katherine A., Matthew W. Johnson, and Roland R. Griffiths. “Mystical Experiences Occasioned by the Hallucinogen Psilocybin Lead to Increases in the Personality Domain of Openness.” Journal of Psychopharmacology 25, no. 11 (2011): 1453–1461.
Borrell, Brendan. “The Psychedelic Evangelist.” New York Times, March 21, 2024.
Ferriss, Tim. “Dr. Roland Griffiths — Psilocybin Research, Mystical Experiences, and the Aftereffects of His Cancer Diagnosis.” The Tim Ferriss Show, episode #641, December 20, 2022. Transcript at tim.blog.
Pahnke, Walter N. “Drugs and Mysticism: An Analysis of the Relationship Between Psychedelic Drugs and the Mystical Consciousness.” PhD diss., Harvard University, 1963.
Pollan, Michael. How to Change Your Mind. Penguin Press, 2018.
Richards, William A. Sacred Knowledge: Psychedelics and Religious Experiences. Columbia University Press, 2016.