Dr. Roland R. Griffiths is a clinical pharmacologist at Johns Hopkins and has been researching mood-altering compounds for over 40 years. As an unusually prolific scientist, having published over 360-times, he's also responsible for having started the psilocybin research program at Johns Hopkins nearly 2 decades ago.

In this 1-hour and 15-minute podcast, we discuss…

00:01:03 - the broader story of Dr. Griffiths 40 years of mood-altering drug research, including what got him started and how taking up a meditation practice ultimately influenced the eventual focuses of his research.
00:02:22 - the effect psilocybin has had in clinical trials in eliciting so-called mystical experiences that can act as a long-term catalyst for meaningful spiritual change and is amenable to being reproduced and clinically studied in a prospective manner.
00:03:45 - what distinguishes psilocybin from other drugs, particularly when reflecting backward on the experience months afterward.
00:05:11 - the process by which Dr. Griffiths and his team create an appropriate “setting” and facilitate feelings of safety for those participating in his trials.
00:06:42 - the elusive fundamental nature of a classical psychedelic experience whereby people often simultaneously describe the experience as ineffable (indescribable) but yet also often assign it a truth value that may even exceed that of everyday consensus reality.
00:07:36 - a description of the core features of a classical mystical experience that overlap with those found in a mystical experience induced by psilocybin.
00:08:58 - the qualities of the experience that Dr. Griffiths believes to most underlie the “reorganizational” potential it can have.
00:10:55 - the interesting potential areas for scientific exploration that the reproducibility of the psilocybin experience makes the substance amenable to.
00:11:25 - the promise psilocybin has shown as an effective therapeutic for anxiety and depression in patients with life-threatening cancer and also treatment-resistant depression in otherwise healthy patients (00:18:46).
00:13:04 - the lack of rigor in the very early trials on these compounds and the way in which cultural stigma surrounding psychedelic drugs ultimately played a role in impeding real, substantive clinical research for decades afterward.
00:16:31 - the long-term resilience of the antidepressant and anxiolytic effect, lasting six months and possibly even longer.
00:21:01 - the effect psilocybin has demonstrated in animal studies to increase hippocampal neurogenesis and enhance extinction of trace fear conditioning.
00:23:07 - the somewhat unintuitive neurobiological mechanism that may tie together some of the antidepressant properties of both psilocybin and ketamine, an anesthetic currently being studied as a rapid-onset antidepressant.
00:25:16 - whether or not the mystical subjective experiences are necessary for drugs like psilocybin to exert their antidepressant or anxiolytic effects.
00:26:43 - what the default mode network is and what its pattern of activity is in depression, long-term meditators, and after the acute use of psilocybin.
00:32:16 - the hard problem of consciousness.
00:37:26 - the challenge of finding the neurological correlates to match the phenomenology of individual’s subjective experiences.
00:38:16 - the promise psilocybin has shown in a small trial on smoking cessation where 60% of the treatment group were still abstinent a year afterward and plans Dr. Griffiths has to expand this area of research
00:41:10 - the possibility that the “reorganizational nature” of these experiences may open up new avenues as trials continue to try to embed the experience within different therapeutic contexts.
00:44:02 - the roadmap to FDA approval for use of psilocybin as a medication, particularly in the context of cancer-associated depression and anxiety.
00:45:05 - the risks inherent in taking psilocybin and the frequency of self-reported negative experiences in the general population.
00:47:22 - the criteria Dr. Griffiths and his colleagues use when screening for volunteers to participate in his studies involving psilocybin.
00:49:21 - the inability for clinicians to predict who is at risk of having challenging experiences defined by fear and anxiety (“bad trip”) and whether or not it is desirable, in terms of achieving a therapeutic outcome, to prevent these types of experiences altogether or not.
00:51:43 - the sort of dosages used in the trials.
00:54:45 - the clever ways devised by Dr. Griffiths to placebo control trials where expectation itself can affect outcome.
00:57:45 - some of the interesting anecdotes gleaned from Dr. Griffiths’ working with long-term meditators participating in the psilocybin trial.
01:05:13 - a brief discussion about some of the other psychedelics besides psilocybin, such as salvia divinorum and DMT (at 01:10:24).
01:12:08 - the historical indigenous use of psychedelics in various cultures spread throughout the world.

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