HoldsUp

FoundMyFitness · 2017-01-19 · Rhonda Patrick (host), Roland Griffiths

Roland Griffiths, Ph.D. on Psilocybin, Psychedelic Therapies & Mystical Experiences

38 claims checked against research: 1 overstated 1 needing context 29 supported 7 unverified

29

Supported by research

0:01:52Roland Griffithssupportedhigh

Classic psychedelics including LSD, psilocybin, DMT, and mescaline are serotonergically-mediated hallucinogens.

"These are serotonergically-mediated classic hallucinogens, LSD, psilocybin in the magic mushroom, DMT, mescaline." (said at 0:01:52)

The classification of classic psychedelics—specifically lysergic acid diethylamide (LSD), psilocybin, N,N-dimethyltryptamine (DMT), and mescaline—as serotonergically mediated hallucinogens is firmly established in neuropharmacology. These compounds exert their characteristic psychoactive and hallucinogenic effects primarily through agonism at serotonin receptors, particularly the 5-HT2A receptor subtype.

0:02:49Roland Griffithssupportedmoderate

Healthy volunteers who receive psilocybin under supportive conditions frequently rate the experience months later as among the top five most personally meaningful and spiritually significant of their lives.

"So, months later, people continue to reflect back on that experience and opine that it's among the most personally meaningful and spiritually significant of their lives. I mean, in the top five if not the single most, comparing these experiences to that of birth of a firstborn child or death of a parent." (said at 0:02:49)

In a double-blind randomized clinical trial evaluating the effects of psilocybin (30 mg/70 kg) versus methylphenidate in 36 hallucinogen-naïve healthy adults under supportive conditions, participants were evaluated at 2 months and 14 months post-session. At the 14-month follow-up, 58% rated the psilocybin session as among the top five most personally meaningful experiences of their lives, and 67% rated it among the top five most spiritually significant experiences. Certainty is moderate due to the relatively small sample size (n = 36).

0:14:38Roland Griffithssupportedmoderate

A pilot study from UCLA evaluated a low dose of psilocybin in cancer patients.

"There had been one pilot study published a couple years ago with a low dose of psilocybin out of UCLA." (said at 0:14:38)

A double-blind, placebo-controlled pilot study conducted at Harbor-UCLA Medical Center (Grob et al., 2011) evaluated the safety and efficacy of psilocybin (0.2 mg/kg) in 12 patients with advanced-stage cancer and reactive anxiety. The study demonstrated the feasibility and safety of psilocybin administration along with significant reductions in trait anxiety at 1 and 3 months and improvement in depressive symptoms at 6 months.

0:15:26Roland Griffithssupportedmoderate

A randomized crossover study in cancer patients showed that psilocybin produced large, sustained reductions in anxiety and depression that persisted up to six months after a single active treatment.

"And interestingly, these people experience very large and sustained decreases in anxiety and depression, and the effects occurred really quite promptly after the administration of the drug. And although the design of the study was such, it was a crossover design so people were crossed over between essentially an inactive dose of psilocybin to an active dose or vice-versa. So the strongest conclusion we can make comparing our placebo condition and our active condition is this effect lasted out to five weeks, but in fact, we followed people out to six months and there was no evidence that there was any significant rate of relapse over that period of time." (said at 0:15:26)

A double-blind, randomized crossover trial of 51 patients with life-threatening cancer (Griffiths et al., 2016) found that high-dose psilocybin produced immediate, large, and statistically significant reductions in clinician-rated and self-rated measures of depression and anxiety compared to a low-dose control condition at the 5-week primary endpoint. At the 6-month follow-up, approximately 80% of participants continued to show sustained, clinically significant reductions in depressive and anxiety symptoms without significant relapse.

0:19:05Roland Griffithssupportedvery low

An uncontrolled pilot study in the UK involving 15 patients with treatment-resistant depression found that psilocybin produced large and sustained antidepressant effects lasting at least several months.

"A group from the UK published this summer an uncontrolled pilot study in, I think, it was 15 volunteers with treatment-resistant depression in which they gave psilocybin. And they showed large effects and sustained effects out to at least a couple of months." (said at 0:19:05)

The speaker accurately describes the 2016 open-label feasibility study led by researchers at Imperial College London (Carhart-Harris et al., The Lancet Psychiatry). In that trial, 12 patients (the speaker tentatively recalled 15) with moderate-to-severe treatment-resistant depression received two doses of psilocybin with psychological support. The study reported marked, statistically significant reductions in depressive symptoms that persisted through the 3-month follow-up period (Hedges' g = 2.0 at 3 months). Because this was an open-label, uncontrolled pilot trial with a very small sample size, the certainty of evidence for therapeutic efficacy from this study alone is very low.

0:20:51Rhonda Patrick (host)supportedvery low

An animal study in mice showed that psilocybin administration increased neurogenesis in the dentate gyrus and facilitated fear extinction.

"And they showed that administering psilocybin, I don't remember the dose, increased neurogenesis in the dentate gyrus region of the brain, and also caused fear extinction." (said at 0:20:51)

Animal research in mice supports the claim that psilocybin administration facilitates fear extinction and promotes hippocampal neurogenesis in the dentate gyrus. In an initial study (Catlow et al., 2013), low-dose psilocybin significantly accelerated the extinction of cued fear conditioning and showed a trend toward increased neurogenesis in the dentate gyrus (though higher doses reduced neurogenesis). A subsequent study (Shao et al., 2023) demonstrated that a single dose of psilocybin facilitated fear extinction and rescued fear-conditioning-induced deficits in dentate gyrus neurogenesis (BrdU- and DCX-positive cells) and synaptic plasticity. Because the evidence is derived exclusively from rodent models, certainty is rated as very low.

0:22:22Roland Griffithssupportedhigh

Psilocybin and classic hallucinogens bind to serotonin 5-HT2A and 5-HT2C receptors, with primary behavioral effects mediated through the 5-HT2A receptor.

"In terms of mechanisms of action of these effects, psilocybin and the classic hallucinogens do bind serotonin 2A and 2C. The effects are believed from antagonism studies to be mediated primarily through 2A" (said at 0:22:22)

Classic serotonergic psychedelics (including psilocybin and its active metabolite psilocin) act as agonists at multiple serotonin receptor subtypes, including 5-HT2A and 5-HT2C. Double-blind, randomized human antagonism studies have consistently demonstrated that pretreatment with the 5-HT2A antagonist ketanserin completely or dose-dependently blocks the characteristic subjective, visual hallucinatory, neurophysiological, and mood-altering effects of psilocybin, confirming that its primary behavioral effects are mediated primarily via the 5-HT2A receptor.

0:23:39Roland Griffithssupportedhigh

Ketamine demonstrates immediate and profound antidepressant effects in treatment-resistant depressed patients, but these effects are short-lived.

"ketamine, as I'm sure you know, has been shown to actually have very significant antidepressant effects in treatment-resistant depressed patients, at least a subtype of them. Those effects are immediate. They're pretty profound but they're very short-lived." (said at 0:23:39)

Meta-analyses and systematic reviews of randomized controlled trials demonstrate that ketamine produces rapid and significant antidepressant effects in patients with treatment-resistant depression (TRD), often peaking within 24 hours. However, after a single dose, these antidepressant benefits are short-lived, typically attenuating or disappearing within 3 to 7 days unless repeated administration or maintenance dosing is provided.

0:26:50Roland Griffithssupportedmoderate

Acute administration of psilocybin decreases activity within the default mode network.

"And so work from the UK and additional work now is showing that at least acutely, psilocybin appears to decrease activity within the default mode network." (said at 0:26:50)

Human neuroimaging studies demonstrate that acute psilocybin administration decreases cerebral blood flow, BOLD activation, and functional connectivity within key hub regions of the default mode network (DMN), including the medial prefrontal cortex and posterior cingulate cortex. Pioneering work from UK researchers (Carhart-Harris et al., 2012) showed that acute psilocybin significantly reduced activity and positive coupling across DMN connector hubs, with subsequent precision-mapping studies confirming that acute network disruption and desynchronization are most pronounced within the default mode network.

0:28:18Roland Griffithssupportedlow

Activity in the default mode network is decreased in long-term meditators.

"and interestingly, activity in the default mode network is decreased in long-term meditators." (said at 0:28:18)

Functional neuroimaging studies comparing experienced or long-term meditators to meditation-naive controls demonstrate that core hubs of the default mode network (DMN), including the medial prefrontal cortex and posterior cingulate cortex, show significantly reduced activation during meditation and at baseline. Because these findings are derived from cross-sectional functional neuroimaging (fMRI) comparisons with modest sample sizes, the GRADE certainty is low.

0:14:48Roland Griffithssupportedhigh

A clinical trial at New York University (NYU) co-published alongside the Johns Hopkins study demonstrated that psilocybin produces significant reductions in anxiety and depression in cancer patients.

"A group at NYU ran a somewhat smaller study and we co-published just this last week, in fact, our results. And the results really were quite striking. They confirmed everything we had seen in the healthy volunteers that is these very vulnerable cancer patients who had very significant anxiety or depression experience the same types of...experiences" (said at 0:14:48)

A double-blind, placebo-controlled crossover trial conducted at New York University (NYU) in 29 cancer patients with psychiatric distress was co-published in December 2016 alongside a concurrent double-blind randomized trial conducted at Johns Hopkins University in 51 cancer patients. The NYU trial demonstrated that a single moderate dose of psilocybin paired with psychotherapy produced immediate, robust, and sustained reductions in anxiety and depression, with 60–80% of participants maintaining clinically significant improvements at 6.5 months follow-up.

0:23:02Roland Griffithssupportedvery low

The downstream neurochemical effects of classic hallucinogens like psilocybin are mediated through the glutamate system.

"it's very likely and I think our current hypotheses would suggest that the major effects that we see are downstream and probably are glutamate-mediated which links this whole thing about psilocybin and depression into this unfolding story about ketamine and depression." (said at 0:23:02)

Preclinical and mechanistic evidence supports the hypothesis that the downstream neurochemical and neuroplastic effects of classic hallucinogens (including psilocybin) in the prefrontal cortex are mediated by increased glutamatergic transmission, sharing convergent neurobiological pathways with ketamine. However, evidence for this mechanism relies primarily on animal models and neurochemical studies.

0:38:44Roland Griffithssupportedmoderate

Psilocybin-occasioned mystical experiences produce enduring increases in the personality domain of openness.

"after these mystical-type experiences, they are enduring changes in the personality dimension of openness." (said at 0:38:44)

Clinical trial evidence directly supports the claim. In a study evaluating healthy adults after high-dose psilocybin sessions, participants who underwent mystical-type experiences demonstrated statistically significant increases in the personality domain of Openness that remained elevated compared to baseline at follow-up more than one year later.

0:39:38Roland Griffithssupportedvery low

A pilot study combining psilocybin with cognitive behavioral therapy in 15 cigarette smokers achieved an 80% smoking abstinence rate at 6 months.

"we've done a pilot study in cigarette smokers, 15 smokers. We embedded the psilocybin manipulation in the context of a cognitive behavior therapy for smoking cessation. And remarkably, we had 80% abstinence rates at 6 months" (said at 0:39:38)

The speaker accurately describes the results of their 2014 open-label pilot study (Johnson et al.), which combined psilocybin sessions with a structured cognitive behavioral therapy (CBT) protocol in 15 treatment-seeking, nicotine-dependent smokers. At the 6-month follow-up, biologically verified 7-day point-prevalence abstinence was observed in 12 of the 15 participants (80%). The certainty of evidence for general efficacy is very low due to the small sample size and lack of a control group in the open-label pilot design.

0:40:23Roland Griffithssupportedhigh

Varenicline yields a 20% to 30% abstinence rate for smoking cessation.

"The varenicline which is probably our best treatment for smoking, 20% to 30%" (said at 0:40:23)

High-certainty evidence from randomized controlled trials and Cochrane systematic reviews confirms that varenicline is one of the most effective monotherapies for smoking cessation, achieving long-term continuous abstinence rates of approximately 20% to 30%. In a pooled meta-analysis of randomized controlled trials (PMID 25846123), continuous abstinence on varenicline was 22% at 52 weeks (and 49% at 9–12 weeks). Cochrane systematic reviews and network meta-analyses also confirm varenicline's superior efficacy compared to placebo, bupropion, and single-form nicotine replacement therapies.

0:45:24Roland Griffithssupportedmoderate

In a survey of approximately 2,000 people about their worst psilocybin mushroom experience, approximately 10% reported putting themselves or others at risk of physical harm.

"we just, actually very recently, completed and published a large survey study of people who...this was about 2000 people, and we asked them, have you ever had a bad trip after taking psilocybin mushrooms? ... we have about 10% who say that they may have put themselves or others at risk of physical harm during the experience." (said at 0:45:24)

A 2016 survey study by Carbonaro and colleagues evaluated 1,993 individuals who reported on their single most psychologically difficult experience (worst "bad trip") following psilocybin mushroom ingestion. In that sample, exactly 11% reported having put themselves or others at risk of physical harm during the experience, directly supporting the speaker's claim.

0:46:20Roland Griffithssupportedlow

In a survey of bad trips on psilocybin, a subset of respondents reported enduring psychological problems for which they sought psychiatric or psychological treatment within a year after the experience.

"And there's some percentage of people who say that they have enduring psychological problems for which they are seeking out psychological or psychiatric help with a year after the experience." (said at 0:46:20)

In a 2016 retrospective online survey by Carbonaro and colleagues investigating individuals' worst 'bad trip' after consuming psilocybin mushrooms (n = 1,993), 7.6% of respondents whose challenging experience had occurred more than one year prior reported seeking professional treatment for enduring psychological symptoms.

0:50:26Roland Griffithssupportedhigh

Approximately 30% of research volunteers in controlled psilocybin sessions report experiencing significant fear or anxiety for some duration of the session.

"we have about 30% of our volunteers who will describe, at least for some duration of time, experiences of significant fear or anxiety come up." (said at 0:50:26)

Double-blind, randomized controlled trials evaluating high-dose psilocybin in controlled laboratory settings document that roughly 30% to 39% of participants report transient episodes of strong fear, anxiety, or psychological struggle during the session, which are typically managed safely with preparation and interpersonal support.

0:52:44Roland Griffithssupportedmoderate

The probability of experiencing very difficult or challenging reactions to psilocybin increases significantly between doses of 20 mg and 30 mg per 70 kg body weight.

"the probability of the very difficult experiences increase pretty significantly between 20 and 30 milligrams per 70 kilogram." (said at 0:52:44)

A double-blind, randomized crossover dose-effect study by Griffiths and colleagues (PMID: 21674151) evaluated oral psilocybin across five dose conditions (0, 5, 10, 20, and 30 mg/70 kg) in healthy adults. The trial found that while mystical-type positive effects plateaued between 20 mg/70 kg and 30 mg/70 kg, acute episodes of extreme anxiety, fear, and challenging psychological experiences increased substantially at the highest dose (30 mg/70 kg), with 39% of participants reporting extreme anxiety/fear during the high-dose sessions.

0:54:21Roland Griffithssupportedhigh

In the cancer-related distress trials involving 51 patients at Johns Hopkins and 29 at NYU, there was no indication that volunteers were psychologically harmed by psilocybin sessions.

"In the 51 volunteers we treated, and the 29 that were treated at NYU, we have no indication that people were harmed by these experiences" (said at 0:54:21)

Two seminal randomized, double-blind crossover trials published simultaneously in 2016 evaluated psilocybin-assisted psychotherapy in patients with life-threatening cancer and associated anxiety or depression: Griffiths et al. at Johns Hopkins University (51 participants) and Ross et al. at New York University (29 participants). Both studies observed rapid, substantial, and sustained improvements in anxiety, depression, and quality of life up to 6 months post-treatment, with no indications of lasting psychological harm or serious adverse psychiatric events resulting from the psilocybin sessions.

0:53:17Roland Griffithssupportedhigh

In the Johns Hopkins study investigating psilocybin for cancer-related distress, the primary high dose administered was 22 mg per 70 kg body weight.

"And with the cancer study, for instance, the dose that we used most often in that was 22 milligrams per 70 kilogram." (said at 0:53:17)

In the landmark Johns Hopkins randomized, double-blind crossover trial evaluating psilocybin for cancer-related depression and anxiety (Griffiths et al., 2016), psilocybin was administered using weight-adjusted dosing. The study compared a very low control dose (1 or 3 mg/70 kg) to a high therapeutic dose (22 or 30 mg/70 kg) administered with psychological support, confirming the use of 22 mg/70 kg as a primary high dose.

0:56:27Roland Griffithssupportedhigh

In the initial Johns Hopkins psilocybin study with hallucinogen-naive participants, high-dose methylphenidate was utilized as an active control, and participants were informed they could receive any of 11 different psychoactive compounds.

"Our first study, we actually gave a pretty high dose of methylphenidate or Ritalin as a control substance, and these were people who had never had a hallucinogen before. And furthermore, they were told that they could get 11 different kinds of psychoactive compounds." (said at 0:56:27)

The landmark 2006 Johns Hopkins study by Roland Griffiths and colleagues evaluated the acute and sustained effects of psilocybin in 36 hallucinogen-naive healthy adults. To control for expectancy and non-specific stimulant effects, the study used a high dose of methylphenidate (40 mg/70 kg) as an active control in a double-blind, counterbalanced crossover design. To further obscure the study design and reduce expectancy biases, participants were instructed that they could receive a drug from a broad list of different psychoactive compounds or placebo across their sessions.

0:40:43Roland Griffithssupportedhigh

Clinical trials investigating psilocybin for substance use disorders include studies on alcohol use disorder at NYU and cocaine dependence at the University of Alabama.

"There's work going on at NYU in alcoholism. There's some work going on at University of Alabama on cocaine dependence." (said at 0:40:43)

The claim accurately reflects clinical trial programs evaluating psilocybin-assisted psychotherapy for substance use disorders. NYU Grossman School of Medicine researchers (led by Michael Bogenschutz) conducted a double-blind, randomized controlled trial investigating psilocybin for alcohol use disorder (NCT02061293), showing significant reductions in heavy drinking days. Concurrently, researchers at the University of Alabama at Birmingham (led by Peter Hendricks) conducted a randomized, placebo-controlled trial evaluating psilocybin for cocaine use disorder (NCT02037126).

1:45:09Rhonda Patrick (host)supportedmoderate

Stress accelerates telomere shortening.

"Stress accelerates telomere shortening." (said at 1:45:09)

Observational meta-analyses and prospective longitudinal studies support the claim that chronic and psychological stress is associated with accelerated telomere shortening and shorter telomere length. A meta-analysis of 22 studies (n=8,724) found perceived stress was associated with shorter age-adjusted telomere length (r = -0.06), with larger effects observed in populations exposed to severe chronic stress. Another meta-analysis of 41 studies (n=30,773) showed significant telomere shortening following early-life stress/adversity (d = -0.35). Prospective longitudinal research in high-stress models (such as medical internship) similarly observed telomere attrition rates several times higher than normal annual baseline rates, correlated with stress exposure.

1:46:58Rhonda Patrick (host)supportedvery low

Dynorphin is part of the thermoregulatory pathway and acts to cool the body down when body temperature rises.

"both endorphin and dynorphin are part of the thermoregulatory pathway. So dynorphin actually cools the body down. And when your body heats up, you increase dynorphin to cool it down." (said at 1:46:58)

Animal and rodent neurobiology studies demonstrate that dynorphin and kappa-opioid receptor (KOR) activation are involved in central thermoregulation, acting as endogenous hypothermic mediators that lower core body temperature. Research shows that dynorphin and KOR signaling counterbalance mu-opioid receptor-mediated hyperthermia to regulate body temperature and facilitate hypothermic responses.

1:50:03Roland Griffithssupportedhigh

The subjective effects of inhaled Salvinorin A last less than 10 minutes, with individuals returning completely to baseline within 20 minutes.

"The effects of Salvinorin, this was inhaled Salvinorin, are very short-lived. Less than 10 minutes. So it's a very rapid onset and people are completely back to baseline within 20 minutes, but most of the effects have resolved much quicker than that." (said at 1:50:03)

Clinical pharmacodynamic studies of inhaled salvinorin A in healthy volunteers confirm that its subjective effects have a rapid onset, peak within 1 to 2 minutes, rapidly dissipate over the first several minutes, and return completely to baseline by approximately 20 minutes after administration.

1:51:08Roland Griffithssupportedhigh

Ayahuasca combines dimethyltryptamine (DMT) with a monoamine oxidase (MAO) inhibitor, which prevents rapid metabolism in the gut and prolongs its duration of action.

"DMT is also the active ingredient in ayahuasca, which is the brew that's consumed mostly in South America, and by some of these syncretic religions. And that's when the DMT is combined with an MAO inhibitor that slows down the metabolism in the gut. And so it changes the duration of action and makes it more like psilocybin" (said at 1:51:08)

The speaker's statement accurately describes the established pharmacological mechanism of ayahuasca. N,N-dimethyltryptamine (DMT) is rapidly degraded in the gastrointestinal tract and liver by monoamine oxidase A (MAO-A) during first-pass metabolism, rendering oral DMT largely inactive on its own. In ayahuasca preparations, DMT-containing plants (such as Psychotria viridis) are combined with plants containing β-carboline alkaloids (such as Banisteriopsis caapi, rich in harmine, harmaline, and tetrahydroharmine). These β-carbolines act as reversible MAO-A inhibitors, preventing peripheral enzymatic breakdown in the gut and liver, thereby conferring oral bioavailability and markedly extending its duration of psychoactive action to several hours, comparable to other classic oral psychedelics like psilocybin.

1:06:44Rhonda Patrick (host)supportedhigh

Dynorphin is an endogenous opioid that binds to kappa-opioid receptors and produces dysphoria.

"the dynorphin pathway, which is an endogenous opioid that we make in our brains, sort of the counter to endorphin because it sort of makes you feel dysphoric rather than euphoric... So dynorphin binds to the kappa-opioid receptor" (said at 1:06:44)

The speaker's statement accurately reflects established neurobiology. Dynorphin is an endogenous opioid peptide that functions as a primary ligand for kappa-opioid receptors (KOR). Activation of the dynorphin/KOR system is well documented to mediate dysphoria, aversion, and anti-reward states, counterbalancing the euphoric and reward-mediating effects typically associated with endorphins and mu-opioid receptor activation.

1:12:31Roland Griffithssupportedhigh

Mescaline, the active compound found in peyote, is a serotonin 5-HT2A receptor agonist.

"Of course, we have peyote, which is mescaline, which is another serotonergic 2A agonist used by the American Indian." (said at 1:12:31)

Mescaline, a psychoactive protoalkaloid found in the peyote cactus (Lophophora williamsii), is well-established in pharmacological and neurobiological literature as a classic serotonergic psychedelic that exerts its primary hallucinogenic and perceptual effects via agonism at the serotonin 5-HT2A receptor.

Unverified means no publication matching the claim was located; it does not prove the claim false. Spotted an error? See the corrections policy - disputes from the people quoted are prioritized.