Roland R Griffiths

• Johns Hopkins Medicine

An interesting aspect of entity encounters during psychedelic experiences is their ability to transform one’s religious beliefs. However, little is known about sex differences in these transformations. This study investigates sex differences in changes in religious beliefs before and after an entity encounter among ayahuasca users. Data were collec...

Introduction: Serotonergic psychedelics, serotonin 2A receptor agonists such as psilocybin that can result in substantially altered states of consciousness, are used in recreational and research settings. The safety of psychedelic experiences in research settings is supported by controlled physical environments, presence of clinical and medical sta...

A recent wave of research in psychiatry and neuroscience has re-examined the properties of ‘classic’ psychedelic substances—also known as serotonergic hallucinogens—such as psilocybin, lysergic acid diethylamide (LSD), and N,N-dimethyltryptamine (DMT). Evidence to date suggests that psychedelics can be given safely in controlled conditions, at mode...

The administration of classic psychedelics has been associated with well-being and mental health benefits as well as risks and adverse events. The acute subjective effects of psychedelics might have a causal role in these risks and therapeutic benefits, but inconsistencies and limitations in the conceptualization and measurement of these acute subj...

We examined if the therapeutic alliance between study participants and intervention facilitators in a psilocybin-assisted therapy (PAT) trial changed over time and whether there were relationships between alliance, acute psilocybin experiences, and depression outcomes. In a randomized, waiting list-controlled clinical trial for major depressive dis...

Despite distinct classes of psychoactive drugs producing putatively unique states of consciousness, there is surprising overlap in terms of their effects on episodic memory and cognition more generally. Episodic memory is supported by multiple subprocesses that have been mostly overlooked in psychopharmacology and could differentiate drug classes....

As individuals and communities around the world confront mounting physical, psychological, and social threats, three complimentary mind-body-spirit pathways toward health, wellbeing, and human flourishing remain underappreciated within conventional practice among the biomedical, public health, and policy communities. This paper reviews literature o...

Introduction The classic psychedelic psilocybin, found in some mushroom species, has received renewed interest in clinical research, showing potential mental health benefits in preliminary trials. Naturalistic use of psilocybin outside of research settings has increased in recent years, though data on the public health impact of such use remain lim...

Importance: Psilocybin shows promise as a treatment for major depressive disorder (MDD). Objective: To evaluate the magnitude, timing, and durability of antidepressant effects and safety of a single dose of psilocybin in patients with MDD. Design, setting, and participants: In this phase 2 trial conducted between December 2019 and June 2022 at...

Rationale: N-methyl-D-aspartate receptor-mediated dissociatives and serotonergic hallucinogens are being increasingly used in therapeutic interventions that involve nonordinary states of consciousness and may represent a unique mental health paradigm wherein pharmacologically induced experiences are conducive to psychological well-being. Objective...

We conducted a meta-analysis using individual participant data from three, two-dose psilocybin trials for depression (N=102) with the aim of assessing the risk of symptom worsening. Clinically significant symptom worsening occurred for a minority of participants in the psilocybin and escitalopram conditions (∼10%) and for a majority of participants...

This study translated and tested the psychometric properties of acute psychedelic effects measures among Spanish-speaking people. The Psychological Insight Questionnaire (PIQ), Challenging Experiences Questionnaire (CEQ), and Mystical Experiences Questionnaire (MEQ) were translated before being incorporated into a web-based survey. We recruited nat...

Psychedelic survey research in predominantly white, middle-to-upper class English-speaking participants suggests that naturalistic psychedelic use is associated with positive perceived effects on mental health conditions. Little is known about what benefits Spanish-speaking users experience from the use of psychedelic drugs or the strategies they u...

Previous research on harm reduction (HR) strategies related to psychedelic use has been limited to primarily white, middle-to-upper class, English-speaking participants, finding a relationship between HR strategy use and acute psychedelic effects. However, nothing is known about the relationship between HR strategy use and acute psychedelic effects...

Background: Psilocybin is being studied for depression, but little is known about how it interacts with common antidepressants. Limited data suggest that psilocybin's effects may be diminished by serotonergic antidepressants acutely and even after a medication washout period. Aims: To learn the extent to which antidepressants may diminish the ef...

Recent studies suggest psychedelic use may be associated with changes in a variety of beliefs or belief-like states, including increased 1) mind perception, 2) non-naturalistic beliefs, and 3) Atheist-Believer status (e.g., believer, agnostic, or non-believer). We conducted a prospective longitudinal study among participants (N = 657) who planned t...

Evidence suggests that psychedelics bring about their therapeutic outcomes in part through the subjective or qualitative effects they engender and how the individual interprets the resulting experiences. However, psychedelics are contraindicated for individuals who have been diagnosed with certain mental illnesses, on the grounds that these subject...

Background: Subjective experiences seem to play an important role in the enduring effects of psychedelic experiences. Although the importance of the subjective experience on the impact of psychedelics is frequently discussed, a more detailed understanding of the subtypes of psychedelic experiences and their associated impacts on mental health has...

Importance Novel treatments for opioid use disorder (OUD) are needed to address both the ongoing opioid epidemic and long-standing barriers to existing OUD treatments that target the endogenous μ-opioid receptor (MOR) system. The goal of this review is to highlight unique clinical trial design considerations for the study of emerging treatments for...

Purpose of Review: A growing body of research suggests psychedelic-assisted therapy (PAT) may be safe and effective for a variety of mental health conditions. Among these, eating disorders have been a recent target of interest. This review provides an up-to-date summary of the potential mechanisms and use of PAT in people diagnosed with eating diso...

Background: Psychedelic use is anecdotally associated with belief changes, although few studies have tested these claims. Aim: Characterize a broad range of psychedelic occasioned belief changes. Survey: A survey was conducted in 2374 respondents who endorsed having had a belief changing psychedelic experience. Participants rated their agreeme...

Background: Psilocybin is being studied for depression, but little is known about how it interacts with common antidepressants. Limited data suggests that psilocybin’s effects may be diminished by serotonergic antidepressants acutely and even after a medication washout period.Aims: To learn the extent to which serotonergic antidepressants may dimin...

This Viewpoint presents impediments to the clinical application of psychedelics created by extreme shifts in public perception while advocating further study and encouraging the dispute of claims not supported by available evidence.

Both psychedelic drug experiences and near-death experiences can occasion changes in perspectives on death and dying, but there have been few direct comparisons of these phenomena. This study directly compared psychedelic occasioned and non-drug experiences which altered individuals’ beliefs about death. Individuals who reported an experience that...

New medicines containing classic hallucinogenic and entactogenic psychedelic substance are under development for various psychiatric and neurological disorders. Many of these, including psilocybin, lysergic acid diethylamide (LSD), and 3,4-methylenedioxymethamphetamine (MDMA) are Schedule I controlled substances of the United States Controlled Subs...

Background: Classic psychedelics, such as psilocybin and LSD, and other serotonin 2A receptor (5-HT2AR) agonists evoke acute alterations in perception and cognition. Altered thalamocortical connectivity has been hypothesized to underlie these effects, which is supported by some functional MRI (fMRI) studies. These studies have treated the thalamus...

BACKGROUND: Psychedelic use is anecdotally associated with belief changes, although few studies have tested these claims.AIM: Characterize a broad range of psychedelic occasioned belief changes.SURVEY: A survey was conducted in 2,374 respondents who endorsed having had a belief changing psychedelic experience. Participants rated their agreement wit...

Psychiatric and existential distress commonly occur in advanced cancer and other serious, life-threatening or end-of-life medical illnesses and are associated with poor medical and psychiatric outcomes. Currently available treatment modalities in this patient population, including medication and psychotherapy, are limited in effectiveness, especial...

Understanding the phenomenology and content of the inhaled N, N, dimethyltryptamine (N, N-DMT) experience is critical to facilitate and support ongoing research and therapeutic models targeting mental health conditions and central nervous system pathology. A qualitative analysis was conducted of all N, N-DMT experiences posted to the r/DMT Reddit c...

Despite distinct classes of psychoactive drugs producing putatively unique states of consciousness, there is surprising overlap in terms of their effects on episodic memory and cognition more generally. Episodic memory is supported by multiple subprocesses that have been mostly overlooked in psychopharmacology and could differentiate drug classes....

Background: Understanding the phenomenology and content of the inhaled N, N, dimethyltryptamine (N, N-DMT) experience is critical to facilitate and support ongoing research and therapeutic models targeting mental health conditions and central nervous system pathology. Methods: Qualitative analysis of all N, N-DMT experiences posted to the r/DMT Red...

Introduction Although the topic of consciousness is both mysterious and controversial, psychedelic drugs are popularly believed to provide unique insights into the nature of consciousness despite a lack of empirical evidence. Methods This study addresses the question of whether psychedelics change the attribution of consciousness to a range of liv...

Background Serotonin 2A receptor (5-HT 2AR ) agonist psychedelics including psilocybin and LSD (“classic” psychedelics) evoke acute alterations in perception and cognition. Altered thalamocortical connectivity has been proposed to underlie these effects, which is supported by some functional MRI (fMRI) studies. Likely due to sample size limitations...

Background: Preliminary data suggest that psilocybin-assisted treatment produces substantial and rapid antidepressant effects in patients with major depressive disorder (MDD), but little is known about long-term outcomes. Aims: This study sought to examine the efficacy and safety of psilocybin through 12 months in participants with moderate to seve...

Psilocybin (a serotonin 2A, or 5-HT 2A , receptor agonist) has shown preliminary efficacy as a treatment for mood and substance use disorders. The current report utilized positron emission tomography (PET) with the selective 5-HT 2A receptor inverse agonist radioligand [ ¹¹ C]MDL 100,907 (a.k.a. M100,907) and cortical regions of interest (ROIs) der...

End of life and palliative care has improved in recent decades but the psychopharmacological options available to clinicians and patients in these contexts remain limited. In particular, psychological factors such as depression, existential distress, and well-being remain challenging to address with current medications. Here, we review recent resea...

Classic psychedelic drugs such as psilocybin and lysergic acid diethylamide (LSD) have recaptured the imagination of both science and popular culture, and may have efficacy in treating a wide range of psychiatric disorders. Human and animal studies of psychedelic drug action in the brain have demonstrated the involvement of the serotonin 2A (5-HT2A...

Psilocybin has shown promise for the treatment of mood disorders, which are often accompanied by cognitive dysfunction including cognitive rigidity. Recent studies have proposed neuropsychoplastogenic effects as mechanisms underlying the enduring therapeutic effects of psilocybin. In an open-label study of 24 patients with major depressive disorder...

Lyme disease (also known as Lyme borreliosis) is the most common vector-borne disease in the United States with an estimated 476,000 cases per year. While historically, the long-term impact of Lyme disease on patients has been controversial, mounting evidence supports the idea that a substantial number of patients experience persistent symptoms fol...

Introduction: Psychedelics show promise in treating unipolar depression, though patients with bipolar disorder have been excluded from recent psychedelic trials. There is limited information on the use of classic psychedelics (e. g., LSD or psilocybin) in individuals using mood stabilizers to treat bipolar disorder. This is important to know, as i...

Psychedelic substances produce unusual and compelling changes in conscious experience which have prompted some to propose that psychedelics may provide unique insights explaining the nature of consciousness. At present, psychedelics, like other current scientific tools and methods, seem unlikely to provide information relevant to the so-called “har...

Introduction: Psychedelics show promise in treating unipolar depression, though patients with bipolar disorder have been excluded from recent psychedelic trials. There is limited information on the use of classic psychedelics (e.g. LSD or psilocybin) in individuals using mood stabilizers to treat bipolar disorder. This is important to know as indiv...

Background Growing evidence suggests psilocybin, a naturally occurring psychedelic, is a safe and promising pharmacotherapy for treatment of mood and substance use disorders when administered as part of a structured intervention. In most trials to date, psilocybin dose has been administered on a weight-adjusted basis rather than the more convenient...

To the Editor: On behalf of our coauthors, we regret to report that we have discovered calculation errors in some of the reported effects in our Original Investigation, “Effects of Psilocybin-Assisted Therapy on Major Depressive Disorder: A Randomized Clinical Trial,”1 that was published in JAMA Psychiatry on November 4, 2020. These calculation e...

This study was designed to identify trends in the top-cited classic psychedelic publications. The top 50 publications on classic psychedelics with the greatest total of number of citations and annual citation rate were identified and pooled. Unique articles (n = 77) were dichotomized by median year of publication (2010); the differential distributi...

Background: Several measures have been developed to examine acute psychedelic effects (e.g. mystical-type and challenging experiences), but no measure assesses acute psychologically insightful experiences that may occur during psychedelic experiences. Aim: The purpose of this study was to develop and examine the psychometric properties of the Psych...

Classic psychedelics produce altered states of consciousness that individuals often interpret as meaningful experiences. Across a number of human studies, when the participant-rated intensity of the overall drug effects are statistically controlled for, certain subjective effects predict therapeutic and other desirable outcomes. Underlying neurobio...

There is a resurgence, some say renaissance, of clinical research on psychedelic substances after decades of dormancy. Recent studies have produced findings suggesting psychedelics may demonstrate substantial efficacy for serious psychiatric conditions such as mood and substance use disorders. As a result, ongoing clinical trials with the psychedel...

Importance: Major depressive disorder (MDD) is a substantial public health burden, but current treatments have limited effectiveness and adherence. Recent evidence suggests that 1 or 2 administrations of psilocybin with psychological support produces antidepressant effects in patients with cancer and in those with treatment-resistant depression. O...

Salvinorin A (SA) is a κ-opioid receptor agonist and atypical dissociative hallucinogen found in Salvia divinorum. Despite the resurgence of hallucinogen studies, the effects of κ-opioid agonists on human brain function are not well-understood. This placebo-controlled, within-subject study used functional magnetic resonance imaging for the first ti...

RationaleAlthough both psilocybin and dextromethorphan (DXM) produce psychedelic-like subjective effects, rates of non-medical use of psilocybin are consistently greater than DXM.Objective New data are presented from a study of psilocybin and DXM relevant to understanding the features of psilocybin subjective effects that may account for its higher...

Psychedelic drugs, including the serotonin 2a (5-HT2A) receptor partial agonist psilocybin, are receiving renewed attention for their possible efficacy in treating a variety of neuropsychiatric disorders. Psilocybin induces widespread dysregulation of cortical activity, but circuit-level mechanisms underlying this effect are unclear. The claustrum...

Background Experiences of having an encounter with seemingly autonomous entities are sometimes reported after inhaling N,N-dimethyltryptamine. Aim The study characterized the subjective phenomena, interpretation, and persisting changes that people attribute to N,N-dimethyltryptamine-occasioned entity encounter experiences. Methods Two thousand, f...

Background: The DSM-5 recognizes caffeine use disorder as a condition for further study, but there is a need to better understand its prevalence and clinical significance among the general population. Methods: A survey was conducted among an online sample of 1006 caffeine-consuming adults using demographic quotas to reflect the U.S. population. Ca...

Psilocybin is a classic psychedelic compound that may have efficacy for the treatment of mood and substance use disorders. Acute psilocybin effects include reduced negative mood, increased positive mood, and reduced amygdala response to negative affective stimuli. However, no study has investigated the long-term, enduring impact of psilocybin on ne...

Background: Kratom, a Southeast Asian plant with opioid-receptor mediated effects, has emerged as a potential substance of abuse, with limited data on its use and effects. This study characterized kratom user demographics, use patterns, and perceived drug effects. Methods: A cross-sectional, anonymous online survey was conducted between January...

Background Observational data and preliminary studies suggest serotonin 2A agonist psychedelics may hold potential in treating a variety of substance use disorders (SUDs), including opioid use disorder (OUD). Aims The study aim was to describe and analyze self-reported cases in which naturalistic psychedelic use was followed by cessation or reduct...

Background and aims 5-Methoxy-N,N-dimethyltryptamine (5-MeO-DMT) is a potent, short-acting psychedelic that produces strong hallucinogenic effects. The association between the context (i.e., set and setting) of 5-MeO-DMT use and the acute and enduring effects of the substance is unknown. Therefore, this study examined these associations using secon...

Prior research has shown that acute subjective psychedelic effects are associated with both spontaneous and intended changes in depression and anxiety. Psychedelics are also theorized to produce increases in psychological flexibility, which could explain decreases in depression and anxiety following a psychedelic experience. Therefore, the present...

Background: Recent reports of naturalistic psychedelic use outside of clinical settings suggest potential positive effects substance use disorders. However, still unknown are the mechanisms of psychedelic-assisted behavior change and what variables might predict who will benefit from psychedelic-assisted behavior change. Methods: This secondary ana...

This presentation was given as part of the Psychedelics as Behavior Change Agents symposium at APA 2019 and describes behavioral economic analyses of enduring changes following psilocybin administration.

Psilocybin has shown to increase social cooperation in an Ultimatum Game and empathy for social partners. Unexamined is whether psilocybin impacts social discounting or responding in a Prisoner’s Dilemma game, and how enduring any changes might be. We administered psilocybin to participants (N = 75) who also started a program of meditation/spiritua...

Background: Major Depressive Disorder (MDD) is a prevalent condition that confers substantial public health burden. Current approved treatments, including pharmacotherapy and psychotherapy, are limited in effectiveness and adherence. Recent evidence suggests that one or two administrations of psilocybin under psychologically supported conditions pr...

Background: Meta-analysis of randomized studies using lysergic acid diethylamide (LSD) for alcohol use disorder (AUD) showed large, significant effects for LSD efficacy compared to control conditions. Clinical studies suggest potential anti-addiction effects of LSD and mechanistically-related classic psychedelics for alcohol and other substance use...

Naturally occurring and psychedelic drug–occasioned experiences interpreted as personal encounters with God are well described but have not been systematically compared. In this study, five groups of individuals participated in an online survey with detailed questions characterizing the subjective phenomena, interpretation, and persisting changes a...

Questionnaire of naturally occurring (i.e. non-drug) God encounter experiences. (PDF)

Supporting information tables A, B, C, D, E, F, G, H, I, and J provide estimated means and standard errors of the estimate for data presented in the published manuscript in Tables 3, 4, 5, 6, 7, 8, 9, 10, 11 and 12, respectively. (PDF)

Questionnaire of God encounter experiences occasioned by classic psychedelics. (PDF)

The present study sought to examine factors associated with psychedelic-occasioned reductions in drug use to better understand possible mechanisms through which psychedelic use may exert such effects. Respondents (n=444; White=82%, male=79%, US resident=67%; cannabis users=37%; opioid users=35%; stimulant users=28%) self-identified as experiencing...

Background: N,N-dimethyltryptamine (DMT) is a naturally occurring psychoactive indolealkylamine. Contemporarily, DMT is typically ingested via inhalation (e.g., smoking) and elicits powerful psychedelic effects with a rapid onset and short duration of action. Anecdotal reports of the acute subjective effects of DMT include having had an encounter w...

5-MeO-DMT is a psychoactive substance found in high concentrations in the bufotoxin of the Colorado River Toad (Bufo alvarius). Emerging evidence suggests that vaporized 5-MeO-DMT may occasion mystical experiences of comparable intensity to those occasioned by more widely studied psychedelics such as psilocybin, but no empirical study has tested th...

The purpose of this paper is to provide an integrative review and offer novel insights regarding human research with classic psychedelics (classic hallucinogens), which are serotonin 2A receptor (5-HT2AR) agonists such as lysergic acid diethylamide (LSD), mescaline, and psilocybin. Classic psychedelics have been administered as sacraments since anc...

5-Methoxy-N,N-Dimethyltryptamine (5-MeO-DMT) is a psychoactive compound found in glandular secretions of Bufo alvarius toads and is synthesized. No human laboratory studies have been conducted, but evidence suggests 5-MeO-DMT may reduce depression and anxiety symptoms among those who use for spiritual or recreational reasons. Probing the effects of...

Background: Caffeine Use Disorder was added to DSM-5 as a diagnosis for further research, but few studies have been conducted to identify effective treatments. This randomized, controlled clinical trial examined the efficacy of a manual-only treatment program for caffeine cessation and reduction among individuals seeking treatment for problematic...

Background: A recent epidemiological study suggested that 5-methoxy-N,N-dimethyltryptamine (5-MeO-DMT) used for spiritual and recreational reasons is associated with subjective improvement in depression and anxiety. Further exploration of the potential psychotherapeutic effects of 5-MeO-DMT could inform future clinical trials. Objectives: We exa...

Objectives: Classic psychedelics (serotonin 2A receptor agonists) and dissociative hallucinogens (NMDA receptor antagonists), though differing in pharmacology, may share neuropsychological effects. These drugs, however, have undergone limited direct comparison. This report presents data from a double-blind, placebo-controlled within-subjects study...

Background: Recent pilot trials suggest feasibility and potential efficacy of psychedelic-facilitated addiction treatment interventions. Fifteen participants completed a psilocybin-facilitated smoking cessation pilot study between 2009 and 2015. Aims: The aims of this study were as follows: (1) to identify perceived mechanisms of change leading to...

Conclusions: (1) psilocybin has an abuse potential appropriate for CSA scheduling if approved as medicine; (2) psilocybin can provide therapeutic benefits that may support the development of an approvable New Drug Application (NDA) but further studies are required which this review describes; (3) adverse effects of medical psilocybin are relativel...

Rationale: Although psilocybin and dextromethorphan (DXM) are hallucinogens, they have different receptor mechanisms of action and have not been directly compared. Objective: This study compared subjective, behavioral, and physiological effects of psilocybin and dextromethorphan under conditions that minimized expectancy effects. Methods: Sing...

Psilocybin can occasion mystical-type experiences with participant-attributed increases in well-being. However, little research has examined enduring changes in traits. This study administered psilocybin to participants who undertook a program of meditation/spiritual practices. Healthy participants were randomized to three groups (25 each): (1) ver...

Objectives Classic hallucinogens (e.g. psilocybin and LSD) have substantial effects on perception, cognition, and emotion that can often be psychologically challenging, however we know very little regarding the source of significant individual variability that has been observed in the frequency and intensity of challenging experiences (i.e. “bad tr...

Psilocybin is a classic (serotonergic) hallucinogen (“psychedelic” drug) that may occasion mystical experiences (characterized by a profound feeling of oneness or unity) during acute effects. Such experiences may have therapeutic value. Research and clinical applications of psychedelics usually include music listening during acute drug effects, bas...

Psilocybin and other 5-hydroxytryptamine2A agonist classic psychedelics have been used for centuries as sacraments within indigenous cultures. In the mid-twentieth century they were a focus within psychiatry as both probes of brain function and experimental therapeutics. By the late 1960s and early 1970s these scientific inquires fell out of favor...