Author
Robert Jesse
Other affiliations: Johns Hopkins University School of Medicine
Bio: Robert Jesse is an academic researcher from Johns Hopkins University. The author has contributed to research in topics: Psilocybin & Entheogen. The author has an hindex of 6, co-authored 7 publications receiving 1916 citations. Previous affiliations of Robert Jesse include Johns Hopkins University School of Medicine.
Papers
More filters
TL;DR: When administered under supportive conditions, psilocybin occasioned experiences similar to spontaneously occurring mystical experiences, and the ability to occasion such experiences prospectively will allow rigorous scientific investigations of their causes and consequences.
Abstract: Rationale Although psilocybin has been used for centuries for religious purposes, little is known scientifically about its acute and persisting effects. Objectives This double-blind study evaluated the acute and longer-term psychological effects of a high dose of psilocybin relative to a comparison compound administered under comfortable, supportive conditions. Materials and methods The participants were hallucinogennaive adults reporting regular participation in religious or spiritual activities. Two or three sessions were conducted at 2-month intervals. Thirty volunteers received orally administered psilocybin (30 mg/70 kg) and methylphenidate hydrochloride (40 mg/70 kg) in counterbalanced order. To obscure the study design, six additional volunteers received methylphenidate in the first two sessions and unblinded psilocybin in a third session. The 8-h sessions were conducted individually. Volunteers were encouraged to close their eyes and direct their attention inward. Study monitors rated volunteers’ behavior during sessions. Volunteers completed questionnaires assessing drug effects and mystical experience immediately after and 2 months after sessions. Community observers rated changes in the volunteer’s attitudes and behavior. Results Psilocybin produced a range of acute perceptual changes, subjective experiences, and labile moods including anxiety. Psilocybin also increased measures of mystical experience. At 2 months, the volunteers rated the psilocybin experience as having substantial personal meaning and spiritual significance and attributed to the experience sustained positive changes in attitudes and behavior consistent with changes rated by community observers. Conclusions When administered under supportive conditions, psilocybin occasioned experiences similar to spontaneously occurring mystical experiences. The ability to occasion such experiences prospectively will allow rigorous scientific investigations of their causes and consequences.
1,017 citations
TL;DR: When administered under supportive conditions, psilocybin occasioned experiences similar to spontaneously occurring mystical experiences that, at 14-month follow-up, were considered by volunteers to be among the most personally meaningful and spiritually significant of their lives.
Abstract: Psilocybin has been used for centuries for religious purposes; however, little is known scientifically about its long-term effects. We previously reported the effects of a double-blind study evaluating the psychological effects of a high psilocybin dose. This report presents the 14-month follow-up and examines the relationship of the follow-up results to data obtained at screening and on drug session days. Participants were 36 hallucinogen-naive adults reporting regular participation in religious/ spiritual activities. Oral psilocybin (30 mg/70 kg) was administered on one of two or three sessions, with methylphenidate (40 mg/70 kg) administered on the other session(s). During sessions, volunteers were encouraged to close their eyes and direct their attention inward. At the 14-month follow-up, 58% and 67%, respectively, of volunteers rated the psilocybin-occasioned experience as being among the five most personally meaningful and among the five most spiritually significant experiences of their lives; 64% indicated that the experience increased well-being or life satisfaction; 58% met criteria for having had a 'complete' mystical experience. Correlation and regression analyses indicated a central role of the mystical experience assessed on the session day in the high ratings of personal meaning and spiritual significance at follow-up. Of the measures of personality, affect, quality of life and spirituality assessed across the study, only a scale measuring mystical experience showed a difference from screening. When administered under supportive conditions, psilocybin occasioned experiences similar to spontaneously occurring mystical experiences that, at 14-month follow-up, were considered by volunteers to be among the most personally meaningful and spiritually significant of their lives.
586 citations
TL;DR: Under supportive conditions, 20 and 30 mg/70 kg psilocybin occasioned mystical-type experiences having persisting positive effects on attitudes, mood, and behavior.
Abstract: Rationale
This dose-effect study extends previous observations showing that psilocybin can occasion mystical-type experiences having persisting positive effects on attitudes, mood, and behavior.
574 citations
TL;DR: Multiple regression analysis showed degree of difficulty was positively associated, and duration was negatively associated, with enduring increases in well-being, and difficulty of experience was positivelyassociated with dose.
Abstract: Acute and enduring adverse effects of psilocybin have been reported anecdotally, but have not been well characterized. For this study, 1993 individuals (mean age 30 yrs; 78% male) completed an online survey about their single most psychologically difficult or challenging experience (worst "bad trip") after consuming psilocybin mushrooms. Thirty-nine percent rated it among the top five most challenging experiences of his/her lifetime. Eleven percent put self or others at risk of physical harm; factors increasing the likelihood of risk included estimated dose, duration and difficulty of the experience, and absence of physical comfort and social support. Of the respondents, 2.6% behaved in a physically aggressive or violent manner and 2.7% received medical help. Of those whose experience occurred >1 year before, 7.6% sought treatment for enduring psychological symptoms. Three cases appeared associated with onset of enduring psychotic symptoms and three cases with attempted suicide. Multiple regression analysis showed degree of difficulty was positively associated, and duration was negatively associated, with enduring increases in well-being. Difficulty of experience was positively associated with dose. Despite difficulties, 84% endorsed benefiting from the experience. The incidence of risky behavior or enduring psychological distress is extremely low when psilocybin is given in laboratory studies to screened, prepared, and supported participants.
242 citations
TL;DR: Both high-dose psilocybin groups showed large significant positive changes on longitudinal measures of interpersonal closeness, gratitude, life meaning/purpose, forgiveness, death transcendence, daily spiritual experiences, religious faith and coping, and community observer ratings.
Abstract: 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 psil...
235 citations
Cited by
More filters
TL;DR: High-dose psilocybin produced large decreases in clinician- and self-rated measures of depressed mood and anxiety, along with increases in quality of life, life meaning, and optimism, and decreases in death anxiety.
Abstract: Cancer patients often develop chronic, clinically significant symptoms of depression and anxiety. Previous studies suggest that psilocybin may decrease depression and anxiety in cancer patients. Th...
1,016 citations
TL;DR: Preliminary support for the safety and efficacy of psilocybin for treatment-resistant depression is provided and motivates further trials, with more rigorous designs, to better examine the therapeutic potential of this approach.
842 citations
TL;DR: Psilocybin was associated with enduring anxiolytic and anti-depressant effects in patients with cancer-related psychological distress, sustained benefits in existential distress and quality of life, as well as improved attitudes towards death.
Abstract: Background:Clinically significant anxiety and depression are common in patients with cancer, and are associated with poor psychiatric and medical outcomes. Historical and recent research suggests a...
823 citations
TL;DR: This study established the feasibility and safety of administering moderate doses of psilocybin to patients with advanced-stage cancer and anxiety and revealed a positive trend toward improved mood and anxiety.
Abstract: CONTEXT Researchers conducted extensive investigations of hallucinogens in the 1950s and 1960s. By the early 1970s, however, political and cultural pressures forced the cessation of all projects. This investigation reexamines a potentially promising clinical application of hallucinogens in the treatment of anxiety reactive to advanced-stage cancer. OBJECTIVE To explore the safety and efficacy of psilocybin in patients with advanced-stage cancer and reactive anxiety. DESIGN A double-blind, placebo-controlled study of patients with advanced-stage cancer and anxiety, with subjects acting as their own control, using a moderate dose (0.2 mg/kg) of psilocybin. SETTING A clinical research unit within a large public sector academic medical center. PARTICIPANTS Twelve adults with advanced-stage cancer and anxiety. MAIN OUTCOME MEASURES In addition to monitoring safety and subjective experience before and during experimental treatment sessions, follow-up data including results from the Beck Depression Inventory, Profile of Mood States, and State-Trait Anxiety Inventory were collected unblinded for 6 months after treatment. RESULTS Safe physiological and psychological responses were documented during treatment sessions. There were no clinically significant adverse events with psilocybin. The State-Trait Anxiety Inventory trait anxiety subscale demonstrated a significant reduction in anxiety at 1 and 3 months after treatment. The Beck Depression Inventory revealed an improvement of mood that reached significance at 6 months; the Profile of Mood States identified mood improvement after treatment with psilocybin that approached but did not reach significance. CONCLUSIONS This study established the feasibility and safety of administering moderate doses of psilocybin to patients with advanced-stage cancer and anxiety. Some of the data revealed a positive trend toward improved mood and anxiety. These results support the need for more research in this long-neglected field. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT00302744.
758 citations
TL;DR: Psilocybin caused a significant decrease in the positive coupling between the mPFC and PCC, which strongly imply that the subjective effects of psychedelic drugs are caused by decreased activity and connectivity in the brain's key connector hubs, enabling a state of unconstrained cognition.
Abstract: Psychedelic drugs have a long history of use in healing ceremonies, but despite renewed interest in their therapeutic potential, we continue to know very little about how they work in the brain. Here we used psilocybin, a classic psychedelic found in magic mushrooms, and a task-free functional MRI (fMRI) protocol designed to capture the transition from normal waking consciousness to the psychedelic state. Arterial spin labeling perfusion and blood-oxygen level-dependent (BOLD) fMRI were used to map cerebral blood flow and changes in venous oxygenation before and after intravenous infusions of placebo and psilocybin. Fifteen healthy volunteers were scanned with arterial spin labeling and a separate 15 with BOLD. As predicted, profound changes in consciousness were observed after psilocybin, but surprisingly, only decreases in cerebral blood flow and BOLD signal were seen, and these were maximal in hub regions, such as the thalamus and anterior and posterior cingulate cortex (ACC and PCC). Decreased activity in the ACC/medial prefrontal cortex (mPFC) was a consistent finding and the magnitude of this decrease predicted the intensity of the subjective effects. Based on these results, a seed-based pharmaco-physiological interaction/functional connectivity analysis was performed using a medial prefrontal seed. Psilocybin caused a significant decrease in the positive coupling between the mPFC and PCC. These results strongly imply that the subjective effects of psychedelic drugs are caused by decreased activity and connectivity in the brain's key connector hubs, enabling a state of unconstrained cognition.
739 citations