The present study in healthy participants sought to extend understanding of possible enduring effects of quantum change experiences generally and psilocybin-occasioned experiences specifically by manipulating psilocybin dose and the intensity with which participants were encouraged to engage in meditation and other spiritual practices. Acute psilocybin effects, retrospective attributions to the experience, and enduring changes in prosocial attitudes and behaviors, and psychological functioning were assessed. More specifically, the present study used an across-group design to compare these outcomes in three groups of 25 healthy participants: (1) low-dose (active placebo) psilocybin with moderate-level (“standard”) support for spiritual practice; (2) high-dose psilocybin with standard support; and (3) high-dose psilocybin with high support.

Although an older literature on psilocybin-assisted psychotherapy in psychiatric patient populations suggests that administration of psilocybin in a psychotherapeutic context may produce enduring decreases in psychopathology and increases in positive worldview and dispositional characteristics, methodological limitations render those reports inconclusive ( Passie, 2004 , 2007 ). However, recent placebo-controlled trials in psychologically distressed cancer patients showed that psilocybin produced decreases in anxiety and depression and increases in quality of life that persisted for at least a month and possibly 6 months or more ( Griffiths et al., 2016 ; Grob et al., 2011 ; Ross et al., 2016 ).

Materials and methods

Participants Participants were recruited from the local community through flyers seeking volunteers interested in developing their spiritual lives by participating in a study of the combined effects of meditation and psilocybin, a psychoactive substance found in mushrooms used as sacraments in some cultures. In total, 1305 individuals were screened by telephone and 184 were further screened in person. Primary reasons for exclusion between phone screen and in-person screening were prior use of psychedelics (312); medical/psychiatric exclusion (288); pre-existing regular meditation or other spiritual practice (261); logistics or lack of interest (220). Eighty-five volunteers were enrolled in the study and 10 did not complete the study. Reasons for non-completion included illness or a disqualifying medical or psychological issue (five volunteers), noncompliance with study procedures for personal or job-related reasons (three volunteers), and missing data on key measures (two volunteers). The 75 study completers (40% male) were medically healthy (as determined by medical history, physical examination, an electrocardiogram, routine medical blood laboratory tests, and urine testing for common drugs of abuse), and psychiatrically healthy. They were without personal or family histories of psychotic disorders or bipolar I or II disorder as determined by structured clinical interviews. Individuals with current alcohol or other drug dependence (including nicotine) were excluded, as were individuals with a past history within the past 5 years of alcohol or drug dependence (excluding nicotine). Twenty-five percent of participants reported past use of a psychedelic, with a mean of 25.1 years since last use. Participants were excluded if they reported any history of either spontaneous or psychedelic-occasioned salient mystical-type experiences. Participants had a mean age of 42 years (range 22 to 69) and a mean weight of 71.5 kg (range 49.2 to 97.5); 89% had college or post-graduate degrees and 87% were full-time employees or students. Although 31% reported practicing seated meditation, the mean frequency of practice was very low (1.1 times per month for the group). Volunteers did not receive monetary compensation for participation. Based on interviews, their motivation for participation was their interest in learning meditation, exploring their spiritual lives, and their curiosity about the effects of psilocybin. The Johns Hopkins IRB approved the study. Written informed consent was obtained from participants.

Study design and overview The study procedures followed recommendations provided for safe conduct of research administering high doses of a classic psychedelic (Johnson et al., 2008). This study investigated the effects of psilocybin dose and the frequency and intensity of support provided for spiritual practice (i.e. meditation, spiritual awareness practice, journaling) on a battery of attitudinal and behavioral outcome measures in 75 healthy participants. The psilocybin dose manipulation was double-blind. The duration of each volunteer’s participation was approximately 6 to 8 months. After enrollment and before the first of two psilocybin sessions (described below), each participant had several preparation meetings with two study staff trained to serve as session “guides.” The two psilocybin sessions were separated by about 1 month. Some measures were assessed during and immediately after sessions, and various longitudinal measures were evaluated immediately after study enrollment (i.e. baseline assessment) and 4 months after the second psilocybin session (i.e. 6-month assessment). Assignment to the three experimental groups After screening and study enrollment, each participant was randomized to one of three groups of 25 each: (1) very low-dose psilocybin (1 mg/70 kg on sessions 1 and 2—functionally a placebo) with standard support for spiritual practice (LD-SS); (2) high-dose psilocybin (20 and 30 mg/70 kg on sessions 1 and 2, respectively) with standard support for spiritual practice (HD-SS); and (3) high-dose psilocybin (20 and 30 mg/70 kg on sessions 1 and 2, respectively) with high support for spiritual practice (HD-HS). An urn randomization procedure (Stout et al., 1994) was used to balance the three groups as closely as possible on six dichotomous variables (gender, age at study intake, lifetime psychedelic use, baseline lifetime Hood Mysticism Scale score, baseline frequency of meditation, and staff judgment about whether the participant was especially likely to engage in spiritual practices). Table 1 shows that these and other demographic characteristics did not differ across the three experimental groups. Table 1. Participant demographics. View larger version Instructions to participants and guides, and the purpose of a third session Study instructions and procedures were designed to minimize some of the effects of expectancy. Participants and guides were told that participants would receive psilocybin during each session, that dose levels could range between very low to high, that each participant would receive two or more different dose levels across two or three sessions, and that all participants would have at least one session with a moderately high or high dose of psilocybin. Although the most important comparative data on attitudinal and behavioral change were obtained in the first two sessions and subsequent follow-up, 39 participants were assigned to receive a third session after the 6-month data assessment in which they received 30 mg/70 kg psilocybin. This design feature was used in part to control expectancies through the 6-month follow-up evaluation. Although participants and guides were informed that over two or three sessions all participants would receive one or more high doses of psilocybin, they were not informed which participants or how many participants would be scheduled for a third session, nor were they told that the third session would be a high dose. In fact, all 25 participants in the low-dose psilocybin group (LD-SS) were assigned to receive a third session. An additional 14 participants (eight and six from HD-SS and HD-HS, respectively) were also assigned to receive a third session. Nine of these 14 participants were distributed within the first one-third (25) participants enrolled in the study. The purpose of scheduling a third session in these 14 participants was to obscure the study design from the guides early in the trial and reduce the possibility that guides would have strong expectancies whether or not a participant would have a third session. Data from the third session and data from several exploratory measures are beyond the scope of this report and are not presented.

Guide–participant meetings and support for spiritual practice The guide–participant meetings served the functions of establishing rapport, providing specific preparation for the psilocybin sessions (see Johnson et al., 2008), and providing instructions and support for spiritual practices. The primary guides had established personal meditation practices as well as extensive experience supporting psilocybin sessions. An assistant guide was usually present at these meetings. Except for the dialogue-group meetings described below, the same primary and assistant guides were paired with a given participant throughout the study. Guide–participant meetings began and ended with a brief period of meditation. Standard-Support groups The frequency of guide–participant meetings differed across the standard vs. high-support conditions. Before the first psilocybin session (in the 1-month period following enrollment) guides and participants in the two standard-support groups (Low-Dose Standard-Support group; High-Dose Standard-Support group) had three 1-hour meetings and one 2-hour meeting (5 total contact hours). After each of the first two psilocybin sessions, participants in the standard-support group met for 1 hour within one or two days (usually one day) and had a 10 minute teleconference with guides about 2 weeks later. Thus, the total guide–participant contact hours for those in the Standard-Support groups from study acceptance to the 6-month follow-up was about 7 hours and 20 minutes. High-Support group Before the first session (in the 1 month period following enrollment) participants and guides in the High-Dose High-Support group had five 2-hour meetings (10 total contact hours). Between the first and second psilocybin sessions (1 month apart) there were three 1-hour participant–guide meetings (3 total contact hours). As with the Standard-Support groups, the first of these meetings was scheduled within a day or two following the session. During the 4-month period after the second psilocybin session, 1-hour participant–guide meetings occurred within a day or two of the session, at weekly intervals for the first 2 weeks, and at twice-monthly intervals for the remainder of the 4 months (10 contact hours). Also during the 4-month period after the second psilocybin session, participants in the High-Support group participated in twice-monthly 90-minute dialogue-group sessions. Approximately eight study participants plus one or two facilitators (study staff) participated in each session. The group membership changed over sessions as individual participants entered and left the group as they progressed through the study. The facilitators provided an opportunity to discuss psilocybin experiences but mainly encouraged dialogue about successes and challenges in implementing and sustaining the regular spiritual practices of meditation, spiritual awareness, and journaling. The total guide–participant contact hours for the High-Support group from study acceptance to the 6-month follow-up was 35 hours. Spiritual practice support At the first guide–participant meeting, each participant was given: (1) a copy of the book, Meditation: A Simple 8-Point Program for Translating Spiritual Ideals into Daily Life (Easwaran, 1991/1978); (2) a blank journal; and (3) a one-page outline of spiritual practice suggestions. All participants were required to read the book on meditation and integration of spiritual values into daily life. This book was used as a primary teaching resource because its approach provides an easily understood, nonsectarian program for spiritual living that has shown increases in measures of spirituality, well-being, self-efficacy, and health outcomes (Flinders et al., 2007; Oman et al., 2006, 2008a,b). The spiritual practice suggestions had three primary elements: meditation (10 to 30 minutes of sitting meditation daily); daily awareness practice (use of mantra and one-pointed attention in daily activities); and daily self-reflective journaling of insights, benefits, and challenges of spiritual practice in daily life. Participants were also encouraged to engage in activities they personally judged to facilitate spiritual growth (e.g. being in nature, contemplative movement, artwork, or service activities). At each of the guide–participant meetings, the guide asked about, encouraged, and offered instructions in the participant’s implementation of the spiritual practice suggestions.

Psilocybin sessions Psilocybin doses were prepared in opaque, size 0 gelatin capsules of identical appearance, with lactose as the inactive capsule filler. On each session, a single capsule was administered with 180 mL water. As described in more detail previously (Griffiths et al., 2006), psilocybin sessions were conducted in an aesthetic living-room-like environment with two guides present. Participants were instructed to consume a low-fat breakfast before arriving at the research unit at about 08:15 in the morning. A urine sample was taken to verify abstinence from common drugs of abuse and that female participants were not pregnant. For most of the time during the session, participants were encouraged to lie down on the couch, use an eye mask to block external visual distractions, and use headphones through which a program of classical and world music was played. The same music program was played for all participants in all sessions. Throughout the session, guides were nondirective and supportive and they encouraged participants to focus their attention on their inner experiences.

Measures assessed throughout the session Ten minutes before and 30, 60, 90, 120, 180, 240, 300, and 360 minutes after capsule administration, blood pressure, heart rate, and monitor ratings were obtained by session guides as described previously (Griffiths et al., 2006). Blood pressure (systolic and diastolic pressure using oscillometric method with the blood-pressure cuff placed on the arm) and heart rate were monitored using a Non-Invasive Patient Monitor Model 507E (Criticare Systems, Inc., Waukesha, WI). At the same time-points the two session guides completed the Monitor Rating Questionnaire, which involved rating or scoring several dimensions of the participant’s behavior or mood (Table 2). The dimensions that are expressed as peak scores in Table 2 were rated on a 5-point scale from 0 to 4. Data were the mean of the two monitor ratings at each time-point. Table 2. Cardiovascular measures and guide ratings of volunteer behavior and mood assessed throughout the session. View larger version

Spiritual practices assessed at the 6-month follow-up Spiritual practices questionnaire This questionnaire assessed engagement with the three primary spiritual practices that were the focus of the spiritual practice teachings, the guide–participant meetings, and the dialogue-group meetings. Participants were instructed to complete the questionnaire based on their spiritual practices over the past 4 months (since the second psilocybin session). Participants rated the frequency and duration of their usual meditation practice, the frequency of their daily awareness practice (e.g. mantra repetition during daily activities), and the frequency of their self-reflective journaling.

Persisting effects assessed at the 6-month follow-up Persisting effects questionnaire This questionnaire assessed changes in attitudes, moods, behavior, and spiritual experience and has been shown sensitive to the effects of psilocybin 14 months after a psilocybin session (Griffiths et al., 2011). Participants were asked to rate any current persisting effects that they attributed to the experiences during either or both of the two psilocybin sessions. One hundred forty items were rated on a 6-point scale (0=none, not at all; 1=so slight cannot decide; 2=slight; 3=moderate; 4=strong; 5=extreme, more than ever before in your life and stronger than 4). Within the questionnaire, the items were labeled in six categories: Attitudes about life (13 positive and 13 negative items); Attitudes about self (11 positive and 11 negative items); Mood changes (9 positive and 9 negative items); Relationships (9 positive and 9 negative items); Behavioral changes (1 positive and 1 negative item); Spirituality (22 positive and 21 negative items). The positive and negative items were intermixed within each category. For purposes of scoring the resulting 12 scales (positive and negative scales for each of six categories) scores were expressed as the percentage of the maximum possible score. The questionnaire included three additional questions (see Griffiths et al., 2006 for more specific wording): (1) How personally meaningful was the experience? (rated from 1 to 8, with 1=no more than routine, everyday experiences; 7=among the five most meaningful experiences of my life; and 8=the single most meaningful experience of my life); (2) Indicate the degree to which the experience was spiritually significant to you? (rated from 1 to 6, with 1=not at all; 5=among the five most spiritually significant experiences of my life; 6=the single most spiritually significant experience of my life); (3) Do you believe that the experience and your contemplation of that experience have led to change in your current sense of personal well-being or life satisfaction? (rated from +3=Increased very much; 0=No change; –3=Decreased very much).