Albert Garcia-Romeu, PhD | Johns Hopkins University School of Medicine (original) (raw)

Papers by Albert Garcia-Romeu, PhD

Current Topics in Behavioral Neurosciences, 2021

Serotonin 2A receptor (5-HT2AR) agonist “classic psychedelics” are drawing increasing interest as... more Serotonin 2A receptor (5-HT2AR) agonist “classic psychedelics” are drawing increasing interest as potential mental health treatments. Recent work suggests psychedelics can exert persisting anxiolytic and antidepressant effects lasting up to several months after a single administration. Data indicate acute subjective drug effects as important psychological factors involved in observed therapeutic benefits. Additionally, animal models have shown an important role for 5-HT2AR agonists in modulating learning and memory function with relevance for Alzheimer’s Disease (AD) and related dementias. A number of biological mechanisms of action are under investigation to elucidate 5-HT2AR agonists’ therapeutic potential, including enhanced neuroplasticity, anti-inflammatory effects, and alterations in brain functional connectivity. These diverse lines of research are reviewed here along with a discussion of AD pathophysiology and neuropsychiatric symptoms to highlight classic psychedelics as potential novel pharmacotherapies for patients with AD. Human clinical research suggests a possible role for high-dose psychedelic administration in symptomatic treatment of depressed mood and anxiety in early-stage AD. Preclinical data indicate a potential for low- or high-dose psychedelic treatment regimens to slow or reverse brain atrophy, enhance cognitive function, and slow progression of AD. In conclusion, rationale and potential approaches for preliminary research with psychedelics in patients with AD are presented, and ramifications of this line of investigation for development of novel AD treatments are discussed.

Journal of Psychopharmacology, 2021

Background: Growing evidence suggests psilocybin, a naturally occurring psychedelic, is a safe an... more 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 procedure of administering a fixed dose.
Aims: The present post hoc analyses sought to determine whether the subjective effects of psilocybin are affected by body weight when psilocybin is administered on a weight-adjusted basis and when psilocybin is administered as a fixed dose.
Methods: We analyzed acute subjective drug effects (mystical, challenging, and intensity) associated with therapeutic outcomes from ten previous studies (total N=288) in which psilocybin was administered in the range 20 to 30mg/70kg (inclusive). Separate multivariate regression analyses examined the relationships between demographic variables including body weight and subjective effects in participants receiving 20 mg/70 kg (n = 120), participants receiving 30mg/70kg (n=182), and participants whose weight-adjusted dose was about 25mg (to approximate the fixed dose that is currently being evaluated in registration trials for major depressive disorder) (n=103).
Results: In the 20mg/70kg and 30mg/70kg weight-adjusted groups, and in the fixed dose group, no significant associations were found between subjective effects and demographic variables including body weight or sex. Across a wide range of body weights (49 to 113kg) the present results showed no evidence that body weight affected subjective effects of psilocybin.
Conclusions: These results suggest that the convenience and lower cost of administering psilocybin as a fixed dose outweigh any potential advantage of weight-adjusted dosing.

Frontiers in Psychiatry, 2020

Background: Observational data and preliminary studies suggest serotonin 2A agonist psychedelics ... more 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 reduction in other substance use.
Methods: An anonymous online survey of individuals reporting cessation or reduction in cannabis, opioid, or stimulant use following psychedelic use in non-clinical settings.
Results: Four hundred forty-four respondents, mostly in the USA (67%) completed the survey. Participants reported 4.5 years of problematic substance use on average before the psychedelic experience to which they attributed a reduction in drug consumption, with 79% meeting retrospective criteria for severe SUD. Most reported taking a moderate or high dose of LSD (43%) or psilocybin-containing mushrooms (29%), followed by significant reduction in drug consumption. Before the psychedelic experience 96% met SUD criteria, whereas only 27% met SUD criteria afterward. Participants rated their psychedelic experience as highly meaningful and insightful, with 28% endorsing psychedelic-associated changes in life priorities or values as facilitating reduced substance misuse. Greater psychedelic dose, insight, mystical-type effects, and personal meaning of experiences were associated with greater reduction in drug consumption.
Conclusions: While these cross-sectional and self-report methods cannot determine whether psychedelics caused changes in drug use, results suggest the potential that psychedelics cause reductions in problematic substance use, and support additional clinical research on psychedelic-assisted treatment for SUD.

Drug and Alcohol Dependence, 2020

Background: Kratom, a Southeast Asian plant with opioid-receptor mediated effects, has emerged as... more 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 and December 2017. Results: 2,798 kratom users-mean age 40 (SD = 12); predominantly White (90 %), female (61 %), and located in the US (97 %)-completed the survey. Kratom was primarily taken orally in doses of 1−3 g (49 %), with daily use (59 %) being most common. Kratom was used for pain (91 %), anxiety (67 %), and depression (65 %), with high ratings of effectiveness. 1,144 (41 %) used kratom to stop or reduce prescription or illicit opioid use, citing decreased opioid withdrawal and craving related to kratom use, with 411 reporting > 1-year continuous abstinence from opioids attributed to kratom use. Roughly one-third of respondents reported adverse effects of kratom, largely rated as mild in severity and lasting ≤24 h. Seventeen participants (0.6 %) sought treatment for adverse effects. Fifty-six individuals (2 %) met DSM-5 criteria for a past-year moderate or severe kratom-related substance use disorder (SUD). When asked how troubled they felt regarding their kratom use, the mean (SD) rating was 3.2 (9.8) on a scale from 0 to 100. Conclusion: Kratom is used among White, middle-aged Americans for symptoms of pain, anxiety, depression, and opioid withdrawal. Although regular use was typical, kratom-related SUD and serious adverse effects were uncommon. Additional research on kratom epidemiology and pharmacology is imperative in light of the present opioid epidemic.

Journal of Psychopharmacology, 2019

Background: Meta-analysis of randomized studies using lysergic acid diethylamide (LSD) for alcoho... more 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 disorders.
Aims: To supplement clinical studies, reports of psychedelic use in naturalistic settings can provide further data regarding potential effects of psychedelics on alcohol use.
Methods: An anonymous online survey of individuals with prior AUD reporting cessation or reduction in alcohol use following psychedelic use in non- clinical settings.
Results: 343 respondents, mostly White (89%), males (78%), in the USA (60%) completed the survey. Participants reported seven years of problematic alcohol use on average before the psychedelic experience to which they attributed reduced alcohol consumption, with 72% meeting retrospective criteria for severe AUD. Most reported taking a moderate or high dose of LSD (38%) or psilocybin (36%), followed by significant reduction in alcohol consumption. After the psychedelic experience 83% no longer met AUD criteria. Participants rated their psychedelic experience as highly meaningful and insightful, with 28% endorsing psychedelic-associated changes in life priorities or values as facilitating reduced alcohol misuse. Greater psychedelic dose, insight, mystical-type effects, and personal meaning of experiences were associated with a greater reduction in alcohol consumption, controlling for prior alcohol consumption and related distress.
Conclusions: Although results cannot demonstrate causality, they suggest that naturalistic psychedelic use may lead to cessation or reduction in problematic alcohol use, supporting further investigation of psychedelic-assisted treatment for AUD.

Humans have used serotonergic hallucinogens (i.e. psychedelics) for spiritual, ceremonial, and re... more Humans have used serotonergic hallucinogens (i.e. psychedelics) for spiritual, ceremonial, and recreational purposes for thousands of years, but their administration as part of a structured therapeutic intervention is still a relatively novel practice within Western medical and psycho- logical frameworks. In the mid-20th century, considerable advances were made in developing therapeutic approaches integrating administration of low (psycholytic) and high (psychedelic) doses of serotonergic hallucinogens for treatment of a variety of conditions, often incorporating psychoanalytic concepts prevalent at that time. This work contributed seminal insights regarding how these substances may be employed with efficacy and safety in targeted therapeutic inter- ventions, including the importance of optimizing set (frame of mind) and setting (therapeutic environment). More recently, clinical and pharmacological research has revisited the effects and therapeutic potential of psychedelics utilizing a variety of approaches. The current article pro- vides an overview of past and present models of psychedelic therapy, and discusses important considerations for future interventions incorporating the use of psychedelics in research and clinical practice.

Background: Opioid overdose (OD) rates in the United States have reached unprece- dented levels. ... more Background: Opioid overdose (OD) rates in the United States have reached unprece- dented levels. Current OD prevention strategies largely consist of distribution of naloxone and in-person trainings, which face obstacles to expedient, widespread dissemination. Web-based interventions have increased opioid-OD response knowledge in patients with opioid-use disorders; however, these interventions have not been tested in the larger population of individuals that are prescribed opioid analgesics. This study assessed a web-based intervention providing education across three knowledge domains: opioid effects, opioid-OD symptoms, and opioid-OD response. Methods: Participants (N = 197) were adults recruited on Amazon Mechanical Turk from May to June 2017, who were prescribed an opioid medication for pain. Participants were randomly assigned to a Presentation (n = 97) intervention communicating relevant facts in each knowl- edge domain, or a Presentation + Mastery (n = 100) intervention including the same facts but requiring that participants respond correctly to ≥80% of embedded questions in each module before advancing. Participants completed the Brief Opioid Overdose Knowledge (BOOK) measure before and after the interventions, and provided feedback on acceptability. Results: Both versions of the intervention resulted in signi cant pre to postintervention increases in BOOK scores across all knowledge domains (p < 0.001), with no signi cant knowledge differences between groups. The Presentation intervention took signi cantly less time to complete (p < 0.001) and was completed by signi cantly more participants than the Presentation + Mastery intervention (p < 0.001). Most participants rated both interventions as highly acceptable. Conclusion: Results replicate a previous study (1) and suggest the web-based Presentation intervention may be a convenient, cost-effective method for disseminating crucial public health information for preventing opioid OD.

Background: Recent pilot trials suggest feasibility and potential efficacy of psychedelic-facilit... more 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 smoking cessation in the pilot study; (2) to identify key themes in participant experiences and long-term outcomes to better understand the therapeutic process. Methods: Participants were invited to a retrospective follow-up interview an average of 30 months after initial psilocybin sessions. Semi-structured interviews were conducted with 12 of the 15 participants. Data were analysed using thematic analysis.
Results: Participants reported gaining vivid insights into self-identity and reasons for smoking from their psilocybin sessions. Experiences of interconnectedness, awe, and curiosity persisted beyond the duration of acute drug effects. Participants emphasised that the content of psilocybin experiences overshadowed any short-term withdrawal symptoms. Preparatory counselling, strong rapport with the study team, and a sense of momentum once engaged in the study treatment were perceived as vital additional factors in achieving abstinence. In addition, participants reported a range of persisting positive changes beyond smoking cessation, including increased aesthetic appreciation, altruism, and pro-social behaviour. Conclusions: The findings highlight the value of qualitative research in the psychopharmacological investigation of psychedelics. They describe perceived connections between drug- and non-drug factors, and provide suggestions for future research trial design and clinical applications.

Data suggest psychedelics such as psilocybin and lysergic acid diethylamide (LSD) may hold therap... more Data suggest psychedelics such as psilocybin and lysergic acid diethylamide (LSD) may hold therapeutic potential in the treatment of addictions, including tobacco dependence. This retrospective cross-sectional anonymous online survey characterized 358 individuals (52 females) who reported having quit or reduced smoking after ingesting a psychedelic in a non-laboratory setting ⩾1 year ago. On average, participants smoked 14 cigarettes/ day for 8 years, and had five previous quit attempts before their psychedelic experience. Of the 358 participants, 38% reported continuous smoking cessation after psychedelic use (quitters). Among quitters, 74% reported >2 years’ abstinence. Of the 358 participants, 28% reported a persisting reduction in smoking (reducers), from a mode of 300 cigarettes/month before, to a mode of 1 cigarette/month after the experience. Among reducers, 62% reported >2 years of reduced smoking. Finally, 34% of the 358 participants (relapsers) reported a temporary smoking reduction before returning to baseline smoking levels, with a mode time range to relapse of 3–6 months. Relapsers rated their psychedelic experience significantly lower in personal meaning and spiritual significance than both other groups. Participants across all groups reported less severe affective withdrawal symptoms (e.g. depression, craving) after psychedelic use compared with previous quit attempts, suggesting a potential mechanism of action for psychedelic- associated smoking cessation/reduction. Changes in life priorities/values were endorsed as the most important psychological factor associated with smoking cessation/reduction. Results suggest psychedelics may hold promise in treating tobacco addiction as potentially mediated by spiritual experience, changed priorities/values, and improved emotional regulation.

Drug and Alcohol Dependence, 2015

Hallucinogens fall into several different classes, as broadly defined by pharmacological mechanis... more Hallucinogens fall into several different classes, as broadly defined by pharmacological mechanism of action, and chemical structure. These include psychedelics, entactogens, dissociatives, and other atypical hallucinogens. Although these classes do not share a common primary mechanism of action, they do exhibit important similarities in their ability to occasion temporary but profound alterations of consciousness, involving acute changes in somatic, perceptual, cognitive, and affective processes. Such effects likely contribute to their recreational use. However, a growing body of evidence indicates that these drugs may have therapeutic applications beyond their potential for abuse. This review will present data on several classes of hallucinogens with a particular focus on psychedelics, entactogens, and dissociatives, for which clinical utility has been most extensively documented. Information on each class is presented in turn, tracing relevant historical insights, highlighting similarities and differences between the classes from the molecular to the behavioral level, and presenting the most up-to-date information on clinically oriented research with these substances, with important ramifications for their potential therapeutic value. Public Health Significance Although most hallucinogens are currently highly restricted, some of these substances may have therapeutic applications for a variety of difficult to treat conditions, such as substance use, anxiety, and mood disorders. This review presents data on several classes of hallucinogens with a particular focus on psychedelics, entactogens, and dissociatives, for which clinical utility has been most extensively documented. Findings presented here suggest several hallucinogens have a favorable safety profile when administered under carefully controlled conditions, and warrant reconsideration as tools for clinical treatment.

Background: A recent open-label pilot study (N = 15) found that two to three moderate to high dos... more Background: A recent open-label pilot study (N = 15) found that two to three moderate to high doses (20 and 30 mg/70 kg) of the serotonin 2A receptor agonist, psilocybin, in combination with cognitive behavioral therapy (CBT) for smoking cessation, resulted in substantially higher 6-month smoking abstinence rates than are typically observed with other medications or CBT alone. Objectives: To assess long-term effects of a psilocybin-facilitated smoking cessation program at ≥12 months after psilocybin administration. Methods: The present report describes biologically verified smoking abstinence outcomes of the previous pilot study at ≥12 months, and related data on subjective effects of psilocybin. Results: All 15 participants completed a 12-month follow-up, and 12 (80%) returned for a long-term (≥16 months) follow-up, with a mean interval of 30 months (range = 16–57 months) between target-quit date (i.e., first psilocybin session) and long-term follow-up. At 12-month follow-up, 10 participants (67%) were confirmed as smoking abstinent. At long-term follow-up, nine participants (60%) were confirmed as smoking abstinent. At 12-month follow-up 13 participants (86.7%) rated their psilocybin experiences among the five most personally meaningful and spiritually significant experiences of their lives. Conclusion: These results suggest that in the context of a structured treatment program, psilocybin holds considerable promise in promoting long-term smoking abstinence. The present study adds to recent and historical evidence suggesting high success rates when using classic psychedelics in the treatment of addiction. Further research investigating psilocybin-facilitated treatment of substance use disorders is warranted.

Incarcerated youth have disproportionately high morbidity and mortality. Prior research has demon... more Incarcerated youth have disproportionately high morbidity and mortality. Prior research has demonstrated that meditation provides physical and mental health benefits to youth, as well as to incarcerated adults, however, no published studies examine whether these courses benefit incarcerated youth. Objective: To assess if a one-day intensive and 10-week meditation course delivered by non-profit agency The Mind Body Awareness Project (MBA Project) enhance the well-being of participating incarcerated youth. Methods: Incarcerated adolescent males in MBA Project's meditation course participated. Two cohorts received a 10-week meditation course plus one-day intensive meditation session (treatment, n=16) and two cohorts received 10-week course alone (controls, n=13). Focus groups were performed with participants of the one-day intensive session to evaluate youth's attitudes towards the intervention (n=6 and 6, ages 15-18). Results were transcribed and qualitative theme analysis was...

Drug and Alcohol Dependence, 2015

Aims: Contingency Management (CM) has demonstrated its efficacy in increasing treatment retention... more Aims: Contingency Management (CM) has demonstrated its efficacy in increasing treatment retention and abstinence across most substance use disorders, including nicotine dependence. Depressive symptoms are usually associated with poorer treatment outcomes in smokers. However, no study to date has explored the influence of depressive symptoms on CM treatment outcomes. The main objective of the present study was to assess the effects of baseline depressive symptoms on CM outcomes.

Drug and Alcohol Dependence, 2014

Psilocybin-occasioned mystical experiences have been linked to persisting effects in healthy volu... more Psilocybin-occasioned mystical experiences have been linked to persisting effects in healthy volunteers including positive changes in behavior, attitudes, and values, and increases in the personality domain of openness. In an open-label pilot-study of psilocybin-facilitated smoking addiction treatment, 15 smokers received 2 or 3 doses of psilocybin in the context of cognitive behavioral therapy (CBT) for smoking cessation. Twelve of 15 participants (80%) demonstrated biologically verified smoking abstinence at 6-month follow-up. Participants who were abstinent at 6 months (n=12) were compared to participants still smoking at 6 months (n=3) on measures of subjective effects of psilocybin. Abstainers scored significantly higher on a measure of psilocybin-occasioned mystical experience. No significant differences in general intensity of drug effects were found between groups, suggesting that mystical-type subjective effects, rather than overall intensity of drug effects, were responsible for smoking cessation. Nine of 15 participants (60%) met criteria for "complete" mystical experience. Smoking cessation outcomes were significantly correlated with measures of mystical experience on session days, as well as retrospective ratings of personal meaning and spiritual significance of psilocybin sessions. These results suggest a mediating role of mystical experience in psychedelic-facilitated addiction treatment.

Abstract A growing body of evidence suggests that mindfulness meditation is associated with a num... more Abstract A growing body of evidence suggests that mindfulness meditation is associated with a number of physiological and psychological benefits in both adult and juvenile populations. Research on mindfulness-based interventions among at-risk and incarcerated youth popula- tions has also shown feasibility as a means of enhancing self-regulation and well-being. This randomized controlled trial examined an 8- to 12-week program in which partic- ipants received individual and group psychotherapy. Partic- ipants in the experimental condition received formal mind- fulness training alongside psychotherapy, while those in the control condition received psychotherapy without mindfulness training. All participants received the group intervention. Participants were recruited from a court- mandated substance abuse group treatment program at a juvenile detention camp in the San Francisco Bay Area. Participants were 35 incarcerated youth (100 % male; 70 % Hispanic; mean age = 16.45). Of these, 27 provided complete pre- and post-treatment assessment data. Mea- sures of mindfulness, locus of control, decision-making, self-esteem, and attitude toward drugs were administered before and after the intervention. Detention camp staff provided behavioral rating points for each participant in
the week prior to beginning the study treatment and in the week after completing the intervention. Significant in- creases in self-esteem (p < 0.05) and decision-making skills (p < 0.01) were observed among the entire study sample. Between-group analyses found significantly greater in- creases in self-esteem (p < 0.05) and staff ratings of good behavior (p < 0.05) in the mindfulness treatment group, consistent with prior research. These results suggest a po- tentially important role for mindfulness-based interventions in improving well-being and decreasing recidivism among this at-risk population.

Abstract: Psilocybin-occasioned mystical experiences have been linked to persisting effects in he... more Abstract: Psilocybin-occasioned mystical experiences have been linked to persisting effects in healthy volunteers including positive changes in behavior, attitudes, and values, and increases in the personality domain of openness. In an open-label pilot-study of psilocybin-facilitated smoking addiction treatment, 15 smokers received 2 or 3 doses of psilocybin in the context of cognitive behavioral therapy (CBT) for smoking cessation. Twelve of 15 participants (80%) demonstrated biologically verified smoking abstinence at 6-month follow-up. Participants who were abstinent at 6 months (n=12) were compared to participants still smoking at 6 months (n=3) on measures of subjective effects of psilocybin. Abstainers scored significantly higher on a measure of psilocybin-occasioned mystical experience. No significant differences in general intensity of drug effects were found between groups, suggesting that mystical-type subjective effects, rather than overall intensity of drug effects, were responsible for smoking cessation. Nine of 15 participants (60%) met criteria for “complete” mystical experience. Smoking cessation outcomes were significantly correlated with measures of mystical experience on session days, as well as retrospective ratings of personal meaning and spiritual significance of psilocybin sessions. These results suggest a mediating role of mystical experience in psychedelic-facilitated addiction treatment.

This study examined the overall psychological effects of inebriation facilitated by the naturally... more This study examined the overall psychological effects of inebriation facilitated by the naturally-occurring plant hallucinogen Salvia divinorum using a double-blind, randomized, placebo-controlled trial. Thirty healthy individuals self-administered Salvia divinorum via combustion and inhalation in a quiet, comfortable research setting. Experimental sessions, post-session interviews, and 8-week follow-up meetings were audio recorded and transcribed to provide the primary qualitative material analyzed here. Additionally, post-session responses to the Hallucinogen Rating Scale provided a quantitative groundwork for mixed-methods discussion. Qualitative data underwent thematic content analysis, being coded independently by three researchers before being collaboratively integrated to provide the final results. Three main themes and 10 subthemes of acute intoxication emerged, encompassing the qualities of the experience, perceptual alterations, and cognitive-affective shifts. The experience was described as having rapid onset and being intense and unique. Participants reported marked changes in auditory, visual, and interoceptive sensory input; losing normal awareness of themselves and their surroundings; and an assortment of delusional phenomena. Additionally, the abuse potential of Salvia divinorum was examined post hoc. These findings are discussed in light of previous research, and provide an initial framework for greater understanding of the subjective effects of Salvia divinorum, an emerging drug of abuse.

Current theories in psychology conceptualize self-transcendence as a personality trait, a develop... more Current theories in psychology conceptualize self-transcendence as a personality trait, a developmental construct, and a particular class of anomalous experience. Despite extensive research on self-transcendence, the process, outcomes, and nature of self-transcendent experience (STE) remain elusive. This study focused on the self-reported narratives of STE in 15 healthy adults. Accounts were collected in face-to-face interviews, transcribed, and thematically analyzed using grounded theory methodology. Qualitative results were recursively examined to construct a preliminary mid-range theory of STE in healthy adults. Three major theme areas emerged from interview data. These were (a) context, (b) phenomenology, and (c) aftermath of STE. Each of these major themes was further divided into distinct sub-themes, including setting, perceptual alterations, and long-term effects. The resulting interpretation of STE is discussed in light of current literature and directions for future research.

Despite suggestive early findings on the therapeutic use of hallucinogens in the treatment of sub... more Despite suggestive early findings on the therapeutic use of hallucinogens in the treatment of substance use disorders, rigorous follow-up has not been conducted. To determine the safety and feasibility of psilocybin as an adjunct to tobacco smoking cessation treatment we conducted an open- label pilot study administering moderate (20 mg/70 kg) and high (30 mg/70 kg) doses of psilocybin within a structured 15-week smoking cessation treatment protocol. Participants were 15 psychiatrically healthy nicotine-dependent smokers (10 males; mean age of 51 years), with a mean of six previous lifetime quit attempts, and smoking a mean of 19 cigarettes per day for a mean of 31 years at intake. Biomarkers assessing smoking status, and self-report measures of smoking behavior demonstrated that 12 of 15 participants (80%) showed seven-day point prevalence abstinence at 6-month follow-up. The observed smoking cessation rate substantially exceeds rates commonly reported for other behavioral and/or pharmacological therapies (typically <35%). Although the open-label design does not allow for definitive conclusions regarding the efficacy of psilocybin, these findings suggest psilocybin may be a potentially efficacious adjunct to current smoking cessation treatment models. The present study illustrates a framework for future research on the efficacy and mechanisms of hallucinogen-facilitated treatment of addiction.

Current Topics in Behavioral Neurosciences, 2021

Serotonin 2A receptor (5-HT2AR) agonist “classic psychedelics” are drawing increasing interest as... more Serotonin 2A receptor (5-HT2AR) agonist “classic psychedelics” are drawing increasing interest as potential mental health treatments. Recent work suggests psychedelics can exert persisting anxiolytic and antidepressant effects lasting up to several months after a single administration. Data indicate acute subjective drug effects as important psychological factors involved in observed therapeutic benefits. Additionally, animal models have shown an important role for 5-HT2AR agonists in modulating learning and memory function with relevance for Alzheimer’s Disease (AD) and related dementias. A number of biological mechanisms of action are under investigation to elucidate 5-HT2AR agonists’ therapeutic potential, including enhanced neuroplasticity, anti-inflammatory effects, and alterations in brain functional connectivity. These diverse lines of research are reviewed here along with a discussion of AD pathophysiology and neuropsychiatric symptoms to highlight classic psychedelics as potential novel pharmacotherapies for patients with AD. Human clinical research suggests a possible role for high-dose psychedelic administration in symptomatic treatment of depressed mood and anxiety in early-stage AD. Preclinical data indicate a potential for low- or high-dose psychedelic treatment regimens to slow or reverse brain atrophy, enhance cognitive function, and slow progression of AD. In conclusion, rationale and potential approaches for preliminary research with psychedelics in patients with AD are presented, and ramifications of this line of investigation for development of novel AD treatments are discussed.

Journal of Psychopharmacology, 2021

Background: Growing evidence suggests psilocybin, a naturally occurring psychedelic, is a safe an... more 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 procedure of administering a fixed dose.
Aims: The present post hoc analyses sought to determine whether the subjective effects of psilocybin are affected by body weight when psilocybin is administered on a weight-adjusted basis and when psilocybin is administered as a fixed dose.
Methods: We analyzed acute subjective drug effects (mystical, challenging, and intensity) associated with therapeutic outcomes from ten previous studies (total N=288) in which psilocybin was administered in the range 20 to 30mg/70kg (inclusive). Separate multivariate regression analyses examined the relationships between demographic variables including body weight and subjective effects in participants receiving 20 mg/70 kg (n = 120), participants receiving 30mg/70kg (n=182), and participants whose weight-adjusted dose was about 25mg (to approximate the fixed dose that is currently being evaluated in registration trials for major depressive disorder) (n=103).
Results: In the 20mg/70kg and 30mg/70kg weight-adjusted groups, and in the fixed dose group, no significant associations were found between subjective effects and demographic variables including body weight or sex. Across a wide range of body weights (49 to 113kg) the present results showed no evidence that body weight affected subjective effects of psilocybin.
Conclusions: These results suggest that the convenience and lower cost of administering psilocybin as a fixed dose outweigh any potential advantage of weight-adjusted dosing.

Frontiers in Psychiatry, 2020

Background: Observational data and preliminary studies suggest serotonin 2A agonist psychedelics ... more 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 reduction in other substance use.
Methods: An anonymous online survey of individuals reporting cessation or reduction in cannabis, opioid, or stimulant use following psychedelic use in non-clinical settings.
Results: Four hundred forty-four respondents, mostly in the USA (67%) completed the survey. Participants reported 4.5 years of problematic substance use on average before the psychedelic experience to which they attributed a reduction in drug consumption, with 79% meeting retrospective criteria for severe SUD. Most reported taking a moderate or high dose of LSD (43%) or psilocybin-containing mushrooms (29%), followed by significant reduction in drug consumption. Before the psychedelic experience 96% met SUD criteria, whereas only 27% met SUD criteria afterward. Participants rated their psychedelic experience as highly meaningful and insightful, with 28% endorsing psychedelic-associated changes in life priorities or values as facilitating reduced substance misuse. Greater psychedelic dose, insight, mystical-type effects, and personal meaning of experiences were associated with greater reduction in drug consumption.
Conclusions: While these cross-sectional and self-report methods cannot determine whether psychedelics caused changes in drug use, results suggest the potential that psychedelics cause reductions in problematic substance use, and support additional clinical research on psychedelic-assisted treatment for SUD.

Drug and Alcohol Dependence, 2020

Background: Kratom, a Southeast Asian plant with opioid-receptor mediated effects, has emerged as... more 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 and December 2017. Results: 2,798 kratom users-mean age 40 (SD = 12); predominantly White (90 %), female (61 %), and located in the US (97 %)-completed the survey. Kratom was primarily taken orally in doses of 1−3 g (49 %), with daily use (59 %) being most common. Kratom was used for pain (91 %), anxiety (67 %), and depression (65 %), with high ratings of effectiveness. 1,144 (41 %) used kratom to stop or reduce prescription or illicit opioid use, citing decreased opioid withdrawal and craving related to kratom use, with 411 reporting > 1-year continuous abstinence from opioids attributed to kratom use. Roughly one-third of respondents reported adverse effects of kratom, largely rated as mild in severity and lasting ≤24 h. Seventeen participants (0.6 %) sought treatment for adverse effects. Fifty-six individuals (2 %) met DSM-5 criteria for a past-year moderate or severe kratom-related substance use disorder (SUD). When asked how troubled they felt regarding their kratom use, the mean (SD) rating was 3.2 (9.8) on a scale from 0 to 100. Conclusion: Kratom is used among White, middle-aged Americans for symptoms of pain, anxiety, depression, and opioid withdrawal. Although regular use was typical, kratom-related SUD and serious adverse effects were uncommon. Additional research on kratom epidemiology and pharmacology is imperative in light of the present opioid epidemic.

Journal of Psychopharmacology, 2019

Background: Meta-analysis of randomized studies using lysergic acid diethylamide (LSD) for alcoho... more 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 disorders.
Aims: To supplement clinical studies, reports of psychedelic use in naturalistic settings can provide further data regarding potential effects of psychedelics on alcohol use.
Methods: An anonymous online survey of individuals with prior AUD reporting cessation or reduction in alcohol use following psychedelic use in non- clinical settings.
Results: 343 respondents, mostly White (89%), males (78%), in the USA (60%) completed the survey. Participants reported seven years of problematic alcohol use on average before the psychedelic experience to which they attributed reduced alcohol consumption, with 72% meeting retrospective criteria for severe AUD. Most reported taking a moderate or high dose of LSD (38%) or psilocybin (36%), followed by significant reduction in alcohol consumption. After the psychedelic experience 83% no longer met AUD criteria. Participants rated their psychedelic experience as highly meaningful and insightful, with 28% endorsing psychedelic-associated changes in life priorities or values as facilitating reduced alcohol misuse. Greater psychedelic dose, insight, mystical-type effects, and personal meaning of experiences were associated with a greater reduction in alcohol consumption, controlling for prior alcohol consumption and related distress.
Conclusions: Although results cannot demonstrate causality, they suggest that naturalistic psychedelic use may lead to cessation or reduction in problematic alcohol use, supporting further investigation of psychedelic-assisted treatment for AUD.

Humans have used serotonergic hallucinogens (i.e. psychedelics) for spiritual, ceremonial, and re... more Humans have used serotonergic hallucinogens (i.e. psychedelics) for spiritual, ceremonial, and recreational purposes for thousands of years, but their administration as part of a structured therapeutic intervention is still a relatively novel practice within Western medical and psycho- logical frameworks. In the mid-20th century, considerable advances were made in developing therapeutic approaches integrating administration of low (psycholytic) and high (psychedelic) doses of serotonergic hallucinogens for treatment of a variety of conditions, often incorporating psychoanalytic concepts prevalent at that time. This work contributed seminal insights regarding how these substances may be employed with efficacy and safety in targeted therapeutic inter- ventions, including the importance of optimizing set (frame of mind) and setting (therapeutic environment). More recently, clinical and pharmacological research has revisited the effects and therapeutic potential of psychedelics utilizing a variety of approaches. The current article pro- vides an overview of past and present models of psychedelic therapy, and discusses important considerations for future interventions incorporating the use of psychedelics in research and clinical practice.

Background: Opioid overdose (OD) rates in the United States have reached unprece- dented levels. ... more Background: Opioid overdose (OD) rates in the United States have reached unprece- dented levels. Current OD prevention strategies largely consist of distribution of naloxone and in-person trainings, which face obstacles to expedient, widespread dissemination. Web-based interventions have increased opioid-OD response knowledge in patients with opioid-use disorders; however, these interventions have not been tested in the larger population of individuals that are prescribed opioid analgesics. This study assessed a web-based intervention providing education across three knowledge domains: opioid effects, opioid-OD symptoms, and opioid-OD response. Methods: Participants (N = 197) were adults recruited on Amazon Mechanical Turk from May to June 2017, who were prescribed an opioid medication for pain. Participants were randomly assigned to a Presentation (n = 97) intervention communicating relevant facts in each knowl- edge domain, or a Presentation + Mastery (n = 100) intervention including the same facts but requiring that participants respond correctly to ≥80% of embedded questions in each module before advancing. Participants completed the Brief Opioid Overdose Knowledge (BOOK) measure before and after the interventions, and provided feedback on acceptability. Results: Both versions of the intervention resulted in signi cant pre to postintervention increases in BOOK scores across all knowledge domains (p < 0.001), with no signi cant knowledge differences between groups. The Presentation intervention took signi cantly less time to complete (p < 0.001) and was completed by signi cantly more participants than the Presentation + Mastery intervention (p < 0.001). Most participants rated both interventions as highly acceptable. Conclusion: Results replicate a previous study (1) and suggest the web-based Presentation intervention may be a convenient, cost-effective method for disseminating crucial public health information for preventing opioid OD.

Background: Recent pilot trials suggest feasibility and potential efficacy of psychedelic-facilit... more 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 smoking cessation in the pilot study; (2) to identify key themes in participant experiences and long-term outcomes to better understand the therapeutic process. Methods: Participants were invited to a retrospective follow-up interview an average of 30 months after initial psilocybin sessions. Semi-structured interviews were conducted with 12 of the 15 participants. Data were analysed using thematic analysis.
Results: Participants reported gaining vivid insights into self-identity and reasons for smoking from their psilocybin sessions. Experiences of interconnectedness, awe, and curiosity persisted beyond the duration of acute drug effects. Participants emphasised that the content of psilocybin experiences overshadowed any short-term withdrawal symptoms. Preparatory counselling, strong rapport with the study team, and a sense of momentum once engaged in the study treatment were perceived as vital additional factors in achieving abstinence. In addition, participants reported a range of persisting positive changes beyond smoking cessation, including increased aesthetic appreciation, altruism, and pro-social behaviour. Conclusions: The findings highlight the value of qualitative research in the psychopharmacological investigation of psychedelics. They describe perceived connections between drug- and non-drug factors, and provide suggestions for future research trial design and clinical applications.

Data suggest psychedelics such as psilocybin and lysergic acid diethylamide (LSD) may hold therap... more Data suggest psychedelics such as psilocybin and lysergic acid diethylamide (LSD) may hold therapeutic potential in the treatment of addictions, including tobacco dependence. This retrospective cross-sectional anonymous online survey characterized 358 individuals (52 females) who reported having quit or reduced smoking after ingesting a psychedelic in a non-laboratory setting ⩾1 year ago. On average, participants smoked 14 cigarettes/ day for 8 years, and had five previous quit attempts before their psychedelic experience. Of the 358 participants, 38% reported continuous smoking cessation after psychedelic use (quitters). Among quitters, 74% reported >2 years’ abstinence. Of the 358 participants, 28% reported a persisting reduction in smoking (reducers), from a mode of 300 cigarettes/month before, to a mode of 1 cigarette/month after the experience. Among reducers, 62% reported >2 years of reduced smoking. Finally, 34% of the 358 participants (relapsers) reported a temporary smoking reduction before returning to baseline smoking levels, with a mode time range to relapse of 3–6 months. Relapsers rated their psychedelic experience significantly lower in personal meaning and spiritual significance than both other groups. Participants across all groups reported less severe affective withdrawal symptoms (e.g. depression, craving) after psychedelic use compared with previous quit attempts, suggesting a potential mechanism of action for psychedelic- associated smoking cessation/reduction. Changes in life priorities/values were endorsed as the most important psychological factor associated with smoking cessation/reduction. Results suggest psychedelics may hold promise in treating tobacco addiction as potentially mediated by spiritual experience, changed priorities/values, and improved emotional regulation.

Drug and Alcohol Dependence, 2015

Hallucinogens fall into several different classes, as broadly defined by pharmacological mechanis... more Hallucinogens fall into several different classes, as broadly defined by pharmacological mechanism of action, and chemical structure. These include psychedelics, entactogens, dissociatives, and other atypical hallucinogens. Although these classes do not share a common primary mechanism of action, they do exhibit important similarities in their ability to occasion temporary but profound alterations of consciousness, involving acute changes in somatic, perceptual, cognitive, and affective processes. Such effects likely contribute to their recreational use. However, a growing body of evidence indicates that these drugs may have therapeutic applications beyond their potential for abuse. This review will present data on several classes of hallucinogens with a particular focus on psychedelics, entactogens, and dissociatives, for which clinical utility has been most extensively documented. Information on each class is presented in turn, tracing relevant historical insights, highlighting similarities and differences between the classes from the molecular to the behavioral level, and presenting the most up-to-date information on clinically oriented research with these substances, with important ramifications for their potential therapeutic value. Public Health Significance Although most hallucinogens are currently highly restricted, some of these substances may have therapeutic applications for a variety of difficult to treat conditions, such as substance use, anxiety, and mood disorders. This review presents data on several classes of hallucinogens with a particular focus on psychedelics, entactogens, and dissociatives, for which clinical utility has been most extensively documented. Findings presented here suggest several hallucinogens have a favorable safety profile when administered under carefully controlled conditions, and warrant reconsideration as tools for clinical treatment.

Background: A recent open-label pilot study (N = 15) found that two to three moderate to high dos... more Background: A recent open-label pilot study (N = 15) found that two to three moderate to high doses (20 and 30 mg/70 kg) of the serotonin 2A receptor agonist, psilocybin, in combination with cognitive behavioral therapy (CBT) for smoking cessation, resulted in substantially higher 6-month smoking abstinence rates than are typically observed with other medications or CBT alone. Objectives: To assess long-term effects of a psilocybin-facilitated smoking cessation program at ≥12 months after psilocybin administration. Methods: The present report describes biologically verified smoking abstinence outcomes of the previous pilot study at ≥12 months, and related data on subjective effects of psilocybin. Results: All 15 participants completed a 12-month follow-up, and 12 (80%) returned for a long-term (≥16 months) follow-up, with a mean interval of 30 months (range = 16–57 months) between target-quit date (i.e., first psilocybin session) and long-term follow-up. At 12-month follow-up, 10 participants (67%) were confirmed as smoking abstinent. At long-term follow-up, nine participants (60%) were confirmed as smoking abstinent. At 12-month follow-up 13 participants (86.7%) rated their psilocybin experiences among the five most personally meaningful and spiritually significant experiences of their lives. Conclusion: These results suggest that in the context of a structured treatment program, psilocybin holds considerable promise in promoting long-term smoking abstinence. The present study adds to recent and historical evidence suggesting high success rates when using classic psychedelics in the treatment of addiction. Further research investigating psilocybin-facilitated treatment of substance use disorders is warranted.

Incarcerated youth have disproportionately high morbidity and mortality. Prior research has demon... more Incarcerated youth have disproportionately high morbidity and mortality. Prior research has demonstrated that meditation provides physical and mental health benefits to youth, as well as to incarcerated adults, however, no published studies examine whether these courses benefit incarcerated youth. Objective: To assess if a one-day intensive and 10-week meditation course delivered by non-profit agency The Mind Body Awareness Project (MBA Project) enhance the well-being of participating incarcerated youth. Methods: Incarcerated adolescent males in MBA Project's meditation course participated. Two cohorts received a 10-week meditation course plus one-day intensive meditation session (treatment, n=16) and two cohorts received 10-week course alone (controls, n=13). Focus groups were performed with participants of the one-day intensive session to evaluate youth's attitudes towards the intervention (n=6 and 6, ages 15-18). Results were transcribed and qualitative theme analysis was...

Drug and Alcohol Dependence, 2015

Aims: Contingency Management (CM) has demonstrated its efficacy in increasing treatment retention... more Aims: Contingency Management (CM) has demonstrated its efficacy in increasing treatment retention and abstinence across most substance use disorders, including nicotine dependence. Depressive symptoms are usually associated with poorer treatment outcomes in smokers. However, no study to date has explored the influence of depressive symptoms on CM treatment outcomes. The main objective of the present study was to assess the effects of baseline depressive symptoms on CM outcomes.

Drug and Alcohol Dependence, 2014

Psilocybin-occasioned mystical experiences have been linked to persisting effects in healthy volu... more Psilocybin-occasioned mystical experiences have been linked to persisting effects in healthy volunteers including positive changes in behavior, attitudes, and values, and increases in the personality domain of openness. In an open-label pilot-study of psilocybin-facilitated smoking addiction treatment, 15 smokers received 2 or 3 doses of psilocybin in the context of cognitive behavioral therapy (CBT) for smoking cessation. Twelve of 15 participants (80%) demonstrated biologically verified smoking abstinence at 6-month follow-up. Participants who were abstinent at 6 months (n=12) were compared to participants still smoking at 6 months (n=3) on measures of subjective effects of psilocybin. Abstainers scored significantly higher on a measure of psilocybin-occasioned mystical experience. No significant differences in general intensity of drug effects were found between groups, suggesting that mystical-type subjective effects, rather than overall intensity of drug effects, were responsible for smoking cessation. Nine of 15 participants (60%) met criteria for "complete" mystical experience. Smoking cessation outcomes were significantly correlated with measures of mystical experience on session days, as well as retrospective ratings of personal meaning and spiritual significance of psilocybin sessions. These results suggest a mediating role of mystical experience in psychedelic-facilitated addiction treatment.

Abstract A growing body of evidence suggests that mindfulness meditation is associated with a num... more Abstract A growing body of evidence suggests that mindfulness meditation is associated with a number of physiological and psychological benefits in both adult and juvenile populations. Research on mindfulness-based interventions among at-risk and incarcerated youth popula- tions has also shown feasibility as a means of enhancing self-regulation and well-being. This randomized controlled trial examined an 8- to 12-week program in which partic- ipants received individual and group psychotherapy. Partic- ipants in the experimental condition received formal mind- fulness training alongside psychotherapy, while those in the control condition received psychotherapy without mindfulness training. All participants received the group intervention. Participants were recruited from a court- mandated substance abuse group treatment program at a juvenile detention camp in the San Francisco Bay Area. Participants were 35 incarcerated youth (100 % male; 70 % Hispanic; mean age = 16.45). Of these, 27 provided complete pre- and post-treatment assessment data. Mea- sures of mindfulness, locus of control, decision-making, self-esteem, and attitude toward drugs were administered before and after the intervention. Detention camp staff provided behavioral rating points for each participant in
the week prior to beginning the study treatment and in the week after completing the intervention. Significant in- creases in self-esteem (p < 0.05) and decision-making skills (p < 0.01) were observed among the entire study sample. Between-group analyses found significantly greater in- creases in self-esteem (p < 0.05) and staff ratings of good behavior (p < 0.05) in the mindfulness treatment group, consistent with prior research. These results suggest a po- tentially important role for mindfulness-based interventions in improving well-being and decreasing recidivism among this at-risk population.

Abstract: Psilocybin-occasioned mystical experiences have been linked to persisting effects in he... more Abstract: Psilocybin-occasioned mystical experiences have been linked to persisting effects in healthy volunteers including positive changes in behavior, attitudes, and values, and increases in the personality domain of openness. In an open-label pilot-study of psilocybin-facilitated smoking addiction treatment, 15 smokers received 2 or 3 doses of psilocybin in the context of cognitive behavioral therapy (CBT) for smoking cessation. Twelve of 15 participants (80%) demonstrated biologically verified smoking abstinence at 6-month follow-up. Participants who were abstinent at 6 months (n=12) were compared to participants still smoking at 6 months (n=3) on measures of subjective effects of psilocybin. Abstainers scored significantly higher on a measure of psilocybin-occasioned mystical experience. No significant differences in general intensity of drug effects were found between groups, suggesting that mystical-type subjective effects, rather than overall intensity of drug effects, were responsible for smoking cessation. Nine of 15 participants (60%) met criteria for “complete” mystical experience. Smoking cessation outcomes were significantly correlated with measures of mystical experience on session days, as well as retrospective ratings of personal meaning and spiritual significance of psilocybin sessions. These results suggest a mediating role of mystical experience in psychedelic-facilitated addiction treatment.

This study examined the overall psychological effects of inebriation facilitated by the naturally... more This study examined the overall psychological effects of inebriation facilitated by the naturally-occurring plant hallucinogen Salvia divinorum using a double-blind, randomized, placebo-controlled trial. Thirty healthy individuals self-administered Salvia divinorum via combustion and inhalation in a quiet, comfortable research setting. Experimental sessions, post-session interviews, and 8-week follow-up meetings were audio recorded and transcribed to provide the primary qualitative material analyzed here. Additionally, post-session responses to the Hallucinogen Rating Scale provided a quantitative groundwork for mixed-methods discussion. Qualitative data underwent thematic content analysis, being coded independently by three researchers before being collaboratively integrated to provide the final results. Three main themes and 10 subthemes of acute intoxication emerged, encompassing the qualities of the experience, perceptual alterations, and cognitive-affective shifts. The experience was described as having rapid onset and being intense and unique. Participants reported marked changes in auditory, visual, and interoceptive sensory input; losing normal awareness of themselves and their surroundings; and an assortment of delusional phenomena. Additionally, the abuse potential of Salvia divinorum was examined post hoc. These findings are discussed in light of previous research, and provide an initial framework for greater understanding of the subjective effects of Salvia divinorum, an emerging drug of abuse.

Current theories in psychology conceptualize self-transcendence as a personality trait, a develop... more Current theories in psychology conceptualize self-transcendence as a personality trait, a developmental construct, and a particular class of anomalous experience. Despite extensive research on self-transcendence, the process, outcomes, and nature of self-transcendent experience (STE) remain elusive. This study focused on the self-reported narratives of STE in 15 healthy adults. Accounts were collected in face-to-face interviews, transcribed, and thematically analyzed using grounded theory methodology. Qualitative results were recursively examined to construct a preliminary mid-range theory of STE in healthy adults. Three major theme areas emerged from interview data. These were (a) context, (b) phenomenology, and (c) aftermath of STE. Each of these major themes was further divided into distinct sub-themes, including setting, perceptual alterations, and long-term effects. The resulting interpretation of STE is discussed in light of current literature and directions for future research.

Despite suggestive early findings on the therapeutic use of hallucinogens in the treatment of sub... more Despite suggestive early findings on the therapeutic use of hallucinogens in the treatment of substance use disorders, rigorous follow-up has not been conducted. To determine the safety and feasibility of psilocybin as an adjunct to tobacco smoking cessation treatment we conducted an open- label pilot study administering moderate (20 mg/70 kg) and high (30 mg/70 kg) doses of psilocybin within a structured 15-week smoking cessation treatment protocol. Participants were 15 psychiatrically healthy nicotine-dependent smokers (10 males; mean age of 51 years), with a mean of six previous lifetime quit attempts, and smoking a mean of 19 cigarettes per day for a mean of 31 years at intake. Biomarkers assessing smoking status, and self-report measures of smoking behavior demonstrated that 12 of 15 participants (80%) showed seven-day point prevalence abstinence at 6-month follow-up. The observed smoking cessation rate substantially exceeds rates commonly reported for other behavioral and/or pharmacological therapies (typically <35%). Although the open-label design does not allow for definitive conclusions regarding the efficacy of psilocybin, these findings suggest psilocybin may be a potentially efficacious adjunct to current smoking cessation treatment models. The present study illustrates a framework for future research on the efficacy and mechanisms of hallucinogen-facilitated treatment of addiction.