Faculty Bibliography

Importance/UNASSIGNED:Although classic psychedelic medications have shown promise in the treatment of alcohol use disorder (AUD), the efficacy of psilocybin remains unknown. Objective/UNASSIGNED:To evaluate whether 2 administrations of high-dose psilocybin improve the percentage of heavy drinking days in patients with AUD undergoing psychotherapy relative to outcomes observed with active placebo medication and psychotherapy. Design, Setting, and Participants/UNASSIGNED:In this double-blind randomized clinical trial, participants were offered 12 weeks of manualized psychotherapy and were randomly assigned to receive psilocybin vs diphenhydramine during 2 day-long medication sessions at weeks 4 and 8. Outcomes were assessed over the 32-week double-blind period following the first dose of study medication. The study was conducted at 2 academic centers in the US. Participants were recruited from the community between March 12, 2014, and March 19, 2020. Adults aged 25 to 65 years with a DSM-IV diagnosis of alcohol dependence and at least 4 heavy drinking days during the 30 days prior to screening were included. Exclusion criteria included major psychiatric and drug use disorders, hallucinogen use, medical conditions that contraindicated the study medications, use of exclusionary medications, and current treatment for AUD. Interventions/UNASSIGNED:Study medications were psilocybin, 25 mg/70 kg, vs diphenhydramine, 50 mg (first session), and psilocybin, 25-40 mg/70 kg, vs diphenhydramine, 50-100 mg (second session). Psychotherapy included motivational enhancement therapy and cognitive behavioral therapy. Main Outcomes and Measures/UNASSIGNED:The primary outcome was percentage of heavy drinking days, assessed using a timeline followback interview, contrasted between groups over the 32-week period following the first administration of study medication using multivariate repeated-measures analysis of variance. Results/UNASSIGNED:A total of 95 participants (mean [SD] age, 46 [12] years; 42 [44.2%] female) were randomized (49 to psilocybin and 46 to diphenhydramine). One participant (1.1%) was American Indian/Alaska Native, 5 (5.3%) were Black, 16 (16.8%) were Hispanic, and 75 (78.9%) were non-Hispanic White. Of the 95 randomized participants, 93 received at least 1 dose of study medication and were included in the primary outcome analysis. Percentage of heavy drinking days during the 32-week double-blind period was 9.7% for the psilocybin group and 23.6% for the diphenhydramine group, a mean difference of 13.9%; (95% CI, 3.0-24.7; F1,86 = 6.43; P = .01). Mean daily alcohol consumption (number of standard drinks per day) was also lower in the psilocybin group. There were no serious adverse events among participants who received psilocybin. Conclusions and Relevance/UNASSIGNED:Psilocybin administered in combination with psychotherapy produced robust decreases in percentage of heavy drinking days over and above those produced by active placebo and psychotherapy. These results provide support for further study of psilocybin-assisted treatment for AUD. Trial Registration/UNASSIGNED:ClinicalTrials.gov Identifier: NCT02061293.

Results from multiple recent studies support further evaluation of 3,4-methylenedioxymethamphetamine (MDMA) in conjunction with psychotherapy (i.e., MDMA-Assisted Therapy) in the treatment of post-traumatic stress disorder (PTSD). In two Phase 3 trials, MDMA-Assisted Therapy comprised a short-term, intensive psychotherapy that included three sessions directly facilitated by MDMA (referred to as "experimental sessions"), as well as a number of non-drug psychotherapy sessions. This treatment model aimed to harness the potential of MDMA to facilitate recall and processing of traumatic memories, and to increase learning in a social context, integrating "top-down" and "bottom-up" approaches to trauma-focused care. To date, the conceptual framework for this treatment has not been described in the scientific literature. This omission has contributed to misunderstandings about both the theoretical underpinnings of this modality and the therapeutic approach that emerges from it. This paper delineates the psychotherapeutic concepts, theories, and historical antecedents underlying the inner-directed approach to MDMA-Assisted Therapy for PTSD. Broadly speaking, this therapeutic framework centered the concept of the participant's inner healing intelligence as the primary agent of change, with the therapeutic relationship being the core facilitative condition fostering the participant's self-directed movement toward recovery and growth. Corollaries to this holistic, self-directed, relational, and trauma-informed framework include a non-pathologizing approach to the participant's embodied experience (including the possibility of intense emotional and somatic expression, experiences of multiplicity, suicidal ideation, and multigenerational and transpersonal experiences), as well as the therapists' own psychodynamic, somatic, and transpersonal awareness, empathic attunement, relational skillfulness, and cultural humility. The use of MDMA in conjunction with this psychotherapy platform outperformed the use of placebo with psychotherapy in Phase 2 and 3 trials, as measured by symptom reduction in participants with PTSD. However, within-group comparisons also identified significant symptom reduction in participants who did not receive MDMA, lending empirical support to the psychotherapy model itself. In addition to comparative efficacy trials, future research should investigate which elements of the conceptual framework and therapeutic approach underlie the clinical benefit in individuals with PTSD.

OBJECTIVE/UNASSIGNED:The timeline followback (TLFB) interview is the gold standard for the quantitative assessment of alcohol use. However, self-reported "drinks" can vary in alcohol content. If this variability is not accounted for, it can compromise the reliability and validity of TLFB data. To improve the precision of the TLFB data, we developed a detailed standard operating procedure (SOP) to calculate standard drinks more accurately from participant reports. METHOD/UNASSIGNED:For the new SOP, the volume and alcohol content by volume (ABV) of distinct types of alcoholic beverages were determined based on product websites and other reliable sources. Recipes for specific cocktails were constructed based on recipes from bartending education websites. One standard drink was defined as 0.6 oz (14 g) of absolute alcohol. Standard drink totals were contrasted for the new SOP approach and the standard procedure, which generally assumed that one self-reported drink was equivalent to one standard drink. RESULTS/UNASSIGNED:Relative to the standard TLFB procedure, higher numbers of standard drinks were reported after implementing the TLFB SOP. CONCLUSIONS/UNASSIGNED:Variability in procedures for conversion of self-reported alcohol consumption to standard drinks can confound the interpretation of TLFB data. The use and reporting of a detailed SOP can significantly reduce the potential for such inconsistencies. Detailed and consistent procedures for calculation of standard drinks can enhance the quality of TLFB drinking data.

Several lines of evidence suggest that classic psychedelics (5-HT_2A receptor agonists or partial agonists) such as psilocybin might facilitate behavior change in individuals with substance use disorders. We conducted a multi-site, double-blind, randomized controlled trial (RCT) to assess the effects of psilocybin-assisted psychotherapy in alcohol-dependent volunteers. In addition to a structured 12-week psychotherapy platform, participants (n = 96) were randomly assigned (1:1) to receive either oral psilocybin or an active placebo (oral diphenhydramine) in each of two dosing sessions (at weeks 4 and 8). Initial doses were 25 mg/70 kg psilocybin or 50 mg diphenhydramine, which could be increased in the second session depending on initial response. The psychotherapy platform combined evidence-based, manualized therapy for alcohol dependence with a supportive context for the dosing sessions. All participants were followed in the RCT through week 36. At the end of the RCT, participants who still met safety criteria were offered an open-label psilocybin session. Data collected at screening, baseline and throughout the study included: demographics, measures of alcohol use, subjective response to psilocybin and diphenhydramine, and safety measures. The primary outcome was the proportion of heavy drinking days during the 32 weeks after the first dosing session (i.e., between week 4 and week 36). Secondary outcomes included safety, additional measures of drinking (e.g., abstinence, drinking days, etc.), craving, self-efficacy, and acute effects. We will also explore moderators and mediators of the primary outcome. The primary outcomes will be published elsewhere. In this paper, we describe the protocol and rationale for our design decisions.

BACKGROUND:Given increasing community-based and off-label use of ketamine for psychiatric indications, we examined current informed consent processes from a convenience sample of outpatient ketamine clinics to identify areas of congruence with current evidence and opportunities for growth. METHODS:Using a rubric developed from existing practice guidelines, we conducted an exploratory analysis of informed consent documents (IC-Docs) from 23 American clinics offering ketamine as a psychiatric treatment. Domains assessed included clinical content, procedures, and syntax. RESULTS:Participating clinics (23/288) varied widely in their constitution, training, and services provided. We found that IC-Docs addressed a majority of consent elements, though did so variably on an item-level. Areas for improvement included communication around long-term adverse effects, treatment alternatives, medical/psychiatric evaluation prior to treatment, medical/psychological support during treatment, adjunctive psychological interventions, and subjective/dissociative-type effects. All forms were limited by poor readability. LIMITATIONS:Our study was limited by convenience sampling along with possible underestimation of verbal consent processes. CONCLUSIONS:As ketamine continues to emerge as a psychiatric intervention, both patients and providers will benefit from a deliberate consent process informed by scientific, ethical, and pragmatic factors toward the goal of shared decision-making regarding treatment.

Psychedelic substances have been central to religious and shamanic healing practices of various cultures for generations. More recently, in western medicine, psychedelic substances have demonstrated promise in the treatment of various mental health indications. A growing evidence base supports not only the therapeutic potential of psychedelic-assisted psychotherapy, but also the importance of integrating spiritual aspects of psychedelic experiences into the traditional therapeutic process. Psilocybin, a classic psychedelic, is a serotonergic hallucinogen that can elicit profound spiritual experiences even in the research setting. Our group is currently conducting a randomized controlled trial exploring the therapeutic potential of psilocybin-assisted psychotherapy for alcohol dependence. Over the course of the trial, many individuals have reported experiences that take a variety of forms, including spiritual insights, beatific visions, and communion with the Divine. Here we present three case studies of experiences involving communion with a deceased loved one, with a holy figure, and with the Divine from our clinical trial. These cases have been selected to illustrate the diverse nature of the spiritual experiences observed in this clinical trial, and to also explore elements of spiritual care that may be supportive in the psychotherapeutic process during and after the medication experiences. Should psychedelic medicine continue to show treatment promise in clinical trial stages, there is a strong possibility that these medicines will become an integral part of psychotherapy, which will require integration of direct spiritual experiences and spiritual care into the healing process. (PsycInfo Database Record (c) 2021 APA, all rights reserved)