Faculty Bibliography

This chapter reviews what is known about the therapeutic uses of the serotonergic or classic hallucinogens, i.e., psychoactive drugs such as LSD and psilocybin that exert their effects primarily through agonist activity at serotonin 2A (5HT2A) receptors. Following a review of the history of human use and scientific study of these drugs, the data from clinical research are summarized, including extensive work on the use of classic hallucinogens in the treatment of alcoholism and other addictions, studies of the use of LSD and psilocybin to relieve distress concerning death, particularly in patients with advanced or terminal cancer, and more limited data concerning the use of classic hallucinogens to treat mood and anxiety disorders. A survey of possible mechanisms of clinically relevant effects is provided. The well-established safety of classic hallucinogens is reviewed. To provide a clinical perspective, case summaries are provided of two individuals who received treatment in recent controlled trials of psilocybin: one being treated for alcoholism, the other suffering from anxiety and depression related to fear of death due to a cancer diagnosis. Although promising early phase research conducted from the 1950s through the early 1970s was discontinued before firm conclusions could be reached concerning the efficacy of any of the classic hallucinogens for any clinical condition, the research that was conducted in that era strongly suggests that classic hallucinogens have clinically relevant effects, particularly in the case of LSD treatment of alcoholism. In the past decade, clinical trials have resumed investigating the effects of classic hallucinogens in the treatment of existential distress in the face of cancer, and in the treatment of addictions including alcoholism and nicotine addiction. The studies that have been completed to date are not sufficient to establish efficacy, but the outcomes have been very encouraging, and larger trials, up to and including phase 3, are now underway or being planned. Although research has elucidated many of the acute neurobiological and psychological effects of classic hallucinogens on humans, animals, and in vitro systems, the mechanisms of clinically relevant persisting effects remain poorly understood.

After a hiatus of some 40 years, clinical research has resumed on the use of classic hallucinogens to treat addiction. Following completion of a small open-label feasibility study, we are currently conducting a double-blind placebo-controlled clinical trial of psilocybin-assisted treatment of alcohol use disorder. Although treatment effects cannot be analyzed until the study is complete, descriptive case studies provide a useful window into the therapeutic process of psychedelic-assisted treatment of addiction. Here we describe treatment trajectories of three participants in the ongoing trial to illustrate the range of experiences and persisting effects of psilocybin treatment. Although it is difficult to generalize from a few cases, several qualitative conclusions can be drawn from the data presented here. Although participants often find it difficult to describe much of their psilocybin experience, pivotal moments tend to be individualized, extremely vivid, and memorable. Often, the qualitative content extends beyond the clinical problem that is being addressed. The participants discussed in this paper experienced acute and lasting alterations in their perceptions of self, in the quality of their baseline consciousness, and in their relationship with alcohol and drinking. In these cases, experiences of catharsis, forgiveness, self-compassion, and love were at least as salient as classic mystical content. Finally, feelings of increased "spaciousness" or mindfulness, and increased control over choices and behavior were reported following the drug administration sessions. Ultimately, psilocybin-assisted treatment appears to elicit experiences that are extremely variable, yet seem to meet the particular needs of the individual.

The aims of this study were to assess the impact of ceremonial use of ayahuasca-a psychedelic brew containing N,N-dimethyltryptamine (DMT) and β-carboline -and attendance at União do Vegetal (UDV) meetings on substance abuse; here we report the findings related to alcohol and tobacco use disorder. A total of 1,947 members of UDV 18+ years old were evaluated in terms of years of membership and ceremonial attendance during the previous 12 months. Participants were recruited from 10 states from all major regions of Brazil. Alcohol and tobacco use was evaluated through questionnaires first developed by the World Health Organization and the Substance Abuse and Mental Health Services Administration. Analyses compared levels of alcohol and tobacco use disorder between the UDV and a national normative sample (n = 7,939). Binomial tests for proportions indicated that lifetime use of alcohol and tobacco was higher in UDV sample compared to the Brazilian norms for age ranges of 25-34 and over 34 years old, but not for the age range of 18-24 years old. However, current use disorders for alcohol and tobacco were significantly lower in the UDV sample than the Brazilian norms. Regression analyses revealed a significant impact of attendance at ayahuasca ceremonies during the previous 12 months and years of UDV membership on the reduction of alcohol and tobacco use disorder.

This article examines the symbolic work of gender as it intersects with race and class in popular media and in local community discourses surrounding the "suburban opioid epidemic," in which national drug policies, and White futures, are thought to be at stake. The study starts with an analysis of the White, middle-class, female "new face of addiction" that has been cultivated by national press coverage of prescription opioid-cum-heroin overdoses in the U.S. and then turns to interviews with community physicians in the front line of a clinical response to the "epidemic" in Staten Island, a White suburban enclave within New York City that is experiencing 3"“4 times the opioid overdose rate of any other City borough. Physicians use the language of family membership to indicate identification with their opioid addiction patients, and many go to lengths to provide holistic care and to incorporate family support for their patients despite lack of insurance reimbursement. White, educated patients describe buprenorphine as a way to maintain their professional identities, while low-income Black and Latino patients describe pharmaceutical maintenance as a socially alienating arm of the criminal justice system. Together, media and clinical responses make up strategies of White racial rescue from threatened social reproduction in an era of substance-induced White downward mobility.

Background: With both agonist and antagonist medications available to treat opioid dependence, and with these differing markedly on a spectrum of parameters - including philosophy of treatment, need for detoxification to initiate treatment, ongoing dependence and withdrawal on stopping treatment, diversion risk, community acceptability and controlled substance restrictions - it's difficult to know which approach to take. What do we tell our patients? How should we choose? Is one approach better for some patients, the other for others? Does choice matter, do patients do better with their preferred treatment than with the alternative? CTN-0051 grows out of these questions and will establish the evidence-base to inform treatment decisions. Methods: Close to a dozen designs, including no-medication treatment-as-usual conditions, SMART designs, and designs taking choice into consideration were considered. The final design was a randomized two-arm, head-to-head effectiveness trial comparing extended-release naltrexone to buprenorphine, both FDA approved treatments, in 570 patients across 8 sites. Recruitment was from inpatient detoxification and short term residential programs. We selected a flexible point of randomization to reflect community medication initiation practices. We predicted differential induction success, and included a mitigation plan to manage the detoxification hurdle. Treatment was for up to six months with follow up visits through nine months postrandomization. The primary outcome measure was timeto- relapse, defined as 7 consecutive use-days or 4 consecutive use-weeks. Secondary outcomes included successful induction, abstinence from opioids, alcohol, tobacco and other drugs, craving, subacute withdrawal, etc., and mediators and moderators of treatment response. Results: Recruitment was completed in May 2016 with 722 participants consented and 570 randomized. Treatment visits were completed in November 2016 and follow up visits in February 2017. Women made up 30% of the population; 17% were Hispanic, 26% non-white; 69% were 25-45 years old, 15% were under 25; 57% had a high school education or less, 66% were never married, 63% were unemployed; 82% identified heroin as their primary abused opioid, 16% prescription drugs; 63% were IV users; 40% were high users defined as IV use of at least 6 bags a day, a stratification variable that we predicted to influence outcome; although all participants expressed willingness to take either medication, 29% indicated that they preferred extended-release naltrexone, and 33% buprenorphine. AEs and SAEs were those expected in this population. Data lock will be in May 2017 after which we will be able to look at outcomes data. Conclusions: We expect to be able to present comparative effectiveness data on induction success, survival without relapse, time-to-relapse, abstinence from opioids and other drugs, successful completion of 24 weeks of treatment, craving, cognitive function, and adverse events including overdose during and after treatment. Findings on the role of choice in influencing outcome, and mediators and moderators of treatment success or failure will be presented. None of these data will be available until after data-lock, precluding more specific "conclusions" per se until early summer

Recent randomized controlled trials of psilocybin-assisted psychotherapy for patients with cancer suggest that this treatment results in large-magnitude reductions in anxiety and depression as well as improvements in attitudes toward disease progression and death, quality of life, and spirituality. To better understand these findings, we sought to identify psychological mechanisms of action using qualitative methods to study patient experiences in psilocybin-assisted psychotherapy. Semistructured interviews were conducted with 13 adult participants with clinically elevated anxiety associated with a cancer diagnosis who received a single dose of psilocybin under close clinical supervision. Transcribed interviews were analyzed using interpretative phenomenological analysis, which resulted in 10 themes, focused specifically on cancer, death and dying, and healing narratives. Participants spoke to the anxiety and trauma related to cancer, and perceived lack of available emotional support. Participants described the immersive and distressing effects of the psilocybin session, which led to reconciliations with death, an acknowledgment of cancer's place in life, and emotional uncoupling from cancer. Participants made spiritual or religious interpretations of their experience, and the psilocybin therapy helped facilitate a felt reconnection to life, a reclaiming of presence, and greater confidence in the face of cancer recurrence. Implications for theory and clinical treatment are discussed.

Experiences of discrimination, or social marginalization and ostracism, may lead to the formation of social networks characterized by inequality. For example, those who experience discrimination may be more likely to develop drug use and sexual partnerships with others who are at increased risk for HIV compared to those without experiences of discrimination. This is critical as engaging in risk behaviors with others who are more likely to be HIV positive can increase one's risk of HIV. We used log-binomial regression models to examine the relationship between drug use, racial and incarceration discrimination with changes in the composition of one's risk network among 502 persons who use drugs. We examined both absolute and proportional changes with respect to sex partners, drug use partners, and injecting partners, after accounting for individual risk behaviors. At baseline, participants were predominately male (70%), black or Latino (91%), un-married (85%), and used crack (64%). Among those followed-up (67%), having experienced discrimination due to drug use was significantly related to increases in the absolute number of sex networks and drug networks over time. No types of discrimination were related to changes in the proportion of high-risk network members. Discrimination may increase one's risk of HIV acquisition by leading them to preferentially form risk relationships with higher-risk individuals, thereby perpetuating racial and ethnic inequities in HIV. Future social network studies and behavioral interventions should consider whether social discrimination plays a role in HIV transmission.

Screening, brief intervention, and referral to treatment (SBIRT) has been widely implemented as a method to address substance use disorders in general medical settings, and some evidence suggests that its use is associated with decreased societal costs. In this paper, we investigated the economic impact of SBIRT using data from Screening, Motivational Assessment, Referral, and Treatment in Emergency Departments (SMART-ED), a multisite, randomized controlled trial. Utilizing self-reported information on medical status, health services utilization, employment, and crime, we conduct a benefit-cost analysis. Findings indicate that neither of the SMART-ED interventions resulted in any significant changes to the main economic outcomes, nor had any significant impact on total economic benefit. Thus, while SBIRT interventions for substance abuse in Emergency Departments may be appealing from a clinical perspective, evidence from this economic study suggests resources could be better utilized supporting other health interventions.

Research activity on the potential clinical value of classic hallucinogens and other psychedelics has increased markedly in the past two decades, and promises to continue to expand. Experimental study of hallucinogen-assisted treatment, and any future clinical use, requires the development of psychotherapeutic models that are appropriate to the disorder being treated and effectively integrated with the pharmacologic component of the treatment. To provide a framework for thinking about possible treatment models, we provide an overview of the history of psychedelic-assisted treatment, review what is known about the therapeutic mechanisms of these treatments, and consider the various purposes of psychotherapy in the context of both research and clinical use of psychedelic-assisted treatment. We then provide a description of a therapy model we have developed and are currently using in a trial of psilocybin-assisted treatment for alcoholism. Finally, we discuss advantages and disadvantages of a range of alternative models, emphasizing the need for research to determine the most effective treatment models for any indications for which efficacy becomes established.