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Psychiatry

The Psychedelic Debriefing in Alcohol Dependence Treatment: Illustrating Key Change Phenomena through Qualitative Content Analysis of Clinical Sessions

Abstract

Research on the clinical applications of psychedelic-assisted psychotherapy has demonstrated promising early results for treatment of alcohol dependence. Detailed description of the content and methods of psychedelic-assisted psychotherapy, as it is conducted in clinical settings, is scarce.

Methods: An open-label pilot (proof-of-concept) study of psilocybin-assisted treatment of alcohol dependence (NCT01534494) was conducted to generate data for a phase 2 RCT (NCT02061293) of a similar treatment in a larger population. The present paper presents a qualitative content analysis of the 17 debriefing sessions conducted in the pilot study, which occurred the day after corresponding psilocybin medication sessions.

Results: Participants articulated a series of key phenomena related to change in drinking outcomes and acute subjective effects of psilocybin.

Discussion: The data illuminate change processes in patients’ own words during clinical sessions, shedding light on potential therapeutic mechanisms of change and how participants express effects of psilocybin. This study is unique in analyzing actual clinical sessions, as opposed to interviews of patients conducted separately from treatment.

Nielson, E. M., May, D. G., Forcehimes, A. A., & Bogenschutz, M. P. (2018). The Psychedelic Debriefing in Alcohol Dependence Treatment: Illustrating Key Change Phenomena through Qualitative Content Analysis of Clinical Sessions. Frontiers in Pharmacology9, 132. 10.3389/fphar.2018.00132
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The re-emergence of hallucinogenic research

Abstract

Due to the intractability, at times, in the treatment of PTSD, clinicians and researchers continue to explore different options for treatment. This article discusses the renewed interest in hallucinogens for such treatment.
Begola, M. J., & Dowben, J. S. (2018). The re‐emergence of hallucinogenic research. Perspectives in psychiatric care. 10.1111/ppc.12263
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The re-emergence of hallucinogenic research

Abstract

Due to the intractability, at times, in the treatment of PTSD, clinicians and researchers continue to explore different options for treatment. This article discusses the renewed interest in hallucinogens for such treatment.
Begola, M. J., & Dowben, J. S. (2018). The re‐emergence of hallucinogenic research. Perspectives in psychiatric care. 10.1111/ppc.12263
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Clinical interpretations of patient experience in a trial of psilocybin-assisted psychotherapy for alcohol use disorder

Abstract

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.

Bogenschutz, M. P., Podrebarac, S. K., Duane, J. H., Amegadzie, S. S., Malone, T. C., Owens, L. T., … & Mennenga, S. E. (2018). Clinical interpretations of patient experience in a trial of psilocybin-assisted psychotherapy for alcohol use disorder. Frontiers in Pharmacology9, 100. 10.3389/fphar.2018.00100
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Features of dissociation differentially predict antidepressant response to ketamine in treatment-resistant depression

Abstract

BACKGROUND:
Ketamine induces rapid and robust antidepressant effects, and many patients also describe dissociation, which is associated with antidepressant response. This follow-up study investigated whether antidepressant efficacy is uniquely related to dissociative symptom clusters.
METHODS:
Treatment-resistant patients with major depressive disorder (MDD) or bipolar disorder (BD) (n = 126) drawn from three studies received a single subanesthetic (0.5 mg/kg) ketamine infusion. Dissociative effects were measured using the Clinician-Administered Dissociative States Scale (CADSS). Antidepressant response was measured using the 17-item Hamilton Depression Rating Scale (HAM-D). A confirmatory factor analysis established the validity of CADSS subscales (derealization, depersonalization, amnesia), and a general linear model with repeated measures was fitted to test whether subscale scores were associated with antidepressant response.
RESULTS:
Factor validity was supported, with a root mean square error of approximation of .06, a comparative fit index of .97, and a Tucker-Lewis index of .96. Across all studies and timepoints, the depersonalization subscale was positively related to HAM-D percent change. A significant effect of derealization on HAM-D percent change was observed at one timepoint (Day 7) in one study. The amnesia subscale was unrelated to HAM-D percent change.
LIMITATIONS:
Possible inadequate blinding; combined MDD/BD datasets might have underrepresented ketamine’s antidepressant efficacy; the possibility of Type I errors in secondary analyses.
CONCLUSIONS:
From a psychometric perspective, researchers may elect to administer only the CADSS depersonalization subscale, given that it was most closely related to antidepressant response. From a neurobiological perspective, mechanistic similarities may exist between ketamine-induced depersonalization and antidepressant response, although off-target effects cannot be excluded.
Niciu, M. J., Shovestul, B. J., Jaso, B. A., Farmer, C., Luckenbaugh, D. A., Brutsche, N. E., … & Zarate, C. A. (2018). Features of dissociation differentially predict antidepressant response to ketamine in treatment-resistant depression. Journal of affective disorders232, 310-315. 10.1016/j.jad.2018.02.049
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Psychedelics and related drugs: therapeutic possibilities, mechanisms and regulation

Abstract

The word “psychedelic” derives from the Greek terms for mind—psyche—and “delos” which means “clear, manifest,” so in essence, psychedelic drugs can be seen as the prototype “window on the mind” concept. The term was originally coined in the 1950s to describe lysergic acid diethylamide (LSD), mescaline, and other hallucinogens, drugs that profoundly alter human experience. These have subsequently been shown to act primarily as agonists at the 5-HT2Areceptor in the brain. Research into the therapeutic potential and mechanisms of action of psychedelic and related drugs peaked in the late 1960s but then stagnated for 50 years after the 1971 UN Psychotropics Convention made psychedelic research with humans almost impossible to carry out (Kyzar et al. 2017).

Recently, however, this area is experiencing a renaissance as drugs often associated with recreational use—such as LSD, ketamine, and cannabis/cannabinoids—have been shown to have therapeutic potential in a range of disorders such as treatment-resistant depression, suicidal ideation, and some pediatric epilepsies. Further, recent pilot studies suggest that MDMA as well as the classic psychedelics, LSD, and psilocybin may contribute to the pharmacopeia for post-traumatic stress disorder (PTSD) and other difficult-to-treat psychiatric disorders. Research has also been stimulated by functional neuroimaging studies of single doses of psychedelics showing that they produce widespread changes in brain connectivity as well as profound alterations to perception and cognition. At the same time, as one would expect from a relatively fledgling area, many questions remain about mechanisms of action, safety, and efficacy. These include what type of psychological therapies best combine with which type of psychedelic drug, whether some types of drug have benefits even without psychological treatment, what the optimal doses are, from single dose through to intermittent or repeated dosing. The current renaissance in empirical psychedelic research stimulated this Special Issue of Psychopharmacology. The articles are grouped into three sections: Clinical efficacy and clinical issues; Effects and Mechanisms of action; Regulation and history.

Curran, H. V., Nutt, D., & de Wit, H. (2018). Psychedelics and related drugs: therapeutic possibilities, mechanisms and regulation. 10.1007/s00213-017-4822-3
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Key interindividual determinants in MDMA pharmacodynamics

Abstract

MDMA, 3,4-methylenedioxymethamphetamine, is a synthetic phenethylamine derivative with structural and pharmacological similarities to both amphetamines and mescaline. MDMA produces characteristic amphetamine-like actions (euphoria, well-being), increases empathy, and induces pro-social effects that seem to motivate its recreational consumption and provide a basis for its potential therapeutic use. Areas covered: The aim of this review is to present the main interindividual determinants in MDMA pharmacodynamics. The principal sources of pharmacodynamic variability are reviewed, with special emphasis on sex-gender, race-ethnicity, genetic differences, interactions, and MDMA acute toxicity, as well as possible therapeutic use. Expert opinion: Acute MDMA effects are more pronounced in women than they are in men. Very limited data on the relationship between race-ethnicity and MDMA effects are available. MDMA metabolism includes some polymorphic enzymes that can slightly modify plasma concentrations and effects. Although a considerable number of studies exist about the acute effects of MDMA, the small number of subjects in each trial limits evaluation of the different interindividual factors and does not permit a clear conclusion about their influence. These issues should be considered when studying possible MDMA therapeutic use.
Papaseit, E., Torrens, M., Pérez-Mañá, C., Muga, R., & Farré, M. (2018). Key interindividual determinants in MDMA pharmacodynamics. Expert opinion on drug metabolism & toxicology, (just-accepted). 10.1080/17425255.2018.1424832
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Serotonergic psychedelics and personality: A systematic review of contemporary research

Abstract

Serotonergic psychedelics act as agonists at cortical 5-HT2A receptors and seem to induce personality changes. We conducted a systematic review of studies assessing the effects of these drugs on personality. Papers published from 1985–2016 were included from PubMed, LILACS, and SciELO databases. Three hundred and sixty-nine studies were identified, and 18 were included. Specific personality traits, such as Absorption and Self-Transcendence, seem to influence the effects of psychedelics, and psychedelic drug users and nonusers appear to differ in some personality traits. Psychedelics administered in controlled settings may induce personality changes, such as increased Openness and Self-Transcendence. Increases in global brain entropy induced by acute psychedelic administration predicted changes in Openness, and Self-Transcendence was negatively correlated with cortical thinning of the posterior cingulate cortex in long-term religious ayahuasca users. Acute and long-term use of psychedelics is associated with personality changes that appear to be modulated by 5-HT2A receptors. These changes seem to induce therapeutic effects that should be further explored in randomized controlled studies.

Bouso, J. C., dos Santos, R. G., Alcázar-Córcoles, M. Á., & Hallak, J. E. (2018). Serotonergic psychedelics and personality: a systematic review of contemporary research. Neuroscience & Biobehavioral Reviews. 10.1016/j.neubiorev.2018.02.004
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The hidden therapist: evidence for a central role of music in psychedelic therapy

Abstract

RATIONALE:
Recent studies have supported the safety and efficacy of psychedelic therapy for mood disorders and addiction. Music is considered an important component in the treatment model, but little empirical research has been done to examine the magnitude and nature of its therapeutic role.
OBJECTIVES:
The present study assessed the influence of music on the acute experience and clinical outcomes of psychedelic therapy.
METHODS:
Semi-structured interviews inquired about the different ways in which music influenced the experience of 19 patients undergoing psychedelic therapy with psilocybin for treatment-resistant depression. Interpretative phenomenological analysis was applied to the interview data to identify salient themes. In addition, ratings were given for each patient for the extent to which they expressed “liking,” “resonance” (the music being experienced as “harmonious” with the emotional state of the listener), and “openness” (acceptance of the music-evoked experience).
RESULTS:
Analyses of the interviews revealed that the music had both “welcome” and “unwelcome” influences on patients’ subjective experiences. Welcome influences included the evocation of personally meaningful and therapeutically useful emotion and mental imagery, a sense of guidance, openness, and the promotion of calm and a sense of safety. Conversely, unwelcome influences included the evocation of unpleasant emotion and imagery, a sense of being misguided and resistance. Correlation analyses showed that patients’ experience of the music was associated with the occurrence of “mystical experiences” and “insightfulness.” Crucially, the nature of the music experience was significantly predictive of reductions in depression 1 week after psilocybin, whereas general drug intensity was not.
CONCLUSIONS:
This study indicates that music plays a central therapeutic function in psychedelic therapy.
Kaelen, M., Giribaldi, B., Raine, J., Evans, L., Timmerman, C., Rodriguez, N., … & Carhart-Harris, R. (2018). The hidden therapist: Evidence for a central role of music in psychedelic therapy. Psychopharmacology235(2), 505-519. 10.1007/s00213-017-4820-5
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Psychedelics and the essential importance of context

Abstract

Psychedelic drugs are making waves as modern trials support their therapeutic potential and various media continue to pique public interest. In this opinion piece, we draw attention to a long-recognised component of the psychedelic treatment model, namely ‘set’ and ‘setting’ – subsumed here under the umbrella term ‘context’. We highlight: (a) the pharmacological mechanisms of classic psychedelics (5-HT2A receptor agonism and associated plasticity) that we believe render their effects exceptionally sensitive to context, (b) a study design for testing assumptions regarding positive interactions between psychedelics and context, and (c) new findings from our group regarding contextual determinants of the quality of a psychedelic experience and how acute experience predicts subsequent long-term mental health outcomes. We hope that this article can: (a) inform on good practice in psychedelic research, (b) provide a roadmap for optimising treatment models, and (c) help tackle unhelpful stigma still surrounding these compounds, while developing an evidence base for long-held assumptions about the critical importance of context in relation to psychedelic use that can help minimise harms and maximise potential benefits.
Carhart-Harris, R. L., Roseman, L., Haijen, E., Erritzoe, D., Branchi, I., & Kaelen, M. (2018). Psychedelics and the essential importance of context. Journal of Psychopharmacology, 0269881118754710.
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