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Psychedelics, placebo effects, and set and setting: insights from common factors theory of psychotherapy
Abstract
Psychedelic-assisted treatment is at first glance markedly different in structure and approach from mainstream forms of psychotherapy in the West. A major criticism of clinical psychedelic research rests on the difficulty of executing placebo-controlled studies and distinguishing drug effects from those of the psychotherapeutic container in which psychedelics are typically presented. Detractors also tend to find fault in spiritual or mystical themes that often arise in the context of psychedelic use. Common factors theory of psychotherapy is a useful and extensively studied framework that can help make sense of these issues, and has much to contribute to our understanding of contextual effects that are often discussed in psychedelic literature as "set and setting." In this paper we examine four major contextual "common factors" shared by various healing traditions-1) the therapeutic relationship, 2) the healing setting, 3) the rationale, conceptual scheme, or myth, and 4) the ritual. We explain how these factors show up in psychedelic-assisted treatment and how they may contribute to therapeutic effects. Lastly, we discuss implications of these factors for the concept of placebo, and for future research.
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Background:
Psilocybin therapy has shown promise as a rapid-acting treatment for depression, anxiety, and demoralization in patients with serious medical illness (e.g., cancer) when paired with individual psychotherapy. This study assessed the safety and feasibility of psilocybin-assisted group therapy for demoralization in older long-term AIDS survivor (OLTAS) men, a population with a high degree of demoralization and traumatic loss.
Methods:
Self-identified gay men OLTAS with moderate-to-severe demoralization (Demoralization Scale-II ≥8) were recruited from the community of a major US city for a single-site open-label study of psilocybin-assisted group therapy comprising 8-10 group therapy visits and one psilocybin administration visit (0·3-0·36 mg/kg po). Primary outcomes were rate and severity of adverse events, and participant recruitment and retention. The primary clinical outcome was change in mean demoralization from baseline to end-of-treatment and to 3-month follow-up assessed with a two-way repeated measures ANOVA. Trial registration: Clinicaltrials.gov (NCT02950467).
Findings:
From 17 July 2017 to 16 January 2019, 18 participants (mean age 59·2 years (SD 4·4)) were enrolled, administered group therapy and psilocybin, and included in intent-to-treat analyses. We detected zero serious adverse reactions and two unexpected adverse reactions to psilocybin; seven participants experienced self-limited, severe expected adverse reactions. We detected a clinically meaningful change in demoralization from baseline to 3-month follow-up (mean difference -5·78 [SD 6·01], ηp2 = 0·47, 90% CI 0·21-0·60).
Interpretation:
We demonstrated the feasibility, relative safety, and potential efficacy of psilocybin-assisted group therapy for demoralization in OLTAS. Groups may be an effective and efficient means of delivering psychotherapy pre- and post-psilocybin to patients with complex medical and psychiatric needs.
Funding:
Carey Turnbull, Heffter Research Institute, NIMH R25 MH060482, NIH UL1 TR001872, River Styx Foundation, Saisei Foundation, Sarlo Foundation, Stupski Foundation, Usona Institute, US Department of Veterans Affairs (Advanced Neurosciences Fellowship and IK2CX001495).
RationaleIs it possible to have a psychedelic experience from a placebo alone? Most psychedelic studies find few effects in the placebo control group, yet these effects may have been obscured by the study design, setting, or analysis decisions.Objective
We examined individual variation in placebo effects in a naturalistic environment resembling a typical psychedelic party.Methods
Thirty-three students completed a single-arm study ostensibly examining how a psychedelic drug affects creativity. The 4-h study took place in a group setting with music, paintings, coloured lights, and visual projections. Participants consumed a placebo that we described as a drug resembling psilocybin, which is found in psychedelic mushrooms. To boost expectations, confederates subtly acted out the stated effects of the drug and participants were led to believe that there was no placebo control group. The participants later completed the 5-Dimensional Altered States of Consciousness Rating Scale, which measures changes in conscious experience.ResultsThere was considerable individual variation in the placebo effects; many participants reported no changes while others showed effects with magnitudes typically associated with moderate or high doses of psilocybin. In addition, the majority (61%) of participants verbally reported some effect of the drug. Several stated that they saw the paintings on the walls “move” or “reshape” themselves, others felt “heavy… as if gravity [had] a stronger hold”, and one had a “come down” before another “wave” hit her.Conclusion
Understanding how context and expectations promote psychedelic-like effects, even without the drug, will help researchers to isolate drug effects and clinicians to maximise their therapeutic potential.
Background:
Psychedelic therapy is gaining recognition and the nature of the psychedelic experience itself has been found to mediate subsequent long-term psychological changes. Much emphasis has been placed on the occurrence of mystical-type experiences in determining long-term responses to psychedelics yet here we demonstrate the importance of another component, namely: emotional breakthrough.
Methods:
Three hundred and seventy-nine participants completed online surveys before and after a planned psychedelic experience. Items pertaining to emotional breakthrough were completed one day after the psychedelic experience, as were items comprising the already validated Mystical Experience Questionnaire and the Challenging Experience Questionnaire. Emotional breakthrough, Mystical Experience Questionnaire and Challenging Experience Questionnaire scores were used to predict changes in well-being (Warwick-Edinburgh Mental Wellbeing Scale) in a subsample of 75 participants with low well-being baseline scores (⩽45).
Results:
Factor analyses revealed six emotional breakthrough items with high internal consistency (Cronbach’s alpha=0.932) and supported our prior hypothesis that emotional breakthrough is a distinct component of the psychedelic experience. Emotional breakthrough scores behaved dose-dependently, and were higher if the psychedelic was taken with therapeutic planning and intent. Emotional breakthrough, Mystical Experience Questionnaire and Challenging Experience Questionnaire scores combined, significantly predicted subsequent changes in well-being (r=0.45, p=0.0005, n=75), with each scale contributing significant predictive value. Emotional breakthrough and Mystical Experience Questionnaire scores predicted increases in well-being and Challenging Experience Questionnaire scores predicted less increases.
Conclusions:
Here we validate a six-item ‘Emotional Breakthrough Inventory’. Emotional breakthrough is an important and distinct component of the acute psychedelic experience that appears to be a key mediator of subsequent longer-term psychological changes. Implications for psychedelic therapy are discussed.
Congruence or genuineness is a relationship element with an extensive and important history within psychotherapy. Congruence is an aspect of the therapy relationship with two facets, one intrapersonal and one interpersonal . This chapter defines and provides clinical examples of congruence. It presents an original meta-analysis of its relation with psychotherapy improvement. Analysis of 21 studies, representing 1,192 patients, resulted in a weighted aggregate effect size ( r ) of .23 or an estimated d of .46. In closing, the chapter addresses patient contributions, limitations of the extant research, diversity considerations, and therapeutic practices that might promote congruence and improve psychotherapy outcomes.
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 nonclinical 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.
Responses to psychedelics are notoriously difficult to predict, yet significant work is currently underway to assess their therapeutic potential and the level of interest in psychedelics among the general public appears to be increasing. We aimed to collect prospective data in order to improve our ability to predict acute- and longer-term responses to psychedelics. Individuals who planned to take a psychedelic through their own initiative participated in an online survey (www.psychedelicsurvey.com). Traits and variables relating to set, setting and the acute psychedelic experience were measured at five different time points before and after the experience. Principle component and regression methods were used to analyse the data. Sample sizes for the five time points were N = 654, N = 535, N = 379, N = 315, and N = 212 respectively. Psychological well-being was increased 2 weeks after a psychedelic experience and remained at this level after 4 weeks. Higher ratings of a “mystical-type experience” had a positive effect on the change in well-being after a psychedelic experience, whereas the other acute psychedelic experience measures, i.e., “challenging experience” and “visual effects”, did not influence the change in well-being after the psychedelic experience. Having “clear intentions” for the experience was conducive to mystical-type experiences. Having a positive “set” as well as having the experience with intentions related to “recreation” were both found to decrease the likelihood of having a challenging experience. The baseline trait “absorption” and higher drug doses promoted all aspects of the acute experience, i.e., mystical-type and challenging experiences, as well as visual effects. When comparing the relative contribution of different types of variables in explaining the variance in the change in well-being, it seemed that baseline trait variables had the strongest effect on the change in well-being after a psychedelic experience. These results confirm the importance of extra-pharmacological factors in determining responses to a psychedelic. We view this study as an early step towards the development of empirical guidelines that can evolve and improve iteratively with the ultimate purpose of guiding crucial clinical decisions about whether, when, where and how to dose with a psychedelic, thus helping to mitigate risks while maximizing potential benefits in an evidence-based manner.
Background:
Despite renewed interest in studying the safety and efficacy of psychedelic-assisted psychotherapy for the treatment of psychological disorders, the enrollment of racially diverse participants and the unique presentation of psychopathology in this population has not been a focus of this potentially ground-breaking area of research. In 1993, the United States National Institutes of Health issued a mandate that funded research must include participants of color and proposals must include methods for achieving diverse samples.
Methods:
A methodological search of psychedelic studies from 1993 to 2017 was conducted to evaluate ethnoracial differences in inclusion and effective methods of recruiting peopple of color.
Results:
Of the 18 studies that met full criteria (n = 282 participants), 82.3% of the participants were non-Hispanic White, 2.5% were African-American, 2.1% were of Latino origin, 1.8% were of Asian origin, 4.6% were of indigenous origin, 4.6% were of mixed race, 1.8% identified their race as "other," and the ethnicity of 8.2% of participants was unknown. There were no significant differences in recruitment methodologies between those studies that had higher (> 20%) rates of inclusion.
Conclusions:
As minorities are greatly underrepresented in psychedelic medicine studies, reported treatment outcomes may not generalize to all ethnic and cultural groups. Inclusion of minorities in futures studies and improved recruitment strategies are necessary to better understand the efficacy of psychedelic-assisted psychotherapy in people of color and provide all with equal opportunities for involvement in this potentially promising treatment paradigm.
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.
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.
Introduction: It is a basic principle of the “psychedelic” treatment model that the quality of the acute experience mediates long-term improvements in mental health. In the present paper we sought to test this using data from a clinical trial assessing psilocybin for treatment-resistant depression (TRD). In line with previous reports, we hypothesized that the occurrence and magnitude of Oceanic Boundlessness (OBN) (sharing features with mystical-type experience) and Dread of Ego Dissolution (DED) (similar to anxiety) would predict long-term positive outcomes, whereas sensory perceptual effects would have negligible predictive value.
Materials and Methods: Twenty patients with treatment resistant depression underwent treatment with psilocybin (two separate sessions: 10 and 25 mg psilocybin). The Altered States of Consciousness (ASC) questionnaire was used to assess the quality of experiences in the 25 mg psilocybin session. From the ASC, the dimensions OBN and DED were used to measure the mystical-type and challenging experiences, respectively. The Self-Reported Quick Inventory of Depressive Symptoms (QIDS-SR) at 5 weeks served as the endpoint clinical outcome measure, as in later time points some of the subjects had gone on to receive new treatments, thus confounding inferences. In a repeated measure ANOVA, Time was the within-subject factor (independent variable), with QIDS-SR as the within-subject dependent variable in baseline, 1-day, 1-week, 5-weeks. OBN and DED were independent variables. OBN-by-Time and DED-by-Time interactions were the primary outcomes of interest.
Results: For the interaction of OBN and DED with Time (QIDS-SR as dependent variable), the main effect and the effects at each time point compared to baseline were all significant (p = 0.002 and p = 0.003, respectively, for main effects), confirming our main hypothesis. Furthermore, Pearson's correlation of OBN with QIDS-SR (5 weeks) was specific compared to perceptual dimensions of the ASC (p < 0.05).
Discussion: This report further bolsters the view that the quality of the acute psychedelic experience is a key mediator of long-term changes in mental health. Future therapeutic work with psychedelics should recognize the essential importance of quality of experience in determining treatment efficacy and consider ways of enhancing mystical-type experiences and reducing anxiety.
Trial Registration: ISRCTN, number ISRCTN14426797, http://www.isrctn.com/ISRCTN14426797
Rationale:
Although psilocybin and dextromethorphan (DXM) are hallucinogens, they have different receptor mechanisms of action and have not been directly compared.
Objective:
This study compared subjective, behavioral, and physiological effects of psilocybin and dextromethorphan under conditions that minimized expectancy effects.
Methods:
Single, acute oral doses of psilocybin (10, 20, 30 mg/70 kg), DXM (400 mg/70 kg), and placebo were administered under double-blind conditions to 20 healthy participants with histories of hallucinogen use. Instructions to participants and staff minimized expectancy effects. Various subjective, behavioral, and physiological effects were assessed after drug administration.
Results:
High doses of both drugs produced similar increases in participant ratings of peak overall drug effect strength, with similar times to maximal effect and time-course. Psilocybin produced orderly dose-related increases on most participant-rated subjective measures previously shown sensitive to hallucinogens. DXM produced increases on most of these same measures. However, the high dose of psilocybin produced significantly greater and more diverse visual effects than DXM including greater movement and more frequent, brighter, distinctive, and complex (including textured and kaleidoscopic) images and visions. Compared to DXM, psilocybin also produced significantly greater mystical-type and psychologically insightful experiences and greater absorption in music. In contrast, DXM produced larger effects than psilocybin on measures of disembodiment, nausea/emesis, and light-headedness. Both drugs increased systolic blood pressure, heart rate, and pupil dilation and decreased psychomotor performance and balance.
Conclusions:
Psilocybin and DXM produced similar profiles of subjective experiences, with psilocybin producing relatively greater visual, mystical-type, insightful, and musical experiences, and DXM producing greater disembodiment.
Users of psychedelic drugs often report that their sense of being a self or ‘I’ distinct from the rest of the world has diminished or altogether dissolved. Neuroscientific study of such ‘ego dissolution’ experiences offers a window onto the nature of self-awareness. We argue that ego dissolution is best explained by an account that explains self-awareness as resulting from the integrated functioning of hierarchical predictive models which posit the existence of a stable and unchanging entity to which representations are bound. Combining recent work on the ‘integrative self' and the phenomenon of self-binding with predictive processing principles yields an explanation of ego dissolution according to which self-representation is a useful Cartesian fiction: an ultimately false representation of a simple and enduring substance to which attributes are bound which serves to integrate and unify cognitive processing across levels and domains. The self-model is not a mere narrative posit, as some have suggested; it has a more robust and ubiquitous cognitive function than that. But this does not mean, as others have claimed, that the self-model has the right attributes to qualify as a self. It performs some of the right kinds of functions, but it is not the right kind of entity. Ego dissolution experiences reveal that the self-model plays an important binding function in cognitive processing, but the self does not exist.
Cancer patients often develop chronic, clinically significant symptoms of depression and anxiety. Previous studies suggest that psilocybin may decrease depression and anxiety in cancer patients. The effects of psilocybin were studied in 51 cancer patients with life-threatening diagnoses and symptoms of depression and/or anxiety. This randomized, double-blind, cross-over trial investigated the effects of a very low (placebo-like) dose (1 or 3 mg/70 kg) vs. a high dose (22 or 30 mg/70 kg) of psilocybin administered in counterbalanced sequence with 5 weeks between sessions and a 6-month follow-up. Instructions to participants and staff minimized expectancy effects. Participants, staff, and community observers rated participant moods, attitudes, and behaviors throughout the study. High-dose psilocybin produced large decreases in clinician- and self-rated measures of depressed mood and anxiety, along with increases in quality of life, life meaning, and optimism, and decreases in death anxiety. At 6-month follow-up, these changes were sustained, with about 80% of participants continuing to show clinically significant decreases in depressed mood and anxiety. Participants attributed improvements in attitudes about life/self, mood, relationships, and spirituality to the high-dose experience, with >80% endorsing moderately or greater increased well-being/life satisfaction. Community observer ratings showed corresponding changes. Mystical-type psilocybin experience on session day mediated the effect of psilocybin dose on therapeutic outcomes.
Trial Registration
ClinicalTrials.gov identifier: NCT00465595
Background:
Clinically significant anxiety and depression are common in patients with cancer, and are associated with poor psychiatric and medical outcomes. Historical and recent research suggests a role for psilocybin to treat cancer-related anxiety and depression.
Methods:
In this double-blind, placebo-controlled, crossover trial, 29 patients with cancer-related anxiety and depression were randomly assigned and received treatment with single-dose psilocybin (0.3 mg/kg) or niacin, both in conjunction with psychotherapy. The primary outcomes were anxiety and depression assessed between groups prior to the crossover at 7 weeks.
Results:
Prior to the crossover, psilocybin produced immediate, substantial, and sustained improvements in anxiety and depression and led to decreases in cancer-related demoralization and hopelessness, improved spiritual wellbeing, and increased quality of life. At the 6.5-month follow-up, psilocybin was associated with enduring anxiolytic and anti-depressant effects (approximately 60-80% of participants continued with clinically significant reductions in depression or anxiety), sustained benefits in existential distress and quality of life, as well as improved attitudes towards death. The psilocybin-induced mystical experience mediated the therapeutic effect of psilocybin on anxiety and depression.
Conclusions:
In conjunction with psychotherapy, single moderate-dose psilocybin produced rapid, robust and enduring anxiolytic and anti-depressant effects in patients with cancer-related psychological distress.
Trial registration:
ClinicalTrials.gov Identifier: NCT00957359.
Acute and enduring adverse effects of psilocybin have been reported anecdotally, but have not been well characterized. For this study, 1993 individuals (mean age 30 yrs; 78% male) completed an online survey about their single most psychologically difficult or challenging experience (worst “bad trip”) after consuming psilocybin mushrooms. Thirty-nine percent rated it among the top five most challenging experiences of his/her lifetime. Eleven percent put self or others at risk of physical harm; factors increasing the likelihood of risk included estimated dose, duration and difficulty of the experience, and absence of physical comfort and social support. Of the respondents, 2.6% behaved in a physically aggressive or violent manner and 2.7% received medical help. Of those whose experience occurred >1 year before, 7.6% sought treatment for enduring psychological symptoms. Three cases appeared associated with onset of enduring psychotic symptoms and three cases with attempted suicide. Multiple regression analysis showed degree of difficulty was positively associated, and duration was negatively associated, with enduring increases in well-being. Difficulty of experience was positively associated with dose. Despite difficulties, 84% endorsed benefiting from the experience. The incidence of risky behavior or enduring psychological distress is extremely low when psilocybin is given in laboratory studies to screened, prepared, and supported participants.
Psychedelic drugs such as lysergic acid diethylamide (LSD) were used extensively in psychiatry in the past and their therapeutic potential is beginning to be re-examined today. Psychedelic psychotherapy typically involves a patient lying with their eyes-closed during peak drug effects, while listening to music and being supervised by trained psychotherapists. In this context, music is considered to be a key element in the therapeutic model; working in synergy with the drug to evoke therapeutically meaningful thoughts, emotions and imagery. The underlying mechanisms involved in this process have, however, never been formally investigated. Here we studied the interaction between LSD and music-listening on eyes-closed imagery by means of a placebo-controlled, functional magnetic resonance imaging (fMRI) study. Twelve healthy volunteers received intravenously administered LSD (75µg) and, on a separate occasion, placebo, before being scanned under eyes-closed resting conditions with and without music-listening. The parahippocampal cortex (PHC) has previously been linked with (1) music-evoked emotion, (2) the action of psychedelics, and (3) mental imagery. Imaging analyses therefore focused on changes in the connectivity profile of this particular structure. Results revealed increased PHC-visual cortex (VC) functional connectivity and PHC to VC information flow in the interaction between music and LSD. This latter result correlated positively with ratings of enhanced eyes-closed visual imagery, including imagery of an autobiographical nature. These findings suggest a plausible mechanism by which LSD works in combination with music listening to enhance certain subjective experiences that may be useful in a therapeutic context.
The debate on the clinical, scientific as well as ethical implication of the placebo and its effects is important, but has mainly focused on placebos with a medicinal and somatic meaning, such as pharmaceutical, surgical, or so called alternative medicinal interventions. However, this perspective omits the role of placebo processes in interventions with a psychotherapeutic meaning, such as psychotherapy. Based on a theoretically derived differentiation of the placebo concept we argue that although it is difficult to prove that psychotherapy is verum, it is possible to use it as placebo and that it can best be described as either a superplacebo or a superverum. Because these conceptualizations of psychotherapy have ethical consequences, the nature of psychotherapy as anything other than a verum needs to be actively addressed by research and practice. (PsycINFO Database Record (c) 2015 APA, all rights reserved)
This study explores the conceptual relationship between the placebo effect and psychotherapy. There is considerable evidence that the placebo effect can be exceptionally powerful under some circumstances. This begs the question: How much of the effectiveness of psychotherapy is attributable to the placebo effect? In an effort to answer this question, researchers have attempted to design sham psychotherapies for use in randomized, controlled trials. However, these efforts to develop placebo psychotherapies have been plagued by definitional and conceptual problems. In the context of medical treatment, placebo effects are relatively easy to define. The placebo effect in medicine is produced by factors other than the physical properties of the treatment. However, the effect of psychotherapy is—by definition of the term psychotherapy—produced by something other than the physical properties of the treatment. Therefore, using the medical definition of placebo, the effects of psychotherapy are ipso facto placebo effects, and psychotherapy is ipso facto a placebo. The problem is that the definition of placebos in medicine does not map well onto the domain of psychotherapy. Therefore, in evaluating the efficacy of psychotherapy, the placebo effect cannot and should not be controlled. We discuss the implications of this proposition, along with a consideration of various objections raised by taking such a position.
There is renewed interest in the therapeutic potential of psychedelic drugs such as lysergic acid diethylamide (LSD). LSD was used extensively in the 1950s and 1960s as an adjunct in psychotherapy, reportedly enhancing emotionality. Music is an effective tool to evoke and study emotion and is considered an important element in psychedelic-assisted psychotherapy; however, the hypothesis that psychedelics enhance the emotional response to music has yet to be investigated in a modern placebo-controlled study.
The present study sought to test the hypothesis that music-evoked emotions are enhanced under LSD.
Ten healthy volunteers listened to five different tracks of instrumental music during each of two study days, a placebo day followed by an LSD day, separated by 5-7 days. Subjective ratings were completed after each music track and included a visual analogue scale (VAS) and the nine-item Geneva Emotional Music Scale (GEMS-9).
Results demonstrated that the emotional response to music is enhanced by LSD, especially the emotions "wonder", "transcendence", "power" and "tenderness".
These findings reinforce the long-held assumption that psychedelics enhance music-evoked emotion, and provide tentative and indirect support for the notion that this effect can be harnessed in the context of psychedelic-assisted psychotherapy. Further research is required to test this link directly.
Ayahuasca (AYA), a natural psychedelic brew prepared from Amazonian plants and rich in dimethyltryptamine (DMT) and harmine, causes effects of subjective well-being and may therefore have antidepressant actions. This study sought to evaluate the effects of a single dose of AYA in six volunteers with a current depressive episode.
Open-label trial conducted in an inpatient psychiatric unit.
Statistically significant reductions of up to 82% in depressive scores were observed between baseline and 1, 7, and 21 days after AYA administration, as measured on the Hamilton Rating Scale for Depression (HAM-D), the Montgomery-Åsberg Depression Rating Scale (MADRS), and the Anxious-Depression subscale of the Brief Psychiatric Rating Scale (BPRS). AYA administration resulted in nonsignificant changes in Young Mania Rating Scale (YMRS) scores and in the thinking disorder subscale of the BPRS, suggesting that AYA does not induce episodes of mania and/or hypomania in patients with mood disorders and that modifications in thought content, which could indicate psychedelic effects, are not essential for mood improvement.
These results suggest that AYA has fast-acting anxiolytic and antidepressant effects in patients with a depressive disorder.
Several lines of evidence suggest that classic (5HT2A agonist) hallucinogens have clinically relevant effects in alcohol and drug addiction. Although recent studies have investigated the effects of psilocybin in various populations, there have been no studies on the efficacy of psilocybin for alcohol dependence. We conducted a single-group proof-of-concept study to quantify acute effects of psilocybin in alcohol-dependent participants and to provide preliminary outcome and safety data. Ten volunteers with DSM-IV alcohol dependence received orally administered psilocybin in one or two supervised sessions in addition to Motivational Enhancement Therapy and therapy sessions devoted to preparation for and debriefing from the psilocybin sessions. Participants' responses to psilocybin were qualitatively similar to those described in other populations. Abstinence did not increase significantly in the first 4 weeks of treatment (when participants had not yet received psilocybin), but increased significantly following psilocybin administration (p < 0.05). Gains were largely maintained at follow-up to 36 weeks. The intensity of effects in the first psilocybin session (at week 4) strongly predicted change in drinking during weeks 5-8 (r = 0.76 to r = 0.89) and also predicted decreases in craving and increases in abstinence self-efficacy during week 5. There were no significant treatment-related adverse events. These preliminary findings provide a strong rationale for controlled trials with larger samples to investigate efficacy and mechanisms.
NCT02061293.
© The Author(s) 2015.
Networks, as efficient representations of complex systems, have appealed to scientists for a long time and now permeate many areas of science, including neuroimaging (Bullmore and Sporns 2009 Nat. Rev. Neurosci.
10, 186–198. (doi:10.1038/nrn2618)). Traditionally, the structure of complex networks has been studied through their statistical properties and metrics concerned with node and link properties, e.g. degree-distribution, node centrality and modularity. Here, we study the characteristics of functional brain networks at the mesoscopic level from a novel perspective that highlights the role of inhomogeneities in the fabric of functional connections. This can be done by focusing on the features of a set of topological objects—homological cycles—associated with the weighted functional network. We leverage the detected topological information to define the homological scaffolds, a new set of objects designed to represent compactly the homological features of the correlation network and simultaneously make their homological properties amenable to networks theoretical methods. As a proof of principle, we apply these tools to compare resting-state functional brain activity in 15 healthy volunteers after intravenous infusion of placebo and psilocybin—the main psychoactive component of magic mushrooms. The results show that the homological structure of the brain's functional patterns undergoes a dramatic change post-psilocybin, characterized by the appearance of many transient structures of low stability and of a small number of persistent ones that are not observed in the case of placebo.
Sacred Knowledge is the first well-documented, sophisticated account of the effect of psychedelics on biological processes, human consciousness, and revelatory religious experiences. Based on nearly three decades of legal research with volunteers, William A. Richards argues that, if used responsibly and legally, psychedelics have the potential to assuage suffering and constructively affect the quality of human life. Richards’s analysis contributes to social and political debates over the responsible integration of psychedelic substances into modern society. His book serves as an invaluable resource for readers who, whether spontaneously or with the facilitation of psychedelics, have encountered meaningful, inspiring, or even disturbing states of consciousness and seek clarity about their experiences. Testing the limits of language and conceptual frameworks, Richards makes the most of experiential phenomena that stretch our conception of reality, advancing new frontiers in the study of belief, spiritual awakening, psychiatric treatment, and social well-being. His findings enrich humanities and scientific scholarship, expanding work in philosophy, anthropology, theology, and religious studies and bringing depth to research in mental health, psychotherapy, and psychopharmacology.
Prior research has shown that acute subjective psychedelic effects are associated with both spontaneous and intended changes in depression and anxiety. Psychedelics are also theorized to produce increases in psychological flexibility, which could explain decreases in depression and anxiety following a psychedelic experience. Therefore, the present cross-sectional survey study sought to examine whether psychological flexibility mediated the relationship between acute psychedelic experiences and spontaneous or intended changes in depression and anxiety among a large international sample of people who reported having used a psychedelic (n=985; male=71.6%; Caucasian/white=84.1%; Mage=32.2, SD=12.6). A regression analysis showed that acute effects (i.e., mystical and insightful effects) were significantly associated with decreases in depression/anxiety following a psychedelic experience. A path analysis revealed that, while controlling for age and sex, increases in psychological flexibility fully mediated the effect of mystical and insightful experiences on decreases in depression and anxiety following a psychedelic experience. This suggests that psychological flexibility may be an important mediator of the therapeutic effects of psychedelic drugs. Future prospective experimental studies should examine the effect of psychedelic drug administration on psychological flexibility in order to gain a better understanding of the psychological processes that predict therapeutic effects of psychedelics.
Cohesion is the most popular relationship construct in the group therapy literature. This chapter reviews common definitions of cohesion and the most frequently studied measures. The authors also discuss a measure that may clarify group relations using two latent factors (quality and structure) to explain common variance among frequently used group relationship instruments. The results of a meta-analysis examining the relation between group cohesion and treatment outcome in 55 studies are presented. Results indicate that the weighted aggregate correlation between cohesion and treatment outcome was statistically significant r = .26, reflecting a moderate effect size ( d = .56). Six moderator variables were found to significantly predict the magnitude of the cohesion–outcome association (type of outcome measure, leader interventions to increase cohesion, theoretical orientation, type of group, emphasis on group interaction, dose or number of group sessions). Patient contributions, diversity considerations, and evidence-based therapeutic practices are highlighted.
The alliance continues to be one of the most investigated variables related to success in psychotherapy irrespective of theoretical orientation. We define and illustrate the alliance (also conceptualized as therapeutic alliance, helping alliance, or working alliance) and then present a meta-analysis of 295 independent studies that covered more than 30,000 patients (published between 1978 and 2017) for face-to-face and Internet-based psychotherapy. The relation of the alliance and treatment outcome was investigated using a three-level meta-analysis with random-effects restricted maximum-likelihood estimators. The overall alliance-outcome association for face-to-face psychotherapy was r = .278 (95% confidence intervals [.256, .299], p < .0001; equivalent of d = .579). There was heterogeneity among the effect sizes, and 2% of the 295 effect sizes indicated negative correlations. The correlation for Internet-based psychotherapy was approximately the same (viz., r = .275, k = 23). These results confirm the robustness of the positive relation between the alliance and outcome. This relation remains consistent across assessor perspectives, alliance and outcome measures, treatment approaches, patient characteristics, and countries. The article concludes with causality considerations, research limitations, diversity considerations, and therapeutic practices. (PsycINFO Database Record (c) 2018 APA, all rights reserved).
Objectives
Classic hallucinogens (e.g. psilocybin and LSD) have substantial effects on perception, cognition, and emotion that can often be psychologically challenging, however we know very little regarding the source of significant individual variability that has been observed in the frequency and intensity of challenging experiences (i.e. “bad trips”) with psychedelics. Previous clinical and observational literature suggests that there may be an association between neuroticism and challenging psychedelic experiences.
Methods
Data from two online surveys of challenging experiences with psilocybin were analyzed. Multivariate analysis was used to estimate the associations between total score and scores from seven sub-factors (fear, grief, physical distress, insanity, isolation, death, and paranoia) of the Challenging Experience Questionnaire (CEQ), and scale scores from the Ten Item Personality Inventory (TIPI) in Study 1 (N = 1993) and the Big Five Inventory (BFI) in Study 2 (N = 981).
Results
CEQ scores were negatively associated with emotional stability scores (the inverse of neuroticism) in Study 1 and positively associated with neuroticism scores in Study 2.
Conclusions
Neuroticism may contribute to the strength of challenging experiences with psychedelics in uncontrolled settings.
Explanatory models of illness – the way people perceive, interpret and respond to it – are mediated not only by the illness itself, but also by cultural and social contexts. This article discusses recent evidence showing how the exploration of explanatory models can help to shape treatment and outcomes for some of the most common categories of mental illness, and presents case studies illustrating dilemmas clinicians face when their explanatory models differ from those of their patients. It concludes with recommendations on how a culturally sensitive clinical approach based on the exploration of explanatory models during assessment and treatment can be used as an effective way of dealing with the complexity of patients' and families' needs.
LEARNING OBJECTIVES
• Appreciate the use of explanatory models in clinical practice
• Understand the relevance of explanatory models in relation to specific diagnostic categories of mental illness
• Recognise that dilemmas may arise if the explanatory models of the clinician and the patient differ, and be able to manage this tension
Background:
At least one-third of patients with major depressive disorder (MDD) have treatment-resistant depression (TRD), defined as lack of response to two or more adequate antidepressant trials. For these patients, novel antidepressant treatments are urgently needed.
Methods:
The current study is a phase IIa open label clinical trial examining the efficacy and tolerability of a combination of dextromethorphan (DM) and the CYP2D6 enzyme inhibitor quinidine (Q) in patients with TRD. Dextromethorphan acts as an antagonist at the glutamate N-methyl-d-aspartate (NMDA) receptor, in addition to other pharmacodynamics properties that include activity at sigma-1 receptors. Twenty patients with unipolar TRD who completed informed consent and met all eligibility criteria we enrolled in an open-label study of DM/Q up to 45/10mg by mouth administered every 12h over the course of a 10-week period, and constitute the intention to treat (ITT) sample. Six patients discontinued prior to study completion.
Results:
There was no treatment-emergent suicidal ideation, psychotomimetic or dissociative symptoms. Montgomery-Asberg Depression Rating Scale (MADRS) score was reduced from baseline to the 10-week primary outcome (mean change: -13.0±11.5, t19=5.0, p<0.001), as was QIDS-SR score (mean change: -5.9±6.6, t19=4.0, p<0.001). The response and remission rates in the ITT sample were 45% and 35%, respectively.
Limitations:
Open-label, proof-of-concept design.
Conclusions:
Herein we report acceptable tolerability and preliminary efficacy of DM/Q up to 45/10mg administered every 12h in patients with TRD. Future larger placebo controlled randomized trials in this population are warranted.
Set and setting is a term which refers to the psychological, social, and cultural parameters which shape the response to psychedelic drugs. The concept is considered fundamental to psychedelic research and has also been used to describe nonpharmacological factors which shape the effects of other agents such as alcohol, heroin, amphetamines, or cocaine. This paper reviews the history and evolution of the concept of set and setting from the 19th-century Parisian Club des Hashischins, through to 1950s psychotomimetic research on nondrug determinants of psychopharmacology, the use of extra-drug techniques by psychedelic therapists of the 1950s, and the invention of the concept of set and setting by Leary. Later developments and expansions on the concept of set and setting are discussed, and the term of collective set and setting is suggested as a theoretical tool to describe the social forces which shape individual set and setting situations. The concept of set and setting, it is argued, is crucial not only for psychedelic research but also for advancing drug research and developing more effective drug policy.
Placebo response theory and set and setting theory are two fields which examine how non-biological factors shape the response to therapy. Both consider factors such as expectancy, preparation and beliefs to be crucial for understanding the extra-pharmacological processes which shape the response to drugs. Yet there are also fundamental differences between the two theories. Set and setting concerns itself with response to psychoactive drugs only; placebo theory relates to all therapeutic interventions. Placebo theory is aimed at medical professionals; set and setting theory is aimed at professionals and drug users alike. Placebo theory is primarily descriptive, describing how placebo acts; set and setting theory is primarily prescriptive, educating therapists and users on how to control and optimize the effects of drugs. This paper examines how placebo theory and set and setting theory can complement and benefit each other, broadening our understanding of how non-biological factors shape response to drugs and other treatment interventions.
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.
Background:
Patient personality traits have been shown to influence treatment outcome in those with major depressive disorder (MDD). The trait agreeableness, which reflects an interpersonal orientation, may affect treatment outcome via its role in the formation of therapeutic alliance. No published studies have tested this hypothesis in patients with MDD.
Method:
Participants were 209 outpatients with MDD who were treated in a randomized control trial. Mediation analyses were conducted to examine the role of therapeutic alliance in the association between pretreatment personality and the reduction of depression symptom severity during treatment. Separate models were estimated for patient- versus therapist-rated therapeutic alliance.
Results:
We found a significant indirect effect of agreeableness on the reduction of depression severity via patient-rated therapeutic alliance. Results were replicated across two well-validated measures of depression symptom severity. Results also partially supported indirect effects for extraversion and openness. Therapist ratings of alliance did not mediate the association between personality and treatment outcomes.
Limitations:
Patients were recruited as part of a randomized control trial, which may limit the generalizability of results to practice-based clinical settings. Due to constraints on statistical power, intervention-specific mediation results were not examined.
Conclusions:
These results highlight the importance of personality and the role it plays in treatment process as well as outcome.
The Relationship Inventory: A complete resource and guide. Wiley, 2015
Godfrey T Barrett-Lennard
This work takes its inspiration from one of Carl Rogers’ most seminal contributions: his conception of the basic conditions leading to healing and growth, in therapy and other life relationship contexts. The major formulations of this theory in the late 1950s implied that change in therapy was powered by crucial ingredient qualities of the therapist’s response that carried through into the awareness of the client. The opening chapters of the book centre on the importance of a progressively refined theory of change and describe a classic research study and testing of core features of Rogers’ theory – as more rigorously formulated for measurement in this research. The new instrumentation that resulted is Barrett-Lennard’s Relationship Inventory (BLRI), which taps crucial ingredient facets of the therapist’s perceived empathic understanding and the other hypothesized core dimensions of response.
The findings of this primary study with some 42 actual clients and their therapists was distinctly supportive of the underlying theory, as reported here in detail. It was clear however that the Relationship Inventory could and should be further refined, and the revision process and outcome is closely reported. A generous spectrum of subsequent studies, and an account of fresh adaptations of the instrument – for example, for use in the study of couple, parent-child and teacher-student relationships – are also carefully outlined. Discussion of new studies and possibilities are discussed and a major appendix of the book includes all of the main existing forms and fresh innovations of the BLRI.
As seen in the outline of chapters (next), counselor training exercises developed and applied as an outgrowth all the BLRI are also presented in practical form for fellow- instructors, students and other interested readers. Finally, the book goes on to present and discuss different later instrument developments by the author, and looks ahead to envisage new levels and theatres of relationship study.
Chapters
1. How change happens: The guidance and refinement of theory
2: The classic investigation of Carl Rogers’ core theory
3: A major revision: Crafting the 64-item RI, and emergent adaptations
4. Mature and travelling: The RI ‘system’ in focus
5. The BLRI story extended: Later work and looking ahead
6. Training applications: Exercises in facilitation
7. The Contextual Selves Inventory – to study self in its diversity
8. Tracking self and relational process in experiential groups
9. Looking ahead: Fresh horizons in relationship study
Appendix 1: The Relationship Inventory forms and scoring keys
Appendix 2: Contextual Selves Inventory, and Triad & Group forms
Ayahuasca is an Amazonian botanical hallucinogenic brew which contains dimethyltryptamine, a 5-HT2A receptor agonist, and harmine, a monoamine-oxidase A inhibitor. Our group recently reported that ayahuasca administration was associated with fast-acting antidepressive effects in 6 depressive patients. The objective of the present work was to assess the antidepressive potentials of ayahuasca in a bigger sample and to investigate its effects on regional cerebral blood flow. In an open-label trial conducted in an inpatient psychiatric unit, 17 patients with recurrent depression received an oral dose of ayahuasca (2.2 mL/kg) and were evaluated with the Hamilton Rating Scale for Depression, the Montgomery-Åsberg Depression Rating Scale, the Brief Psychiatric Rating Scale, the Young Mania Rating Scale, and the Clinician Administered Dissociative States Scale during acute ayahuasca effects and 1, 7, 14, and 21 days after drug intake. Blood perfusion was assessed eight hours after drug administration by means of single photon emission tomography. Ayahuasca administration was associated with increased psychoactivity (Clinician Administered Dissociative States Scale) and significant score decreases in depression-related scales (Hamilton Rating Scale for Depression, Montgomery-Åsberg Depression Rating Scale, Brief Psychiatric Rating Scale) from 80 minutes to day 21. Increased blood perfusion in the left nucleus accumbens, right insula and left subgenual area, brain regions implicated in the regulation of mood and emotions, were observed after ayahuasca intake. Ayahuasca was well tolerated. Vomiting was the only adverse effect recorded, being reported by 47% of the volunteers. Our results suggest that ayahuasca may have fast-acting and sustained antidepressive properties. These results should be replicated in randomized, double-blind, placebo-controlled trials.
This article is a republication of a classic paper in which Rosenzweig introduced the concept of common factors in psychotherapy. This seminal idea-which refers to the finding that all forms of psychotherapy seem to share, to some degree, a small number of effective change ingredients-remains highly influential in psychotherapy integration today. Rosenzweig reviewed the data presented by then current forms of psychotherapy and argued that the theories that describe the change principles in each psychotherapy are inadequate to capture those deeper common factors.
The second edition of The Great Psychotherapy Debate has been updated and revised to expand the presentation of the Contextual Model, which is derived from a scientific understanding of how humans heal in a social context and explains findings from a vast array of psychotherapies studies. This model provides a compelling alternative to traditional research on psychotherapy, which tends to focus on identifying the most effective treatment for particular disorders through emphasizing the specific ingredients of treatment. The new edition also includes a history of healing practices, medicine, and psychotherapy, an examination of therapist effects, and a thorough review of the research on common factors such as the alliance, expectations, and empathy.
The common factors have a long history in the field of psychotherapy theory, research and practice. To understand the evidence supporting them as important therapeutic elements, the contextual model of psychotherapy is outlined. Then the evidence, primarily from meta-analyses, is presented for particular common factors, including alliance, empathy, expectations, cultural adaptation, and therapist differences. Then the evidence for four factors related to specificity, including treatment differences, specific ingredients, adherence, and competence, is presented. The evidence supports the conclusion that the common factors are important for producing the benefits of psychotherapy.
Component studies, which involve comparisons between a treatment package and the treatment package without a theoretically important component or the treatment package with an added component, use experimental designs to test whether the component is necessary to produce therapeutic benefit. A meta-analysis was conducted on 27 component studies culled from the literature. It was found that the effect size for the difference between a package with and without the critical components was not significantly different from zero, indicating that theoretically purported important components are not responsible for therapeutic benefits. Moreover, the effect sizes were homogeneous, which suggests that there were no important variables moderating effect sizes. The results cast doubt on the specificity of psychological treatments.
LSD's short but colorful history in North America carries with it the distinct cachet of counterculture and government experimentation. The truth about this mind-altering chemical cocktail is far more complex—and less controversial—than generally believed.
Psychedelic Psychiatry is the tale of medical researchers working to understand LSD’s therapeutic properties just as escalating anxieties about drug abuse in modern society laid the groundwork for the end of experimentation at the edge of psychopharmacology. Historian Erika Dyck deftly recasts our understanding of LSD to show it as an experimental substance, a medical treatment, and a tool for exploring psychotic perspectives—as well as a recreational drug. She recounts the inside story of the early days of LSD research in small-town, prairie Canada, when Humphry Osmond and Abram Hoffer claimed incredible advances in treating alcoholism, understanding schizophrenia and other psychoses, and achieving empathy with their patients.
In relating the drug’s short, strange trip, Dyck explains how concerns about countercultural trends led to the criminalization of LSD and other so-called psychedelic drugs—concordantly opening the way for an explosion in legal prescription pharmaceuticals—and points to the recent re-emergence of sanctioned psychotropic research among psychiatric practitioners. This challenge to the prevailing wisdom behind drug regulation and addiction therapy provides a historical corrective to our perception of LSD’s medical efficacy.
This article provides a review of published, counseling‐relevant literature on the physical environment, with a focus on physical elements that may enhance or detract from the counseling process. Specifically, it describes environmental variables that are relevant to counseling, providing examples of their practical importance, and in several cases describes possible application to counseling settings. Finally, this article identifies research implications and proposes a 3‐part future research agenda.
Objective
Various control conditions have been employed in psychotherapy trials, but there is growing suspicion that they may lead to different effect size estimates. The present study aims to examine the differences among control conditions including waiting list (WL), no treatment (NT) and psychological placebo (PP).Method
We comprehensively searched for all randomized controlled trials (RCTs) comparing cognitive-behaviour therapies (CBT) against various control conditions in the acute phase treatment of depression, and applied network meta-analysis (NMA) to combine all direct and indirect comparisons among the treatment and control arms.ResultsWe identified 49 RCTs (2730 participants) comparing WL, NT, PP and CBT. This network of evidence was consistent, and the effect size estimates for CBT were substantively different depending on the control condition. The odds ratio of response for NT over WL was statistically significant at 2.9 (95% CI: 1.3–5.7). However, the quality of evidence, including publication bias, was less than ideal and none of the preplanned sensitivity analyses limiting to high-quality studies could be conducted, while findings of significant differences did not persist in post hoc sensitivity analyses trying to adjust for publication bias.Conclusion
There may be important differences in control conditions currently used in psychotherapy trials.