Article

Positive effects of psychedelics on depression and wellbeing scores in individuals reporting an eating disorder

September 2020
Eating and weight disorders: EWD 26(1)

Authors:

Imperial College London

Purpose: Psychedelic therapy is showing promise for a broad range of mental health conditions, indicative of a transdiagnostic action. While the efficacy of symptom-focused treatments for eating disorders (EDs) is limited, improved mental health and psychological wellbeing are thought to contribute to greater treatment outcomes. This study provides the first quantitative exploration of the psychological effects of psychedelics in those reporting an ED diagnosis. Methods: Prospective, online data were collected from individuals planning to take a psychedelic drug. Twenty-eight participants reporting a lifetime ED diagnosis completed measures of depressive symptomology (Quick Inventory of Depressive Symptomology; QIDS-SR16) and psychological wellbeing (Warwick-Edinburgh Mental Wellbeing Scale; WEMWBS) 1-2 weeks before, and 2 weeks after a psychedelic experience. Twenty-seven of these participants also completed a measure of emotional breakthrough [Emotional Breakthrough Inventory (EBI)] in relation to the acute psychedelic experience. Results: Bayesian t tests demonstrated overwhelming evidence for improvements in depression and wellbeing scores following the psychedelic experience. Marginal evidence was also found for a correlation between emotional breakthrough and the relevant mental health improvements. Conclusion: These findings provide supportive evidence for positive psychological aftereffects of a psychedelic experience that are relevant to the treatment of EDs. It is hoped that this will encourage further research and will bolster initiatives to directly examine the safety and efficacy of psychedelic assisted therapy as a treatment of EDs in future clinical trials. Level of evidence: Level III, cohort study.

Medical Use of Cannabinoids and Psychedelic Compounds

Chapter

Full-text available

Sep 2024

Perspectives and preliminary experiences of psychedelics for the treatment of eating disorders: A systematic scoping review

Article

Full-text available

May 2024
EUR EAT DISORD REV

Objective Research regarding the therapeutic application of psychedelics and psychedelic‐assisted psychotherapy in the treatment of eating disorders (EDs) has begun to emerge. This systematic scoping review aimed to map and synthesise the existing evidence regarding the participant reported efficacy and perspectives concerning psychedelics in the treatment of EDs, and to identify significant research gaps. Method A systematic search was undertaken across several databases in accordance with Preferred Reporting Items for Systematic reviews and Meta‐Analyses extension for Scoping Reviews guidelines. Results 1290 publications were identified, 1135 after duplicates removed, with 17 meeting full‐eligibility criteria. Overall, findings suggested that most participants reported experiencing a meaningful reduction in their ED symptoms and having positive experiences or an openness to explore psychedelics as a treatment for ED symptoms, although some noted concerns of adverse effects and the importance of having psychological support to increase safety and efficacy. Conclusions While preliminary research suggests psychedelics and psychedelic‐assisted psychotherapy may be a viable treatment option for ED symptoms, further research with more robust research designs is required to increase confidence in its efficacy, generalisability, and safety as a therapeutic medium.

Ayahuasca ceremony leaders' perspectives on special considerations for eating disorders

Article

Nov 2023
Eat Disord

Eating disorders (EDs) are difficult conditions to resolve, necessitating novel treatments. Ayahuasca, a psychedelic plant medicine originating in Indigenous Amazonian communities, is being investigated. Aspects of ceremonial ayahuasca use (purging, dietary restrictions) appear similar to ED behaviors, raising questions about ayahuasca's suitability as an intervention for individuals with EDs. This study explored the perspectives of ayahuasca ceremony leaders on these and other considerations for ceremonial ayahuasca drinking among individuals with EDs. A qualitative content analysis of interviews was undertaken with 15 ayahuasca ceremony leaders, the majority of whom were from the West/Global North. Screening for EDs, purging and dietary restrictions, potential risks and dangers, and complementarity with conventional ED treatment emerged as categories. The findings offer ideas, including careful screening and extra support, to promote safe and beneficial ceremony experiences for ceremony participants with EDs. More research is needed to clarify the impacts of ceremony-related purging and preparatory diets. To evolve conventional models of treatment, the ED field could consider Indigenous approaches to mental health whereby ayahuasca ceremony leaders and ED researchers and clinicians collaborate in a decolonizing, bidirectional bridging process between Western and Indigenous paradigms of healing.

Outcomes of usage of psychedelics by people reporting an eating disorder in clinical and non-clinical settings: a scoping review

Article

Jul 2023

Objective To map the studies reporting the use of psychedelics in clinical and non-clinical settings by people reporting an eating disorder (ED) and their outcomes. Method To be included, peer-reviewed articles had to be written in English or Spanish and had to address the usage of psychedelics by people reporting an ED. Searches were conducted on PubMed, Scopus, and Web of Science. Data on key study characteristics and the findings from the studies were charted using a standardised form. Two reviewers independently charted the data from the included articles. Quality appraisal was conducted for all included studies. Results Six studies reporting the use of ayahuasca, DMT/5-MEO-DMT, LSD/1P-LSD, San Pedro/mescaline, psilocybin, and ketamine were included. After the psychedelic experiences, many participants reported diminished ED symptoms, reductions in anxiety, self-harm, suicidality, and problematic substance use, significant improvements in depression and wellbeing, and changes in self-perception, and some showed complete remission. Several participants felt profound spiritual healing and reported achieving deep insights into the psychological origins of their ED. All the qualitative studies met 100% of the quality appraisal criteria, whereas the quantitative studies were rated from between 20% and 60%. Discussion All included studies suggest that psychedelics promise therapeutic value for eating disorders. These findings are preliminary, and randomised controlled trials are necessary to prove psychedelic-assisted psychotherapy efficacy and long-term implications for eating disorders. Major changes in drug policy are urgent to facilitate research about psychedelics.

Research into Psychedelic-Assisted Psychotherapy for Anorexia Nervosa Should be Funded

Article

Dec 2022

Lauren Otterman

Eating disorders are debilitating diseases that have twin impacts on the body and mind and are associated with a number of physiological and psychological comorbidities (Blinder, Cumella, and Sanathara 2006; Casiero and Frishman 2006), including increased suicide risk (Arcelus et al. 2011; Lipson and Sonneville 2020). In addition, eating disorders are growing in prevalence (Gilmache et al. 2019) and impact women at much higher rates than men (Bearman, Martinez, and Stice 2006), especially in adolescence (Spriggs, Kettner, and Carhart-Harris 2021). Anorexia nervosa (AN) is a particularly devastating eating disorder, with one of the highest mortality rates of any psychiatric disorder (Sullivan 1995). Despite the severity of the condition, current treatments for AN are limited in their efficacy (Khalsa et al. 2017). Based on the growing body of evidence demonstrating the short-term and long-term efficacy of psychedelic-assisted psychotherapy for the treatment of other mental illnesses, I argue that research into psychedelic-assisted psychotherapy for AN should be funded.

Psilocybin Therapy for Females With Anorexia Nervosa: A Phase 1, Open-Label Feasibility Study

Article

Jun 2024

Psychological effects of psychedelics in adolescents

Article

Full-text available

Jun 2024

This study aimed to investigate differences in long-term psychological effects, acute subjective effects, and side effects associated with psychedelic use in adolescents (aged 16–24), compared with adults (aged 25+). Data from two observational online survey cohorts was pooled, involving adolescents (average age 20.4 ± 2.2, N = 435) and adults (average age 36.5 ± 9.7, range = 25–71, N = 654) who self-initiated a psychedelic experience and were tracked via online surveys from a pre-experience baseline to four weeks post-use. Self-reported measures of well-being were collected one week before, and two and four weeks after psychedelic use. Acute subjective drug effects, dosage and contextual variables pertaining to the setting of use were measured on the day after the session. Repeated-measures analyses of covariance, t - and z -tests, as well as exploratory correlational and regression analyses tested differences in psychological changes, acute drug effects, and side effects between the two groups. Psychological well-being significantly improved in adolescents two and four weeks following psychedelic use, with a clinically relevant mean change score of 3.3 points (95% CI: 1.1–5.5). on the Warwick-Edinburgh Mental Wellbeing Scale [ F (1.8, 172.9) = 13.41, η ² G = .04, p < .001], statistically indistinguishable from changes in adults. Acute subjective effects differed between the age groups; adolescents reported significantly higher challenging experiences and ego-dissolution. In adolescents, visual symptoms related to “hallucinogen persisting perceptual disorder” (HPPD) were reported at a higher prevalence than in adults (73.5% vs. 34.2%, p < .001) but were reported as distressing by only one adolescent participant. To our knowledge, this is the first prospective study to examine the psychological effects of psychedelic use specifically in adolescents. Statistically significant improvements in psychological well-being and other domains of mental health were observed, consistent with effects seen previously in adults, providing tentative evidence for the potential utility of psychedelic interventions in adolescents. However, differences in acute subjective effects, specifically the less positive role of ego-dissolution experiences for long-term changes in adolescents, as well as a higher prevalence of HPPD-related symptoms suggest that special considerations might be required when assessing psychedelic treatment design and risks.

Psilocybin therapy for females with anorexia nervosa: a phase 1, open-label feasibility study

Article

Full-text available

Jul 2023
NAT MED

Anorexia nervosa (AN) is a deadly illness with no proven treatments to reverse core symptoms and no medications approved by the US Food and Drug Administration. Novel treatments are urgently needed to improve clinical outcomes. In this open-label feasibility study, 10 adult female participants (mean body mass index 19.7 kg m⁻²; s.d. 3.7) who met Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) criteria for AN or pAN (partial remission) were recruited to a study conducted at an academic clinical research institute. Participants received a single 25-mg dose of synthetic psilocybin in conjunction with psychological support. The primary aim was to assess safety, tolerability and feasibility at post-treatment by incidences and occurrences of adverse events (AEs) and clinically significant changes in electrocardiogram (ECG), laboratory tests, vital signs and suicidality. No clinically significant changes were observed in ECG, vital signs or suicidality. Two participants developed asymptomatic hypoglycemia at post-treatment, which resolved within 24 h. No other clinically significant changes were observed in laboratory values. All AEs were mild and transient in nature. Participants’ qualitative perceptions suggest that the treatment was acceptable for most participants. Results suggest that psilocybin therapy is safe, tolerable and acceptable for female AN, which is a promising finding given physiological dangers and problems with treatment engagement.

Pattern breaking: a complex systems approach to psychedelic medicine

Article

Full-text available

Jul 2023

Recent research has demonstrated the potential of psychedelic therapy for mental health care. However, the psychological experience underlying its therapeutic effects remains poorly understood. This paper proposes a framework that suggests psychedelics act as destabilizers, both psychologically and neurophysiologically. Drawing on the ‘entropic brain’ hypothesis and the ‘RElaxed Beliefs Under pSychedelics’ model, this paper focuses on the richness of psychological experience. Through a complex systems theory perspective, we suggest that psychedelics destabilize fixed points or attractors, breaking reinforced patterns of thinking and behaving. Our approach explains how psychedelic-induced increases in brain entropy destabilize neurophysiological set points and lead to new conceptualizations of psychedelic psychotherapy. These insights have important implications for risk mitigation and treatment optimization in psychedelic medicine, both during the peak psychedelic experience and during the subacute period of potential recovery.

Therapeutic uses of psychedelics for eating disorders and body dysmorphic disorder

Article

Dec 2022
J PSYCHOPHARMACOL

Background Clinical use of psychedelics has gained considerable attention, with promising benefits across a range of mental disorders. Current pharmacological and psychotherapeutic treatments for body dysmorphic disorder (BDD) and eating disorders (EDs) have limited efficacy. As such, other treatment options such as psychedelic-assisted therapies are being explored in these clinical groups. Aims This systematic review evaluates evidence related to the therapeutic potential of psychedelics in individuals diagnosed with BDD and EDs. Methods Following Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, we conducted a systematic review of all study designs published to the end of February 2022 that identified changes in ED/BDD symptom severity from psychedelics using validated measures to assess symptom changes. Results Our search detected a total of 372 studies, of which five met inclusion criteria (two exploratory studies, two case reports, and one prospective study). These were included in the data evaluation. Effects of psychedelics on BDD and various ED symptoms were identified mostly through thematic analyses and self-reports. Conclusions Our findings highlight that more research is needed to determine the safety and efficacy of psychedelics in BDD and EDs and we suggest avenues for future exploration.

Body mass index (BMI) does not predict responses to psilocybin

Article

Full-text available

Nov 2022
J PSYCHOPHARMACOL

Background Psilocybin is a serotonin type 2A (5-HT 2A ) receptor agonist and naturally occurring psychedelic. 5-HT 2A receptor density is known to be associated with body mass index (BMI), however, the impact of this on psilocybin therapy has not been explored. While body weight-adjusted dosing is widely used, this imposes a practical and financial strain on the scalability of psychedelic therapy. This gap between evidence and practice is caused by the absence of studies clarifying the relationship between BMI, the acute psychedelic experience and long-term psychological outcomes. Method Data were pooled across three studies using a fixed 25 mg dose of psilocybin delivered in a therapeutic context to assess whether BMI predicts characteristics of the acute experience and changes in well-being 2 weeks later. Supplementing frequentist analysis with Bayes Factors has enabled for conclusions to be drawn regarding the null hypothesis. Results Results support the null hypothesis that BMI does not predict overall intensity of the altered state, mystical experiences, perceptual changes or emotional breakthroughs during the acute experience. There was weak evidence for greater ‘dread of ego dissolution’ in participants with lower BMI, however, further analysis suggested BMI did not meaningfully add to the combination of the other covariates (age, sex and study). While mystical-type experiences and emotional breakthroughs were strong predictors of improvements in well-being, BMI was not. Conclusions These findings have important implications for our understanding of pharmacological and extra-pharmacological contributors to psychedelic-assisted therapy and for the standardization of a fixed therapeutic dose in psychedelic-assisted therapy.

Serotonergic psychedelic treatment for obesity and eating disorders: potential expectations and caveats for emerging studies

Article

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May 2022
J PSYCHIATR NEUROSCI

Beyond the numbers: reimagining healing with psychedelics for eating disorders

Article

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Sep 2024

Psychedelics and schizophrenia: a double-edged sword

Article

Full-text available

Sep 2024

Psychedelics have shown promising effects in several psychiatric diseases as demonstrated by multiple clinical trials. However, no clinical experiments on patients with schizophrenia have been conducted up to date, except for some old semi-anecdotal studies mainly performed in the time-span '50s-'60s. Notably, these studies reported interesting findings, particularly on the improvement of negative symptoms and social cognition. With no doubts the lack of modern clinical studies is due to the psychomimetic properties of psychedelics, a noteworthy downside that could worsen positive symptoms. However, a rapidly increasing body of evidence has suggested that the mechanisms of action of such compounds partially overlaps with the pathogenic underpinnings of schizophrenia but in an opposite way. These findings suggest that, despite being a controversial issue, the use of psychedelics in the treatment of schizophrenia would be based on a strong biological rationale. Therefore, the aim of our perspective paper is to provide a background on the old experiments with psychedelics performed on patients with schizophrenia, interpreting them in the light of recent molecular findings on their ability to induce neuroplasticity and modulate connectivity, the immune and TAARs systems, neurotransmitters, and neurotropic factors. No systematic approach was adopted in reviewing the evidence given the difficulty to retrieve and interpret old findings. Interestingly, we identified a therapeutic potential of psychedelics in schizophrenia adopting a critical point of view, particularly on negative symptoms and social cognition, and we summarized all the relevant findings. We also identified an eligible subpopulation of chronic patients predominantly burdened by negative symptoms, outlining possible therapeutic strategies which encompass very low doses of psychedelics (microdosing), carefully considering safety and feasibility, to pave the way to future clinical trials.

Co-administration of midazolam and psilocybin: differential effects on subjective quality versus memory of the psychedelic experience

Article

Full-text available

Sep 2024

Aspects of the acute experience induced by the serotonergic psychedelic psilocybin predict symptomatic relief in multiple psychiatric disorders and improved well-being in healthy participants, but whether these therapeutic effects are immediate or are based on memories of the experience is unclear. To examine this, we co-administered psilocybin (25 mg) with the amnestic benzodiazepine midazolam in 8 healthy participants and assayed the subjective quality of, and memory for, the dosing-day experience. We identified a midazolam dose that allowed a conscious psychedelic experience to occur while partially impairing memory for the experience. Furthermore, midazolam dose and memory impairment tended to associate inversely with salience, insight, and well-being induced by psilocybin. These data suggest a role for memory in therapeutically relevant behavioral effects occasioned by psilocybin. Because midazolam blocks memory by blocking cortical neural plasticity, it may also be useful for evaluating the contribution of the pro-neuroplastic properties of psychedelics to their therapeutic activity.

Large language models auto-profile conscious awareness changes under psychedelic drug effects

Preprint

Full-text available

Aug 2024

Psychedelic experiences open a colorful view into drug-induced changes in conscious awareness. Small-sample studies on psychedelic drug action have gained traction in recent years. Yet, today’s means for measuring changes in subjective experience are mostly limited to legacy questionnaires of pre-assumed relevance, which could be complemented by bottom-up explorations of semantic facets that underlie experience reports. Here, we show how to harness large language models (LLMs) to i) design from scratch, ii) annotate at scale, and iii) evaluate with rigor a vast portfolio of experience dimensions during psychoactive drug influence, yielding > 2 million automatic dimension ratings that would otherwise have been done by hand. Investigator-independent LLM scoring of these drug effects on the human mind alone allowed to robustly discriminate the unique mental effects of 30 psychoactive substances. Successful knowledge integration of how psychedelics mediate shifts in subjective awareness will be an unavoidable milestone towards charting the full drug design space.

Psilocybin-Assisted Therapy for Mental Health Treatment: Effectiveness, Safety and Public Support for Legalization in the State of New Jersey

Article

Full-text available

May 2024

The Psilocybin Behavioral Health Access and Services Act (Bill S2283) was introduced to the New Jersey State Senate in January 2024. If passed in its current form, one of, but not the only, major policies of the bill would be to legalize the professionally supervised administration and use of psilocybin (the psychoactive compound in psychedelic “magic mushrooms”) in licensed “psilocybin service centers” for the purposes of supporting mental health treatment. Based on a literature review of randomized clinical trials that have assessed the safety and effectiveness of psilocybin-assisted therapies used to treat clinical depression and anxiety, we summarize evidence that the professionally supervised administration of just one or two doses of psilocybin results in quick and long-lasting reductions in symptoms of depressive and anxiety disorders. Further, this review also provides evidence that professionally supervised use of psilocybin poses minimal physical and psychological safety risks. Based on an original public poll we conducted, we found, in what we believe to be the first-ever publicly published poll assessing public support in the state of New Jersey for the legalization of medicinal uses of psilocybin, that a slim majority (55%) of individuals support such legalization. Support for such legalization was stronger for individuals who are aware of the medicinal uses of psychedelic drugs for the purposes of treating mental health compared to individuals who are not aware of this, indicating that education about the scientific knowledge of the anti-depressant/anti-anxiety effects of professionally supervised psychedelic drug use is an important factor predicting support for this policy. Further, those who have used psychedelic drugs in the past were more likely to support this policy than individuals who have never used such drugs, indicating that personal experience in using psychedelic drugs is an important factor predicting support for this policy. As detailed in the report, support for the policy significantly varied by age, race/ethnicity, highest level of education, income, and political party affiliation, but did not significantly vary by the region of New Jersey the respondent resided in (North vs. South vs. Central) or gender. In sum, this report indicates that professionally supervised use of psilocybin for mental health treatment is an effective and safe practice whose legalization is seemingly supported by the majority of New Jersey adults. Such legalization seems like a promising policy to pursue to achieve the objective of offering adults in the state an alternative strategy for treating the mental health problems they may experience.

On serotonin, psychedelics, entactogens and psychoplastogens in depression, anxiety, post-traumatic stress, and related disorders.

Preprint

May 2024

Daniel Hoyer

There is controversy about a causal role of serotonin (5-HT) in depression, some arguing that there is no proof for impaired brain 5-HT function in depressed patients. Major depressive disorder comes with multiple endophenotypes; not surprisingly classical antidepressants (tricyclics, MAO inhibitors, SSRIs, SNRIs) are not universally effective. Most antidepressants target the 5-HT system, partially if not exclusively, but treatment-resistant depression (TRD) remains a major issue. The most recent and heavily investigated class of potential rapid acting antidepressant, anxiolytic, and/or anti PTSD drugs, namely psychedelics (psilocybin, LSD, DMT, ayahuasca, etc..) or entactogens (MDMA, ibogaine), all target the 5-HT system, at least in part. Phase II / III clinical trials support psychedelics- and/or MDMA-assisted psychotherapy as a new class of rapid acting treatments for GAD, MDD, TRD, PTSD, and other disorders. Psilocybin and MDMA have FDA breakthrough status for TRD/MDD and PTSD, respectively, whereas LSD just received FDA breakthrough status for GAD. All psychedelics act as 5-HT2A receptor agonists, although LSD, DMT, psilocybin may also target other 5-HT and/or dopamine receptors. Psychedelics produce rapid onset and long-lasting antidepressant effects after one or two administrations. They all promote synaptogenesis and synaptic plasticity. Neuroinflammation plays a major role in anxiety, depression, PTSD. Interestingly, psychedelic-induced 5-HT2A receptor agonism has profound anti-(neuro)inflammatory effects. Altogether, the 5-HT system plays an essential, but not unique role in MDD and related disorders. MDD, TRD and PTSD may be considered as biochemical, neurological and immune conditions, given the emerging role of neuroplasticity and neuroinflammation, which until recently, have been overlooked.

‘Psychedelics are no magic pill’: the narrative and embodied dimensions of psychedelic integration in Denmark

Article

Full-text available

Mar 2024

Sidsel Marie

Within recent years, an increasing number of people and researchers in the Global North have become interested in psychedelic substances and their therapeutic application. While much of the current media attention and research effort mainly concentrate on the therapeutic potential and actions of the individual's acute psychedelic experience, this article explores the user‐perceived, therapeutic dynamics of psychedelics in a more long‐term perspective by charting the lived experiences and practices of ‘integration’ among psychedelic users in Denmark. Based on ethnographic fieldwork from November 2020 to June 2021, I offer a dual typology of self‐related integration as narrative and experiential‐somatic . Combining the two, I argue that psychedelic integration in contemporary Denmark can be viewed as a processual self‐transformation of the users' experiential orientation where understandings and/or modes of being from the acute psychedelic experience are woven into, prolonged, and/or embodied in their everyday existence .

The Effects of Ayahuasca on Psychological Disorders: A Systematic Literature Review

Article

Full-text available

Mar 2024

Ayahuasca is an original Amazonian brew made from the vines and leaves of Psychotroa viridis and Banisteriopsis caapi. Both P. viridis and B. caapi give this brew its unique psychedelic properties which have been revered over centuries. In recent years, ayahuasca has gained attention as a potential therapeutic tool for mental health disorders, including substance abuse and depression. The uniqueness of ayahuasca’s therapeutic potential is that it is an amalgamation of its biochemical makeup and the ritual guided by a shaman, along with the interpretation of the participant of their experience. The boom of “ayahuasca tourism” has brought forth testimonies of feeling “cured” of depression, and substance abuse and an improvement in overall well-being. This systematic literature review focuses on summarizing the recently available research on the effectiveness of ayahuasca as a treatment for depression, anxiety, substance abuse, eating disorders, and post-traumatic stress disorder. It also focuses on understanding the effects it has on personality traits that play a significant role in the manifestation of the above-listed mental health conditions effects. Additionally, the review investigates the importance and role the ritual itself plays, often described as the “mystical experience”. This systematic literature review aims to explore the current state of knowledge regarding the use of ayahuasca for numerous mental health conditions by analyzing medical research papers published no earlier than September 2017 to no later than May 2023 from Google Scholar and PubMed. A total of 43 articles met the criteria and were used for detailed analysis. This review will synthesize the findings of the studies, examining the potential therapeutic effects of ayahuasca on multiple mental health disorders, the significance of the “mystical experience,” and the mechanisms of action underlying its effects. Through the review, ayahuasca proves to be a worthwhile therapeutic tool that if used in the right setting influences mind, body, and spirit. It is important to note that most studies used in this article relied on surveys and self-reporting proving to be a limitation as no clear standard has been achieved to test the efficacy of ayahuasca. The respect for the culture and origin needs to be retained as Western medicine dwells deeper into ayahuasca’s benefits.

When the Trial Ends: The Case for Post-Trial Provisions in Clinical Psychedelic Research

Article

Full-text available

Nov 2023

The ethical value—and to some scholars, necessity—of providing trial patients with post-trial access (PTA) to an investigational drug has been subject to significant attention in the field of research ethics. Although no consensus has emerged, it seems clear that, in some trial contexts, various factors make PTA particularly appropriate. We outline the atypical aspects of psychedelic clinical trials that support the case for introducing the provision of PTA within research in this field, including the broader legal status of psychedelics, the nature of the researcher-therapist/participant relationship, and the extended time-frame of the full therapeutic process. As is increasingly understood, the efficacy of psychedelic-assisted psychotherapy is driven as much by extrapharmacological elements and the cultural therapeutic container as by the drug itself. As such, we also advocate for a refocusing of attention from post-trial access to a broader concept encompassing other elements of post-trial care. We provide an overview of some of the potential post-trial care provisions that may be appropriate in psychedelic clinical trials. Although the World Medical Association’s Declaration of Helsinki calls on researchers, sponsors, and governments to make provisions for post-trial access, such provision may feel impracticable or out-of-reach within psychedelic trials that are already constrained by a high resource demand and significant bureaucratic burden. We show how conceiving of post-trial provision as an integral site of the research process, and an appropriate destination for research funding, will serve to develop the infrastructure necessary for the post-legalisation psychedelic medicine ecosystem.

The Key Role of Intracellular 5-HT2A Receptors: A Turning Point in Psychedelic Research?

Article

Full-text available

Oct 2023

Jacopo Sapienza

Psychedelics could have revolutionary potential in psychiatry, although, until recently, the pharmacodynamic properties of such compounds have not seemed to differ much from those of serotonin, whose levels are raised by Serotonin Reuptake Inhibitors (SSRI). The cardinal point is that serotonergic compounds, such as antidepressive drugs, do not have the potential to induce long-lasting neuroplasticity as psychedelics do. Therefore, the biological underpinnings of the peculiar effect of such compounds had not been fully understood until new astonishing molecular findings came out this year to shed new light on them. Specifically, the phenomena of neuroplasticity are triggered by the stimulation of a peculiar type of receptors: the intracellular 5-HT2A receptors. Interestingly, psychedelics can reach this pool of intracellular receptors due to their lipophilic properties, as they can cross the lipophilic neuronal membrane while serotonin cannot. The importance of such a discovery should not be underestimated as the specific mechanisms involved have not yet been elucidated and a better understanding of them could pave the way to the development of new drugs (and/or new tailored therapeutic strategies) able to sustain neuroplasticity while minimizing side effects.

Co-use of MDMA with psilocybin/LSD may buffer against challenging experiences and enhance positive experiences

Article

Full-text available

Aug 2023

Psilocybin and lysergic acid diethylamide (LSD) experiences can range from very positive to highly challenging (e.g., fear, grief, and paranoia). These challenging experiences contribute to hesitancy toward psychedelic-assisted psychotherapy among health care providers and patients. Co-use of 3,4-Methylenedioxy methamphetamine (MDMA) with psilocybin/LSD anecdotally reduces challenging experiences and enhances positive experiences associated with psilocybin/LSD. However, limited research has investigated the acute effects of co-use of MDMA and psilocybin/LSD. In a prospective convenience sample (N = 698) of individuals with plans to use psilocybin/LSD, we examined whether co-use of MDMA with psilocybin/LSD (n = 27) is associated with differences in challenging or positive experiences. Challenging experiences were measured using the Challenging Experiences Questionnaire and positive experiences were measured using the Mystical Experience Questionnaire and single-item measures of self-compassion, compassion, love, and gratitude. Potentially confounding variables were identified and included as covariates. Relative to psilocybin/LSD alone, co-use of psilocybin/LSD with a self-reported low (but not medium–high) dose of MDMA was associated with significantly less intense total challenging experiences, grief, and fear, as well as increased self-compassion, love and gratitude. Co-use of psilocybin/LSD and MDMA was not associated with differences in mystical-type experiences or compassion. Findings suggest co-use of MDMA with psilocybin/LSD may buffer against some aspects of challenging experiences and enhance certain positive experiences. Limitations include use of a convenience sample, small sample size, and non-experimental design. Additional studies (including controlled dose–response studies) that examine the effects and safety of co-administering MDMA with psilocybin/LSD (in healthy controls and clinical samples) are warranted and may assist the development of personalized treatments.

Cost-effectiveness of psilocybin-assisted therapy for severe depression: exploratory findings from a decision analytic model

Article

Full-text available

Jun 2023
PSYCHOL MED

Background: There is growing evidence to support the use of the psychedelic drug psilocybin for difficult-to-treat depression. This paper compares the cost-effectiveness of psilocybin-assisted psychotherapy (PAP) with conventional medication, cognitive behavioural therapy (CBT), and the combination of conventional medication and CBT. Methods: A decision model simulated patient events (response, remission, and relapse) following treatment. Data on probabilities, costs and quality-adjusted life years (QALYs) were derived from previous studies or from best estimates. Expected healthcare and societal costs and QALYs over a 6-month time period were calculated. Sensitivity analyses were used to address uncertainty in parameter estimates. Results: The expected healthcare cost of PAP varied from £6132 to £7652 depending on the price of psilocybin. This compares to £3528 for conventional medication alone, £4250 for CBT alone, and £4197 for their combination. QALYs were highest for psilocybin (0.310), followed by CBT alone (0.283), conventional medication alone (0.278), and their combination (0.287). Psilocybin was shown to be cost-effective compared to the other therapies when the cost of therapist support was reduced by 50% and the psilocybin price was reduced from its initial value to £400 to £800 per person. From a societal perspective, psilocybin had improved cost-effectiveness compared to a healthcare perspective. Conclusions: Psilocybin has the potential to be a cost-effective therapy for severe depression. This depends on the level of psychological support that is given to patients receiving psilocybin and the price of the drug itself. Further data on long-term outcomes are required to improve the evidence base.

Effects of serotonergic psychedelics on mitochondria: Transdiagnostic implications for mitochondria-related pathologies

Article

Full-text available

Apr 2023
J PSYCHOPHARMACOL

The use of serotonergic psychedelics has gained increasing attention in research, clinical practice and society. Growing evidence suggests fast-acting, transdiagnostic health benefits of these 5-hydroxytryptamine 2A receptor agonists. Here, we provide a brief overview of their benefits for psychological, cardiovascular, metabolic, neurodegenerative, and immunological pathologies. We then review their effect on mitochondria including mitochondrial biogenesis, functioning and transport. Mitochondrial dysregulation is a transdiagnostic mechanism that contributes to the aforementioned pathologies. Hence, we postulate that psychedelic-induced effects on mitochondria partially underlie their transdiagnostic benefits. Based on this assumption, we propose new treatment indications for psychedelics and that the health benefits induced by psychedelics depend on patient-specific mitochondrial dysregulation.

Investigating the therapeutic efficacy of psychedelics for anorexia nervosa using animal models

Thesis

Full-text available

Aug 2022

Janika Ruuska

Individuals suffering from anorexia nervosa (AN) have one of the highest mortality rates of all psychiatric disorders, as a consequence of health complications that follows severe malnutrition. The impairments in cognitive flexibility, including an extreme focus on restricting food despite a rapid decline in body weight in AN, also plays an important role in the development of the disorder and has been suggested as a hallmark of AN. This cognitive inflexibility, common among many psychiatric disorders such as depression and obsessive-compulsive disorder, is linked to alterations in serotonin (5-HT) signaling in the medial prefrontal cortex (mPFC). Reduced 5-HT2A receptor activity and potentially increased 5-HT1A receptor activity are evident in the mPFC in individuals with AN and may be linked to impaired cognitive flexibility, however, the mechanisms through which 5-HT and inflexibility interact in AN are not fully understood. A better understanding of this link could pave the way toward more effective pharmacological treatments for AN. Psilocybin, a psychedelic compound produced by so-called "magic" mushrooms, has a high affinity for several 5-HT receptor subtypes including 5-HT1A and 5-HT2A receptors, and has now been empirically demonstrated to increase cognitive flexibility in individuals with major depressive disorder (MDD).

Examining the Rationale for Studying Psychedelic-Assisted Psychotherapy for the Treatment of Caregiver Distress

Article

Full-text available

Mar 2023

Background: More than 50 million people in the United States serve as uncompensated informal caregivers to chronically ill friends or family members. Providing care to a sick loved one can contribute to personal growth but can also cause significant strain. Caregiver distress refers to a constellation of physiological, psychological , interpersonal, and spiritual impairments that typically result when an individual's own health becomes affected while caring for another. Caregiver distress is highly prevalent, affecting an estimated 30-70% of individuals across various caregiver populations. Although evidence-based treatments for care-giver distress exist, they do not sufficiently address all its components. In recent years, clinical trials have demonstrated that psychedelic-assisted psychotherapy (PAP) may have applications for treating a range of medical and psychiatric conditions that have significant overlap in symptoms to those seen in caregiver distress. While no studies to date have examined PAP for caregiver distress, this article provides a rationale for investigating PAP as a potential novel treatment for this indication. Methods: A narrative review on the effects and clinical applications of PAP that significantly overlap with the dimensions of caregiver distress was conducted. Safety considerations, psychedelic selection, and therapeutic structure for studying PAP in the treatment of caregiver distress were also examined. Results: Psychologically, PAP has been shown to treat anxiety, depression, and reduce suicidal ideation. Physiologically, evidence suggests that psychedelics have anti-inflammatory properties, which may aid caregivers suffering from chronic inflammation. Interpersonally, PAP has been demonstrated to enhance feelings of empathy, connectedness, and strengthen social relationships, which can often become strained while caregiving. Spiritually, PAP has been shown to ameliorate existential distress and hopelessness in cancer patients, which may similarly benefit demoralized caregivers. Conclusion: PAP has the potential to comprehensively treat all biopsychosocial-spiritual dimensions of caregiver distress.

Investigation of self-treatment with lysergic acid diethylamide and psilocybin mushrooms: Findings from the Global Drug Survey 2020

Article

Full-text available

Mar 2023

Background: Growing numbers of people are using psychedelics for personal psychotherapy outside clinical settings, but research on such use is scarce. Aims: This study investigated the patterns of use, self-reported outcomes and outcome predictors of psychedelic 'self-treatment' of mental health conditions or specific worries/concerns in life. Methods: We use data from the Global Drug Survey 2020, a large online survey on drug use collected between November 2019 and February 2020. In all, 3364 respondents reported their self-treatment experiences with lysergic acid diethylamide (N = 1996) or psilocybin mushrooms (N = 1368). The primary outcome of interest was the 17-item self-treatment outcome scale, items reflecting aspects of well-being, psychiatric symptoms, social-emotional skills, and health behaviours. Results: Positive changes were observed across all 17 outcome items, with the strongest benefits on items related to insight and mood. Negative effects were reported by 22.5% of respondents. High intensity of psychedelic experience, seeking advice before treatment, treating with psilocybin mushrooms and treating post-traumatic stress disorder were associated with higher scores on the self-treatment outcome scale after averaging values across all 17 items. Younger age, high intensity of experience and treating with LSD were associated with increased number of negative outcomes. Conclusions: This study brings important insights into self-treatment practices with psychedelics in a large international sample. Outcomes were generally favourable, but negative effects appeared more frequent than in clinical settings. Our findings can help inform safe practices of psychedelic use in the community, and inspire clinical research. Future research can be improved with utilisation of prospective designs and additional predictive variables.

Are You Tripping Comfortably? Investigating the Relationship Between Harm Reduction and the Psychedelic experience

Preprint

Full-text available

Mar 2022

Background Alongside a recent revival in the use of psychedelics in clinical settings, there have been increases in the prevalence of recreational use, with many using psychedelics to deal with difficult emotions or to improve wellbeing. While clinical research is conducted in carefully controlled settings, this is not necessarily the case for recreational use. In this mixed-methods study, we aimed to develop an understanding of frequently used psychedelic harm reduction practices in recreational settings and how their use relates to the psychedelic experience. We also aimed to characterise users’ first and most recent psychedelic trips to understand how harm reduction changes with experience. Methods Participants (n = 163) recounted their first and most recent psychedelic experience by providing details about the harm reduction practices they employed and completing the Challenging Experience Questionnaire (CEQ) and Emotional Breakthrough Inventory (EBI). We also asked open ended questions for a more in-depth qualitative understanding of their views on psychedelic harm reduction. Results Using ANOVA, we observe greater use of harm reduction practices for participants’ most recent versus first psychedelic experience and that use of these practices is positively associated with EBI scores and negatively associated with CEQ scores (particularly for the first experience). Participants engaged in a wide range of harm reduction practices and we provide details of those which are most commonly used and those which are deemed most important by experienced users. Our qualitative analysis indicated that participants were largely positive about psychedelics and many recounted profound positive experiences. While specifics of the drug they were taking was important for aspects of harm reduction, participants largely focused on the importance of ensuring a good ‘set and setting’ for enhancing positive effects. Conclusions Our research helps us understand how engagement in harm reduction may increase with experience. Our mixed methods data sheds light on the perceived importance of different harm reduction practices and examines their association with the psychedelic experience itself. Together, our research has important implications for the development of psychedelic harm reduction advice and provides opportunities for future research to explore the importance of these different practices in more detail.

Psychedelic integration challenges: Participant experiences after a psilocybin truffle retreat in the Netherlands

Article

Full-text available

Jan 2023

This article reports on integration challenges that were experienced by nine individuals who attended a three-day legal psilocybin truffle retreat in the Netherlands. The study employed a qualitative phenomenological approach, using semi-structured interviews to gain an understanding of participants' (n = 30) psilocybin experiences and their after-effects. While the study did not actively seek to measure integration issues or unexpected side effects, nine out of thirty participants (30%) spontaneously reported a post-experience integration challenge. These challenges included: mood fluctuations, ‘post-ecstatic blues’, disconnection from community, re-experiencing symptoms, spiritual bypass and perceived lack of support. Integration challenges were transient; they occurred immediately after the psilocybin experience (once the main psychedelic effects had worn off) and in the days and weeks following the retreat, and resolved with time. Integration challenges were also correlated with positive after-effects including long-term remission of significant health conditions. The experiences related in this article align with existing literature that describes the ‘spiritual emergency’ phenomenon; that is, the potential challenges that can arise after ecstatic experiences and how these challenges may be integral to the transformative potential of such experiences. We discuss the implications for psychedelic integration and harm reduction practices and for future psychedelic research.

Psychedelic-Assisted Therapy for People with Eating Disorders

Article

Full-text available

Nov 2022
Curr Psychiatr Rep

Purpose of Review: A growing body of research suggests psychedelic-assisted therapy (PAT) may be safe and effective for a variety of mental health conditions. Among these, eating disorders have been a recent target of interest. This review provides an up-to-date summary of the potential mechanisms and use of PAT in people diagnosed with eating disorders, with a focus on anorexia nervosa. Recent Findings: Classic psychedelics may have transdiagnostic efficacy through several mechanisms relevant to eating disorder pathology. Interest in, and efforts to increase access to PAT are both high. Early clinical trials are focused on establishing the safety and utility of this treatment in eating disorders, and efficacy remains unclear. Summary: High-quality published data to support the use of PAT for people with eating disorders remains lacking. Recent studies however suggest PAT has the potential to augment the efficacy of current interventions for these difficult-to-treat conditions.

"Getting to the Root": Ayahuasca Ceremony Leaders' Perspectives on Eating Disorders

Article

Sep 2022
J PSYCHOACTIVE DRUGS

Given the mortality, chronicity, and treatment drop-out rates observed among individuals with eating disorders (EDs), innovative approaches are needed. Ayahuasca, a psychedelic plant medicine from the Amazon, is currently being investigated. This study expands on prior exploratory research by describing the perspectives of ayahuasca ceremony leaders regarding their conceptualizations of EDs and the potential therapeutic mechanisms of action of ayahuasca for individuals with EDs. Qualitative content analysis of interviews with 15 ayahuasca ceremony leaders produced two main categories, with relevant subcategories. The first category encompassed the leaders' theories of EDs from a shamanic perspective, including that EDs are symptomatic of an underlying concern, serve a function and affect health in multiple domains. The second category described leaders' perspectives on the potential mechanisms of action of ayahuasca for EDs, including that ayahuasca facilitates "energetic healing"; helps identify, process, and integrate the "root" of the ED; promotes holistic healing; and enhances and/or reorganizes relationships. From the perspectives of ceremony leaders and consistent with previous exploratory research, ceremonial ayahuasca use may offer a potentially useful, novel and complementary intervention for EDs.

Prenatal Choline Supplementation During Maternal Obesity Alters Offspring Response to Western Diets

Thesis

Aug 2022

Hunter Wade Korsmo

Maternal obesity has led to an increase in adverse offspring developmental outcomes and a greater risk for long-term metabolic diseases. Choline, a semi-essential nutrient, can be incorporated into phosphatidylcholine (PC) as well as sphingomyelin (SM) and donate its labile methyl group for the remethylation of homocysteine after choline is oxidized to betaine. Prenatal choline insufficiency has been related to maternal obesity and metabolic diseases, such as metabolic associated fatty liver disease (MAFLD). Choline may interact with maternal obesity to influence the programming offspring. Chapter 1 presents an introduction of choline and the various clinical outcomes associated with choline supplementation during pregnancy. Chapter 2 presents findings of altered whole-body glucose tolerance in choline supplemented (CS) male offspring prenatally challenged by a maternal HF diet (HF+CS). Here we demonstrate benefits of choline on blood glucose control and metabolic regulation of the visceral adipose tissue. Chapter 3 presents an investigation into the global and site-specific methylation in fetal and postnatal liver and brain in response to maternal HF and CS. Here we demonstrate an increase in DNA methylation and decrease in gene expression of Srebp1, a gene that mediates de novo lipogenesis, by maternal CS in the HF condition during the fetal period. However, this epigenetic change was not maintained in adulthood. Global DNA methylation of liver and adipose demonstrates increased methylation during the prenatal period yet decreased methylation during postnatal HF feeding of maternal CS offspring, suggesting that methylation marks established by maternal CS cannot be maintained during postnatal HF feeding. Chapter 4 explores the lipidomic changes in the fetal and postnatal period in response to maternal HF and CS. We found increases in ether-linked phospholipids (plasmalogens) which serve as antioxidants for cellular membrane lipids in HFCS male offspring, suggesting a potential role of maternal CS in redox regulation and membrane integrity. Chapter 5 explores the metabolic outcomes of mouse offspring exposed to prenatal HFCS and 16-weeks of postnatal western diet (WD) challenge. Results suggest that prenatal HFCS has mixed effects on offspring phenotypes and MAFLD biomarkers, and the effects were sexually dimorphic. Further, systems approaches were used to assess the transcriptomic and lipidomic changes related to maternal HFCS after the 16-week WD challenge in offspring. Chapter 6 presents the rationale for a systems approach in interpreting the findings presented, discusses limitations in the study and future directions for research in preventing MASH (steatohepatitis) pathogenesis.

The Watts Connectedness Scale: a new scale for measuring a sense of connectedness to self, others, and world

Article

Full-text available

Aug 2022
PSYCHOPHARMACOLOGY

Rationale A general feeling of disconnection has been associated with mental and emotional suffering. Improvements to a sense of connectedness to self, others and the wider world have been reported by participants in clinical trials of psychedelic therapy. Such accounts have led us to a definition of the psychological construct of ‘connectedness’ as ‘a state of feeling connected to self, others and the wider world’. Existing tools for measuring connectedness have focused on particular aspects of connectedness, such as ‘social connectedness’ or ‘nature connectedness’, which we hypothesise to be different expressions of a common factor of connectedness. Here, we sought to develop a new scale to measure connectedness as a construct with these multiple domains. We hypothesised that (1) our scale would measure three separable subscale factors pertaining to a felt connection to ‘self’, ‘others’ and ‘world’ and (2) improvements in total and subscale WCS scores would correlate with improved mental health outcomes post psychedelic use. Objectives To validate and test the ‘Watts Connectedness Scale’ (WCS). Methods Psychometric validation of the WCS was carried out using data from three independent studies. Firstly, we pooled data from two prospective observational online survey studies. The WCS was completed before and after a planned psychedelic experience. The total sample of completers from the online surveys was N = 1226. Exploratory and confirmatory factor analysis were performed, and construct and criterion validity were tested. A third dataset was derived from a double-blind randomised controlled trial (RCT) comparing psilocybin-assisted therapy (n = 27) with 6 weeks of daily escitalopram (n = 25) for major depressive disorder (MDD), where the WCS was completed at baseline and at a 6-week primary endpoint. Results As hypothesised, factor analysis of all WCS items revealed three main factors with good internal consistency. WCS showed good construct validity. Significant post-psychedelic increases were observed for total connectedness scores (η2 = 0.339, p < 0.0001), as well as on each of its subscales (p < 0.0001). Acute measures of ‘mystical experience’, ‘emotional breakthrough’, and ‘communitas’ correlated positively with post-psychedelic changes in connectedness (r = 0.42, r = 0.38, r = 0.42, respectively, p < 0.0001). In the RCT, psilocybin therapy was associated with greater increases in WCS scores compared with the escitalopram arm (ηp2 = 0.133, p = 0.009). Conclusions The WCS is a new 3-dimensional index of felt connectedness that may sensitively measure therapeutically relevant psychological changes post-psychedelic use. We believe that the operational definition of connectedness captured by the WCS may have broad relevance in mental health research.

Antidepressant effects of a psychedelic experience in a large prospective naturalistic sample

Article

Full-text available

Aug 2022
J PSYCHOPHARMACOL

Background Over the last two decades, a number of studies have highlighted the potential of psychedelic therapy. However, questions remain to what extend these results translate to naturalistic samples, and how contextual factors and the acute psychedelic experience relate to improvements in affective symptoms following psychedelic experiences outside labs/clinics. The present study sought to address this knowledge gap. Aim Here, we aimed to investigate changes in anxiety and depression scores before versus after psychedelic experiences in naturalistic contexts, and how various pharmacological, extrapharmacological and experience factors related to outcomes. Method Individuals who planned to undergo a psychedelic experience were enrolled in this online survey study. Depressive symptoms were assessed at baseline and 2 and 4 weeks post-psychedelic experience, with self-rated Quick Inventory of Depressive Symptomatology (QIDS-SR-16) as the primary outcome. To facilitate clinical translation, only participants with depressive symptoms at baseline were included. Sample sizes for the four time points were N = 302, N = 182, N = 155 and N = 109, respectively. Results Relative to baseline, reductions in depressive symptoms were observed at 2 and 4 weeks. A medicinal motive, previous psychedelic use, drug dose and the type of acute psychedelic experience (i.e. specifically, having an emotional breakthrough) were all significantly associated with changes in self-rated QIDS-SR-16. Conclusion These results lend support to therapeutic potential of psychedelics and highlight the influence of pharmacological and non-pharmacological factors in determining response. Mindful of a potential sample and attrition bias, further controlled and observational longitudinal studies are needed to test the replicability of these findings.

Are you tripping comfortably? Investigating the relationship between harm reduction and the psychedelic experience

Article

Full-text available

Jul 2022

Background Alongside a recent revival in the use of psychedelics in clinical settings, there have been increases in the prevalence of recreational use, with many using psychedelics to deal with difficult emotions or to improve well-being. While clinical research is conducted in carefully controlled settings, this is not necessarily the case for recreational use. In this mixed methods online survey study, we aimed to develop an understanding of frequently used psychedelic harm reduction practices in recreational settings and how their use relates to the psychedelic experience. We also aimed to characterise users’ first and most recent psychedelic trips to understand how harm reduction changes with experience. Methods Participants ( n = 163) recounted their first and most recent psychedelic experience by providing details about the harm reduction practices they employed and completing the Challenging Experience Questionnaire (CEQ) and Emotional Breakthrough Inventory (EBI). We also asked open-ended questions for a more in-depth qualitative understanding of their views on psychedelic harm reduction. Results Using ANOVA, we observe greater use of harm reduction practices for participants’ most recent versus first psychedelic experience and that use of these practices is positively associated with EBI scores and negatively associated with CEQ scores (particularly for the first experience). Participants engaged in a wide range of harm reduction practices and we provide details of those which are most commonly used and those which are deemed most important by experienced users. Our qualitative analysis indicated that participants were largely positive about psychedelics and many recounted profound positive experiences. While specifics of the drug they were taking was important for aspects of harm reduction, participants largely focused on the importance of ensuring a good “set and setting” for enhancing positive effects. Conclusions Our research helps us understand how engagement in harm reduction may increase with experience. Our mixed methods data shed light on the perceived importance of different harm reduction practices and examine their association with the psychedelic experience itself. Together, our research has important implications for the development of psychedelic harm reduction advice and provides opportunities for future research to explore the importance of these different practices in more detail.

Psychedelic therapy for body dysmorphic disorder

Article

Full-text available

Jun 2022

In this opinion piece we propose the investigation of psychedelic-assisted psychotherapy for the treatment of body dysmorphic disorder (BDD). BDD is a psychiatric disorder characterised by appearance-based preoccupations and accompanying compulsions. While safe and effective treatments for BDD exist, non-response and relapse rates remain high. Therefore, there is a need to investigate promising new treatment options for this highly debilitating condition. Preliminary evidence suggests safety, feasibility, and potential efficacy of psychedelic treatments in disorders that share similar psychopathological mechanisms with BDD. Drawing on this evidence, as well as on relevant qualitative reports and theoretical proposals, we argue that it would be worthwhile to conduct a phase 2a study aimed at assessing the safety and feasibility of psychedelic-assisted psychotherapy in BDD. We also offer some suggestions for how future research ought to proceed.

The psychological processes of classic psychedelics in the treatment of depression: a systematic review protocol

Article

Full-text available

May 2022

Background There is currently renewed interest in the use of psychedelic therapy in the treatment of psychiatric disorders, including depression. The proposed systematic review will aim to identify, evaluate and summarise the psychological processes of change underlying psychedelic therapy for depression in the current literature and consider the implications these processes may have on the psychotherapy component of treatment. Methods Scopus, PsycINFO, PubMed and Web of Science databases will be searched using relevant terms. Studies will be included if they discuss the use of a classic psychedelic to treat depression symptomology in an adult population and report or propose psychological processes responsible for depression symptom change. Two authors will independently screen articles, complete quality assessment tools and conduct data extraction. Empirical and non-empirical research will be extracted and synthesised separately. A narrative synthesis approach will be used to report psychological processes identified in the literature. Discussion This systematic review will be the first to collate available evidence on the psychological processes associated with psychedelic therapy for depression. The preliminary nature of this research field is expected to result in the review having several limitations, namely heterogeneity between studies and the inclusion of limited empirical research. We intend for this review to present the current state of the literature, identify gaps and generate candidate variables that warrant further investigation. Systematic review PROSPERO CRD42020197202

Narrowing down the therapeutic task in ISTDP

Article

Nov 2024

Effective use of the therapeutic alliance is key to successful therapy across different treatment modalities. In this article we argue that one of the distinctive features of ISTDP is how the therapist manages the therapeutic alliance by narrowing down the therapeutic task again and again throughout the treatment. ISTDP therapists need to strive for absolute clarity about different emotional and defensive responses, in order to keep the therapeutic alliance firmly directed towards emotional experiencing and resistance relinquishing. What is more, the patient must also share this understanding of the task at hand and bring full willingness to join with the therapist to accomplish it. This process is illustrated by pieces of transcript from a successful treatment course, where we show how the therapeutic task is developing along the different stages of the therapeutic process. Maintaining a narrowly defined task is the central means to keep treatment intensity up, and a sine qua non of facilitating major unlockings of the unconscious.

Pharmacotherapeutic strategies for the treatment of anorexia nervosa - novel targets to break a vicious cycle

Article

Nov 2024
EXPERT OPIN PHARMACO

The Effect of Psychedelics on Individuals with a Personality Disorder: Results from two Prospective Cohort Studies

Preprint

Full-text available

Apr 2024

Background: Personality disorders (PDs) are characterized by impairments in psychological functioning for which pharmacologic treatments have demonstrated limited efficacy. Psychedelics may offer a possible PD treatment, given preliminary evidence for their potential long-term positive effects on psychological functioning. However, little is known about safety or potential therapeutic effects of psychedelics among individuals with a PD. Therefore, we examined the effects of psychedelic use on mental health among individuals who reported a PD diagnosis. Methods: Study 1 included three prospective observational studies where 21 individuals who reported a PD diagnosis completed mental health measures (depression symptoms, anxiety, and suicidal ideation [SI]) before, 2 weeks, and 4 weeks after psychedelic use. Study 2 was a prospective observational study where 55 individuals who reported a PD diagnosis completed mental health measures (anxiety, depressive symptoms, cognitive flexibility, expressive suppression, and cognitive reappraisal) before, 2-4 weeks, and 2-3 months after psychedelic use. Results: In Study 1, all participants with high baseline risk of suicidal behavior (6.67%) became low-risk post-psychedelic use. Post-psychedelic increases in SI were rare (6.67%) with no increases to high risk of suicidal behavior. SI reduced at 4 weeks (Hedges’ g=0.52). There were few cases of clinically significant worsening anxiety (Study 1:0.0%; Study 2:7.7%-8.2%) and depression symptoms (Study 1:0.0%-7.1%; Study 2:0.0%). However, across both studies, psychedelic use was associated with reductions in anxiety (Study 1:g=-0.46–-0.57; Study 2:g=-0.52–-0.89) and depression (Study 1 g=-0.54–-0.59; Study 2 rs=.52–.57). In Study 2, there were transient increases in cognitive flexibility at 2-4 weeks (g=0.26) and sustained increases in cognitive reappraisal up to 2-3 months (g=0.36). Increases in cognitive reappraisal were associated with reductions in anxiety (r=-.33) and depression (rs=-.37). Conclusion: For individuals who reported a PD diagnosis, psychedelic use was associated with improvements in mental health outcomes. There were no clinically significant post-psychedelic increases in SI but there were a few cases of clinically significant increases in anxiety and depression severity. The studies are limited by a small sample size, self-reported data, and lack of differentiation between PDs. Further research is needed to explore the safety and potential therapeutic effects of psychedelics among individuals with PD.

Probing the functional magnetic resonance imaging response to psilocybin in functional neurological disorder (PsiFUND): study protocol

Article

Jul 2024

Background Functional neurological disorder (FND) is a common cause of neurological symptoms including paralysis, seizures, and movement disorders. It is often debilitating, is associated with high health and social care costs, and can have a poor prognosis. Functional magnetic resonance imaging (fMRI) has suggested FND is a multi-network disorder; the default mode network (DMN) may be specifically implicated. Converging evidence suggests that other variable mechanisms including dissociation, interoception, and motor agency may be differentially abnormal in people with FND. Psychedelics are currently under investigation for numerous neuropsychiatric disorders and have been shown to disrupt functional networks such as the DMN. Administering psychedelics to people with FND will help us to probe mechanistic theories of the disorder. Protocol In this open-label neuroimaging study, we will administer 25mg oral psilocybin with psychological support to people with chronic FND (target n = 24). Participants will undergo resting-state and task-based (Libet’s clock, a measure of motor agency) fMRI sequences which will be compared in a pre-post manner. Additional mechanistic outcomes including measures of interoception (heartbeat tracking task), somatisation, illness perceptions, imaginative suggestibility, and dissociation will be collected. Data on expectancy, preparedness, and subjective experience of the psychedelic experience will also be gathered. Participants will be followed up for three months following psilocybin administration. fMRI changes in networks such as the DMN will be analysed using seed-based approaches, and additional exploratory analysis of resting-state imaging will take place. Discussion The study will help us to probe the mechanisms thought to potentially underpin FND. As the first modern study of psychedelics in FND, it will also help us to understand whether psychedelic administration alongside psychological support might be safe and feasible in this patient population.

The Effect of Psychedelics on Individuals with a Personality Disorder: Results from two Prospective Cohort Studies

Preprint

Full-text available

Apr 2024

Background: Personality disorders (PDs) are characterized by impairments in psychological functioning for which pharmacologic treatments have demonstrated limited efficacy. Psychedelics may offer a potential PD treatment, given support for their potential enduring positive effects on psychological functioning. However, little is known about the safety or therapeutic effects of psychedelics among individuals with a PD. Therefore, we examined the effects of psychedelic use on mental health among individuals with a PD. Methods: Study 1 included three prospective observational studies where 21 individuals with a PD diagnosis completed mental health measures (depressive symptoms, anxiety, and suicidal ideation [SI]) before, 2 weeks (except SI), and 4 weeks after psychedelic use. Study 2 was a prospective observational study in which 55 individuals with a PD diagnosis completed mental health measures (anxiety, depressive symptoms, cognitive flexibility, expressive suppression, and cognitive reappraisal) before, 2-4 weeks, and 2-3 months after psychedelic use. Results: In Study 1, elevations in SI were rare (6.67%) with no elevations to high risk of suicidal behavior post-psychedelic use. All participants with high baseline risk of suicidal behavior (6.67%) were at low-risk post-psychedelic use. SI reduced at 4 weeks (Hedges’ g=0.52). There were several cases of increased anxiety (Study 1: 13.6%-25.0%; Study 2: 16.3%-11.5%) and clinically significant worsening of depression symptoms (Study 1: 14.3%-14.2%; Study 2: 10.0%-8.0%). Across both studies, psychedelic use was associated with reductions in anxiety (Study 1: g=-.46–-.57; Study 2 g=-.52–-.89) and depression (Study 1 g=-.54–-0.59; Study 2 rs= .52–.57) . In Study 2, there were transient increases in cognitive flexibility at 2-4 weeks (g=.26) and sustained increases in cognitive reappraisal up to 2-3 months (g=.36). Increases in cognitive reappraisal were associated with reductions in anxiety (r=.33) and depression (rs=.37). Conclusion: For individuals with PD, psychedelic use was associated with improvements in psychological functioning. There were no clinically significant elevations in SI and several cases of elevations in anxiety and depression severity. The studies are limited by a small sample size, self-reported data, and lack of differentiation between PDs. Further research should explore the safety and potential therapeutic effects of psychedelics among individuals with PD.

THE CONNECTION BETWEEN THE INDIVIDUAL SUBJECTIVE WELL-BEING AND THE MYSTICAL EXPERIENCE PRODUCED BY THE USE OF PSYCHEDELICS

Article

Full-text available

Jul 2023

Respondents with experience in the use of psychedelics (psilocybin, LSD, ketamine, MDMA, etc.) participated in the study. Based on the subjective assessment of the level of awareness in the topic of psychedelics, it was found that 49% of respondents have a high level, 47% have an average level, and 4% have a low level of awareness in the topic. Most of the study participants were in Ukraine (84%); outside Ukraine, in particular in such countries as Germany, Israel, Bulgaria, the USA, England, Switzerland, Spain and the Czech Republic were 16% of participants. With the help of correlation analysis and the analysis of the significance of the differences between the average values of the studied indicators, the nature of the connection between the psychological well-being of the individual and the mystical experience produced by psychedelics was revealed. It has been established that the subjective awareness of the subject of psychedelics is not directly related to the actual mystical experience that arises as a result of the use of psychedelics, therefore the mystical experience is not a part of "self-suggestion", it is a real phenomenon. The mystical experience produced by psychedelics has been shown to be related to the subjective well-being of the individual, especially to happiness as its structural element, particularly in terms of a sense of unity, euphoria, and a sense of timelessness or boundary-breaking.

Mechanisms of integration in psychedelic-assisted therapy

Article

Dec 2023

LAY SUMMARY Psychedelic pharmacotherapies combined with structured psychotherapy have shown promise in the treatment of several psychological conditions. This type of therapy is known as psychedelic-assisted psychotherapy (PAP) and includes three phases: preparation, in-session support, and integration. The purpose of this review was to identify randomized controlled trials (RCTs) that used psychedelics to treat a psychological condition and to summarize the literature on changes that may be associated with clinical outcomes, as measured with MRI and various psychologically based tools. Psychedelics were administered in 17 RCTs, and 16 of these did so within a PAP framework. A total of 19 studies were identified that looked at MRI or psychological outcomes during the integration phase. Changes in brain networks during integration were identified but were not consistent between studies because of small sample sizes and inconsistent methodology. Some evidence suggests that changes in the executive control network may occur after psychedelic administration. Psychological changes after psychedelic administration were related to cognitive flexibility and personality traits such as openness and neuroticism. Overall, studies in this field should be repeated with a greater number of participants and other MRI-based techniques.

N-Cyclohexyltryptamine: freebase, bromide and fumarate

Article

Full-text available

Jul 2023

The solid-state structures of N-cyclohexyltryptamine (I) {systematic name: N-[2-(1H-indol-3-yl)ethyl]cyclohexanamine}, C16H22N2, and two of its salts, N-cyclohexyltryptammonium bromide (II) {systematic name: N-[2-(1H-indol-3-yl)ethyl]cyclohexanaminium bromide}, C16H23N2 ⁺·Br⁻, and N-cyclohexyltryptammonium fumarate (III) (systematic name: bis{N-[2-(1H-indol-3-yl)ethyl]cyclohexanaminium} (2E)-but-2-enedioate), 2C16H23N2 ⁺·C4H2O4 ²⁻, were determined by single-crystal X-ray diffraction. The freebase compound forms infinite chains along [010] through N—H⋯N hydrogen bonds. The bromide salt is held together by N—H⋯Br interactions in two-dimensional sheets along (001). The fumarate salt is held together in infinite three-dimensional frameworks by N—H⋯O hydrogen bonds.

Psychedelics in the treatment of eating disorders: Rationale and potential mechanisms

Article

Full-text available

Jun 2023

Eating disorders are serious illnesses showing high rates of mortality and comorbidity with other mental health problems. Psychedelic-assisted therapy has recently shown potential in the treatment of several common comorbidities of eating disorders, including mood disorders, post-traumatic stress disorder, and substance use disorders. The theorized therapeutic mechanisms of psychedelic-assisted therapy suggest that it could be beneficial in the treatment of eating disorders as well. In this review, we summarize preliminary data on the efficacy of psychedelic-assisted therapy in people with anorexia nervosa, bulimia nervosa, and binge eating disorder, which include studies and case reports of psychedelic-assisted therapy with ketamine, MDMA, psilocybin, and ayahuasca. We then discuss the potential therapeutic mechanisms of psychedelic-assisted therapy in these three eating disorders, including both general therapeutic mechanisms and those which are relatively specific to eating disorders. We find preliminary evidence that psychedelic-assisted therapy may be effective in the treatment of anorexia nervosa and bulimia nervosa, with very little data available on binge eating disorder. Regarding mechanisms, psychedelic-assisted therapy may be able to improve beliefs about body image, normalize reward processing, promote cognitive flexibility, and facilitate trauma processing. Just as importantly, it appears to promote general therapeutic factors relevant to both eating disorders and many of their common comorbidities. Lastly, we discuss potential safety concerns which may be associated with these treatments and present recommendations for future research.

Psychedelic assisted EMDR therapy (PsyA-EMDR): A memory consolidation approach to psychedelic healing

Research Proposal

Full-text available

Feb 2023

As access to psychedelic therapy is rolled out, there is a need to develop comprehensive preparation and integration protocols, particularly to support individuals with an impaired capacity to self-regulate. Moreover, there is an immediate need to develop comprehensive, trauma-informed harm reduction and risk minimalisation models as illegal, underground psychedelic therapy rapidly expands. This article outlines a 12-session protocol for psychedelic-assisted eye movement desensitisation and reprocessing therapy (PsyA-EMDR), where the 8-phases are utilised to enhance the preparation and integration stages of this groundbreaking psychotherapeutic intervention. Because the memory consolidation model of EMDR is suited to support complex post-traumatic stress disorder (cPTSD), it is proposed that it would also work well in supporting those experiencing regressed ego states as well as the somatic dysregulation that is often caused during work with psychedelics. This trauma-informed framework focuses on stabilisation, resourcing, tolerance testing, and embodiment before individuals receive any psychedelic treatments.

Seeking the Psilocybiome: Psychedelics meet the microbiota-gut-brain axis

Article

Full-text available

Apr 2023
INT J CLIN HLTH PSYC

Moving towards a systems psychiatry paradigm embraces the inherent complex interactions across all levels from micro to macro and necessitates an integrated approach to treatment. Cortical 5-HT2A receptors are key primary targets for the effects of serotonergic psychedelics. However, the therapeutic mechanisms underlying psychedelic therapy are complex and traverse molecular, cellular, and network levels, under the influence of biofeedback signals from the periphery and the environment. At the interface between the individual and the environment, the gut microbiome, via the gut-brain axis, plays an important role in the unconscious parallel processing systems regulating host neurophysiology. While psychedelic and microbial signalling systems operate over different timescales, the microbiota-gut-brain (MGB) axis, as a convergence hub between multiple biofeedback systems may play a role in the preparatory phase, the acute administration phase, and the integration phase of psychedelic therapy. In keeping with an interconnected systems-based approach, this review will discuss the gut microbiome and mycobiome and pathways of the MGB axis, and then explore the potential interaction between psychedelic therapy and the MGB axis and how this might influence mechanism of action and treatment response. Finally, we will discuss the possible implications for a precision medicine-based psychedelic therapy paradigm.

Views on Using Psychoactive Substances to Self-Manage Functional Neurological Disorder: Online Patient Survey Results

Article

May 2022

Objective: Functional neurological disorder (FND) causes a high burden of disability and distress. Although it is a common disorder, there is a pressing need for improved access to evidence-based treatments. With difficulties in finding effective treatment, some people with FND may seek alternative means of symptom relief, such as legal and illicit psychoactive substances, although the prevalence and nature of such self-management strategies are currently unclear. Additionally, psychoactive substances may represent novel treatment research opportunities, particularly for those with suboptimal improvement. The investigators examined the use of self-management techniques, as well as perspectives on novel therapies, in this patient population. Methods: An online survey was created to assess self-management strategies and views on novel treatments for FND, including psychedelic therapy. The survey was accessible for 1 month, and respondents were recruited internationally through social media and patient groups. A total of 1,048 respondents from 16 countries completed the survey. Results: Almost half (46%) of 980 respondents reported having tried legal psychoactive substances for the management of their FND symptoms and, on average, nicotine, alcohol, and cannabidiol were reported as modestly effective. Additionally, 15% of respondents reported having used illicit substances, mostly cannabis, to manage FND, with the majority reporting moderate effectiveness and experiencing no or minimal physical (90%) and psychological (95%) sequelae. Many respondents (46%) reported that they would be willing to try medically supervised psychedelic therapy (with 19% of respondents ambivalent) if it were found to be safe and effective. Conclusions: Many people with FND seek alternative means of symptom management outside usual medical care, including legal and illicit psychoactive substances. Further research exploring novel treatment options, such as psychedelics, in FND may be warranted.

Post-Psychedelic Reductions in Experiential Avoidance Are Associated With Decreases in Depression Severity and Suicidal Ideation

Article

Full-text available

Aug 2020

Psychedelic therapy shows promise as a novel intervention for a wide range of mental health concerns but its therapeutic action is incompletely understood. In line with acceptance and commitment therapy’s (ACT’s) transdiagnostic model, qualitative research has suggested that reductions in experiential avoidance are an important component of therapeutic outcomes associated with psychedelics. However, limited research has quantitatively explored the association between decreases in experiential avoidance and therapeutic outcomes associated with psychedelics. Therefore, in two prospective studies, using convenience samples of individuals with plans to use a psychedelic, we explored the impact of psychedelic use on experiential avoidance, depression severity, and suicidal ideation, as well as relationships between changes in these outcomes. Participants (Study 1, N=104; Study 2, N=254) completed self-report questionnaires of depression severity, suicidal ideation, and experiential avoidance: 1) before using a psychedelic (in ceremonial and non-ceremonial contexts), as well as 2) 2-weeks and 3) 4-weeks after psychedelic use. Across both studies, repeated measures ANOVAs indicated significant decreases in experiential avoidance, depression severity, and suicidal ideation after psychedelic use. Furthermore, decreases in experiential avoidance were significantly associated with decreases in depression severity and suicidal ideation. These results suggest that psychedelics may lead to significant decreases in experiential avoidance, depression severity, and suicidal ideation. Additionally, these findings imply that reduced experiential avoidance may be a transdiagnostic mechanism mediating treatment success within psychedelic therapy. We conclude that integrating psychedelics with psychotherapeutic interventions that target experiential avoidance (e.g. ACT) may enhance therapeutic outcomes.

Recent advances in therapies for eating disorders

Article

Full-text available

Sep 2019

Eating disorders are serious psychiatric illnesses with high rates of morbidity and mortality. Effective treatments have traditionally included behaviorally focused therapies as well as several medication strategies. Recent years have seen promising developments in these treatments, including additional support for family-based approaches for children and adolescents, new evidence for “third-wave” behavioral therapies, and new support for the use of lisdexamfetamine for binge eating disorder and olanzapine for anorexia nervosa. Case study and pilot data are beginning to show limited support for neuromodulatory interventions targeting brain regions thought to be involved in eating disorders. This review summarizes treatment developments over the last several years and points towards future directions for the field.

The use of electron microscopy in the diagnosis of focal segmental glomerulosclerosis: are current pathological techniques missing important abnormalities in the glomerular basement membrane?

Article

Full-text available

Jul 2019

Background: There is an increasing appreciation that variants of the collagen IV genes may be associated with the development of focal segmental glomerulosclerosis (FSGS). On electron microscopy, such variants may produce characteristic changes within the glomerular basement membrane (GBM). These changes may be missed if glomerular lesions histologically diagnosed as FSGS on light microscopy are not subjected to electron microscopy. Methods: We conducted a retrospective cohort analysis of all patients presenting to two hospitals who received a primary histological diagnosis of FSGS to see if these samples underwent subsequent electron microscopy. Each such sample was also scrutinised for the presence of characteristic changes of an underlying collagen IV disorder Results: A total of 43 patients were identified. Of these, only 30 underwent electron microscopy. In two samples there were histological changes detected that might have suggested the underlying presence of a collagen IV disorder. Around one in three biopsy samples that had a histological diagnosis of FSGS were not subjected to electron microscopy. Conclusion: Renal biopsy samples that have a histological diagnosis of primary FSGS not subjected to subsequent electron microscopy may potentially miss ultrastructural changes in the GBM that could signify an underlying collagen IV disorder as the patient’s underlying disease process. This could potentially affect both them and their families’ investigative and management decisions given potential for implications for transplant, heritability and different disease pathogenesis. This represents a gap in care which should be reflected upon and rectified via iterative standard care and unit-level quality assurance initiatives.

Emotional breakthrough and psychedelics: Validation of the Emotional Breakthrough Inventory

Article

Full-text available

Jul 2019

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.

Predicting Responses to Psychedelics: A Prospective Study

Article

Full-text available

Nov 2018

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.

Identifying fundamental criteria for eating disorder recovery: A systematic review and qualitative meta-analysis

Article

Full-text available

Nov 2017

Background Outcome studies for eating disorders regularly measure pathology change or remission as the only outcome. Researchers, patients and recovered individuals highlight the importance of using additional criteria for measuring eating disorder recovery. There is no clear consensus on which additional criteria are most fundamental. Studies focusing on the perspectives of recovered patients show criteria which are closely related to dimensions of positive functioning as conceptualized in the complete mental health model. The aim of this study was to identify fundamental criteria for eating disorder recovery according to recovered individuals. Methods A systematic review and a qualitative meta-analytic approach were used. Eighteen studies with recovered individuals and meeting various quality criteria were included. The result sections of the included papers were searched for themes that were stated as criteria for recovery or ‘being recovered’. All themes were analyzed using a meta-summary technique. Themes were labeled into criteria for recovery and the frequency of the found criteria was examined. Results In addition to the remission of eating disorder pathology, dimensions of psychological well-being and self-adaptability/resilience were found to be fundamental criteria for eating disorder recovery. The most frequently mentioned criteria were: self-acceptance, positive relationships, personal growth, decrease in eating disorder behavior/cognitions, self-adaptability/resilience and autonomy. Conclusions People who have recovered rate psychological well-being as a central criterion for ED recovery in addition to the remission of eating disorder symptoms. Supplementary criteria, besides symptom remission, are needed to measure recovery. We recommend including measurements of psychological well-being and self-adaptability/resilience in future research, such as outcome studies and in routine outcome measurement.

Nourishing the Spirit: Exploratory Research on Ayahuasca Experiences along the Continuum of Recovery from Eating Disorders

Article

Full-text available

Sep 2017

Eating disorders (EDs) are serious health conditions that are among the most difficult to treat. Innovative treatments are needed and modalities from across cultures must be considered. Ayahuasca is a psychoactive plant-based tea originally used by Amazonian indigenous groups. A growing body of research points to its promise in the healing of various mental health issues. This study explored the potential therapeutic value of ayahuasca in the context of EDs, including the perceived impact of the preparatory diet and the ayahuasca purge. Sixteen individuals previously diagnosed with an ED participated in a semi-structured interview relating to their experiences with ceremonial ayahuasca drinking. Interviews were analyzed using thematic analysis. Themes presented relate to the reduction or cessation of ED and mental health symptoms, shifts in body perception, and the importance of a ceremonial setting and after-care. For some, the preparatory diet resulted in familiar patterns of concern; however, none felt triggered by the purge in ayahuasca. Ceremonial ayahuasca drinking shows promise in the healing of EDs and warrants further research.

Psychological well-being in out-patients with eating disorders: A controlled study

Article

Full-text available

Apr 2014
INT J EAT DISORDER

Positive functioning is widely neglected in research on eating disorders (EDs). The aim of this exploratory study was to assess psychological well-being (PWB) in out-patients with ED and in controls. The authors assessed PWB in 245 out-patients with EDs [105 with bulimia nervosa (BN), 57 with anorexia nervosa (AN), and 83 with binge eating disorder (BED) who met DSM-IV-TR] and 60 controls. They tested whether PWB was associated with eating attitude test (EAT) scores and if such associations differed among ED groups while taking into account confounding variables. Significant differences between groups in all PWB scales were found. While individuals with BN reported significantly lower scores in all PWB dimensions than healthy controls, patients with BED scored significantly lower than controls in PWB autonomy, environmental mastery, and self-acceptance scales. Patients with AN showed similar scores to controls in all PWB dimensions, except for positive relationships and self-acceptance. In all ED groups, most PWB dimensions resulted significantly and negatively associated with EAT scales, except for AN where oral control was found to positively correlate with a high sense of purpose in life. All results were maintained even after adjusting for possible confounding variables. Patients with EDs reported an impairment in PWB. The paucity of PWB was not necessarily dependent on the presence of high levels of psychological distress and on the severity of the disorder. Such assessments may therefore yield a more comprehensive evaluation in this clinical population. © 2013 Wiley Periodicals, Inc. (Int J Eat Disord 2013;).

The Split-Apply-Combine Strategy for Data Analysis

Article

Full-text available

Apr 2011
J STAT SOFTW

Wickham Hadley

Many data analysis problems involve the application of a split-apply-combine strategy, where you break up a big problem into manageable pieces, operate on each piece independently and then put all the pieces back together. This insight gives rise to a new R package that allows you to smoothly apply this strategy, without having to worry about the type of structure in which your data is stored.The paper includes two case studies showing how these insights make it easier to work with batting records for veteran baseball players and a large 3d array of spatio-temporal ozone measurements.

The Warwick-Edinburgh mental well-being scale (WEMWBS): Development and UK validation

Article

Full-text available

Feb 2007
HEALTH QUAL LIFE OUT

There is increasing international interest in the concept of mental well-being and its contribution to all aspects of human life. Demand for instruments to monitor mental well-being at a population level and evaluate mental health promotion initiatives is growing. This article describes the development and validation of a new scale, comprised only of positively worded items relating to different aspects of positive mental health: the Warwick-Edinburgh Mental Well-Being Scale (WEMWBS). WEMWBS was developed by an expert panel drawing on current academic literature, qualitative research with focus groups, and psychometric testing of an existing scale. It was validated on a student and representative population sample. Content validity was assessed by reviewing the frequency of complete responses and the distribution of responses to each item. Confirmatory factor analysis was used to test the hypothesis that the scale measured a single construct. Internal consistency was assessed using Cronbach's alpha. Criterion validity was explored in terms of correlations between WEMWBS and other scales and by testing whether the scale discriminated between population groups in line with pre-specified hypotheses. Test-retest reliability was assessed at one week using intra-class correlation coefficients. Susceptibility to bias was measured using the Balanced Inventory of Desired Responding. WEMWBS showed good content validity. Confirmatory factor analysis supported the single factor hypothesis. A Cronbach's alpha score of 0.89 (student sample) and 0.91 (population sample) suggests some item redundancy in the scale. WEMWBS showed high correlations with other mental health and well-being scales and lower correlations with scales measuring overall health. Its distribution was near normal and the scale did not show ceiling effects in a population sample. It discriminated between population groups in a way that is largely consistent with the results of other population surveys. Test-retest reliability at one week was high (0.83). Social desirability bias was lower or similar to that of other comparable scales. WEMWBS is a measure of mental well-being focusing entirely on positive aspects of mental health. As a short and psychometrically robust scale, with no ceiling effects in a population sample, it offers promise as a tool for monitoring mental well-being at a population level. Whilst WEMWBS should appeal to those evaluating mental health promotion initiatives, it is important that the scale's sensitivity to change is established before it is recommended in this context.

Kaye W. Neurobiology of anorexia and bulimia nervosa. Physiol Behav 94: 121-135

Article

Full-text available

May 2008
PHYSIOL BEHAV

Walter H Kaye

Anorexia nervosa (AN) and bulimia nervosa (BN) are related disorders of unknown etiology that most commonly begin during adolescence in women. AN and BN have unique and puzzling symptoms, such as restricted eating or binge-purge behaviors, body image distortions, denial of emaciation, and resistance to treatment. These are often chronic and relapsing disorders, and AN has the highest death rate of any psychiatric disorder. The lack of understanding of the pathogenesis of this illness has hindered the development of effective interventions, particularly for AN. Individuals with AN and BN are consistently characterized by perfectionism, obsessive-compulsiveness, and dysphoric mood. Individuals with AN tend to have high constraint, constriction of affect and emotional expressiveness, ahendonia and asceticism, whereas individuals with BN tend to be more impulsive and sensation seeking. Such symptoms often begin in childhood, before the onset of an eating disorder, and persist after recovery, suggesting they are traits that create a vulnerability for developing an ED. There is growing acknowledgement that neurobiological vulnerabilities make a substantial contribution to the pathogenesis of AN and BN. Considerable evidence suggests that altered brain serotonin (5-HT) function contributes to dysregulation of appetite, mood, and impulse control in AN and BN. Brain imaging studies, using 5-HT specific ligands, show that disturbances of 5-HT function occur when people are ill, and persist after recovery from AN and BN. It is possible that a trait-related disturbance of 5-HT neuronal modulation predates the onset of AN and contributes to premorbid symptoms of anxiety, obsessionality, and inhibition. This dysphoric temperament may involve an inherent dysregulation of emotional and reward pathways which also mediate the hedonic aspects of feeding, thus making these individuals vulnerable to disturbed appetitive behaviors. Restricting food intake may become powerfully reinforcing because it provides a temporary respite from dysphoric mood. Several factors may act on these vulnerabilities to cause AN to start in adolescence. First, puberty-related female gonadal steroids or age-related changes may exacerbate 5-HT dysregulation. Second, stress and/or cultural and societal pressures may contribute by increasing anxious and obsessional temperament. Individuals with AN may discover that reduced dietary intake, by reducing plasma tryptophan availability, is a means by which they can modulate brain 5-HT functional activity and anxious mood. People with AN enter a vicious cycle which accounts for the chronicity of this disorder because caloric restriction results in a brief respite from dysphoric mood. However, malnutrition and weight loss, in turn, produce alterations in many neuropeptides and monoamine function, perhaps in the service of conserving energy, but which also exaggerates dysphoric mood. In summary, this article reviews findings in brain chemistry and neuroimaging that shed new light on understanding the psychopathology of these difficult and frustrating disorders.

Psychedelic Psychiatry’s Brave New World

Article

Apr 2020
CELL

After a legally mandated, decades-long global arrest of research on psychedelic drugs, investigation of psychedelics in the context of psychiatric disorders is yielding exciting results. Outcomes of neuroscience and clinical research into 5-Hydroxytryptamine 2A (5-HT2A) receptor agonists, such as psilocybin, show promise for addressing a range of serious disorders, including depression and addiction.

Ggplot2: Elegant Graphics for Data Analysis

Book

Jan 2009

Hadley Wickham

The meaning of (quality of) life in patients with eating disorders: A comparison of generic and disease-specific measures across diagnosis and outcome

Article

Apr 2014
INT J EAT DISORDER

Compare general and disease-specific health-related quality of life (HRQoL) among female patients with an eating disorder (ED). Female patients (n = 221; 95.3% Caucasian; 94.0% never married) completed the Medical Outcome Short Form Health Survey (SF-36) and Eating Disorders Quality of Life (EDQoL) as part of a study of treatment outcomes. Multivariate regression models were used to compare HRQoL differences across initial ED diagnosis (85 AN-R, 19 AN-B/P, 27 BN, 90 EDNOS) and ED diagnostic classification at time of outcome assessment (140 no ED, 38 subthreshold ED, 43 full threshold ED). There were no significant differences across ED diagnosis at initial assessment on either of the SF-36 Component Summary scores. However, patients with AN-B/P scored poorer on the work/school EDQoL subscales than other ED diagnoses, and on the psychological EDQoL subscale compared to AN-R and EDNOS. At outcome assessment, comparisons across full threshold, subthreshold and no ED classification indicated that those with no ED reported better HRQoL than those with full threshold ED on the SF-36 Mental Components Summary and three of four EDQoL subscales. Furthermore, those with no ED reported better psychological HRQoL than those with subthreshold ED. Disease-specific HRQOL measures are important to use when comparing HRQoL in ED patients across treatment and outcome, and may have the sensitivity to detect meaningful differences by diagnosis more so than generic instruments. EDQoL scores from patients remitted from symptoms approach but do not reach scores for unaffected college females; thus, treatment should continue until quality of life is restored. © 2013 Wiley Periodicals, Inc. (Int J Eat Disord 2013;).

Assessing rumination in eating disorders: Principal component analysis of a minimally modified ruminative response scale

Article

Dec 2011

A process account of eating disorders (EDs) (Park et al., in press-a) proposes that preoccupation with ruminative themes of eating, weight and shape may be important in ED maintenance. No self-report measure exists to capture disorder-specific rumination in EDs. 275 healthy participants rated rumination items and completed self-report measures of ED symptoms, depression and anxiety. Principal component analysis revealed two factors, reflection and brooding. The final nine-item Ruminative Response Scale for Eating Disorders (RRS-ED) demonstrated good convergent and discriminant validity and test-retest reliability. The psychometric properties were replicated in an anorexia nervosa sample. The findings support the notion that rumination in EDs is distinct from rumination in depression and is not adequately captured by existing measures.

The 16-Item Quick Inventory of Depressive Symptomatology (QIDS), Clinician Rating (QIDS-C), and Self-Report (QIDS-SR): A psychometric evaluation in patients with chronic major depression

Article

Oct 2003
BIOL PSYCHIAT

The 16-item Quick Inventory of Depressive Symptomatology (QIDS), a new measure of depressive symptom severity derived from the 30-item Inventory of Depressive Symptomatology (IDS), is available in both self-report (QIDS-SR(16)) and clinician-rated (QIDS-C(16)) formats. This report evaluates and compares the psychometric properties of the QIDS-SR(16) in relation to the IDS-SR(30) and the 24-item Hamilton Rating Scale for Depression (HAM-D(24)) in 596 adult outpatients treated for chronic nonpsychotic, major depressive disorder. Internal consistency was high for the QIDS-SR(16) (Cronbach's alpha =.86), the IDS-SR(30) (Cronbach's alpha =.92), and the HAM-D(24) (Cronbach's alpha =.88). QIDS-SR(16) total scores were highly correlated with IDS-SR(30) (.96) and HAM-D(24) (.86) total scores. Item-total correlations revealed that several similar items were highly correlated with both QIDS-SR(16) and IDS-SR(30) total scores. Roughly 1.3 times the QIDS-SR(16) total score is predictive of the HAM-D(17) (17-item version of the HAM-D) total score. The QIDS-SR(16) was as sensitive to symptom change as the IDS-SR(30) and HAM-D(24), indicating high concurrent validity for all three scales. The QIDS-SR(16) has highly acceptable psychometric properties, which supports the usefulness of this brief rating of depressive symptom severity in both clinical and research settings.

Post-Psychedelic Reductions in Experiential Avoidance Are Associated With Decreases in Depression Severity and Suicidal Ideation

R Zeifman
A C Zagner
R Watts
H Kettner
L J Mertens
R L Carhart-Harris

Zeifman R, Zagner AC, Watts R, Kettner H, Mertens LJ, Carhart-Harris RL (2020) Post-Psychedelic Reductions in Experiential Avoidance Are Associated With Decreases in Depression Severity and Suicidal Ideation. Frontiers Psychiatry 11

Neurobiology of anorexia and bulimia nervosa

Positive effects of psychedelics on depression and wellbeing scores in individuals reporting an eating disorder

Abstract

No full-text available

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