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Psychology

Compassionate use of psychedelics

Abstract

In the present paper, we discuss the ethics of compassionate psychedelic psychotherapy and argue that it can be morally permissible. When talking about psychedelics, we mean specifically two substances: psilocybin and MDMA. When administered under supportive conditions and in conjunction with psychotherapy, therapies assisted by these substances show promising results. However, given the publicly controversial nature of psychedelics, compassionate psychedelic psychotherapy calls for ethical justification. We thus review the safety and efficacy of psilocybin- and MDMA-assisted therapies and claim that it can be rational for some patients to try psychedelic therapy. We think it can be rational despite the uncertainty of outcomes associated with compassionate use as an unproven treatment regime, as the expected value of psychedelic psychotherapy can be assessed and can outweigh the expected value of routine care, palliative care, or no care at all. Furthermore, we respond to the objection that psychedelic psychotherapy is morally impermissible because it is epistemically harmful. We argue that given the current level of understanding of psychedelics, this objection is unsubstantiated for a number of reasons, but mainly because there is no experimental evidence to suggest that epistemic harm actually takes place.
Greif, A., & Šurkala, M. (2020). Compassionate use of psychedelics. Medicine, Health Care, and Philosophy.,
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Efficacy of Psychoactive Drugs for the Treatment of Posttraumatic Stress Disorder: A Systematic Review of MDMA, Ketamine, LSD and Psilocybin

Abstract

The aim of this systematic review was to examine the efficacy of MDMA, ketamine, LSD, and psilocybin for the treatment of posttraumatic stress disorder (PTSD). A search of four databases for English language, peer-reviewed literature published from inception to 18th October 2019 yielded 2,959 records, 34 of which were screened on full-text. Observational studies and RCTs which tested the efficacy of MDMA, ketamine, LSD, or psilocybin for reducing PTSD symptoms in adults, and reported changes to PTSD diagnosis or symptomatology, were included. Nine trials (five ketamine and four MDMA) met inclusion criteria. Trials were rated on a quality and bias checklist and GRADE was used to rank the evidence. The evidence for ketamine as a stand-alone treatment for comorbid PTSD and depression was ranked “very low”, and the evidence for ketamine in combination with psychotherapy as a PTSD treatment was ranked “low”. The evidence for MDMA in combination with psychotherapy as a PTSD treatment was ranked “moderate”.

Varker, T., Watson, L., Gibson, K., Forbes, D., & O’Donnell, M. L. (2021). Efficacy of Psychoactive Drugs for the Treatment of Posttraumatic Stress Disorder: A Systematic Review of MDMA, Ketamine, LSD and Psilocybin. Journal of psychoactive drugs, 53(1), 85–95. https://doi.org/10.1080/02791072.2020.1817639

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Beyond ecstasy: Alternative entactogens to 3,4-methylenedioxymethamphetamine with potential applications in psychotherapy

Abstract

The last two decades have seen a revival of interest in the entactogen 3,4-methylenedioxy-N-methylamphetamine (MDMA) as an adjunct to psychotherapy, particularly for the treatment of post-traumatic stress disorder. While clinical results are highly promising, and MDMA is expected to be approved as a treatment in the near future, it is currently the only compound in its class of action that is being actively investigated as a medicine. This lack of alternatives to MDMA may prove detrimental to patients who do not respond well to the particular mechanism of action of MDMA or whose treatment calls for a modification of MDMA’s effects. For instance, patients with existing cardiovascular conditions or with a prolonged history of stimulant drug use may not fit into the current model of MDMA-assisted psychotherapy, and could benefit from alternative drugs. This review examines the existing literature on a host of entactogenic drugs, which may prove to be useful alternatives in the future, paying particularly close attention to any neurotoxic risks, neuropharmacological mechanism of action and entactogenic commonalities with MDMA. The substances examined derive from the 1,3-benzodioxole, cathinone, benzofuran, aminoindane, indole and amphetamine classes. Several compounds from these classes are identified as potential alternatives to MDMA.

Oeri H. E. (2021). Beyond ecstasy: Alternative entactogens to 3,4-methylenedioxymethamphetamine with potential applications in psychotherapy. Journal of psychopharmacology (Oxford, England), 35(5), 512–536. https://doi.org/10.1177/0269881120920420

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Janis Phelps on training the first psychedelic therapists

Professor Janis Phelps PhD

Janis Phelps is the founder and director of the CIIS Center for Psychedelic Therapies and Research, which conducts the first academically accredited, professional certificate training programme for psychedelic-assisted therapy and research. 
At ICPR 2020, Dr. Phelps will address her experience in setting up a licensed training program for people working in research and therapy with psychedelics. 

You founded the first licensed training program for psychedelic therapists. How did this come about ?
The genesis of this program came about in 2014 at a Heffter Research Institute board meeting, where one of the trustees of our college heard the dire need for psychedelic therapists to be trained.
Our university has been training about 250 therapists a year in 6 different programmes for over 30 years. Stan Grof, Ralph Metzner and other psychedelic researchers have been teaching at CIIS for decades. CIIS trustees gave us seed money for a 3-year grant. I was the founder and creator of the programme, and the opportunities for this were very rich.
We wanted to bring in indigenous ways of knowing as well as the approach typically used in the research protocols for both psilocybin and MDMA.
What are the challenges you faced in this process ?
Well, we were creating something in a vacuum. There were no guidelines yet for how to do this, because no-one had done it before. For a year, I consulted with researchers, underground and above-ground therapists, and in related areas such as hospice care centres and emergency rooms, on how to work with people in altered states.
To devise the programme, we drew from anthropology, clinical and transpersonal psychology, psychoanalysis and ceremonial uses. The challenge was to try to integrate all these in the best possible way.
However, we chose to emphasise the research approach for now, because of the need for therapists to be in FDA-approved clinics. This is a compromise we made, but the upside is that now our graduates get hired by these research entities and they’re opening clinics that will be ready to use MDMA and psilocybin in the next couple of years.
Things seem to be progressing quite fast these days. Are you sometimes concerned they may be going too fast?
I’m concerned about the decriminalisation movements in the US. They’re going quicker than I’m comfortable with. The general public is not sufficiently aware of the hazards and the benefits of the use of plant medicines. Even physicians and nurses don’t know enough, and neither do school teachers.
So we’re working on scaling up our programme to include the general public and give them information online for free: interactions with medications, incompatibilities with certain psychological difficulties, how parents can talk to their kids about psychedelics, etc. I’m concerned there might be another backlash like we had in the sixties if these medicines are not used responsibly.
My other concern is that we’re training only 75 people a year, about 300 so far. MAPS has only trained about 250. We need thousands of therapists trained. I’m concerned that when the medicines get rescheduled, there won’t be enough therapists, with resulting insufficient access to the medicines for patients. So we’re looking to scale it up and develop affiliations with other universities.
What have you taken away from this whole adventure so far?
I’ve been delighted to witness the integrity of the therapists and medical doctors wanting to come into this space. They want to see healing happen, they’re concerned about what’s happening on the planet in terms of politics, genocides and global warming.
They know that psychedelics are not the only way for people to heal, of course, but the kind of therapy we can do is augmented tremendously by the use of plant medicines. I see them changing psychiatry and psychology for nothing but the good.
On average, the professionals who apply for the programme have 15 years of licensed practice, so they’re quite experienced in their work. Some were retired medical doctors who reactivated their license in order to do this work. I also witnessed our students building community with each other, creating associations, building salons, and it’s very exciting to see this flourish across the United States, into Canada, South America and the EU. I realised once again how desperate people are for community. And finally, it’s been wonderful to meet the new generation, I’m very happy to pass the hat to younger people.
Dr. Phelps’ talk at ICPR 2020 will be titled: “Training future psychedelic therapists

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

Abstract

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.

Spriggs, M. J., Kettner, H., & Carhart-Harris, R. L. (2021). Positive effects of psychedelics on depression and wellbeing scores in individuals reporting an eating disorder. Eating and weight disorders : EWD, 26(4), 1265–1270. https://doi.org/10.1007/s40519-020-01000-8

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Total Recall: Lateral Habenula and Psychedelics in the Study of Depression and Comorbid Brain Disorders

Abstract

Depression impacts the lives and daily activities of millions globally. Research into the neurobiology of lateral habenula circuitry and the use of psychedelics for treating depressive states has emerged in the last decade as new directions to devise interventional strategies and therapies. Several clinical trials using deep brain stimulation of the habenula, or using ketamine, and psychedelics that target the serotonergic system such as psilocybin are also underway. The promising early results in these fields require cautious optimism as further evidence from experiments conducted in animal systems in ecologically relevant settings, and a larger number of human studies with improved spatiotemporal neuroimaging, accumulates. Designing optimal methods of intervention will also be aided by an improvement in our understanding of the common genetic and molecular factors underlying disorders comorbid with depression, as well as the characterization of psychedelic-induced changes at a molecular level. Advances in the use of cerebral organoids offers a new approach for rapid progress towards these goals. Here, we review developments in these fast-moving areas of research and discuss potential future directions.

Vitkauskas, M., & Mathuru, A. S. (2020). Total Recall: Lateral Habenula and Psychedelics in the Study of Depression and Comorbid Brain Disorders. International journal of molecular sciences, 21(18), 6525. https://doi.org/10.3390/ijms21186525

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Psilocybin as a New Approach to Treat Depression and Anxiety in the Context of Life-Threatening Diseases-A Systematic Review and Meta-Analysis of Clinical Trials

Abstract

Psilocybin is a naturally occurring tryptamine known for its psychedelic properties. Recent research indicates that psilocybin may constitute a valid approach to treat depression and anxiety associated to life-threatening diseases. The aim of this work was to perform a systematic review with meta-analysis of clinical trials to assess the therapeutic effects and safety of psilocybin on those medical conditions. The Beck Depression Inventory (BDI) was used to measure the effects in depression and the State-Trait Anxiety Inventory (STAI) was used to measure the effects in anxiety. For BDI, 11 effect sizes were considered (92 patients) and the intervention group was significantly favored (WMD = -4.589; 95% CI = -4.207 to -0.971; p-value = 0.002). For STAI-Trait, 11 effect sizes were considered (92 patients), being the intervention group significantly favored when compared to the control group (WMD = -5.906; 95% CI = -7.852 to -3.960; p-value ˂ 0.001). For STAI-State, 9 effect sizes were considered (41 patients) and the intervention group was significantly favored (WMD = -6.032; 95% CI = -8.900 to -3.164; p-value ˂ 0.001). The obtained results are promising and emphasize the importance of psilocybin translational research in the management of symptoms of depression and anxiety, since the compound may be effective in reducing symptoms of depression and anxiety in conditions that are either resistant to conventional pharmacotherapy or for which pharmacologic treatment is not yet approved. Moreover, it may be also relevant for first-line treatment, given its safety.

Vargas, A. S., Luís, Â., Barroso, M., Gallardo, E., & Pereira, L. (2020). Psilocybin as a New Approach to Treat Depression and Anxiety in the Context of Life-Threatening Diseases-A Systematic Review and Meta-Analysis of Clinical Trials. Biomedicines, 8(9), 331. https://doi.org/10.3390/biomedicines8090331

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The Antidepressant Effect of Ketamine Is Dampened by Concomitant Benzodiazepine Medication

Abstract

The rapid antidepressant effect of ketamine has become a breakthrough in the research and treatment of depression. Although predictive and modulating factors of the response to ketamine are broadly studied, little is known about optimal concurrent medication protocols. Concerning gamma-aminobutyric acid neurotransmission being a shared target for both ketamine and benzodiazepines (BZD), we evaluated the influence of BZD on the antidepressant effect of a single ketamine infusion in depressed patients. Data from 47 patients (27 females) with major depression (MADRS ≥ 20, ≥ 1 prior nonresponse to antidepressant treatment in current episode) who participated in two previous studies (EudraCT Number: 2009-010625-39 and 2013-000952-17) entered the analysis. All of the subjects were given an infusion of a subanesthetic dose of racemic ketamine (0.54 mg per kg) as an add-on medication to ongoing antidepressant treatment. Thirteen patients (28%) reached ≥ 50% reduction in MADRS within one week after ketamine administration. Nineteen (40%) patients took concomitant benzodiazepines on a daily basis. The doses of BZDs were significantly higher in nonresponders (p=0.007). ROC analysis distinguished responders from nonresponders by a criterion of >8mg of diazepam equivalent dose (DZ equivalent) with a sensitivity of 80% and a specificity of 85% (p<0.001). RM-ANOVA revealed a different time pattern of response to ketamine between the BZD+ (>8mg of DZ equivalent) and BZD- (≤8mg of DZ equivalent) groups, with a significantly worse outcome in BZD+ on day 3 (p=0.04) and day 7 (p=0.02). The results of the study indicate that concomitant benzodiazepine treatment in higher doses may attenuate ketamine’s antidepressant effect. The pathophysiological, clinical and methodological implications of this finding should be considered in future research and ketamine treatment.

Andrashko, V., Novak, T., Brunovsky, M., Klirova, M., Sos, P., & Horacek, J. (2020). The Antidepressant Effect of Ketamine Is Dampened by Concomitant Benzodiazepine Medication. Frontiers in psychiatry, 11, 844. https://doi.org/10.3389/fpsyt.2020.00844

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The therapeutic potential of microdosing psychedelics in depression

Abstract

Microdosing psychedelics is the repeated use of small doses of, for example, lysergic acid diethylamide (LSD) and psilocybin, typically for a few weeks. Despite the popular and scientific attention in recent years, and claims by users that it has therapeutic value in affective disorders like depression, little scientific knowledge is available to back this. The purpose of this review was to investigate whether there are scientific grounds to state that this practice could be helpful in the treatment of affective disorders, and safe to use repeatedly. To that end, the literature (PubMed, MedLine) was searched, looking for (controlled) experimental studies with low doses of LSD and/or psilocybin, in healthy volunteers and patient samples. After a selection process and the addition of relevant articles, 14 experimental studies entered this review. Findings show that both LSD (10-20 mcg) and psilocybin (<1-3 mg) have subtle (positive) effects on cognitive processes (time perception, convergent and divergent thinking) and brain regions involved in affective processes. Besides the pleasant experience, increased anxiety and a cycling pattern of depressive and euphoric mood were also found. With regard to safety, it was demonstrated that low doses are well tolerated (in healthy volunteers) and have no-to-minimal effects on physiological measures. While it is yet unclear whether psychedelic microdosing is of therapeutic value for depression, the aforementioned effects on selective processes suggest that low doses of psychedelics could play a role in depression by inducing some kind of cognitive flexibility, which might lead to decreased rumination. While previous studies were conducted mostly in small samples of healthy volunteers, future placebo-controlled clinical trials in depressed patients are required to understand the therapeutic value of microdosing psychedelics, how this differs from therapy using full psychedelic doses, and whether different psychedelics have different effect patterns. The proposed research will give new insights into the potential of future alternative psychiatric treatment forms that are fiercely needed.

Kuypers K. (2020). The therapeutic potential of microdosing psychedelics in depression. Therapeutic advances in psychopharmacology, 10, 2045125320950567. https://doi.org/10.1177/2045125320950567

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P300-mediated modulations in self-other processing under psychedelic psilocybin are related to connectedness and changed meaning: A window into the self-other overlap

Abstract

The concept of self and self-referential processing has a growing explanatory value in psychiatry and neuroscience, referring to the cognitive organization and perceptual differentiation of self-stimuli in health and disease. Conditions in which selfhood loses its natural coherence offer a unique opportunity for elucidating the mechanisms underlying self-disturbances. We assessed the psychoactive effects of psilocybin (230 μg/kg p.o.), a preferential 5-HT1A/2A agonist known to induce shifts in self-perception. Our placebo-controlled, double-blind, within-subject crossover experiment (n = 17) implemented a verbal self-monitoring task involving vocalizations and participant identification of real-time auditory source- (self/other) and pitch-modulating feedback. Subjective experience and task performance were analyzed, with time-point-by-time-point assumption-free multivariate randomization statistics applied to the spatiotemporal dynamics of event-related potentials. Psilocybin-modulated self-experience, interacted with source to affect task accuracy, and altered the late phase of self-stimuli encoding by abolishing the distinctiveness of self- and other-related electric field configurations during the P300 timeframe. This last effect was driven by current source density changes within the supragenual anterior cingulate and right insular cortex. The extent of the P300 effect was associated with the intensity of psilocybin-induced feelings of unity and changed meaning of percepts. Modulations of late encoding and their underlying neural generators in self-referential processing networks via 5-HT signaling may be key for understanding self-disorders. This mechanism may reflect a neural instantiation of altered self-other and relational meaning processing in a stimulus-locked time domain. The study elucidates the neuropharmacological foundation of subjectivity, with implications for therapy, underscoring the concept of connectedness.

Smigielski, L., Kometer, M., Scheidegger, M., Stress, C., Preller, K. H., Koenig, T., & Vollenweider, F. X. (2020). P300‐mediated modulations in self–other processing under psychedelic psilocybin are related to connectedness and changed meaning: A window into the self–other overlap. Human brain mapping41(17), 4982-4996; 10.1002/hbm.25174

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Online Event - Psychedelic Care in Recreational Settings - 3 October 2024

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interested in becoming a trained psychedelic-assisted therapist?