Psychedelic Therapy Research Articles

Leveraging meditation research for the study of psychedelic-related adverse effects

Psychedelics have shown early evidence for a range of benefits and low harm profiles in extant research. However, adverse effects (AEs) research in psychedelics has been limited, leading to underspecified AE profiles, inconsistent measurement, and potential undercounting of AEs. The development of safe, effective psychedelic therapies and treatments for AEs when they occur requires a thorough assessment of psychedelic-related AEs, their phenomenology, risk factors, and longitudinal duration. This article proposes that research on meditation-related AEs, which overlap in important ways with the phenomenological and contextual characteristics of psychedelic-related AEs, has engaged many methodological challenges present in the study of psychedelic-related AEs. Thus, meditation-related AE research offers thematic and methodological insights that are valuable to psychedelic AE research. An integrative review of extant AE research in both psychedelics and meditation is provided, and an agenda for leveraging meditation research to advance the investigation of psychedelic AEs is recommended. This includes the utility of meditation-related AEs as a comparator condition for psychedelic-related AEs, as well as recommendations for the adoption of (1) detailed and comprehensive, (2) user-informed, (3) impact-based, (4) standardized, (5) unbiased, and (6) representative measures of AEs and (7) examining factors that influence their impacts and trajectories.

That men should put an enemy in their mouths to steal away their brains: Reconsidering the origins of model psychosis

The promises of the Prozac century have fallen short; the number of novel, therapeutically significant medications successfully completing development shrinks every year; and the demand for better treatments constantly grows. Answering these hardships is a renewed optimism concerning the efficacy of controlled psychedelic therapy, a renaissance that has seen the resurgence of a familiar concept: intoxication as model psychosis. And yet, little has been made of where this peculiar idea originates. Why did we come to liken psychosis to intoxication, and why is this an idea we find so hard to shake? Questioning the conventional narrative that identifies the concept as emerging in the mid 19th century, this article seeks to uncover the conceptual foundations underlying what is now intended by ‘model psychosis’. This investigation begins with an assessment of both Moreau de Tours’s concept of hashish madness in 1845 and Emil Kraepelin’s study of artificial insanity in the 1880s–90s. In seeking to contextualize these ideas, this article further considers the deeper historical association between intoxication and psychosis, instead proposing that intoxication represents an originary conception of madness. Bringing this examination into the 19th century, it becomes apparent that perceptions of intoxicants, and intoxication, were immanently participatory in the emerging understanding of psychosis. The contemporary understanding of model psychosis comes into focus when these elements coalesce with the advent of psychological modelling. Ultimately, the goal is not merely to understand how and why model psychosis became thinkable, but to examine how overlooked concepts have engendered new ways of being neuro-psychiatric subjects.

Amid magic and menace: psychiatrists' attitudes to psilocybin therapy.

Understanding variations in knowledge and attitudes of psychiatrists to psilocybin therapy is important for the collective discourse about the potential impact on clinical practice and public health in Ireland. A 28-item questionnaire was designed based on previous studies and distributed to psychiatrists in Ireland via online mailing lists and at in-person academic events. 151 psychiatrists completed the questionnaire (73.3% were under 40 years of age, 76.0% were trainees, and 49.0% were female). In the total sample, 81.5% agreed that psilocybin therapy shows promise in the treatment of psychiatric disorders and 86.8% supported funding research, 86.8% would be willing to refer a patient if it was licensed and indicated, and 78.1% would consider the treatment for themselves, if indicated. Conversely, 6.6% agreed that psilocybin therapy was unsafe even under medical supervision, and 21.9% thought it was potentially addictive. 15.9% of the total sample reported at least one concern including, lack of robust evidence, long-term effectiveness, superiority to current interventions, potential harmful effects, cost and accessibility, and impartiality. Less than half of respondents felt knowledgeable (40.0%) and 9.9% felt adequately prepared to participate in psilocybin therapy. Consultant psychiatrists trended towards less optimism for a potential role in bipolar depression and emotionally unstable personality disorder compared to trainee psychiatrists. Overall psychiatrists in Ireland held positive attitudes towards psilocybin therapy. However, there was a lack of knowledge evident. Addressing the knowledge gap and aligning with the best available evidence will be key if psychedelic therapy is to prevail in a clinical setting.

Embark psychedelic therapy for depression: A new approach for the whole person

Embark psychedelic therapy for depression: A new approach for the whole person

“The mushroom was more alive and vibrant”: Patient reports of synthetic versus organic forms of psilocybin

AbstractInterest in psychedelic research in the West is surging, however, clinical trials have almost exclusively studied synthetic compounds such as MDMA, ketamine, DMT, LSD, ibogaine, and psilocybin. To date, few clinical trials have utilized whole mushroom/plant material like Psilocybe mushrooms, Iboga, or Ayahuasca. Individuals participating in the Roots To Thrive Psilocybin-Assisted Therapy for End of Life Distress program were administered synthetic psilocybin, whole Psilocybe cubensis, and mycological extract on separate occasions and post-treatment interview transcripts were qualitatively analyzed to discern themes and patterns. There was broad consensus that all three forms were helpful and similar, all generating visual and perceptual distortions, emotional and cognitive insight, and mystical experiences. However, synthetic psilocybin was said to feel less natural compared to organic forms, and the overall quality of experience of synthetic psilocybin was inferior to the organic forms. Research should be conducted with whole psychedelic mushrooms and extract in addition to synthetic psilocybin given this preliminary data, especially when considering that medicine keepers around the world have utilized whole mushrooms and plant material for millennia.

How Psychedelics Modulate Multiple Memory Mechanisms in Posttraumatic Stress Disorder.

Posttraumatic stress disorder (PTSD) is a psychiatric disorder with defining abnormalities in memory, and psychedelics may be promising candidates for the treatment of PTSD given their effects on multiple memory systems. Most PTSD and psychedelic research has investigated memory with fear conditioning and extinction. While fruitful, conditioning and extinction provide a limited model of the complexity of PTSD and phenomenology of psychedelics, thereby limiting the refinement of therapies. In this review, we discuss abnormalities in fear conditioning and extinction in PTSD and review 25 studies testing psychedelics on these forms of memory. Perhaps the most reliable effect is that the acute effects of psychedelics can enhance extinction learning, which is impaired in PTSD. However, the post-acute effects may also enhance extinction learning, and the acute effects can also enhance fear conditioning. We then discuss abnormalities in episodic and semantic memory in PTSD and review current knowledge on how psychedelics impact these memory systems. Although PTSD and psychedelics acutely impair the formation of hippocampal-dependent episodic memories, psychedelics may acutely enhance cortical-dependent learning of semantic memories that could facilitate the integration of trauma memories and disrupt maladaptive beliefs. More research is needed on the acute effects of psychedelics on episodic memory consolidation, retrieval, and reconsolidation and post-acute effects of psychedelics on all phases of episodic memory. We conclude by discussing how targeting multiple memory mechanisms could improve upon the current psychedelic therapy paradigm for PTSD, thereby necessitating a greater emphasis on assessing diverse measures of memory in translational PTSD and psychedelic research.

Innovative Psychedelic Therapies: Harnessing 5-MeO-DMT and DMT for Mental Health Treatment

Innovative Psychedelic Therapies: Harnessing 5-MeO-DMT and DMT for Mental Health Treatment

Rapid and sustained reduction of treatment-resistant PTSD symptoms after intravenous ketamine in a real-world, psychedelic paradigm.

Traditional treatments for post-traumatic stress disorder (PTSD) often show limited success with high dropout. Ketamine, an N-methyl-D-aspartate antagonist known for rapid antidepressant effects, has decreased PTSD symptoms in some studies but not in others. Administering ketamine in ways that parallel psychedelic-assisted treatments-including preparatory, integration, sensory immersion, and psychotherapy sessions-could decrease PTSD symptoms meaningfully. A retrospective sample of 117 screened outpatients with elevated PTSD Checklist for DSM-5 (PCL-5) scores received intravenous ketamine in supportive environments. The protocol included preparation, intention-setting, and integration sessions accompanying at least six administrations. Administration sessions included eye shades and evocative music paralleling typical psychedelic therapy trials. Mean PCL scores decreased from 52.54 (SD = 12.01) to 28.78 (SD = 16.61), d = 1.64. Patients tolerated treatment well, with no serious adverse events. Covariates, including age, gender, days between PCL assessments, number of psychiatric medications, and suicidal ideation were not significant moderators; concomitant psychotherapy did reach significance, d = 0.51. Of the 117 patients' final PCL scores, 88 (75.21%) measures suggested clinically meaningful improvement and 72 (61.54%) suggested remission of PTSD symptoms. Intravenous ketamine in supportive environments, with hallmarks of psychedelic therapy, preceded large reductions in PTSD symptoms. These results highlight ketamine's potential when delivered in this manner, suggesting environmental factors might account for some variation seen in previous work. Given the molecule's cost, minimal interaction with other psychiatric medications, and legal status, intravenous ketamine in a psychedelic paradigm may be a promising option for PTSD unresponsive to other treatments.

Existential feelings as a phenomenological framework for psychedelic therapy

ABSTRACT This article provides a phenomenological account of the role of existential feelings in the acute and lasting effects of psychedelic therapy and attempts to elucidate phenomenologically why certain psychedelic experiences in specific contexts have the potential of providing long-term relief from mental suffering. First, we explain Matthew Ratcliffe’s theory of existential feelings and use it to highlight shared phenomenological characteristics between various mental disorders. Next, we discuss the phenomenology of oceanic feelings to specify the kind of existential feeling that is involved in acute psychedelic experiences and connect this to the existential reorientation that may occur after the use of psychedelics. Following this, we show how this framework of existential feelings allows us to (1) characterize the phenomenological process that takes during therapeutic use of psychedelics, and (2) describe various conditions required for a successful therapeutic psychedelic experience.

Psychedelic research, assisted therapy and the role of the anaesthetist: A review and insights for experimental and clinical practices.

Recent years have witnessed an unprecedented increase in the search for the use of psychedelics in improving physical and mental health. Anaesthesia has evolved since very early times, born from the need to eliminate pain and reduce suffering and there are reports of the use of anaesthetics to achieve mystical states since the nineteenth century. Nowadays, the renaissance of psychedelics in anaesthesia has been inspired by their potential in the treatment of chronic pain syndromes, palliative care and in the emergency department and pre-hospital care with the administration of psychedelics in cases of ischaemia, given their potential in neuroprotection. Although there are already some published protocols for the administration of psychedelics in patients with mental illness, little has been addressed concerning non-mental medical applications. In this sense, in patients with multiple comorbidities, functional limitations and polymedicated, the anaesthetist may play a fundamental role, not only in clinical practice, but also in translational research. This article focuses on the description of psychedelics, with a particular focus on dimethyltryptamine (DMT) and ayahuasca pharmacology, effects, safety and toxicity. A detailed description of the role of the anaesthetist in clinical and experimental research is provided, from participant's screening to preparation and dosing session, expected adverse effects and how to manage them, based on the protocol and standard procedures of a current study with neuroimaging during the psychedelic experience. Specific considerations regarding the management of psychedelic toxicity are also provided as well as future directions for safe psychedelic use in clinical practice.

History, Hype, and Responsible Psychedelic Medicine: A Qualitative Study of Psychedelic Researchers.

Background Psychedelic medicine is a rapidly growing area of research and policy change. Australia recently became the first country to legalize the prescription of psychedelics and serves as a case study of issues that may emerge in other jurisdictions. Despite their influence as a stakeholder group, there has been little empirical exploration of psychedelic researchers' views on the development of psychedelic research and the ethical concerns. Methods We thematically analysed fourteen interviews with Australian psychedelic researchers. Results Three themes were constructed from the data: 1) coming out of the shadow of the 1960s, 2) challenges and affordances in engaging stakeholders, and 3) growing pains in innovation and translation. Conclusion The results illustrated tensions arising from the rapid growth of psychedelic research from a small group of dedicated individuals with a similar worldview, to a multi-interest, regulated industry. Participants' experiences and viewpoints were influenced by the history of psychedelic research, and this was met with an overarching concern for protecting the field from premature discontinuation, as well as maximizing potential positive impacts. Targets for stakeholder collaboration and initiatives to support responsible innovation in psychedelics include equitable access, sustainable industry involvement, productive research agendas, responsible reporting of evidence, and risk-taking within the relative safety of clinical trials.

Attitudes toward psychedelics and psychedelic-assisted therapy among potential mental health service users and the general population in Australia.

Despite rapid advances in psychedelic sciences and the increasing number of countries legalizing psychedelics for the treatment of mental illnesses, the attitudes, knowledge and readiness of both mental health consumers and the general population remain largely unknown. A cross-sectional survey was conducted among Australians, targeting individuals with mental illness as potential mental health service users. A sub-sample of individuals free of mental illness was also surveyed to assess attitudes in the general population. Participants completed the Attitudes on Psychedelics Questionnaire, the Basic Knowledge of Psychedelics Test and a questionnaire by Corrigan et al. to capture attitudes toward psychedelic therapy by mental health service users. Of the 502 respondents, 64.5% self-identified as having a mental illness. A significant proportion favored legalizing psychedelics for medical use (43%) and were open to their use (52.4%), yet fewer viewed their effects positively (24%) or considered them safe (33%). Most participants reported to be psychedelic naive (61%). Participants with mental illness had significantly more experience with psychedelics than participant free of mental illness (44.1% vs 29.7%). Experience, perceived knowledge and actual knowledge significantly predicted attitudes toward legalization, effects, risks and openness to psychedelics. While a large proportion of Australians are in favor of legalizing psychedelics for medical purposes, concerns about safety remain. People with self-identified mental illness, those with previous recreational psychedelic experience and those with greater knowledge of psychedelics were more likely to have positive attitudes toward psychedelics and psychedelic-assisted therapy.

Harnessing Pharmacogenomics in Clinical Research on Psychedelic-Assisted Therapy.

Psychedelics have recently re-emerged as potential treatments for various psychiatric conditions that impose major public health costs and for which current treatment options have limited efficacy. At the same time, personalized medicine is increasingly being implemented in psychiatry to provide individualized drug dosing recommendations based on genetics. This review brings together these topics to explore the utility of pharmacogenomics (a key component of personalized medicine) in psychedelic-assisted therapies. We summarized the literature and explored the potential implications of genetic variability on the pharmacodynamics and pharmacokinetics of psychedelic drugs including lysergic acid diethylamide (LSD), psilocybin, N,N-dimethyltryptamine (DMT), 5-methoxy-N,N-dimethyltryptamine (5-MeO-DMT), ibogaine and 3,4-methylenedioxymethamphetamine (MDMA). Although existing evidence is limited, particularly concerning pharmacodynamics, studies investigating pharmacokinetics indicate that genetic variants in drug-metabolizing enzymes, such as cytochrome P450, impact the intensity of acute psychedelic effects for LSD and ibogaine, and that a dose reduction for CYP2D6 poor metabolizers may be appropriate. Furthermore, based on the preclinical evidence, it can be hypothesized that CYP2D6 metabolizer status might contribute to altered acute psychedelic experiences with 5-MeO-DMT and psilocybin when combined with monoamine oxidase inhibitors. In conclusion, considering early evidence that genetic factors can influence the effects of certain psychedelics, we suggest that pharmacogenomic testing should be further investigated in clinical research. This is necessary to evaluate its utility in improving the safety and therapeutic profile of psychedelic therapies and a potential future role in personalizing psychedelic-assisted therapies, should these treatments become available.

An exploration of psychotherapists' readiness to join the psychedelic renaissance

AbstractBackgroundResearch on psychedelics centres on two key areas: the action of psychedelics on the brain and the protocol for delivering therapy. There is little research that considers the implications of this novel therapy on the therapist delivering the treatment. This research study sought to explore this.Aim and ObjectivesThe aim of this research was to explore the considerations for psychotherapists interested in delivering psychedelic therapy. Objectives were to examine the therapeutic conditions needed for effective outcomes, to explore the perceived differences between the practice of standard psychotherapy and psychedelic therapy and to determine the challenges for therapists working in the field.MethodSix semi‐structured interviews were conducted with therapists who work in clinical or retreat settings. Interview transcripts were analysed using qualitative thematic analysis.FindingsThree themes emerged that highlight the importance of preparation for effective clinical outcomes, the differences in standard and psychedelic practice and the personal and professional implications for therapists.ConclusionsThe results highlighted challenges and revealed the need for clear protocols for integrating psychedelics into psychotherapy practice.

Psychedelic research at a crossroads

There is an urgent need to develop better treatments for mental health conditions that affect one in every eight people in the world. To combat this concern, psychedelic drugs have been combined with psychotherapy and studied in clinical trials in the United States and Europe. Psychedelics are hallucinogenic drugs that alter brain activity and facilitate altered states of consciousness. The proposed benefits of psychedelic-assisted therapy (PAT) include relatively short treatment times and stronger effects compared to other treatments. Although results of trials using MDMA for trauma or psilocybin for depression are promising, PAT is controversial because many questions about its safety and effectiveness are unanswered. This is evident in the recent ruling by the US Food and Drug Administration against the approval of MDMA therapy for post-traumatic stress disorder and the retraction of several papers about MDMA trials owing to unethical conduct by study therapists and data integrity, among other concerns. This field is at a crossroads, and the research community must address several obstacles to transition from exploratory trials to established, evidence-based treatments while avoiding pitfalls that can hinder advancement.

Going Underground: Demographics, Services, and Best Practices Endorsed by Practitioners Providing Support for Naturalistic Psychedelic Use

ABSTRACT Psychedelic-assisted therapy (PAT) has shown preliminary efficacy for psychiatric and physical health conditions. Although some people report naturalistic psychedelic use with so-called “underground” practitioners, little is known about PAT that occurs outside of controlled clinical settings or perspectives of these practitioners. We conducted an anonymous online survey of individuals who reported providing psychedelic support services (e.g. trip sitting and/or preparatory/follow-up psychotherapy) in naturalistic settings. We investigated demographics, including education and licensing, details about services provided, and reported client outcomes. Among 107 participants, 40.2% held a full or in-progress license and 44.9% had not obtained a relevant graduate degree. Almost all participants reported pre-screening clients before treatment, offering preparation, integration, and trip-sitting services, and most employed a range of therapeutic modalities, centering primarily on non-directive approaches. Participants reported that clients most commonly consumed psilocybin, and treated numerous conditions, primarily aligning with indications targeted in psychedelic clinical research. Perceptions of clients’ symptom changes were largely positive, although a small proportion reported worsened personality disorder symptoms. Further research delineating client and practitioner perspectives of naturalistic PAT services is warranted, and such work may shed light on the benefits and risks specific to naturalistic PAT as well as inform best practices for practitioners.

Naturalistic psychedelic therapy: The role of relaxation and subjective drug effects in antidepressant response.

Psychedelic-assisted therapy (PAT) is permitted in Switzerland under its limited medical use program. Data from patients in this program represent a unique opportunity to analyze the real-world practice of PAT. This study compared the subjective effects of lysergic acid diethylamide (LSD) and psilocybin between patients undergoing PAT and healthy volunteers. For the patients, it also investigated the relationship between antidepressant effects and six measures of acute drug effects. We compared data on acute psychedelic drug effects between 28 PAT patients with data from 28 healthy participants who participated in a randomized, double-blind crossover trial. All participants received varying doses of psilocybin and LSD. Subjective effects were assessed on an hourly basis during the acute drug effects, and the Mystical Experience Questionnaire (MEQ) was completed retrospectively. For patients, depressive symptoms were assessed using the Montgomery-Åsberg Depression Rating Scale (MADRS). Ratings of overall drug effect and mystical experience were similar across groups. Compared with healthy controls, patients reported lower ratings of ego dissolution. Patients showed a significant decrease in MADRS scores, and the greatest predictor of antidepressant outcome was relaxation during the PAT session. We did not observe a relationship between mystical-type experiences and antidepressant effects. Most patients experienced mild adverse effects which resolved within 48 h. PAT reduced depressive symptoms in this heterogeneous patient group. Patients may experience more challenging psychedelic effects and reduced ego dissolution. Hourly assessment of drug effects may predict clinical outcomes better than retrospectively assessed mystical experiences, and the impact of relaxation during PAT should be investigated further.

Autonomic nervous system activity correlates with peak experiences induced by DMT and predicts increases in well-being.

Non-ordinary states of consciousness induced by psychedelics can be accompanied by so-called "peak experiences," characterized at the emotional level by their intensity and positive valence. These experiences are strong predictors of positive outcomes following psychedelic-assisted therapy, and it is therefore important to better understand their biology. Despite growing evidence that the autonomic nervous system (ANS) plays an important role in mediating emotional experiences, its involvement in the psychedelic experience is poorly understood. The aim of this study was to investigate to what extent changes in the relative influence of the sympathetic (SNS) and parasympathetic nervous systems (PNS) over cardiac activity may reflect the subjective experience induced by the short-acting psychedelic N,N-Dimethyltryptamine (DMT). We derived measures of SNS and PNS activity from the electrocardiograms of 17 participants (11 males, mean age = 33.8 years, SD = 8.3) while they received either DMT or placebo. Results show that the joint influence of SNS and PNS ("sympathovagal coactivation") over cardiac activity was positively related to participants' ratings of "Spiritual Experience" and "Insightfulness" during the DMT experience, while also being related to improved well-being scores 2 weeks after the session. In addition, we found that the state of balance between the two ANS branches ("sympathovagal balance") before DMT injection predicted scores of "Insightfulness" during the DMT experience, as well as subsequent sympathovagal coactivation. These findings demonstrate the involvement of the ANS in psychedelic-induced peak experiences and may pave the way to the development of biofeedback-based tools to enhance psychedelic therapy.

Psychoanalysis and psychedelics: The censored story in Argentina

This essay examines the combination of psychoanalytic therapy and psychedelic substances in mid-20th century Argentina. Through document analysis, it examines the intersection of psychedelics and psychoanalysis, drawing from historical texts and writings by local psychoanalysts to develop a comprehensive understanding of the distinctive clinical practices and therapeutic approaches in the Argentine context. It details the experimental use of these substances, the clinical practices developed, and the professional and societal challenges encountered. Notably, psychoanalysts Luisa de Álvarez de Toledo, Alberto Tallaferro, and Alberto Fontana conducted pioneering research, exploring the therapeutic potential of these substances and publishing their findings in academic papers and books. According to these psychoanalysts, the use of psychedelic drugs in therapy could enhance transference, catalyze catharsis, and circumvent unconscious defenses, allowing for a vivid exploration of the patient's psyche that necessitated interpretation. Despite the innovative nature of this work, resistance from within the Argentine Psychoanalytic Association led to the eventual cessation of psychedelic research in this country. The essay calls for a reconsideration of the psychoanalytic community's relationship with psychedelics, emphasizing the potential for renewed dialogue and incorporation of these substances in contemporary therapeutic practices. In conclusion, this article sheds light on an overlooked chapter of psychoanalysis in a local setting and serves as a call for future explorations in broader scenarios. The resurgence of interest in psychedelics for mental health treatment presents an opportunity for psychoanalysts to engage with emerging research, enriching both theory and practice.

The Epidemiology of Psychedelic Use Among United States Military Veterans

ABSTRACT We sought to identify patterns of psychedelic use among United States military veterans, compare demographic variables and perspectives of those who did and did not report use, and characterize benefits and adverse outcomes associated with use. Respondents (N = 426) were recruited to complete an online cross-sectional survey. Approximately one-half (51%) reported using psychedelics. Most did so for healing/treatment (70%) and/or spiritual purposes (48%), and most (85%) reported benefiting from use. Those who used psychedelics reported they would be more likely to use VA services (p < .001, d = 0.64) and to return to the VA for care (p < .001, d = 0.79) if psychedelic therapy was offered. Almost two-thirds (59%) reported adverse outcomes associated with use. Equivalent proportions rated their psychedelic experiences as beneficial among those who did (89%) and did not (81%) report adverse outcomes. Fewer adverse outcomes were associated with being older, using psilocybin, feeling prepared and confident in the reasons for use, being in a comfortable setting, and being able to “trust, let go, and be open” (Rc = 0.77; p < .001). Psychedelics may offer benefits but may also lead to adverse outcomes without proper preparation and support. Future research should examine the utility of psychedelic-based approaches for veteran mental health care.