LSD, madness and healing: Mystical experiences as possible link between psychosis model and therapy model.

BACKGROUND: For a century, psychedelics have been investigated as models of psychosis for demonstrating phenomenological similarities with psychotic experiences and as therapeutic models for treating depression, anxiety, and substance use disorders. This study sought to explore this paradoxical relationship connecting key parameters of the psychotic experience, psychotherapy, and psychedelic experience. METHODS: In a randomized, double-blind, placebo-controlled, crossover design, 24 healthy volunteers received 50 µg d-lysergic acid diethylamide (LSD) or inactive placebo. Psychotic experience was assessed by aberrant salience (Aberrant Salience Inventory, ASI), therapeutic potential by suggestibility (Creative Imagination Scale, CIS) and mindfulness (Five Facet Mindfulness Questionnaire, FFMQ; Mindful Attention Awareness Scale, MAAS; Experiences Questionnaire, EQ), and psychedelic experience by four questionnaires (Altered State of Consciousness Questionnaire, ASC; Mystical Experiences Questionnaire, MEQ; Challenging Experiences Questionnaire, CEQ; Ego-Dissolution Inventory, EDI). Relationships between LSD-induced effects were examined. RESULTS: LSD induced psychedelic experiences, including alteration of consciousness, mystical experiences, ego-dissolution, and mildly challenging experiences, increased aberrant salience and suggestibility, but not mindfulness. LSD-induced aberrant salience correlated highly with complex imagery, mystical experiences, and ego-dissolution. LSD-induced suggestibility correlated with no other effects. Individual mindfulness changes correlated with aspects of aberrant salience and psychedelic experience. CONCLUSIONS: The LSD state resembles a psychotic experience and offers a tool for healing. The link between psychosis model and therapeutic model seems to lie in mystical experiences. The results point to the importance of meaning attribution for the LSD psychosis model and indicate that psychedelic-assisted therapy might benefit from therapeutic suggestions fostering mystical experiences.

The Shipibo Ceremonial Use of Ayahuasca to Promote Well-Being: An Observational Study.

Promoting well-being is one of the main goals to improve health in the world. We examined the well-being and quality of life over the course of one year in a sample that participated in an Indigenous Shipibo healing program where traditional healers work in a series of ayahuasca ceremonies. We also explored the role of decentering as a mediator of psychological well-being. Participants who attended the program responded to an online survey that included a Psychological Well-Being Scale; Oxford Happiness Questionnaire; The World Health Organization Quality of Life Spirituality, Religiousness, and Personal Beliefs scale; the WHO Quality of Life-BREF scale; and Decentering scale. Baseline (T0) and postassessment (T1) were completed by 200 individuals. Of these, 101 completed the follow-up assessment at three months (T2), 91 at 6 months (T3), and 94 at 12 months follow-up (T4) after leaving the center. ANOVA test was performed in a representative subsample to control the passing of time two months before attending the program (T-1). Pearson's test was performed to examine the relationship between psychological well-being and decentering during the period of T0 and T1. A significant increase was observed in all the scales at all time points (p ≤ 0.01). The subgroup analysis performed in a representative subsample allowed us to infer that the significant differences in outcomes are due to the effect of their stay at the center and not the passing of time. We found a relationship between decentering and the improvement of psychological well-being (r = 0.57; p < 0.01). Our results suggest that the Indigenous Shipibo healing work with ayahuasca has value to improve long-term well-being and quality of life for Westerners.

Therapeutic potential of ayahuasca in grief: a prospective, observational study.

RATIONALE: Recent studies have assessed the therapeutic potential of ayahuasca for the treatment of depression with promising preliminary results. OBJECTIVES: Here, we examine the course of grief over 1 year of follow-up in a bereaved sample that attended a center in Peru to participate in indigenous Shipibo ayahuasca ceremonies. We also explore the roles of experiential avoidance and decentering as mechanisms of change. METHODS: Bereaved participants who attended the ayahuasca center responded to an online survey that included the Texas Revised Inventory of Grief, Symptom Assessment-45, WHO Quality of Life-Bref, Acceptance and Action Questionnaire, and Decentering. Baseline assessment was completed by 50 individuals (T0). Of these, 39 completed the post-assessment at 15 days (T1), 31 at 3 months (T2), 29 at 6 months (T3), and 27 at 12 months (T4) after leaving the retreat. Pearson's analysis was performed to examine the relationship between the severity of grief and mechanisms of change during the period of T0 and T1. RESULTS: A significant decrease in Texas Revised Inventory was observed at all time points (T1: Cohen's d = 0.84; T2: Cohen's d = 1.38; T3: Cohen's d = 1.16; T4: Cohen's d = 1.39). We found a relationship between experiential avoidance (r = 0.55; p < .01), decentering (r = - 0.47; p < .01), and a reduction in the severity of grief. CONCLUSIONS: Our results suggest that the ceremonial use of ayahuasca has therapeutic value by reducing the severity of grief. Acceptance and decentering are both psychological processes that mediate the improvement of grief symptoms.

Corrigendum: Four Weekly Ayahuasca Sessions Lead to Increases in "Acceptance" Capacities: A Comparison Study with a Standard 8-Week Mindfulness Training Program.

[This corrects the article DOI: 10.3389/fphar.2018.00224.].

Four Weekly Ayahuasca Sessions Lead to Increases in "Acceptance" Capacities: A Comparison Study With a Standard 8-Week Mindfulness Training Program.

Background: The therapeutic effects of the Amazonian plant tea ayahuasca may relate to its ability to enhance mindfulness capacities. Ayahuasca induces a modified state of awareness through the combined action of its active principles: the psychedelic N,N-dimethyltryptamine (DMT) and a series of centrally acting ß-carbolines, mainly harmine and tetrahydroharmine. To better understand the therapeutic potential of ayahuasca, here we compared the impact on mindfulness capacities induced by two independent interventions: (a) participation in four ayahuasca sessions without any specific purpose related to improving mindfulness capacities; and (b) participation in a standard mindfulness training course: 8 weeks mindfulness-based stress reduction (MBSR), with the specific goal of improving these skills. Methods: Participants of two independent groups completed two self-report instruments: The Five Facet Mindfulness Questionnaire (FFMQ) and the Experiences Questionnaire (EQ). The MINDSENS Composite Index was also calculated, including those EQ and FFMQ items that have proven to be the most sensitive to meditation practice. Group A (n = 10) was assessed before and after the last of four closely spaced consecutive ayahuasca sessions. Group B (n = 10) was assessed before and after completion of a standard 8-week MBSR course. Results: MBSR training led to greater increases in overall mindfulness scores after the 8-week period. MBSR but not ayahuasca led to increases in the MINDSENS Composite Index. However, the ayahuasca sessions induced comparable increases in the Non-Judging subscale of the FFMQ, specifically measuring "acceptance." Improving this capacity allows for a more detached and less judgmental stance toward potentially distressing thoughts and emotions. Results: The present findings suggest that a small number of ayahuasca sessions can be as effective at improving acceptance as more lengthy and costly interventions. Future studies should address the benefits of combining ayahuasca administration with mindfulness-based interventions. This will allow us to investigate if ayahuasca will improve the outcome of psychotherapeutic interventions.

Correction to: The hidden therapist: evidence for a central role of music in psychedelic therapy.

The article The hidden therapist: evidence for a central role of music in psychedelic therapy, written by Mendel Kaelen, Bruna Giribaldi, Jordan Raine, Lisa Evans, Christopher Timmerman, Natalie Rodriguez, Leor Roseman, Amanda Feilding, David Nutt, Robin Carhart-Harris, was originally published electronically on the publisher's internet portal.

The hidden therapist: evidence for a central role of music in psychedelic therapy.

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

Assessing the Psychedelic "After-Glow" in Ayahuasca Users: Post-Acute Neurometabolic and Functional Connectivity Changes Are Associated with Enhanced Mindfulness Capacities.

Background: Ayahuasca is a plant tea containing the psychedelic 5-HT2A agonist N,N-dimethyltryptamine and harmala monoamine-oxidase inhibitors. Acute administration leads to neurophysiological modifications in brain regions of the default mode network, purportedly through a glutamatergic mechanism. Post-acutely, ayahuasca potentiates mindfulness capacities in volunteers and induces rapid and sustained antidepressant effects in treatment-resistant patients. However, the mechanisms underlying these fast and maintained effects are poorly understood. Here, we investigated in an open-label uncontrolled study in 16 healthy volunteers ayahuasca-induced post-acute neurometabolic and connectivity modifications and their association with mindfulness measures. Methods: Using 1H-magnetic resonance spectroscopy and functional connectivity, we compared baseline and post-acute neurometabolites and seed-to-voxel connectivity in the posterior and anterior cingulate cortex after a single ayahuasca dose. Results: Magnetic resonance spectroscopy showed post-acute reductions in glutamate+glutamine, creatine, and N-acetylaspartate+N-acetylaspartylglutamate in the posterior cingulate cortex. Connectivity was increased between the posterior cingulate cortex and the anterior cingulate cortex, and between the anterior cingulate cortex and limbic structures in the right medial temporal lobe. Glutamate+glutamine reductions correlated with increases in the "nonjudging" subscale of the Five Facets Mindfulness Questionnaire. Increased anterior cingulate cortex-medial temporal lobe connectivity correlated with increased scores on the self-compassion questionnaire. Post-acute neural changes predicted sustained elevations in nonjudging 2 months later. Conclusions: These results support the involvement of glutamate neurotransmission in the effects of psychedelics in humans. They further suggest that neurometabolic changes in the posterior cingulate cortex, a key region within the default mode network, and increased connectivity between the anterior cingulate cortex and medial temporal lobe structures involved in emotion and memory potentially underlie the post-acute psychological effects of ayahuasca.

Psilocybin with psychological support for treatment-resistant depression: an open-label feasibility study.

BACKGROUND: Psilocybin is a serotonin receptor agonist that occurs naturally in some mushroom species. Recent studies have assessed the therapeutic potential of psilocybin for various conditions, including end-of-life anxiety, obsessive-compulsive disorder, and smoking and alcohol dependence, with promising preliminary results. Here, we aimed to investigate the feasibility, safety, and efficacy of psilocybin in patients with unipolar treatment-resistant depression. METHODS: In this open-label feasibility trial, 12 patients (six men, six women) with moderate-to-severe, unipolar, treatment-resistant major depression received two oral doses of psilocybin (10 mg and 25 mg, 7 days apart) in a supportive setting. There was no control group. Psychological support was provided before, during, and after each session. The primary outcome measure for feasibility was patient-reported intensity of psilocybin's effects. Patients were monitored for adverse reactions during the dosing sessions and subsequent clinic and remote follow-up. Depressive symptoms were assessed with standard assessments from 1 week to 3 months after treatment, with the 16-item Quick Inventory of Depressive Symptoms (QIDS) serving as the primary efficacy outcome. This trial is registered with ISRCTN, number ISRCTN14426797. FINDINGS: Psilocybin's acute psychedelic effects typically became detectable 30-60 min after dosing, peaked 2-3 h after dosing, and subsided to negligible levels at least 6 h after dosing. Mean self-rated intensity (on a 0-1 scale) was 0·51 (SD 0·36) for the low-dose session and 0·75 (SD 0·27) for the high-dose session. Psilocybin was well tolerated by all of the patients, and no serious or unexpected adverse events occurred. The adverse reactions we noted were transient anxiety during drug onset (all patients), transient confusion or thought disorder (nine patients), mild and transient nausea (four patients), and transient headache (four patients). Relative to baseline, depressive symptoms were markedly reduced 1 week (mean QIDS difference -11·8, 95% CI -9·15 to -14·35, p=0·002, Hedges' g=3·1) and 3 months (-9·2, 95% CI -5·69 to -12·71, p=0·003, Hedges' g=2) after high-dose treatment. Marked and sustained improvements in anxiety and anhedonia were also noted. INTERPRETATION: This study provides preliminary support for the safety and efficacy of psilocybin for treatment-resistant depression and motivates further trials, with more rigorous designs, to better examine the therapeutic potential of this approach. FUNDING: Medical Research Council.

LSD modulates music-induced imagery via changes in parahippocampal connectivity.

Psychedelic drugs such as lysergic acid diethylamide (LSD) were used extensively in psychiatry in the past and their therapeutic potential is beginning to be re-examined today. Psychedelic psychotherapy typically involves a patient lying with their eyes-closed during peak drug effects, while listening to music and being supervised by trained psychotherapists. In this context, music is considered to be a key element in the therapeutic model; working in synergy with the drug to evoke therapeutically meaningful thoughts, emotions and imagery. The underlying mechanisms involved in this process have, however, never been formally investigated. Here we studied the interaction between LSD and music-listening on eyes-closed imagery by means of a placebo-controlled, functional magnetic resonance imaging (fMRI) study. Twelve healthy volunteers received intravenously administered LSD (75µg) and, on a separate occasion, placebo, before being scanned under eyes-closed resting conditions with and without music-listening. The parahippocampal cortex (PHC) has previously been linked with (1) music-evoked emotion, (2) the action of psychedelics, and (3) mental imagery. Imaging analyses therefore focused on changes in the connectivity profile of this particular structure. Results revealed increased PHC-visual cortex (VC) functional connectivity and PHC to VC information flow in the interaction between music and LSD. This latter result correlated positively with ratings of enhanced eyes-closed visual imagery, including imagery of an autobiographical nature. These findings suggest a plausible mechanism by which LSD works in combination with music listening to enhance certain subjective experiences that may be useful in a therapeutic context.

Ayahuasca: Pharmacology, neuroscience and therapeutic potential.

Ayahuasca is the Quechua name for a tea obtained from the vine Banisteriopsis caapi, and used for ritual purposes by the indigenous populations of the Amazon. The use of a variation of the tea that combines B. caapi with the leaves of the shrub Psychotria viridis has experienced unprecedented expansion worldwide for its psychotropic properties. This preparation contains the psychedelic 5-HT2A receptor agonist N,N-dimethyltryptamine (DMT) from P. viridis, plus ß-carboline alkaloids with monoamine-oxidase-inhibiting properties from B. caapi. Acute administration induces a transient modified state of consciousness characterized by introspection, visions, enhanced emotions and recollection of personal memories. A growing body of evidence suggests that ayahuasca may be useful to treat substance use disorders, anxiety and depression. Here we review the pharmacology and neuroscience of ayahuasca, and the potential psychological mechanisms underlying its therapeutic potential. We discuss recent findings indicating that ayahuasca intake increases certain mindfulness facets related to acceptance and to the ability to take a detached view of one's own thoughts and emotions. Based on the available evidence, we conclude that ayahuasca shows promise as a therapeutic tool by enhancing self-acceptance and allowing safe exposure to emotional events. We postulate that ayahuasca could be of use in the treatment of impulse-related, personality and substance use disorders and also in the handling of trauma. More research is needed to assess the full potential of ayahuasca in the treatment of these disorders.

Exploring the therapeutic potential of Ayahuasca: acute intake increases mindfulness-related capacities.

BACKGROUND: Ayahuasca is a psychotropic plant tea used for ritual purposes by the indigenous populations of the Amazon. In the last two decades, its use has expanded worldwide. The tea contains the psychedelic 5-HT2A receptor agonist N,N-dimethyltryptamine (DMT), plus ß-carboline alkaloids with monoamine-oxidase-inhibiting properties. Acute administration induces an introspective dream-like experience characterized by visions and autobiographic and emotional memories. Studies of long-term users have suggested its therapeutic potential, reporting that its use has helped individuals abandon the consumption of addictive drugs. Furthermore, recent open-label studies in patients with treatment-resistant depression found that a single ayahuasca dose induced a rapid antidepressant effect that was maintained weeks after administration. Here, we conducted an exploratory study of the psychological mechanisms that could underlie the beneficial effects of ayahuasca. METHODS: We assessed a group of 25 individuals before and 24 h after an ayahuasca session using two instruments designed to measure mindfulness capacities: The Five Facets Mindfulness Questionnaire (FFMQ) and the Experiences Questionnaire (EQ). RESULTS: Ayahuasca intake led to significant increases in two facets of the FFMQ indicating a reduction in judgmental processing of experiences and in inner reactivity. It also led to a significant increase in decentering ability as measured by the EQ. These changes are classic goals of conventional mindfulness training, and the scores obtained are in the range of those observed after extensive mindfulness practice. CONCLUSIONS: The present findings support the claim that ayahuasca has therapeutic potential and suggest that this potential is due to an increase in mindfulness capacities.

Functional connectivity measures after psilocybin inform a novel hypothesis of early psychosis.

Psilocybin is a classic psychedelic and a candidate drug model of psychosis. This study measured the effects of psilocybin on resting-state network and thalamocortical functional connectivity (FC) using functional magnetic resonance imaging (fMRI). Fifteen healthy volunteers received intravenous infusions of psilocybin and placebo in 2 task-free resting-state scans. Primary analyses focused on changes in FC between the default-mode- (DMN) and task-positive network (TPN). Spontaneous activity in the DMN is orthogonal to spontaneous activity in the TPN, and it is well known that these networks support very different functions (ie, the DMN supports introspection, whereas the TPN supports externally focused attention). Here, independent components and seed-based FC analyses revealed increased DMN-TPN FC and so decreased DMN-TPN orthogonality after psilocybin. Increased DMN-TPN FC has been found in psychosis and meditatory states, which share some phenomenological similarities with the psychedelic state. Increased DMN-TPN FC has also been observed in sedation, as has decreased thalamocortical FC, but here we found preserved thalamocortical FC after psilocybin. Thus, we propose that thalamocortical FC may be related to arousal, whereas DMN-TPN FC is related to the separateness of internally and externally focused states. We suggest that this orthogonality is compromised in early psychosis, explaining similarities between its phenomenology and that of the psychedelic state and supporting the utility of psilocybin as a model of early psychosis.