Psychedelics and disorders of consciousness: the current landscape and the path forward.

Modern medicine has been shaken by the surge of psychedelic science that proposes a new approach to mitigate mental disorders, such as depression and post-traumatic stress disorder. Clinical trials to investigate whether psychedelic substances can treat psychiatric conditions are now underway, yet less discussion gravitates around their use in neurological disorders due to brain injury. One suggested implementation of brain-complexity enhancing psychedelics is to treat people with post-comatose disorders of consciousness (DoC). In this article, we discuss the rationale of this endeavour, examining possible outcomes of such experiments by postulating the existence of an optimal level of complexity. We consider the possible counterintuitive effects of both psychedelics and DoC on the functional connectivity of the default mode network and its possible impact on selfhood. We also elaborate on the role of computational modelling in providing complementary information to experimental studies, both contributing to our understanding of the treatment mechanisms and providing a path towards personalized medicine. Finally, we update the discourse surrounding the ethical considerations, encompassing clinical and scientific values.

Virtual reality hypnosis prior to radiofrequency thermocoagulation for patients with chronic pain: an exploratory clinical trial.

Background: The management of chronic pain may involve an array of tools, including radiofrequency thermocoagulation (Rf-Tc) of sensory nerve terminals. Like many other invasive procedures, Rf-Tc can generate anxiety in a lot of patients, either during the expectation of the procedure or in the course of it. Virtual reality hypnosis (VRH) is a promising tool for managing anxiety and pain in several situations, but its anxiolytic property has not been investigated in participants with chronic pain and going through a Rf-Tc procedure. Objectives: The goal of this study was to evaluate the effectiveness of VRH for reducing self-assessed anxiety in participants with chronic pain, when received in preparation for Rf-Tc. Materials and methods: This prospective, controlled trial was conducted in the Interdisciplinary Algology Centre of the University Hospital of Liège (Belgium). Participants were assigned to two groups: VRH or control (usual care). Assessment was carried-out at 4 time points: T0 (one week before Rf-Tc); T1 (pre-intervention, on the day of Rf-Tc); T2 (immediately after the VRH intervention outside of the Rf-Tc room); and T3 (right after Rf-Tc). Medical, sociodemographic data, anxiety trait and immersive tendencies were collected at T0. Anxiety state and pain intensity were assessed at each time points. Satisfaction was examined at T3. Results: Forty-two participants were quasi-randomly assigned to the VRH or control group. No statistically significant interaction group by time was observed regarding all measured variables, including primary endpoint. However, a significant effect of time was found for anxiety and pain when considering both groups together, toward a progressive reduction. Conclusion: In the context of our study, there appears to be no significant effect of VRH at reducing anxiety in participants with chronic pain undergoing Rf-Tc. Anxiety decreases along the procedure, while pain is attenuated by the local anesthetic infiltration of the Rf site. Our results suggest that the presence of a caregiver throughout the procedure might explain the progressive decrease in anxiety. Future randomized controlled trials are needed to precisely study the effectiveness of the VRH tool, and the possibility of using it as a complementary approach for anxiety during invasive procedures.

Autonomic nervous system modulation during self-induced non-ordinary states of consciousness.

Self-induced cognitive trance (SICT) is a voluntary non-ordinary state of consciousness characterized by a lucid yet narrowed awareness of the external surroundings. It involves a hyper-focused immersive experience of flow, expanded inner imagery, modified somatosensory processing, and an altered perception of self and time. SICT is gaining attention due to its potential clinical applications. Similar states of non-ordinary state of consciousness, such as meditation, hypnosis, and psychedelic experiences, have been reported to induce changes in the autonomic nervous system. However, the functioning of the autonomic nervous system during SICT remains poorly understood. In this study, we aimed to investigate the impact of SICT on the cardiac and respiratory signals of 25 participants proficient in SICT. To accomplish this, we measured various metrics of heart rate variability (HRV) and respiration rate variability (RRV) in three conditions: resting state, SICT, and a mental imagery task. Subsequently, we employed a machine learning framework utilizing a linear discriminant analysis classifier and a cross-validation scheme to identify the features that exhibited the best discrimination between these three conditions. The results revealed that during SICT, participants experienced an increased heart rate and a decreased level of high-frequency (HF) HRV compared to the control conditions. Additionally, specific increases in respiratory amplitude, phase ratio, and RRV were observed during SICT in comparison to the other conditions. These findings suggest that SICT is associated with a reduction in parasympathetic activity, indicative of a hyperarousal state of the autonomic nervous system during SICT.

Personality traits and pattern of beliefs of near-death(-like) experiencers.

Introduction: Little is known about the potential personality and psychological predictors of near-death experiences (NDEs), and fewer yet those of near-death-like experiences (NDEs-like; similar phenomenology reported after a non-life-threatening context). This study investigated whether personality traits (Openness, Extraversion, Pleasantness, Conscientiousness, and Neuroticism), dissociative experiences, Fantasy proneness, disposition toward auditory hallucinations, absorption trait, and endorsement of paranormal and spiritual beliefs could be associated with the recall of NDEs(-like). Methods: To this aim, we invited four groups of people to retrospectively fill in questionnaires assessing the following factors: NDE experiencers (n = 63), NDE(-like) experiencers (n = 31), controls with a life-threatening situation but no NDE(-like) (n = 43), and controls without a life-threatening situation or an NDE(-like) (n = 44). We carried out univariate analyses for each factor and then performed a multiple regression analysis and a discriminant analysis. Results: The multivariate logistic regression analysis revealed that the endorsement of spiritual beliefs was associated with the recall of NDEs-like while Openness and Fantasy proneness were associated with the recall of NDEs. The discriminant analysis showed that these variables produce 35% of correct classification. Discussion: Albeit retrospective, these results pave the way for future research on psychological predictors of NDEs(-like) by highlighting the influence of Spirituality, Openness, and Fantasy proneness on these phenomena.

Virtual reality hypnosis in the management of pain: Self-reported and neurophysiological measures in healthy subjects.

BACKGROUND: Virtual reality hypnosis (VRH) has emerged as a new and promising option for pain management. Nonetheless, neural dynamics of pain modulation during VRH have not been investigated yet. The aim of this study was to measure the effects of VRH on pain, combining neurophysiological and self-reported measurements. METHODS: Eighteen healthy subjects underwent noxious electrical stimulations in both normal wakefulness and VRH conditions. Dissociation, absorption, time perception, anxiety, pain intensity and unpleasantness, heart rate variability and breathing were reported for each condition. EEG signals were analysed using event-related potentials (ERP) and time-frequency response (TFR) time-locked to stimuli. Neurophysiological features were correlated with self-reported data. RESULTS: VRH condition was associated with lower pain and higher dissociation. VRH significantly decreased amplitudes of N100 and P200 ERP components, reduced EEG power between 1 and 5 Hz from 100 to 560 ms, and increased EEG power from 5 to 11 Hz from 340 to 800 ms. These findings were observed at frontal, central and posterior electrodes. Heart rate variability was significantly higher and breathing frequency reduced with VRH. Correlations were found between the self-reported level of pain and ERP components. CONCLUSION: VRH modulates cerebral pain processes and body physiology, leading to reduced pain levels. These findings offer a first insight on the analgesic mechanisms of VRH and suggest that VRH is an effective approach to reduce experimental pain. SIGNIFICANCE: VRH decreases experimental pain perception, increases subject level of dissociation and modulates cerebral pain processing mechanisms. Pain can be managed with analgesic medication but also through complementary interventions. Among these, hypnosis and virtual reality (VR) are known to reduce pain for patients and healthy individuals. In recent years, an innovative technique combining hypnosis and VR has been proposed to help patients in managing pain. However, to our knowledge, no study has focused on the underlying mechanisms of this VR/hypnosis combination. We showed that VR combined with hypnosis decreases experimental pain, increases dissociation and influences EEG modulation.

Neurophysiology of hypnosis in chronic pain: A review of recent literature.

Chronic pain is a complex phenomenon which includes biological, psychological, and socio-professional factors that undermine patients' everyday life. Currently, only few patients significantly benefit from pharmacological treatments and many have to stop them because of negative side effects. Moreover, no medication or treatment addresses all aspects of chronic pain at once (i.e., sensations, emotions, behaviors, and cognitions), positioning chronic pain as an important public health issue and thus contributing to high health-care costs. Consequently, patients and health-care providers are increasingly turning to complementary non-pharmacological techniques such as hypnosis. Clinical research has demonstrated a decrease of pain perception, pain interference, depression and anxiety, and an increase in global quality of life when patients with chronic pain have benefited from hypnosis learning. Neuroimaging studies offer a possible explanation of these results by focusing on neural processes of pain modulation in chronic pain patients' brain. Studies conducted with chronic pain patients showed a modulation of pain matrix activity during hypnosis with a specific involvement of the anterior cingulate cortex (related to emotional and cognitive processing of pain). Therefore, hypnosis seems to act upon regions underlying emotion and cognition, with an influence on pain perception and emotional regulation. In this review, we propose to carry out a review of the recent literature on hypnosis in chronic pain management. A better understanding of the beneficial effects of hypnosis on chronic pain and its neurophysiology should enable more systematic use of this technique in the management of this complex health problem.

Virtual reality and hypnosis for anxiety and pain management in intensive care units: A prospective randomised trial among cardiac surgery patients.

BACKGROUND: Virtual reality and hypnosis are little studied in complex contexts, such as intensive care, where patients need significant physical and psychological assistance. OBJECTIVES: To compare and combine hypnosis and virtual reality benefits on anxiety and pain on patients before and after cardiac surgery. DESIGN: Prospective randomised controlled clinical trial. SETTING: The study was conducted in the University Hospital of Liege (Belgium) from October 2018 to January 2020. PATIENTS: One hundred patients (66 ±â€Š11.5 years; 24 women, 76 men) were included. Participants were adults undergoing cardiac surgery. Exclusion criteria: psychiatric diseases, claustrophobia, acrophobia, hearing loss, visual impairment, extreme fatigue, confusion surgery cancelled. INTERVENTIONS: Patients were randomly assigned to four arms (control; hypnosis; virtual reality; virtual reality hypnosis) and had 20 min of one of the techniques the day before and the day after surgery. MAIN OUTCOMES MEASURES: Anxiety, pain, fatigue, relaxation, physiological parameters, and opioid use were evaluated before and after each session. RESULTS: The main results did not show any significant differences between the groups. In all groups, anxiety decreased and pain increased from baseline to the postoperative day. Relaxation increased in all groups in the pre-operative (P < 0.0001) and postoperative period (P = 0.03). There were no significant differences for fatigue, physiological measures, or opioid use. CONCLUSION: As there were no significant differences between groups for the measured variables, we cannot affirm that one technique is better than another. Additional studies are required to compare and evaluate the cost-effectiveness of these techniques for critical care patients and caregivers. TRIAL REGISTRATION: ClinicalTrials.gov: NCT03820700. https://clinicaltrials.gov/ct2/show/NCT03820700. Retrospectively registered on 29 January 2019.

Complementary treatment comparison for chronic pain management: A randomized longitudinal study.

BACKGROUND: In chronic pain, it seems that the effect of cognitive-behavioral therapy (CBT) is boosted when it is combined with hypnosis. The aim of this study was to assess the efficacy of self-hypnosis combined with self-care (i.e., a type of CBT) compared to music/self-care, self-care and psychoeducation/CBT and to evaluate their long-term effects. METHODS: An open label randomized clinical trial enrolled patients with chronic pain and was carried out at the University Hospital of Liège (Belgium). Patients were randomized into four groups: self-hypnosis/self-care, music/self-care, self-care, psychoeducation/CBT (7 monthly sessions of 2 hours). Two follow-up sessions were delivered at 6- and 12-month. Levels of pain, fatigue intensity, anxiety, depression, insomnia severity, disability, health locus of control, mental and physical quality of life and attitudes (control, disability, harm, emotion, medical cure, medication, solicitude) towards pain were assessed before and after the treatments, and at follow-up. RESULTS: 203 patients were randomized: 52 in self-hypnosis/self-care, 59 in music/self-care, 47 in self-care, and 45 in psychoeducation/CBT. No group effect was found. A significant time effect was showed. Directly after the treatment, all groups decreased in pain attitudes and physical quality of life. Perceived control increased. At 6-month, all patients kept their levels of physical quality of life and perceived control, and showed decrease in pain intensity, harm, emotion and medical cure. At 12-month, scores that had change previously remained ameliorated, a decrease in insomnia severity and an increase in internal locus of control were observed. CONCLUSIONS: The present findings are encouraging as they display long-term beneficial effects of complementary biopsychosocial-based treatments in chronic pain. It seems that patients continued to apply the learnt strategies as improvements were observed one year after the treatments had ended.

Drop-out from chronic pain treatment programmes: Is randomization justified in biopsychosocial approaches?

OBJECTIVE: To identify profiles of patients who are at risk of dropping out from biopsychosocial approaches to chronic pain management. PATIENTS: A total of 575 patients were included in the study. Of these, 203 were randomized into 4 treat-ment groups: self-hypnosis/self-care; music/self-care; self-care; and psychoeducation/cognitive behavioural therapy. The remaining 372 patients were not randomized, as they presented with the demand to learn self-hypnosis/self-care, and therefore were termed a "self-hypnosis/self-care demanders" group. METHODS: Socio-demographics and behavioural data were included in the analyses. Univariates analyses, comparing early drop-outs (never attended treatment), late drop-outs (6/9 sessions' treatment) and continuers were conducted in order to select variables to include in a multivariate logistic regression. RESULTS: Univariate analyses yielded 8 variables, out of 18 potential predictors for drop-out, which were eligible for inclusion in the multivariate logistic regression. The model showed that having an intermediate or high educational level protects against dropping out early or late in the pain management process. Having to wait for more than 4 months before starting the treatment increases the risk of never starting it. Being randomized increases the risk of never starting the treatment. CONCLUSION: In a context in which randomization is considered a "gold standard" in evidence-based practice, these results indicate that this very principle could be deleterious to pain management in patients with chronic pain.

Hypnosis Associated with 3D Immersive Virtual Reality Technology in the Management of Pain: A Review of the Literature.

Hypnosis is well documented in the literature in the management of acute and chronic pain. Virtual reality (VR) is currently gaining credibility in the same fields as hypnosis for medical applications. Lately, the combination of hypnosis and VR was considered. The aim of this scoping review is to understand the current studied contexts and effects of virtual reality hypnosis (VRH) for the management of pain. We searched on PubMed, Taylor & Francis Online, and ProQuest databases with the following terms: "virtual reality," "3D," "hypnosis," and "pain". We included 8 studies that combined hypnosis and VR. All articles are in English. Two included healthy volunteers and six are clinical studies. Short-term results indicated significant decreases in pain intensity, pain unpleasantness, time spent thinking about pain, anxiety, and levels of opioids. However, results are not consistent for all patients all the days. VR alone seems to reduce pain independently of the hypnotizability level. One study claimed that VR and hypnosis could alter each other's effects and another argued that VR did not inhibit the hypnotic process and may even facilitate it by employing visual imagery. We cannot affirm that VR added value to hypnosis when they are combined. These trials and case series gave us indications about the possible applications of VRH in different contexts. Additional randomized clinical trials on VRH in the future will have to test this technique in clinical practice and help define guidelines for VRH utilization in pain management.