Dreams and Psychedelics: Neurophenomenological Comparison and Therapeutic Implications

Background: A resurgence of neurobiological and clinical research is currently underway into the therapeutic potential of serotonergic or ‘classical’ psychedelics, such as the prototypical psychedelic drug lysergic acid diethylamide (LSD), psilocybin (4-phosphoryloxy-N,Ndimethyltryptamine), and ayahuasca – a betacarboline- and dimethyltryptamine (DMT)-containing Amazonian beverage. The aim of this review is to introduce readers to the similarities and dissimilarities between psychedelic states and night dreams, and to draw conclusions related to therapeutic applications of psychedelics in psychiatry. Methods: Research literature related to psychedelics and dreaming is reviewed, and these two states of consciousness are systematically compared. Relevant conclusions with regard to psychedelicassisted therapy will be provided. Results: Common features between psychedelic states and night dreams include perception, mental imagery, emotion activation, fear memory extinction, and sense of self and body. Differences between these two states are related to differential perceptual input from the environment, clarity of consciousness and meta-cognitive abilities. Therefore, psychedelic states are closest to lucid dreaming which is characterized by a mixed state of dreaming and waking consciousness. Conclusion: The broad overlap between dreaming and psychedelic states supports the notion that psychedelics acutely induce dreamlike subjective experiences which may have long-term beneficial effects on psychosocial functioning and well-being. Future clinical studies should examine how therapeutic outcome is related to the acute dreamlike effects of psychedelics. Keywords: Dreams, psychedelics, subjective experience, perception, mental imagery, emotion activation, fear memory extinction, sense of self and body

Neuropsychodynamic Approach to Depression: Integrating Resting State Dysfunctions of the Brain and Disturbed Self-Related Processes

A mechanism-based approach was developed focusing on the psychodynamic, psychological and neuronal mechanisms in healthy and depressed persons. In this integrative concept of depression, the self is a core dimension in depression. It is attributed to negative emotions (e.g., failure, guilt). The increased inward focus in depression is connected with a decreased environmental focus. The development of neuropsychodynamic hypotheses of the altered self-reference is based on the investigation of the emotional-cognitive interaction in depressed patients. It may be hypothesized that the increased negative self-attributions—as typical characteristics of an increased self-focus in depression—may result from altered neuronal activity in subcortical-cortical midline structures in the brain, especially from hyperactivity in the cortical-subcortical midline regions and hypoactivity in the lateral regions. The increased resting state activity in depression is especially associated with an increased resting state activity in the default mode network (DMN) and a dysbalance between DMN and executive network (EN) activity. Possible therapeutic consequences of the neuropsychodynamic approach to depression involve the necessary emotional attunement in psychotherapy of depressed patients and the adequate timing of therapeutic interventions. The hypotheses which have been developed in the context of the neuropsychodynamic model of depression may be used for more specific psychotherapeutic interventions, aiming at specific mechanisms of compensation and defence, which are related to the increased resting state activity and the disturbed resting state-stimulus-interaction

Early Linguistic Markers of Trauma-Specific Processing Predict Post-trauma Adjustment

Identifying early predictors for psychiatric disorders, such as post-traumatic stress disorder (PTSD), is crucial for effective treatment and prevention efforts. Obtaining such predictors is challenging and methodologically limited, for example by individuals' distress, arousal, and reduced introspective ability. We investigated the predictive power of language-based, implicit markers of psychological processes (N = 163) derived from computerized text-analysis of trauma and control narratives provided within 18 days post-trauma. Trauma narratives with fewer cognitive processing words (indicating less cognitive elaboration), more death-related words (indicating perceived threat to life), and more first-person singular pronouns (indicating self-immersed processing) predicted greater PTSD symptoms at 6 months. These effects were specific to trauma narratives and held after controlling for early PTSD symptom severity and verbal intelligence. When self-report questionnaires of related processes were considered together with the trauma narrative linguistic predictors, use of more first-person singular pronouns remained a significant predictor alongside self-reported mental defeat. Language-based processing markers may complement questionnaire measures in early forecasting of post-trauma adjustment

Too Imperfect to Fall Asleep: Perfectionism, Pre-sleep Counterfactual Processing, and Insomnia

Previous research suggests that certain dimensions of perfectionism are associated with insomnia. However, the exact processes whereby perfectionism may influence sleep have as yet remained unexplored. The present study tested the hypothesis that perfectionistic individuals are particularly prone to engage in counterfactual thinking and to experience counterfactual emotions (regret, shame, and guilt) at bedtime, which have been shown to impair sleep. One hundred eighty university students completed questionnaires on perfectionism, counterfactual processing, and insomnia severity. Analyses revealed that three dimensions of perfectionism were significantly related to insomnia severity: Concern over mistakes and doubts about action showed positive correlations, whereas organization showed a negative correlation. Moreover, the frequency of counterfactual thoughts and emotions at bedtime largely mediated the effects of these dimensions of perfectionism on insomnia severity. These findings highlight how personality-related patterns of behavior may translate into affective arousal at bedtime, thereby increasing the risk of insomnia

The fabric of meaning and subjective effects in LSD-induced states depend on serotonin 2A receptor activation

A core aspect of the human self is the attribution of personal relevance to everyday stimuli enabling us to experience our environment as meaningful [1]. However, abnormalities in the attribution of personal relevance to sensory experiences are also critical features of many psychiatric disorders [2, 3]. Despite their clinical relevance, the neurochemical and anatomical substrates enabling meaningful experiences are largely unknown. Therefore, we investigated the neuropharmacology of personal relevance processing in humans by combining fMRI and the administration of the mixed serotonin (5-HT) and dopamine receptor (R) agonist lysergic acid diethylamide (LSD), well known to alter the subjective meaning of percepts, with and without pretreatment with the 5-HT2AR antagonist ketanserin. General subjective LSD effects were fully blocked by ketanserin. In addition, ketanserin inhibited the LSD-induced attribution of personal relevance to previously meaningless stimuli and modulated the processing of meaningful stimuli in cortical midline structures. These findings point to the crucial role of the 5-HT2AR subtype and cortical midline regions in the generation and attribution of personal relevance. Our results thus increase our mechanistic understanding of personal relevance processing and reveal potential targets for the treatment of psychiatric illnesses characterized by alterations in personal relevance attribution

Modern Clinical Research on LSD

All modern clinical studies using the classic hallucinogen lysergic acid diethylamide (LSD) in healthy subjects or patients in the last 25 years are reviewed herein. There were five recent studies in healthy participants and one in patients. In a controlled setting, LSD acutely induced bliss, audiovisual synesthesia, altered meaning of perceptions, derealization, depersonalization, and mystical experiences. These subjective effects of LSD were mediated by the 5-HT2A receptor. LSD increased feelings of closeness to others, openness, trust, and suggestibility. LSD impaired the recognition of sad and fearful faces, reduced left amygdala reactivity to fearful faces, and enhanced emotional empathy. LSD increased the emotional response to music and the meaning of music. LSD acutely produced deficits in sensorimotor gating, similar to observations in schizophrenia. LSD had weak autonomic stimulant effects and elevated plasma cortisol, prolactin, and oxytocin levels. Resting-state functional magnetic resonance studies showed that LSD acutely reduced the integrity of functional brain networks and increased connectivity between networks that normally are more dissociated. LSD increased functional thalamocortical connectivity and functional connectivity of the primary visual cortex with other brain areas. The latter effect was correlated with subjective hallucinations. LSD acutely induced global increases in brain entropy that were associated with greater trait openness 14 days later. In patients with anxiety associated with life-threatening disease, anxiety was reduced for 2 months after two doses of LSD. In medical settings, no complications of LSD administration were observed. These data should contribute to further investigations of the therapeutic potential of LSD in psychiatry

Neuropsychodynamic Approach to Depression: Integrating Resting State Dysfunctions of the Brain and Disturbed Self-Related Processes

A mechanism-based approach was developed focusing on the psychodynamic, psychological and neuronal mechanisms in healthy and depressed persons. In this integrative concept of depression, the self is a core dimension in depression. It is attributed to negative emotions (e.g., failure, guilt). The in depression is connected with a . The development of neuropsychodynamic hypotheses of the altered self-reference is based on the investigation of the emotional-cognitive interaction in depressed patients. It may be hypothesized that the increased negative self-attributions-as typical characteristics of an increased self-focus in depression-may result from altered neuronal activity in subcortical-cortical midline structures in the brain, especially from hyperactivity in the cortical-subcortical midline regions and hypoactivity in the lateral regions. The increased resting state activity in depression is especially associated with an increased resting state activity in the default mode network (DMN) and a dysbalance between DMN and executive network (EN) activity. Possible therapeutic consequences of the neuropsychodynamic approach to depression involve the necessary emotional attunement in psychotherapy of depressed patients and the adequate timing of therapeutic interventions. The hypotheses which have been developed in the context of the neuropsychodynamic model of depression may be used for more specific psychotherapeutic interventions, aiming at specific mechanisms of compensation and defence, which are related to the increased resting state activity and the disturbed resting state-stimulus-interaction

Experimental Psychosis Research and Schizophrenia-Similarities and Dissimilarities in Psychopathology

The aim of experimental psychopathology is to delineate overlapping functional disorders of psychoneurobiologically-defined systems where a set of common symptoms may correspond to a variety of nosological entities. According to the vulnerability model of psychosis, experimental research needs to go beyond categories such as "schizophrenia". Prospective studies of the effects of psychoactive substances in normal control subjects offer several methodological advantages over routine clinical reviews of schizophrenic patients, especially in terms of standardization. Carefully designed studies utilizing a model psychosis paradigm are a step toward symptom-oriented research. Combining psychological and neurobiological techniques, the experimental psychopathological approach can provide us with a valuable tool for psychiatric research

LSD increases primary process thinking via serotonin 2A receptor activation

Rationale: Stimulation of serotonin 2A (5-HT2A) receptors by lysergic acid diethylamide (LSD) and related compounds such as psilocybin has previously been shown to increase primary process thinking - an ontologically and evolutionary early, implicit, associative, and automatic mode of thinking which is typically occurring during altered states of consciousness such as dreaming. However, it is still largely unknown whether LSD induces primary process thinking under placebo-controlled, standardized experimental conditions and whether these effects are related to subjective experience and 5-HT2A receptor activation. Therefore, this study aimed to test the hypotheses that LSD increases primary process thinking and that primary process thinking depends on 5-HT2A receptor activation and is related to subjective drug effects. Methods: Twenty-five healthy subjects performed an audio-recorded mental imagery task 7 h after drug administration during three drug conditions: placebo, LSD (100 mcg orally) and LSD together with the 5-HT2A receptor antagonist ketanserin (40 mg orally). The main outcome variable in this study was primary index (PI), a formal measure of primary process thinking in the imagery reports. State of consciousness was evaluated using the Altered State of Consciousness (5D-ASC) rating scale. Results: LSD, compared with placebo, significantly increased primary index (p < 0.001, Bonferroni-corrected). The LSD-induced increase in primary index was positively correlated with LSD-induced disembodiment (p < 0.05, Bonferroni-corrected), and blissful state (p < 0.05, Bonferroni-corrected) on the 5D-ASC. Both LSD-induced increases in primary index and changes in state of consciousness were fully blocked by ketanserin. Conclusion: LSD induces primary process thinking via activation of 5-HT2A receptors and in relation to disembodiment and blissful state. Primary process thinking appears to crucially organize inner experiences during both dreams and psychedelic states of consciousness

Crowding deficits in the visual periphery of schizophrenia patients

Accumulating evidence suggests that basic visual information processing is impaired in schizophrenia. However, deficits in peripheral vision remain largely unexplored. Here we hypothesized that sensory processing of information in the visual periphery would be impaired in schizophrenia patients and, as a result, crowding - the breakdown in target recognition that occurs in cluttered visual environments - would be stronger. Therefore, we assessed visual crowding in the peripheral vision of schizophrenia patients and healthy controls. Subjects were asked to identify a target letter that was surrounded by distracter letters of similar appearance. Targets and distracters were displayed at 8° and 10° of visual angle from the fixation point (eccentricity), and target-distracter spacing was 2°, 3°, 4°, 5°, 6°, 7° or 8° of visual angle. Eccentricity and target-distracter spacing were randomly varied. Accuracy was defined as the proportion of correctly identified targets. Critical spacing was defined as the spacing at which target identification accuracy began to deteriorate, and was assessed at viewing eccentricities of 8° and 10°. Schizophrenia patients were less accurate and showed a larger critical spacing than healthy individuals. These results indicate that crowding is stronger and sensory processing of information in the visual periphery is impaired in schizophrenia. This is in line with previous reports of preferential magnocellular dysfunction in schizophrenia. Thus, deficits in peripheral vision may account for perceptual alterations and contribute to cognitive dysfunction in schizophrenia