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

Final devoicing and vowel lengthening in Friulian: A representational approach

This paper proposes an account of final devoicing in Friulian which relies on contrastive feature specification and feature geometry to explicate the connection between final devoicing and vowel lengthening. It is proposed that obstruents which are the outcome of final devoicing are phonologically distinct from true voiceless obstruents, being completely unspecified for laryngeal features. It is argued that the representational deficiency of such delaryngealized obstruents is directly connected to their inability to license a mora, which opens the way to vowel lengthening. More generally, the paper shows how feature geometrymay be adapted to capture the effects of contrastive specification and express markedness relations, and proposes a novel approach to hierarchies involving the sonority of coda segments

Return of the lysergamides. Part IV: Analytical and pharmacological characterization of lysergic acid morpholide (LSM-775)

Lysergic acid diethylamide (LSD) is perhaps one of the best-known psychoactive substances and many structural modifications of this prototypical lysergamide have been investigated. Several lysergamides were recently encountered as “research chemicals” or new psychoactive substances (NPS). Although lysergic acid morpholide (LSM-775) appeared on the NPS market in 2013, there is disagreement in the literature regarding the potency and psychoactive properties of LSM-775 in humans. The present investigation attempts to address the gap of information that exists regarding the analytical profile and pharmacological effects of LSM-775. A powdered sample of LSM-775 was characterized by X-ray crystallography, nuclear magnetic resonance stereoscopy (NMR), gas chromatography mass spectrometry (GC-MS), high mass accuracy electrospray MS/MS, HPLC diode array detection, HPLC quadrupole MS, and GC solid-state infrared analysis. Screening for receptor affinity and functional efficacy revealed that LSM-775 acts as a nonselective agonist at 5-HT1A and 5-HT2A receptors. Head twitch studies were conducted in C57BL/6J mice to determine whether LSM-775 activates 5-HT2A receptors and produces hallucinogen-like effects in vivo. LSM-775 did not induce the head twitch response unless 5-HT1A receptors were blocked by pretreatment with the antagonist WAY-100,635 (1 mg/kg, subcutaneous). These findings suggest that 5-HT1A activation by LSM-775 masks its ability to induce the head twitch response, which is potentially consistent with reports in the literature indicating that LSM-775 is only capable of producing weak LSD-like effects in humans

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

Psychedelics, meditation, and self-consciousness

In recent years, the scientific study of meditation and psychedelic drugs has seen remarkable developments. The increased focus on meditation in cognitive neuroscience has led to a cross-cultural classification of standard meditation styles validated by functional and structural neuroanatomical data. Meanwhile, the renaissance of psychedelic research has shed light on the neurophysiology of altered states of consciousness induced by classical psychedelics, such as psilocybin and LSD, whose effects are mainly mediated by agonism of serotonin receptors. Few attempts have been made at bridging these two domains of inquiry, despite intriguing evidence of overlap between the phenomenology and neurophysiology of meditation practice and psychedelic states. In particular, many contemplative traditions explicitly aim at dissolving the sense of self by eliciting altered states of consciousness through meditation, while classical psychedelics are known to produce significant disruptions of self-consciousness, a phenomenon known as drug-induced ego dissolution. In this article, we discuss available evidence regarding convergences and differences between phenomenological and neurophysiological data on meditation practice and psychedelic drug-induced states, with a particular emphasis on alterations of self-experience. While both meditation and psychedelics may disrupt self-consciousness and underlying neural processes, we emphasize that neither meditation nor psychedelic states can be conceived as simple, uniform categories. Moreover, we suggest that there are important phenomenological differences even between conscious states described as experiences of self-loss. As a result, we propose that self-consciousness may be best construed as a multidimensional construct, and that “self-loss,” far from being an unequivocal phenomenon, can take several forms. Indeed, various aspects of self-consciousness, including narrative aspects linked to autobiographical memory, self-related thoughts and mental time travel, and embodied aspects rooted in multisensory processes, may be differently affected by psychedelics and meditation practices. Finally, we consider long-term outcomes of experiences of self-loss induced by meditation and psychedelics on individual traits and prosocial behavior. We call for caution regarding the problematic conflation of temporary states of self-loss with “selflessness” as a behavioral or social trait, although there is preliminary evidence that correlations between short-term experiences of self-loss and long-term trait alterations may exist

The fortis-lenis distinction in Thurgovian, or Where is the syllable in Swiss German?

This paper argues that the Swiss German dialect of Thurgovian makes a fortis-lenis distinction based on length, fortis consonants being long or geminates and lenis consonants being short or singletons. With the illustration of relevant empirical data, it is shown that obstruents (stops and fricatives) display a number of systematic differences from consonants (nasals and lateral liquid) with regard to (a) the surface variants of lenes, (b) the syllabification of fortes, and (c) the anchoring mechanism of fortes to syllabic structure. It is argued that the primary source of these differences are the segmental representations, which are assumed to involve both the segmental tier (root node plus dependents) and the syllable tier (terminal positions of syllables). The phrasal syllabification domain of Thurgovian facilitates maintenance of fortis-lenis distinctions not only within words, but also at word edges. The combination of geminate segments plus the phrasal syllabification domain is responsible for non-crisp edges between syllable and segment boundaries as well as between syllable and word boundaries