Analysis of recreational psychedelic substance use experiences classified by substance

Rationale and objectives Differences among psychedelic substances regarding their subjective experiences are clinically and scientifically interesting. Quantitative linguistic analysis is a powerful tool to examine such differences. This study compared five psychedelic substance report groups and a non-psychedelic report group on quantitative linguistic markers of psychological states and processes derived from recreational use-based online experience reports. Methods Using 2947 publicly available online reports, we compared Ayahuasca and N,N-dimethyltryptamine (DMT, analyzed together), ketamine, lysergic acid diethylamide (LSD), 3,4-methylenedioxymethamphetamine (MDMA), psilocybin (mushroom), and antidepressant drug use experiences. We examined word frequencies related to various psychological states and processes and semantic proximity to psychedelic and mystical experience scales. Results Linguistic markers of psychological function indicated distinct effect profiles. For example, MDMA experience reports featured an emotionally intensifying profile accompanied by many cognitive process words and dynamic-personal language. In contrast, Ayahuasca and DMT experience reports involved relatively little emotional language, few cognitive process words, increased analytical thinking-associated language, and the most semantic similarity with psychedelic and mystical experience descriptions. LSD, psilocybin mushroom, and ketamine reports showed only small differences on the emotion-, analytical thinking-, psychedelic, and mystical experience-related language outcomes. Antidepressant reports featured more negative emotional and cognitive process-related words, fewer positive emotional and analytical thinking-related words, and were generally not similar to mystical and psychedelic language. Conclusion This article addresses an existing research gap regarding the comparison of different psychedelic drugs on linguistic profiles of psychological states, processes, and experiences. The large sample of experience reports involving multiple psychedelic drugs provides valuable information that would otherwise be difficult to obtain. The results could inform experimental research into psychedelic drug effects in healthy populations and clinical trials for psychedelic treatments of psychiatric problems.

Simulated visual hallucinations in virtual reality enhance cognitive flexibility

Historically, psychedelic drugs are known to modulate cognitive flexibility, a central aspect of cognition permitting adaptation to changing environmental demands. Despite proof suggesting phenomenological similarities between artificially-induced and actual psychedelic altered perception, experimental evidence is still lacking about whether the former is also able to modulate cognitive flexibility. To address this, we measure participants' cognitive flexibility through behavioral tasks after the exposure to virtual reality panoramic videos and their hallucinatory-like counterparts generated by the DeepDream algorithm. Results show that the estimated semantic network has a flexible structure when preceded by altered videos. Crucially, following the simulated psychedelic exposure, individuals also show an attenuated contribution of the automatic process and chaotic dynamics underlying the decision process. This suggests that simulated altered perceptual phenomenology enhances cognitive flexibility, presumably due to a reorganization in the cognitive dynamics that facilitates the exploration of uncommon decision strategies and inhibits automated choices.

Pharmacologic analysis of non-synonymous coding 5-HT2A SNPs reveals alterations psychedelic drug potencies and efficacies

Serotonin (5-Hydroxytryptamine; 5-HT) 2A receptor (5-HT2AR) signaling is essential for the actions of classical psychedelic drugs. In this study, we examined whether random sequence variations in the gene (single nucleotide polymorphisms, SNPs) encoding the 5-HT2AR affect the signaling of four commonly used psychedelic drugs. We examined the in vitro pharmacology of seven non-synonymous SNPs, which give rise to S12N, T25N, D48N, I197V, A230T, A447V, and H452Y variant 5-HT2A serotonin receptors. We found that these non-synonymous SNPs exert statistically significant, although modest, effects on the efficacy and potency of four therapeutically relevant hallucinogens. Significantly, the in vitro pharmacological effects of the SNPs drug actions at 5-HT2AR are drug specific.

Psychedelic Epistemology: William James and the “Noetic Quality” of Mystical Experience

William James proposed in 1902 that states of mystical experience, central to his idea of religious experience, can be identified based on their ineffability and their noetic quality. The epistemological category of the noetic quality, modified by W. T. Stace in 1960, plays a central but somewhat confounding role in today’s biomedical research involving psychedelic drugs such as psilocybin and LSD. Using scales based on James, it can be shown that psychedelics “reliably occasion” intense subjective states of experience or mystical states. It is debated whether these states are necessary for the wide range of possible mental health therapeutic benefits that appear to follow. This paper reviews what James said about the noetic quality and its relationship to religious experience, epistemology, and states of mystical experience. It explores how the noetic quality is measured in today’s research, addressing a growing list of concerns that psychedelic science can be epistemologically biased, that it is hostile to atheistic or physicalist views, that it injects religion unduly into science, or that it needs to find ways to eliminate the mystical element, if not the entire intense subjective experience altogether.

Psychedelics alter metaphysical beliefs

Can the use of psychedelic drugs induce lasting changes in metaphysical beliefs? While it is popularly believed that they can, this question has never been formally tested. Here we exploited a large sample derived from prospective online surveying to determine whether and how beliefs concerning the nature of reality, consciousness, and free-will, change after psychedelic use. Results revealed significant shifts away from ‘physicalist’ or ‘materialist’ views, and towards panpsychism and fatalism, post use. With the exception of fatalism, these changes endured for at least 6 months, and were positively correlated with the extent of past psychedelic-use and improved mental-health outcomes. Path modelling suggested that the belief-shifts were moderated by impressionability at baseline and mediated by perceived emotional synchrony with others during the psychedelic experience. The observed belief-shifts post-psychedelic-use were consolidated by data from an independent controlled clinical trial. Together, these findings imply that psychedelic-use may causally influence metaphysical beliefs—shifting them away from ‘hard materialism’. We discuss whether these apparent effects are contextually independent.

Self-Medication for Chronic Pain Using Classic Psychedelics: A Qualitative Investigation to Inform Future Research

Background: Chronic Pain is among the leading causes of disability worldwide with up to 60% of patients suffering from comorbid depression. Psychedelic-assisted therapy has recently been found effective in treating a host of mental health issues including depression and has historically been found to be useful in treating pain. Reports of self-medication for chronic pain using psychedelic drugs have been widely documented, with anecdotal evidence indicating widespread success in a range of pathologies.Aims: In preparation for an upcoming trial, to better understand how those with lived experience of chronic pain self-medicate with psychedelic drugs, and to establish, in detail, their therapeutic protocols and practices for success.Methods: As part of patient-involvement (PI) for an upcoming trial in this population, 11 individuals who reported self-medicating with psychedelic drugs took part in a 1-h semi-structured discussion, which was then transcribed and thematically analyzed.Results: Across a range of psychedelic substances and doses, reported pain scores improved substantially during and after psychedelic experiences. Two processes, Positive Reframing and Somatic Presence, were reliably identified as playing a role in improvements in mental wellbeing, relationship with pain, and physical (dis)comfort. Inclusion of other strategies such as mindfulness, breathwork, and movement were also widely reported. Due to the data's subjective nature, this paper is vulnerable to bias and makes no claims on causality or generalisability. Together, these results have been used to inform study design for a forthcoming trial.Conclusion: This pre-trial PI work gives us confidence to test psychedelic therapy for chronic pain in a forthcoming controlled trial. The results presented here will be instrumental in improving our ability to meet the needs of future study participants.

Natural Language as a Window into the Subjective Effects and Neurochemistry of Psychedelic Drugs

Psychedelics are drugs capable of eliciting profound alterations in the subjective experience of the users, sometimes with long-lasting consequences. Because of this, psychedelic research tends to focus on human subjects, given their capacity to construct detailed narratives about the contents of their consciousness experiences. In spite of its relevance, the interaction between serotonergic psychedelics and language production is comparatively understudied in the recent literature. This review is focused on two aspects of this interaction: how the acute effects of psychedelic drugs impact on speech organization regardless of its semantic content, and how to characterize the subjective effects of psychedelic drugs by analyzing the semantic content of written retrospective reports. We show that the computational characterization of language production is an emergent powerful tool to predict the therapeutic outcome of individual experiences, relate the effects elicited by psychedelics with those associated with other altered states of consciousness, draw comparisons between the psychedelic state and the symptomatology of certain psychiatric disorders, and investigate the neurochemical profile and mechanism of action of different psychedelic drugs. We conclude that researchers studying psychedelics can considerably expand the range of their potential scientific conclusions by analyzing brief interviews obtained before, during and after the acute effects. Finally, we list a series of questions and open problems that should be addressed to further consolidate this approach.

Why was early therapeutic research on psychedelic drugs abandoned?

Background Advocates of the therapeutic use of psychedelic drugs have argued that a promising approach to treatment was prematurely abandoned in the 1960s primarily because of Richard Nixon's ‘War on Drugs’. This paper (1) briefly describes research in the 1950s and 1960s in North America on the use of LSD to treat alcohol dependence, anxiety in terminal illness, and anxiety and depression; and (2) discusses the factors that led to its abandonment. Method An analysis of historical scholarship on psychedelic research in the 1950s, 1960s and 1970s in North America. Results Research on psychedelic drugs in psychiatry was abandoned for a number of reasons that acted in concert. A major factor was that clinical research on psychedelic drugs was caught up in the tighter regulation of pharmaceutical research after the Thalidomide disaster in 1963. Psychedelic drugs also presented special challenges for randomised, placebo-controlled clinical trials in the 1970s that were not as positive as the claims made by their advocates in the 1950s and 1960s. Clinical research became more difficult after 1965 when Sandoz ceased providing psychedelic drugs for research and their nonmedical use was prohibited in 1970. Conclusions The demise of psychedelic drug research was not solely due to the ‘War on Drugs’. It was hastened by tighter regulation of pharmaceutical research, the failure of controlled clinical trials to live up to the claims of psychedelic advocates, and the pharmaceutical industry's lack of interest in funding clinical trials.