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Abstract

Hallucinogenic psilocybin is known to alter the subjective experience of time. However, there is no study that systematically investigated objective measures of time perception under psilocybin. Therefore, we studied dose-dependent effects of the serotonin (5-HT)2A/1A receptor agonist psilocybin (4-phosphoryloxy-N, N-dimethyltryptamine) on temporal processing, employing tasks of temporal reproduction, sensorimotor synchronization and tapping tempo. To control for cognitive and subjective changes, we assessed spatial working memory and conscious experience. Twelve healthy human volunteers were tested under placebo, medium (115 microg/kg), and high (250 microg/kg) dose conditions, in a double-blind experimental design. Psilocybin was found to significantly impair subjects' ability to (1) reproduce interval durations longer than 2.5 sec, (2) to synchronize to inter-beat intervals longer than 2 sec and (3) caused subjects to be slower in their preferred tapping rate. These objective effects on timing performance were accompanied by working-memory deficits and subjective changes in conscious state, namely increased reports of 'depersonalization' and 'derealization' phenomena including disturbances in subjective 'time sense.' Our study is the first to systematically assess the impact of psilocybin on timing performance on standardized measures of temporal processing. Results indicate that the serotonin system is selectively involved in duration processing of intervals longer than 2 to 3 seconds and in the voluntary control of the speed of movement. We speculate that psilocybin's selective disruption of longer intervals is likely to be a product of interactions with cognitive dimensions of temporal processing -presumably via 5-HT2A receptor stimulation.
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... Furthermore, psychedelics may disengage the claustral control of cortical areas and thereby impair attentional control (Doss et al., 2021). The acute effects of psychedelics in human tests of executive function include psilocybin-induced deficits in attention in the AX-CPT task and in working memory (Wittmann et al., 2007), as well as LSD-induced impairment of cognitive flexibility (Pokorny et al., 2019). Some rodent cognition tests have higher face validity to the human tests, compared ...
... Psychedelics alter the way humans perceive time (Wittmann et al., 2007;Yanakieva et al., 2019), suggesting that 5-HT2ARs are involved in cognitive domains of temporal processing. ...
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Psychedelic-assisted psychotherapy holds great promise in the treatment of mental health disorders. Research into 5-hydroxytryptamine 2A receptor (5-HT2AR) agonist psychedelic compounds has increased dramatically over the past two decades. In humans, these compounds produce drastic effects on consciousness, and their therapeutic potential relates to changes in the processing of emotional, social, and self-referential information. The use of animal behavior to study psychedelics is under debate, and this review provides a critical perspective on the translational value of animal behavior studies in psychedelic research. Acute activation of 5-HT2ARs produces head twitches and unique discriminative cues, disrupts sensorimotor gating, and stimulates motor activity while inhibiting exploration in rodents. The acute treatment with psychedelics shows discrepant results in conventional rodent tests of depression-like behaviors but generally induces anxiolytic-like effects and inhibits repetitive behavior in rodents. Psychedelics impair waiting impulsivity but show discrepant effects in other tests of cognitive function. Tests of social interaction also show conflicting results. Effects on measures of time perception depend on the experimental schedule. Lasting or delayed effects of psychedelics in rodent tests related to different behavioral domains appear to be rather sensitive to changes in experimental protocols. Studying the effects of psychedelics on animal behaviors of relevance to effects on psychiatric symptoms in humans, assessing lasting effects, publishing negative findings, and relating behaviors in rodents and humans to other more translatable readouts, such as neuroplastic changes, will improve the translational value of animal behavioral studies in psychedelic research. SIGNIFICANCE STATEMENT: Psychedelics like LSD and psilocybin have received immense interest as potential new treatments of psychiatric disorders. Psychedelics change high-order consciousness in humans, and there is debate about the use of animal behavior studies to investigate these compounds. This review provides an overview of the behavioral effects of 5-HT2AR agonist psychedelics in laboratory animals and discusses the translatability of the effects in animals to effects in humans. Possible ways to improve the utility of animal behavior in psychedelic research are discussed.
... An up-to-date meta-analysis review of 12 studies on mood disorders and psychedelics indicates that classic psychedelic-assisted therapy surpassed placebo with a large-effect size for various mental health disorders, including unipolar depression and anxiety (Galvao-Coelho et al., 2021). 7 of these studies were conducted on healthy individuals (Dolder et al., 2016;Griffiths et al., 2006;Hasler et al., 2004;Kometer et al., 2012;Kraehenmann, 2017;Schmid et al., 2015;Wittman et al., 2007) while the remaining (Gasser et al., 2014;Griffiths et al., 2016;Grob et al., 2011;Palhano-Fontes et al., 2019;Ross et al., 2016) was on people who are diagnosed with anxiety, depression, life-threatening illness, and treatment-resistant depression. The classic psychedelics included in the studies were LSD, ayahuasca, and psilocybin. ...
... The classic psychedelics included in the studies were LSD, ayahuasca, and psilocybin. The majority of them administered the drugs only once (Dolder et al., 2016;Griffiths et al., 2006Griffiths et al., , 2016Grob et al., 2011;Kometer et al., 2012;Kraehenmann, 2017;Palhano-Fontes et al., 2019;Ross et al., 2016;Schmid et al., 2015) and two of the studies (LSD and psilocybin) (Gasser et al., 2014;Wittman et al., 2007) administered twice and only one (Hasler et al., 2004) ...
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Public and scientific interest in the effect of psychedelic drugs on wellbeing has risen significantly. Preliminary data show that psychedelic drugs, specifically classic psychedelics (DMT, psilocybin, mescaline, and LSD), may have the potential to treat mood disorders and increase wellbeing through their acute subjective effects. The acute subjective effects and enduring effects of psychedelics on wellbeing seem to relate to positive psychological frameworks (e.g., resilience factors and PERMA) considerably. Moreover, optimizing acute subjective effects indicates the importance of set (individual’s internal (mental) factors) and setting (individual’s external factors) in psychedelics administration as moderating factors. A new subfield in positive psychology, positive humanities, has the potential to inform set and setting studies significantly. This literature review investigates the potential for positive psychology and positive humanities in enhancing psychedelic studies, specifically the research areas of acute subjective effects and set and setting. Due to the seeming alignment between the operation of psychedelic drugs and both positive psychology and the positive humanities, there appear to be opportunities for research and scholarship at the intersection of these fields.
... This dose range corresponds to a moderate psychoactive dose. 12,13 Notably, compared to other published clinical trials using psilocybin for the treatment of depression, the dose used in this study is lower and was only administered once (compared to two administrations in previous studies). 6,9 After medical screening, participants completed two preparatory visits (visits 2 and 3) 4-6 and 1 day before psilocybin/placebo administration. ...
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Background Psilocybin has been suggested as a novel, rapid-acting treatment for depression. Two consecutive doses have been shown to markedly decrease symptom severity in an open-label setting or when compared to a waiting list group. To date, to our knowledge, no other trial compared a single, moderate dose of psilocybin to a placebo condition. Methods In this double-blind, randomised clinical trial, 52 participants diagnosed with major depressive disorder and no unstable somatic conditions were allocated to receive either a single, moderate dose (0.215 mg/kg body weight) of psilocybin or placebo in conjunction with psychological support. MADRS and BDI scores were assessed to estimate depression severity, while changes from baseline to 14 days after the intervention were defined as primary endpoints. The trial took place between April 11th, 2019 and October 12th, 2021 at the psychiatric university hospital in Zürich, Switzerland and was registered with clinicaltrials.gov (NCT03715127). Findings The psilocybin condition showed an absolute decrease in symptom severity of −13.0 points compared to baseline and were significantly larger than those in the placebo condition (95% CI −15.0 to −1.3; Cohens' d = 0.97; P = 0.0011; MADRS) and −13.2 points (95% CI; −13.4 to −1.3; Cohens’ d = 0.67; P = 0.019; BDI) 14 days after the intervention. 14/26 (54%) participants met the MADRS remission criteria in the psilocybin condition. Interpretation These results suggest that a single, moderate dose of psilocybin significantly reduces depressive symptoms compared to a placebo condition for at least two weeks. No serious adverse events were recorded. Larger, multi-centric trials with longer follow-up periods are needed to inform further optimisation of this novel treatment paradigm. Funding The study was funded by the Swiss National Science Foundation, Crowdfunding, the Swiss Neuromatrix Foundation, and the Heffter Research Institute.
... People can go through phases that can be interpreted as psychodynamic, causing changes in self-image as well as having spiritual dimensions (Nour & Carhart-Harris, 2017). The perception of time is strikingly altered during this process, as a systematic study on time estimation and temporal control of motor activity was able to reveal (Wittmann et al., 2007). As assessed with validated questionnaires, the changes in time perception are accompanied by a feeling of unity of the ego and the world (subject and object of experience becoming one) as well as a feeling of loss of the bodily self (Studerus et al. 2010). ...
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Through my contribution in this symposium on subjective time, I wish to bring attention to the body. The physiological processes of the body are a necessary prerequisite for understanding how we, as humans, perceive time on the scale of seconds to minutes. My talk will proceed as follows: (1) First I will introduce the standard cognitive model of time perception and I will speak about some empirical research that tested that model. (2) Then I will try to explain why, when it comes to investigating the perception of time, so many research models exist. To put it humorously, I like to say that when we gather five researchers who work on the topic of time, such as here at the Bial symposium, we may very well end up listening to the presentation of six different models. (3) Then I will discuss my line of research on embodied time, i.e. arguing how the corporal processes govern our sense of time. I will present current and historical evidence that shows how body signals inform us about the passage of time. (4) Finally, I will talk about altered states of consciousness such as those induced through meditation, flotation-REST, and psychedelics. In such specific cases, the bodily self and subjective time are modulated in unison, in peak states of consciousness potentially culminating in timelessness and (body) selflessness. Research on altered states of consciousness can help us understand the nature of consciousness and, in particular, of time consciousness.
... The limited amount of existing data suggests that psilocybin administration is followed by a transient slowing motor function. These alterations should be taken into consideration in assessments that involve motor functions such as reaction time (see [80,81,131]). Evidently, this understudied domain requires more studies characterizing the role of psilocybin in the function of the sensorimotor system. ...
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