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Effects of psilocybin on time perception and temporal control of behaviour in humans
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.
... Finally, 20 articles involving 2,959 participants met the inclusion criteria and were included in this systematic review. 12,[24][25][26][27][28][29][30][31][32][33][34][35][36][37][38][39][40][41][42][43] Study selection details are indicated in Figure 1 and the quality assessment results are outlined in Fig. S1. We also included eight registered clinical trials; detailed characteristics can be found in Table S1 and Figs. ...
... 37 Two studies assessed working memory with the spatial span test. 31,34 Carter et al. 34 investigated the impact of 215 μg/kg psilocybin on spatial working memory (SWM) in eight healthy volunteers. They discovered no significant influence on the correct recall of boxes in sequence ('span length') for both drug and time. ...
... Furthermore, the total number of errors in sequence order or location ('total errors') remained unaffected by drug administration or time of testing, further affirming the lack of psilocybin's impact on SWM performance. 34 Wittmann et al. 31 examined the impact of high (250 μg/kg) and medium (115 μg/kg) doses of psilocybin on the SWM of 12 healthy individuals using the same test. The test was accomplished at 0, 100 and 360 min after drug/placebo intake. ...
Psilocybin is a classic psychedelic with demonstrated preliminary clinical efficacy in a range of psychiatric disorders. Evaluating the impact of psilocybin on cognitive function is essential to unravel its potential benefits and risks. In this systematic review, we assessed psilocybin's effect on cognitive function through a comprehensive search of electronic databases from inception to January 2024, identifying 20 articles involving 2,959 participants. While 85% of studies were conducted in healthy volunteers, most of these studies (85%) used macrodoses, ranging from 45 μg/kg to 30 mg/70 kg. Various cognitive aspects were evaluated and yielded mixed results. Global cognitive function, and processing speed remained mostly unchanged in healthy individuals; However, a limited number of studies reported improvements in certain areas such as sustained attention, working memory, and executive function especially in patients with treatment-resistant depression (TRD). Emotional processing was positively modified, particularly in TRD patients. Psilocybin was observed to enhance emotional empathy without significantly altering cognitive empathy and social cognition. Cognitive flexibility and creative cognition were noted to initially decline but could potentially improve over time. Additionally, with respect to learning and memory skills, psilocybin showed promise in improving specific memory types such as semantic associations and associative learning, while its effects on episodic and verbal memory have been less pronounced compared to other cognitive enhancers. The observed mixed findings underscore the complexity of psilocybin's cognitive influence. Further research is essential to provide a clearer understanding of psilocybin's impact on cognitive domains and to guide the development of safe and effective interventions.
... Supplementary Table S2 provides an overview of study design, participants, and tests administered. Cognitive tests were conducted between 10 69 and 360 70,71 min after drug administration, with four studies [70][71][72][73] involving repeated assessments. LSD dosages ranged from 40 µg 74 to 2 µg/ kg 75 , psilocybin dosages ranged from 45 76 to ~ 430 µg/kg 71 , DMT dosages ranged from 0.17 69 to 0.32 mg/kg 77,78 , one study administered 100 ml of ayahuasca 79 , and ten studies involved multiple dosages 70 124,127,[132][133][134]137,[140][141][142]144,145,149 showed no effect in 13 tasks. ...
... Sixteen studies 73 ...
... Notably, under microdosing conditions which lack the perceptual alterations of psychedelics 184 , those effects on cognition disappear 156,159,160,163 . While this may suggest that the nature of the psychedelic alterations might be inherently distracting, this could also be the result of dose-dependent effects, as studies with multiple dosages of psilocybin showed dose-dependent effects on cognitive performance 71,73,73,76 . ...
Classic psychedelics and MDMA have a colorful history of recreational use, and both have recently been re-evaluated as tools for the treatment of psychiatric disorders. Several studies have been carried out to assess potential long-term effects of a regular use on cognition, delivering distinct results for psychedelics and MDMA. However, to date knowledge is scarce on cognitive performance during acute effects of those substances. In this systematic review and meta-analysis, we investigate how cognitive functioning is affected by psychedelics and MDMA during the acute drug effects and the sub-acute (“afterglow”) window. Our quantitative analyses suggest that acute cognitive performance is differentially affected by psychedelics when compared to MDMA: psychedelics impair attention and executive function, whereas MDMA primarily affects memory, leaving executive functions and attention unaffected. Our qualitative analyses reveal that executive functioning and creativity may be increased during a window of at least 24 h after the acute effects of psychedelics have subsided, whereas no such results have been observed for MDMA. Our findings may contribute to inform recommendations on harm reduction for recreational settings and to help fostering differential approaches for the use of psychedelics and MDMA within a therapeutic framework.
... Regarding the number of participants with previous psilocybin experience, that is, those who ingested psilocybin at least once during their lifetime, five studies did not specify it Hasler et al., 2004;Mallaroni et al., 2023;Mason et al., 2021;Vollenweider et al., 2007). Contrarily, one investigation used a sample with only experienced individuals (Gabay et al., 2018); in another two, more than half of the sample had a psilocybin experience (Carter, Burr, et al., 2005;Nikolič et al., 2023); and in the remaining studies, half or less than half of the participants had an experience Kometer et al., 2012;Pokorny et al., 2017;Quednow et al., 2012;Rucker et al., 2022;Wittmann et al., 2007). ...
... Regarding the RCT, one was single-blind (Umbricht et al., 2003) and 15 were double-blind (see Table 1), with two of them having an independent control group receiving inactive placebo Rucker et al., 2022). Thirteen studies used a within-subjects arrangement with at least one placebo session, mostly inactive Carter et al., 2007;Carter, Burr, et al., 2005;Hasler et al., 2004;Kometer et al., 2012;Mallaroni et al., 2023;Nikolič et al., 2023;Pokorny et al., 2017;Quednow et al., 2012;Spitzer et al., 1996;Vollenweider et al., 2007;Wittmann et al., 2007). Within the studies with clinically depressed subjects, one was open-label (Doss et al., 2021) and participants were randomly assigned to an immediate treatment and delayed treatment group (see Table 2). ...
... Nine studies administered psilocybin in one session (Gabay et al., 2018;Gouzoulis-Mayfrank et al., 2002;Mallaroni et al., 2023;Mason et al., 2021;Nikolič et al., 2023;Pokorny et al., 2017;Rucker et al., 2022;Spitzer et al., 1996;Umbricht et al., 2003) and four in multiple sessions, while maintaining the dosage Carter, Burr, et al., 2005;Kometer et al., 2012;Quednow et al., 2012). The remaining seven, including the two with individuals with depression, applied a dose escalation approach with weekly or monthly intervals between sessions Doss et al., 2021;Hasler et al., 2004;Stroud et al., 2018;Vollenweider et al., 2007;Wittmann et al., 2007). The total number of dosing sessions of any substance was never more than five (see Tables 1 and 2). ...
Introduction:
Psilocybin, a naturally occurring serotonergic agonist in some mushroom species, has shown promise as a novel, fast-acting pharmacotherapy seeking to overcome the limitations of conventional first-line antidepressants. Studying psilocybin effects on cognition and emotional processing may help to clarify the mechanisms underlying the therapeutic potential of psilocybin and may also support studies with people suffering from depression. Thus, this review aims to provide a comprehensive overview of the current literature regarding the effects of psilocybin on these two key areas in both healthy and depressed populations.
Method:
A systematic search was performed on 29 January 2024, in the PubMed, EBSCOhost, Web of Science and SCOPUS databases. After duplicates removal, study selection was conducted considering pre-specified criteria. Data extraction was then performed. The quality assessment of the studies was carried out using the Cochrane Collaboration tools for randomized (RoB 2.0) and non-randomized (ROBINS-I) controlled trials.
Results:
Twenty articles were included, with 18 targeting healthy adults and two adults with depression. Results point to impairments within attentional and inhibitory processes, and improvements in the domains of creativity and social cognition in healthy individuals. In the population with depression, only cognitive flexibility and emotional recognition were affected, both being enhanced. The comparison of outcomes from both populations proved limited.
Conclusions:
Psilocybin acutely alters several cognitive domains, with a localized rather than global focus, in a dose- and time-dependent manner. However, the significant methodological constraints call for further research, in the context of depression and with standardized protocols, with longitudinal studies also imperative.
... The efficacy of psychedelic therapy seems to rest, in part, on the character of psychedelic experiences themselves (Yaden & Griffiths, 2021), which often involve profound alterations to the experience of time Preller & Vollenweider, 2016;Wittmann, 2018;Wittmann et al., 2007). For instance, a variety of psychedelic experiences, known as "mystical experiences", are often described as involving timelessness or a sense of transcending time (Ko et al., 2022). ...
Current evidence suggests that the efficacy of psychedelic therapy depends, in part, on the character of psychedelic experiences themselves. One pronounced aspect of psychedelic experiences is alterations to the experience of time, including reports of timelessness or transcending time. However, how we should interpret such reports remains unclear, and this lack of clarity has philosophical and clinical implications. For instance, “true” timelessness may be considered antithetical to having any experience at all, and descriptions of experiences involving “timelessness” are known to be diverse and of varying clinical significance. In this article, we utilize a phenomenological approach to the study of temporality to highlight ambiguities in current constructs used to assess psychedelic experiences. In doing so, we advance some preliminary phenomenological accounts of psychedelic therapy’s mechanisms of action, such as psychedelic temporality acting as a kind of counterpoint for depressive temporality. We conclude by outlining how a dedicated phenomenological research program can provide a nuanced map of psychedelic temporality, guiding future research in a manner that addresses both philosophical and clinical ambiguities.
... The first 3-4 hours after ingestion are typically referred to as the 'peak'in which the user experiences more vivid visuals and distortions in reality. The effects can seem to last much longer for the user because of psilocybin's ability to alter time perception 21 . ...
Cancer patients are more vulnerable to developing psychiatric disorders like anxiety and depression. These conditions give an additional burden leading to poor quality of life. The available antidepressant and antianxiety drugs are not very useful in improving quality of life by reducing anxiety and depressive episodes. Therefore, there is a need for good drugs to alleviate the psychiatric problems among cancer patients. The recent reviews deal with the pharmacodynamics, pharmacokinetics and efficacy of psilocybin in the treatment of patients suffering from anxiety and depression.
... We present below studies based on our embodied notion of self and time investigating altered states of consciousness (ASC) during meditative practice. Other induction methods, such as hypnosis (Cardeña and Terhune 2019), when immersed in a homogenous sensory environment (Glicksohn et al. 2017), in sensory deprivation of Floatation-REST (Reduced Environmental Stimulation Therapy; Hruby et al. 2024), and using psychedelics (Shanon 2001;Wittmann et al. 2007) have all demonstrated that the sense of time and self are often downregulated in ASC. ...
In accordance with Bud (A.D.) Craig’s theories, we maintain that ascending physiological signals in their temporal dynamics are a necessary prerequisite for human time judgments. Functional neuroimaging and psychophysiological evidence have increasingly demonstrated that the subjective judgment of time is based on the physical and emotional self. The psychological literature reveals how emotions and related body feelings shape subjective time. Empirical studies of altered states of consciousness, namely meditative states, are also of prime interest as the perception of the physical state is strongly modulated and thereby affects the subjective experience of time. Our conclusion is that the sense of time is strongly embodied.
... The revitalization of psychedelic science during the second wave (2000-present) has produced numerous studies that have purposefully addressed the concerns that plagued the first wave of psychedelic research. Initial research focused on the pharmacological and perceptual changes induced by psychedelics (Carter et al., 2004;Wittmann et al., 2007) as well as clinical safety, rather than mental health treatment. Clinical researchers established guidelines to address the safe and ethical administration of psychedelics in human participants (Johnson et al., 2008) and many studies utilized an empirical, double-blind, placebo-controlled approach. ...
Although obsessive-compulsive disorder (OCD) is associated with clinically significant distress, many OCD patients do not seek treatment. Studies show that Black Americans with OCD are even less likely to obtain treatment due to differences in access. This study explored demographic and symptom outcomes associated with mental health service use for obsessions and compulsions among a nationally representative sample of African American adults (n = 3,570). The analytic sample for this analysis is African Americans who endorsed either obsessions (n = 435) or compulsions (n = 543). Few respondents sought care from their doctor for obsessions (14.25%, n = 62) and even fewer sought care for compulsions (7.55%, n = 36). Respondents were significantly more likely to seek care for obsessions if they had poorer self-rated mental health and perceived impairment due to obsessions—however, they were significantly less likely to seek care for obsessions if they had a high school education or less. Additionally, respondents were more likely to seek care for compulsions if they had poorer self-rated mental health. Our findings suggest that demographic factors, such as level of education, can impact care-seeking behaviors and, therefore, treatment outcomes for African Americans with obsessive-compulsive symptoms. Knowledge of factors associated with OCD care-seeking behavior can help inform potential barriers to treatment and strategies to ensure equity in access to mental health care for this population. Clinical implications and future directions are discussed.
Psychedelics are known to induce profound perceptual distortions, yet the neural mechanisms underlying these effects, particularly within the auditory system, remain poorly understood. In this study, we investigated the effects of the psychedelic compound 2,5-Dimethoxy-4-iodoamphetamine (DOI), a serotonin 2A receptor agonist, on the activity of neurons in the auditory cortex of awake mice. We examined whether DOI administration alters sound-frequency tuning, variability in neural responses, and deviance detection (a neural process reflecting the balance between top-down and bottom-up processing). Our results show that while DOI does not alter the frequency selectivity of auditory cortical neurons in a consistent manner, it increases trial-by-trial variability in responses and consistently diminishes the neural distinction between expected (standard) and unexpected (oddball) stimuli. This reduction in deviance detection was primarily driven by a decrease in the response to oddball sounds, suggesting that DOI dampens the auditory cortex’s sensitivity to unexpected events. These findings provide insights into how psychedelics disrupt sensory processing and shed light on the neural mechanisms underlying the altered perception of auditory stimuli observed in the psychedelic state.
hypothesis on the use of psilocybin and midazolam in the treatment of pathologies in the psychiatric environment. Abstract Some of the hallucinogenic mushrooms underwent a compound called Psilocybin, which is converted into psilocin when it´s dephosphorylated. The action of psilocin is mainly performed on serotonin 5-HT 2A receptors, causing excitation and inhibition of these, resulting in a "neuronal reset", this being the main reason for the benefits. Studies on various pathologies that have been treated with psilocybin are reviewed and a hypothesis is presented for the use of psilocybin along with midazolam in patients presenting with psychiatric disorders such as psychosis.
Psychedelics produce lasting therapeutic responses in neuropsychiatric diseases suggesting they may disrupt entrenched associations and catalyze learning. Here, we examine psychedelic 5-HT2A/2C agonist, DOI, effects on dopamine signaling in the nucleus accumbens (NAc) core, a region extensively linked to reward learning, motivation, and drug-seeking. We measure phasic dopamine transients following acute DOI administration in rats during well learned Pavlovian tasks in which sequential cues predict rewards. We find that DOI (0.0-1.2 mg/kg, i.p.) increases dopamine signals, photometrically measured using GRABDA optical sensor, to rewards and proximal reward cues, but not to the distal cues that predict these events. We determine that the elevated dopamine produced by DOI to reward cues occurs independently of DOI-induced changes in reward value. The increased dopamine associated with predictable reward cues and rewards supports DOI-induced increases in prediction error signaling. These findings lay a foundation for developing psychedelic strategies aimed at engaging error-driven learning mechanisms to disrupt entrenched associations or produce new associations.
Differences in duration judgments made by younger and older adults were reviewed. Previous research is unclear about whether such differences exist and, if so, how they may be explained. The meta-analyses revealed substantial age-related differences. Older adults gave larger verbal estimates and made shorter productions of duration than did younger adults. There were no age-related differences in reproduction of duration or in psychophysical slope relating judged and target duration. Older adults’ duration estimates were more variable than were those of younger ones. Findings are discussed in terms of pacemaker rate and attentional resources. An explanation regarding divided attention between nontemporal and temporal information processing best explains the findings.
It is proposed that the cognitive system imposes patterns on the world according to a simplicity principle: Choose the pattern that provides the briefest representation of the available information. The simplicity principle is normatively justified-patterns that support simple representations provide good explanations and predictions on the basis of which the agent can make decisions and actions. Moreover, the simplicity principle appears to be consistent with empirical data from many psychological domains, including perception, similarity, learning, memory, and reasoning. Thus, the simplicity principle promises to serve as the starting point for the rational analysis of a wide range of cognitive processes, in Anderson's (1990, 1991a) sense. The simplicity principle also provides a framework for integrating a wide range of existing psychological proposals.
Abstract The concept of a temporal integration process in the timing mechanisms in the brain, postulated on the basis of experimental observations from various paradigms (for a review see P$oUppel, 1978), has been explored in a sensorimotor synchronization task. Subjects synchronized their finger taps to sequences of auditory stimuli with interstimulus-onset intervals (ISIs) between 300 and 4800 msec in different trials. Each tonal sequence consisted of 110 stimuli; the tones had a frequency of 500 Hz and a duration of 100 msec. As observed previously, response onsets preceded onsets of the stimuli by some tens of milliseconcls for ISIs in the range from about 600 to 1800 msec. For ISIs longer than or equal to 2400 msec, the ability to time the response sequence in such a way that the response 5 were placed right ahead of the stimuli started to break clown, i.e., the task was fulfilled by reactions to the stimuli rather than by advanced responses. This observation can he understood within the general framework of a temporal integration puce 55 that is supposed to have a maximal capacity (integration interval) of approximately 3 sec. Only if successive stimuli fall within one integration period, can motor programs be initiated properly by a prior stimulus and thus lead to an appropriate synchronization between the stimulus sequence and corresponding motor acts.
Basic perceptual or motor skills involving the central nervous system as well as the subjective present require the orderly temporal organization of internal and external information. Current research in schizophrenia increasingly centers on the accompanying neurocognitive deficits with frequent reports of altered temporal processes. There has been, however, less explicit research on the basic phenomenon of temporal order. Using concrete operationalized neuropsychological procedures the present study addressed the question whether chronic schizophrenic patients (28 medicated as well as 7 unmedicated) differ in their ability to correctly judge the temporal order of visual or acoustic stimuli when compared with a healthy control group (n = 26). Within this context we found a significant impairment in basal temporal perception among patients. Moderating variables such as medication, attention deficits or the effects of motivation as an essential explanatory factor for this finding could be excluded by statistical analysis. Instead, our findings point to a fundamental disturbance in the temporal coordination of neuronal network functions in association with schizophrenic psychoses. Within this context neurophysiological, neurochemical, neuroanatomical and neuropsychological overlapping of schizophrenia and temporal perception are being presented along with a discussion of the hypothesis that disturbances in neuronal synchronization and in timing processes at different levels are of essence and a possible underlying substrate in the schizophrenic spectrum.
Subjects tracked intervals in a synchronization paradigm at interval durations of 180, 210, 240, 270, 300, 400, 500, 600, 700, 800, 900, and 1,000 ms. The variability of intertap intervals (ITIs) shows a sudden increase near 300 ms. This increase is interpreted as indicating the transition from automatic to controlled movement. It is suggested that the sudden change in the variability of ITIs does not reflect the operation of different timing mechanisms at short and long intervals, but differences in the way in which attentional processes come to bear on movement initiation for different interval durations. In contrast to previous findings reported in the literature, a U-shaped function between interval duration and variability in the 300-to-1,000-ms range was not observed.
Basic perceptual skills involving the central nervous system require the orderly temporal integration of internal as well as external information. Current research in schizophrenia increasingly centers on the accompanying neurocognitive deficits. In association with schizophrenic psychoses, there have been frequent reports of altered temporal processes, but explicit research on the perception of temporal relationship is still rare. Using concrete operationalized neuropsychological procedures, the present pilot study addressed the question whether schizophrenic patients (n=27) differ from a healthy control group (n=18) concerning their ability to judge correctly the temporal order of visual stimuli. We found a significant impairment in basal temporal perception among patients. Moderating variables such as antipsychotic medication, attention deficits, or motivation effects did not appear to be essential explanatory factors for this finding. Thus, our findings indicate a fundamental disturbance in the temporal coordination of neuronal network functions in association with schizophrenic psychoses and are in line with neurophysiological, neuroanatomical, and neuropsychological overlappings of schizophrenia and temporal perception.
Several cognitive models of time estimation have been proposed. We discuss the different role of attention in prospective and retrospective time estimation processes, the empirical evidences and methodological problems in the study of attention, and the relationship between attention, temporal uncertainly and temporal relevance-toward a general theoretical framework for understanding time estimation processes.