Psychedelic Cognition—The Unreached Frontier of Psychedelic Science

This paper (2022) reviews the current state of research regarding the effect psychedelics have on different aspects of cognition. The gaps regarding the acute effects psychedelics have on cognition are discussed as well as the findings related to how psychedelics impact memory, attention, reasoning, social cognition, and creativity.

Abstract

“Psychedelic compounds hold the promise of changing the face of neuroscience and psychiatry as we know it. There have been numerous proposals to use them to treat a range of neuropsychiatric conditions such as depression, anxiety, addiction and PTSD; and trials to date have delivered positive results in favour of the novel therapeutics. Further to the medical use, the wider healthy population is gaining interest in these compounds. We see a surge in personal use of psychedelic drugs for reasons not limited to spiritual enhancement, improved productivity, aiding the management of non-pathological anxiety and depression, and recreational interests. Notably, microdosing—the practice of taking subacute doses of psychedelic compounds—is on the rise. Our knowledge about the effects of psychedelic compounds, however, especially in naturalistic settings, is still fairly limited. In particular, one of the largest gaps concerns the acute effects on cognition caused by psychedelics. Studies carried out to date are riddled with limitations such as having disparate paradigms, small sample sizes, and insufficient breadth of testing on both unhealthy and healthy volunteers. Moreover, the studies are majoritarily limited to laboratory settings and do not assess the effects at multiple dosages within the same paradigm nor at various points throughout the psychedelic experience. This review aims to summarize the studies to date in relation to how psychedelics acutely affect different domains of cognition. In the pursuit of illuminating the current limitations and offering long-term, forward-thinking solutions, this review compares and contrasts findings related to how psychedelics impact memory, attention, reasoning, social cognition, and creativity.”

Authors: Maria Bălăet̨

Summary

INTRODUCTION

Psychedelic drugs are making a strong come-back in the research, clinical, and public spheres. They are being promoted as cognitive enhancers, spiritual catalysts, and general wellbeing aids, and are being used as microdosing by professionals working in office jobs and in the creative industries.

Psychedelic substances were placed under Schedule I in 1970, and today there is a shift in the discourse, with decriminalization and/or legalization on the horizon in some countries. This has led to increased recreational use of substances such as LSD and DMT. Psychedelics are notorious for inducing “ego dissolution” and transporting people to seemingly different realms, but small laboratory-based studies are driving changes in law. Large empirical studies are needed to inform harm reduction measures and subsequently, policies.

The research on psychedelics’ effect on cognition has been neglected, and most efforts have focused on mental health outcomes and brain activity. There is a large gap in knowledge about how psychedelics affect cognition acutely. This review aims to summarize existing research in the psychedelics field assessing the acute effects of psychedelics on human cognition, identify incongruent results, point out the limitations of studies to date, and provide guidance toward improving the current body of knowledge. The literature covered has been selected through a manual search of the PubMed1 and Google Scholar2 databases for the terms “cognition psychedelics”, “memory psychedelics”, “attention psychedelics”, “reasoning psychedelics”, “creativity psychedelics” and “social cognition psychedelics”.

UNDERSTANDING COGNITION

Cognition is a multifactorial process comprising several discrete cognitive domains, including memory, attention, reasoning, language, and social cognition. Certain higher order cognitive processes require the integration of multiple domains, such as planning, which engages working memory as well as decision-making abilities.

Psychedelic drugs activate the serotonergic 2A receptors, which are essential for optimal cognition. The effects of psychedelics have been studied in vivo in mice, rats, rabbits, and monkeys.

Previous studies looking at how psychedelic drugs impact cognition have produced mixed results. The effects of psychedelics on cognition have been studied using a variety of paradigms, but there is no body of work attempting to integrate all knowledge of the effects on the multiple domains of cognition.

The present review aims to provide a synthesis of how psychedelic drugs affect each cognitive domain in turn, identify where conclusions are in contradiction, and point toward how these could be resolved in future studies.

MEMORY

Memory is an essential cognitive process, and alterations in the 5-HT2A receptors could be underlying cognitive dysfunction in depression or schizophrenia. However, Carter et al. (2005) found no effects on spatial working memory upon psilocybin administration, but other studies have shown effects on memory.

Psilocybin has been found to have no effect on working memory in eight healthy volunteers, but Wittmann et al. (2007) found significant impairments in spatial working memory at medium and high doses of psilocybin. Psilocybin increases response time on Letter N-back but has no impact on accuracy. LSD microdoses have no effect on working memory in 20 healthy volunteers or 48 healthy volunteers.

Studies have shown that working memory is impaired at high doses of psychedelics, but unaffected at medium and lower doses. Amongst many unanswered questions, one is whether psychedelics affect memory in naturalistic settings, and whether they can be used to treat diseases. Further studies are needed to address these questions, as well as to determine the people who would be at increased risk from consuming them.

ATTENTION

Attention is the ability to focus on a particular stimulus without interference from other stimuli. Psilocybin administration can affect attention but not 5-HT2A receptors.

The findings around how psychedelics impact attention are mixed, with the consensus being that DMT impairs attention, specifically inhibition of return, which is an otherwise protective mechanism against distracting stimuli.

Psilocybin and DMT impaired sustained attention in several studies, while LSD enhanced attention in the majority of the 24 healthy volunteers on the Psychomotor Vigilance Task. However, Family et al. (2020) found no effect of LSD microdosing on attention in all 48 volunteers using the Rapid Visual Information Processing Task from CANTAB.

Due to the strong implications of using psychedelics to improve attention, more research is needed to understand how psychedelics impact attention. This will help to elucidate where the tipping point lies, and whether psychedelics can be beneficial for people suffering from conditions such as dementia, TBI, ADHD etc.

REASONING

Reasoning involves several cognitive domains, including memory, attention, cognitive control, and executive function. Psychedelics increase the activation of regions involved in complex reasoning.

The literature on how reasoning is affected by psychedelics is scarce. Studies using the Switching Stroop task suggest psilocybin impairs executive function, while studies using the Tower of London planning task suggest accuracy is maintained under the influence.

Microdosing psilocybin and LSD does not appear to affect reasoning, however, Bershad et al. (2019) and Hutten et al. (2020) found that there was an impairment seen on the performance of this task under the effects of LSD at the low dose of 20 g.

The current body of literature on psychedelics is very limited and needs to be replicated with larger samples and extended experiments that include all psychedelics at different doses.

EMOTIONAL/SOCIAL COGNITION

Classical hallucinogens such as psilocybin and LSD have been shown to influence social cognition by enhancing empathy and sociality, and by reducing fear recognition on fMRI and EEG.

The majority of studies looking at the effects of psychedelics on social cognition have investigated psilocybin. Psilocybin increases emotional empathy but not cognitive empathy, and ayahuasca increases emotional empathy but not cognitive empathy. Psilocybin reduced social rejection and social exclusion, and participants felt less excluded from the social circle under the influence, but received the same amount of ball throws as placebo.

Studies looking at LSD illustrated that it increases emotional empathy, specifically for positive facial cues, in a dose-dependent fashion. However, when testing LSD microdosing, no effects were present on affective rating using the Emotional Images Task.

Psychedelic drugs can improve social cognition, make people more empathic, and decrease feelings of social exclusion. However, they can also make people more susceptible to deceit and accepting unfair deals.

CREATIVITY, SUGGESTIBILITY AND LANGUAGE

Creativity is the ability to generate ideas, solutions, or products that are both novel and appropriate. Recent imaging studies have shown that networks associated with creative thinking are modulated during the psychedelic experience, but no study so far has linked psychedelic effects mediated by the 5-HT2A receptor to enhanced creativity.

LSD increases suggestibility on the Creative Imagination Scale and adaptation to opinions expressed by a control group, but only if those opinions are not too different from participants’ own opinions.

Microdosing psychedelics can enhance creativity in healthy adults. This is shown by increased divergent thinking, fluency, flexibility, and originality scores, without affecting analytical thinking. Researchers have found that psilocybin impairs divergent thinking, but increases convergent thinking once the dose wears off. Additionally, microdosing LSD has been shown to have no effect on convergent thinking measured with the Remote Associations Task in 20 healthy volunteers.

Language processing is an essential cognitive function concerning the detection and comprehension of human speech. Studies have shown that machine learning classifiers can distinguish between normal sober speech and speech under the influence of psychedelics.

Early studies showed that LSD use leads to disorganized speech characterized by increased verbosity and reduced lexicon, similar to what is observed in schizophrenia. Furthermore, the effects of LSD on language processing and creativity may persist even after the dose wears off.

The problem of human creativity and psychedelics is multifactorial, since creativity remains elusive to study and psychedelics may make people highly suggestible. Furthermore, spontaneous insight and creative thought under the influence of psychedelics are difficult to replicate under laboratory settings.

LIMITATIONS

Despite tremendous progress in reigniting the flame of psychedelics research, it is difficult to integrate the findings in order to generate strong insights about the effects these drugs have on cognition. This problem is of great importance because psychedelics are increasingly used for both research and recreational purposes.

The difficulty in carrying out a study looking at cognition, as well as the length and demands that characterize classical cognitive assessment, could have deterred researchers from focusing on the acute effects psychedelics have on cognition.

Research on how psychedelics affect cognition acutely has been carried out using a variety of paradigms, which has led to inconsistent results. More recent research has used citizen science online cognitive testing technologies to test how cognition is impacted by psychedelics.

Current studies on psychedelics only assess effects at baseline and during the peak of the experience. This suggests that the effects on cognition and perception vary during a trip, and that a finer grain understanding of how psychedelics affect cognition is needed.

Limitations in previous studies have also been noted, such as the different dosages of psychedelics that have been assessed at. This makes it difficult to generalize and establish the tipping point at which a psychedelic dose could cause impairment.

Small sample sizes are the main culprits when considering limitations of the current studies on cognition. However, with the use of within subject study designs and more volunteers, the number of studies on cognition has increased and provides sufficient statistical power to detect psychedelic-induced changes in cognition. Since psychedelics are proposed as treatments for neurological and psychiatric disorders, further research is needed to understand their impact on cognition.

Although existing research provides grounds for optimism, there are still numerous gaps to be addressed in order to fully understand the impact and safety of these substances on individuals. Few studies report the effects of psychedelics in naturalistic settings, and extrapolating from findings within laboratory/therapeutic settings to predict outcomes of the psychedelic experience in naturalistic settings is not only scientifically incorrect but also dangerous.

FUTURE DIRECTIONS

The field of psychedelic research offers a plethora of opportunities for scientific inquiry, but it is important to address the limitations posed by existing studies before psychedelics are used for therapies.

For therapeutic purposes, more research needs to be done on non-classical drugs often used recreationally, and on how cognition is impacted at baseline levels in the same participants in a within-subject study design, rather than in comparison with completely different control samples. In some microdose studies, there were no effects on cognition, but participants reported headaches. Headaches have been reported in other serotonergic hallucinogens, notably psilocybin.