Chapter 5 A Methodology for Microdosing Research: Cognitive behavioral tasks as investigative tools for tracking low-dose effects of psilocybin

Nicole Amada, PhD. Candidate, The Graduate Center, CUNY, May 25 2018

5.1 Abstract

Modern day research on psychedelics offers strong evidence for the use of these substances to further our understanding of the brain, as well as to treat mental illness and addiction. While research in clinical science and neuroscience is flourishing, behavioral data, as well as research tracking low-dose effects, known as ‘microdoses,’ is lacking. Cognitive behavioral tasks may provide a unique contribution to psychedelic research through their ability to target specific cognitive functions and measure objective changes. This is particularly relevant to understanding the effects of microdosing, which may not be robust enough to be reliably captured with neuroimaging and may not be conscious enough to be reliably captured with self-reports alone. This paper pairs specific psychedelic effects with validated experimental tasks to systematically track low-dose effects of psilocybin. Cognitive behavioral data may also offer practical information for how these substances can be used and for what purposes.

5.2 Introduction

Psychedelic substances are serotonergic hallucinogens (e.g. psilocybin, i.e. ‘magic mushrooms’ and LSD, i.e. lysergic acid diethylamide) that exert widespread effects in the brain through activation of the serotonin 5-HT2A receptor found primarily on the fifth layer of the cortex, (Carhart-Harris et al., 2015) but also found within the limbic system and brain-stem (Kent, 2012; Carter et al., 2005). The excitation of these neurons results in the recruitment of different cell-types, (Martin & Nichols, 2016) and greatly alters the nature of communication between brain regions. Together, these dose-dependent effects make psychedelic substances primary candidates for manipulating cognitive mechanisms. For the purpose of this paper, the research methods proposed here are for investigating the low-dose effects of psilocybin, as opposed to including all serotonergic hallucinogens.

The psychedelic state is characterized by altered cognition, sensory perception, and emotionality, resulting in changes in one’s sense of self and perceptions of reality, (Nour, Evans, & Carhart-Harris, 2016; Letheby & Gerrans, 2017; Wittman, et al., 2007) as well as personality characteristics, beliefs, and social attitudes (Carhart-Harris, Erritzoe, Kaelen, & Watts, 2018; Bouso et al., 2015; Lerner & Lyvers, 2006). While clinical and neuroscience research has tracked dose-dependent changes in subjective-reports (Griffiths et al., 2011) and neurophysiology (Nichols et al., 2003), there is far less work looking at dose-dependent changes in cognitive processes. The field of psychedelic research will require a multitude of various methodologies to fully capture the diverse effects of psilocybin. While the efforts of this paper are focused on employing these methods for low-dose research, cognitive psychologists who are interested in psychedelic research should also consider using these methods for higher-dose effects as well.

Cognitive behavioral tasks may be especially fitting for microdosing research in their ability to track the onset and nature of changes in specific cognitive processes. The objective of this paper is to pair specific psychedelic drug effects with cognitive-behavioral tasks to elucidate the effects of microdosing. Cognitive data for microdosing research may be able to track changes that cannot be measured by subjective-report or neuroimaging alone. These methods are also important for answering practical questions about the effects of microdosing psilocybin or LSD on everyday functioning to help guide judgment on when and how to use them.

Leading research on the effects of these substances from neuroscience and clinical fields are presented and briefly summarized, followed by an introduction and explication of microdosing. Psychedelic drug effects are then further explicated and appropriately paired with cognitive behavioral tasks. Lastly, comments for employing these methods in future research and concluding remarks are presented.

5.3 The Third Wave of Psychedelic Science

The present section introduces and summarizes modern clinical and neuroscience research on psychedelic drug effects. While the focus of this paper is not to review previous research, summarizations are kept minimal, with the sole intention of capturing the essence of these two branches. This is important to the efforts of this paper because it establishes the foundation for why these substances should be used in research, which is (unfortunately) still a controversial topic in psychology.

5.3.1 Clinical Science

The resurgence of psychedelic research was pioneered by clinical scientists and psychotherapists. In clinical research, psychedelics are paired with psychoanalysis to catalyze change in patients’ perception and perspective of themselves, life events, and their own suffering. Essentially, psychedelic substances generate an altered state whereby the agent is having a meaningfully-heightened experience. Here, he/she can process internal struggles from a unique emotional and cognitive state in order to transform them (with the help of a psychotherapist) into a self-narrative that is agentic and empathetic, rather than disempowering and critical.

“…psychedelics engage the self in a humanistic transformative process which is (somewhat) transparent and meaning-respecting, rather than performing sub-personal surgery on the constituent parts of a passive self.” Chris Letheby (2015) comparing the nature of healing with psychedelics to other pharmacological interventions.

Illnesses that have been ameliorated by psychedelic therapies include OCD (Moreno et al., 2006), near-death anxiety and depression (Ross et al., 2016; Gasser, Kirchner, & Passie, 2014), and addiction (Vollenweider and Kometer, 2010; Garcia-Romeu, Griffiths, & Johnson 2014; Bogenschultz et al., 2015; Krebs & Johansen, 2012). While all of these disorders may share neurophysiological underpinnings, they are also likely linked by their common and interrelated symptomology. The concept of demoralization may encompass the possible commonalities between these disorders, and is defined here as the inability or lack of will to adaptively cope due to a real or perceived lack of control over his/her situation, as well a loss of life meaning and/or purpose (Vehling, 2017).

Results from psychedelic-assisted psychotherapy have shown (generally) that psychedelic experiences tend to result in an enhanced sense of insight, meaning, and agency over ones choices and actions. Evidence also suggests that psychedelic experiences might ‘loosen the grip’ of maladaptive coping, (drug/alcohol dependency, unhealthy patterns of thoughts and behaviors) through an experiential and neurophysiological ‘re-perceiving’ and ‘re-wiring’ process, respectively.

Clinical research has proven beyond a doubt that these substances can be used to treat mental illness in a way unlike any other pharmacological intervention. The multidisciplinary framework and holistic approach of this treatment makes it a unique and effective method that empowers individuals and produces lasting effects on cognitive and emotional processing.

5.3.2 Neuroscience

The neurophysiological effects of psychedelic molecules are highly complex and widespread, causing direct and indirect effects across functional networks in the brain (Tagliazucchi et al., 2014). As this is not the focus of this paper, I will briefly summarize modern ‘big-picture’ theories of the psychedelic state at the brain level rather than delve into the details of neuropharmacology (for an in-depth review of the neuropharmacology of psychedelics, see Martin & Nichols, 2016; Halberstadt, 2015)

“…5-HT2A receptor agonism leads to desynchronization of oscillatory activity, disintegration of intrinsic integrity in the [default mode network] and related brain networks, and an overall brain dynamic characterized by increased between-network global functional connectivity, expanded signal diversity, and a larger repertoire of structured neurophysiological activation patterns.” Swanson (2018)

Carhart-Harris and colleagues (2014) proposed the Entropic Brain Theory (EBT), which seeks to explain a given conscious state by its corresponding levels of entropy in the brain. Entropy is a measure of a systems physical order/disorder and informational certainty/uncertainty. EBT proposes that the phenomenological qualities of a conscious state can be mapped onto a scale ranging from low entropy (high order/high certainty) to high entropy (low order/low certainty) (Carhart-Harris et al., 2014). While normal waking consciousness is ‘sub-critical,’ and stable, psychedelic states are characterized by instability and uncertainty. This theory comes out of a series of neuroimaging studies that suggests these substances cause a diversification of functional networks (Tagliazucchi, 2014), as well as desynchronization of networks that would normally ‘suppress’ entropy, sustain a coherent sense of self, and maintain informational certainty about oneself, others, and the world (Muthukumaraswamy et al., 2013; see Carhart-Harris et al., 2014; Carhart-Harris, 2018 for a full description of this theory).

Complementary to EBT, Swanson’s (2018) call for a unified theory of psychedelic drug effects expresses promise (as well as highlights some major contradictions), in predictive processing (PP) theories (Muthukamaraswamy et al., 2013; Pink-Haskes et al., 2015; Friston, 2010; Corlett, 2009). PP accounts of psychedelic drug effects extend out from the theory that normal conscious states are a sort of ‘controlled hallucination’ whereby the brain is simulating reality based on accurate predictions of sensory information (Clark, 2015). In PP models, the brain’s higher cortical structures seek to minimize prediction error in the brain by generating top-down signals that ‘match’ and inhibit lower-level processing in order to make sense of and accurately represent sensory information and bodily states (Friston, 2010, Clark 2013). The psychedelic state is therefore a ‘less controlled’ hallucination (Swanson, 2018) as a result of the hyper excitation of the cortex, therefore producing dream-like internal simulations of reality (see Swanson, 2018 for an in-depth review of predictive processing theories of psychedelic drug effects; Friston, 2010; Clark 2015). Exactly why and how psychedelics alter PP is largely unknown.

5.3.3 Summary

Clinical and neuroscience fields have provided deep insight into the nature of psychedelic drug effects. Perhaps one of the most significant and consistent findings is the ability for these substances to catalyze immense change, cognitively and neurophysiologically. It is critical to acknowledge that the nature of that change, will be partially dependent on the individual’s unique experiences, prior neural structure, and then subsequent integration processes. While the phenomenological effects of psychedelics are highly complex and likely underpinned by an amalgamation of altered processing, cognitive-behavioral tasks may help to tease out which cognitive processes are being effected across individuals.

5.4 Microdosing

Microdoses are 1/10-1/5 of a standard dose of a psychedelic substance (10-30 micrograms for LSD, 0.10-1.0 grams of psilocybin). A microdosing program is continuing to microdose 1-2 times a week for a period of 4-6 weeks (Fadiman, 2011). Due to the void of research on this topic, the effects of microdosing are unknown. Therefore, opportunities for research are plenty but will be largely exploratory. Longitudinal designs will be integral to microdosing research, as it is vital to understand whether or not these effects persist once the program has ceased. Whether or not the researcher is interested in acute effects from a single microdose, cumulative effects of continuous microdosing, or short-, medium-, or long-term effects will determine which methodologies are employed.

Microdoses are sub-perceptual, meaning, the amount is not enough to “trip” but has been anecdotally reported to produce meaningful changes in cognition and emotionality (Johnstad, 2018). Anecdotal reports include increased energy, positive mood, less reactivity, enhanced focus, increased creativity, as well as amelioration of brooding, rumination, mild-depressive symptoms, and a significant amount of microdosers also report improving their habits and health-related behaviors (Fadiman, 2011; Gregoire, 2017; Johnstad, 2018; Waldman, 2017; Wong 2017). Despite these substantial anecdotal reports, there is very little work looking at the effects of microdosing, and controlled longitudinal studies are non-existent.

5.5 Tasks to Target Psychedelic Drug Effects

This section presents the effects of psychedelics on perception and cognition and then pairs those effects with appropriate tasks. Cognitive behavioral tasks always involve some level of perceptual processing, therefore tasks were selected based on the function that they most prominently target. First, tasks that primarily focus on cognitive functions, such as attention, decision making, and problem solving will be discussed in relation to cognitive psychedelic effects. Second, tasks that focus primarily on perceptual processes, such as the ability to organize and identify sensory information will be discussed in relation to perceptual psychedelic effects.

Deciding which tasks may capture low-dose psilocybin-induced changes in perceptual and cognitive processing is difficult at this stage in the research, so initial studies will be largely exploratory. However, insights from medium- and high-dose neuroimaging research will be drawn upon.

5.5.1 Cognitive Effects

Psychedelic-induced alterations in brain activity increases cognitive flexibility while decreasing cognitive control and stability (Carhart-Harris, 2014, 2016), resulting in less controlled thought-processes, reduced performance in attentional tasks (Carter et al., 2005; Vollenweider et al., 2007), increased divergent thinking (Kuypers et al., 2016), expanded semantic activation (Family et al., 2016), and a tendency to attribute new meaning to perceptual stimuli (Preller et al., 2017). Long-term improvements in creative problem solving (Sweat et al., 2016), as well as increases in optimism, and trait ‘openness’ have also been reported in the literature (Maclean et al., 2011; Lebedev et al., 2016).

Enhanced focus, sustained attention, clarity of mind, and increased cognitive control have been anecdotally reported by microdosers. Perhaps it is the case that microdosing does not result in any impairments of stability or control, rather an enhancement of these processes. If this is the case, it is important to identify whether creativity and flexibility are also enhanced or impaired. If microdosing does produce clarity in thought processes, researchers may find improved performance in processes that are effected by mind-wandering such as attention (Tang et al., 2009) and inhibition (Zeiden & Faust, 2008).

The following tasks were chosen to target attention, control, and flexibility. Research on microdosing may be able to discover critical points at which cognitive impairments and cognitive enhancements emerge. Microdosing research should expand the upper limit to 1/10-2/5 of a standard dose in order to identify when cognitive impairments escalate to a point that hinders normal functioning.

5.5.2 Working-Memory and Inhibition Tasks

Working memory is a cognitive system or systems generally defined as the ability to hold information “on-line” and manipulating the information in processes of reason, comprehension, and/or learning (Baddeley, 2010). While there are many different theories about this function, what matters here is that it is a real process that allows human beings to hold information in the mind and think about it, and also that this ability has certain limitations.

One of the only studies that used cognitive tasks to investigate psychedelic effects on cognitive functioning was done by Bouso and colleagues (2013), who investigated the effects of ayahuasca on working memory in 24 ayahuasca users (11 long-term and 13 occasional users). The researchers used the Stroop task, The Sternberg Task, and Tower of London Task prior and following ayahuasca intake. Their results indicate that, while working memory was impaired (shown by more errors in the Sternberg), stimulus-response interference was decreased (shown by decreased reaction times in the Stroop). They also found impairments of working memory only had negative effects in the less experienced group.

The Stroop Color and Word Test (SCWT) was selected because it is a well-established and validated tool for investigating the ability to inhibit inappropriate responses and select appropriate responses (Scarpina & Tagini, 2017). This will also keep consistency in the research to be able to make inferences about effects across studies. The task requires the participant to select the color that a word is presented in when the word itself is a different color. For example, the word “RED” will be presented in green ink and the participant must select “GREEN” to be correct, this is the incongruent condition. The congruent condition is when a word is presented, “RED” for example, and it is presented in red ink. In the congruent condition, the participant clicks “RED” for a correct response. Because reading the word is the more automatic response, the longer reaction times in incongruent trials is known as the Stroop effect (Stroop, 1935).

The “n-back task” is widely used in cognitive science as a measure of working memory ability. The task requires participants to attend to a series of objects (typically numbers or words) presented on the computer screen, and to respond when an object is the same as the one that was presented n trials back (usually 2- or 3-back) (Meule, 2017). Here, the participant has to hold the previously presented objects in the mind while paying attention to the object that is currently being presented. In some n-back tasks, the participant is required to press one key when the object presented is not a match with the object n-back and another when it is a match. As to limit the number of cognitive functions required to perform, participants should be required to press a button only when the object presented is a match. Dependent variables that will be compared between groups is accuracy and reaction times.

While it may not yield any significant differences, it would be interesting to modify the n-back to see whether or not the valence of a word would affect performance in the n-back task. In this case, a within-subjects variable would be the valence of words, with some trials being low in meaningfulness (chair, cup, hairbrush, toothpick, etc.), some trials with high positive valence (love, trust, beauty, honesty), and some trials being high in negative valence (hate, bully, outcast, violence). Although there’s not any direct evidence from psychedelic research that lends one to believe there would be differences, some exploration in this task could yield interesting results.

5.5.3 Cognitive Flexibility Tasks

The ability to appropriately and efficiently adjust cognitive processing in response to a changing condition is perhaps the root of adaptability. Cognitive flexibility is this capacity, whereby an individual is able to switch from one strategy or mindset to another, in response to new or changing conditions, to achieve a desired goal. While tasks in the previous section focused on more automatic cognitive functions, tasks that measure cognitive flexibility must capture changes in more complex cognition or behavior after a person has been performing a task for some time (Cañas, Fajardo, & Salmerón, 2018). Tasks must therefore have several elements such as an acquisition to a task, some environmental changes, and then a required adjustment to those changes in order to successfully perform.

An individual’s cognitive flexibility is predictive factor for a range of adaptive outcomes (Zeytinoglu, Calkins, & Leerkes, 2018). Individuals with high cognitive flexibility have shown higher levels of resiliency, (Genet & Siemer, 2011) creativity, (Chen et al., 2014), and quality of life (Davis et al., 2010). The inability to shift strategies or mindsets when a current behavior or psychological state is not helpful can be described as cognitive rigidity (cognitive inflexibility). Cognitive rigidity can manifest mildly in unhealthy habits of mind and body that leave an individual in harmful loops and repetitions. It can also take more severe forms such as obsessive compulsive disorder and depressive rumination, both of which are characterized by rigid cognition (Meiran, Diamond, Toder, & Nemets, 2010). Research on generalized anxiety disorder also reports cognitive rigidity underlies perseverative cognition (i.e. worry or rumination) (Ottaviani et al., 2015, 2016). In addition, research on eating disorders and social anxiety have both shown strong positive correlations with cognitive rigidity (Arlt et al., 2016).

Microdosers report access to a greater repertoire of mindsets and perspectives, reflecting a shift from rigidity to flexibility. Bringing validity to these claims is a great challenge for cognitive scientists and deserves great efforts, as enhancing this ability could have positive effects in other aspects of mental life and wellbeing. A good assessment of whether or not microdoses of psychedelic substances can enhance cognitive flexibility would be tasks that require an individual to switch from one strategy or mindset to another to achieve a goal. Two tasks are presented that target different levels of cognitive processing. The first is a test of a more automatic ability to switch from one set of rules to another and respond very quickly. The second requires one to switch between higher-order processing strategies from identifying details of a story to comprehension of the overarching message of a story.

The Simon Switch Task (SST) requires individuals to respond differently depending on the type of stimuli presented (adopted from Liu et al., 2016, originally Simon & Barbaum, 1988, 1990). The task starts with a fixation point for about 800 ms, followed by an arrow that is either red or blue. If the arrow is red, participants must hit the arrow key that is the same as the direction of the arrow presented (congruent). If the arrow is blue, participants must hit the arrow key that is the opposite direction of the one presented (incongruent). Some blocks of trials will require a switch from blue to red arrows, while others will not. Switching involves the inhibition of a previously activated rule and the activation of the appropriate rule to employ the appropriate response. This type of switching can be considered a form of attentional flexibility, which is more automatic and requires less complex cognitions compared to the following task.

The second task was selected to capture how microdosing psychedelics may alter one’s ability to perform complex cognitive flexibility tasks. Cañas and colleagues (2004) designed a cognitive flexibility task that requires participants to select the optimal strategy for solving a complex problem. The task is designed such that the participant must act quickly to put out a wild fire while considering the instruments and resources available to them, as well as environmental constraints such as wind speed and type of land. The researchers gave the participants several blocks with different task scenarios in which they had to adaptively adjust strategies given resource and environmental constraints. In every scenario, there was an optimal strategy that would successfully cover the most land in the shortest time. In order to capture the level of adjustment to new conditions, participants will get acclimated to responding in a certain scenario, and then switch the resources and constraints to see how quickly and effectively they solve the problem.

The fire-fighter task could be an emotionally arousing experience for some individuals, leading to a decrease in performance as a result of physiological arousal. Research has shown decreased right-amygdala reactivity to negative and neutral stimuli after psilocybin administration, which was related to increases in positive mood. It could be that, for this task, the increased performance is partially or fully resulting from less emotional and physiological arousal, rather than an enhancement of cognitive flexibility. It is important that this task is counter-balanced with a task that is equally as cognitively demanding, but lacks any negative valence. While other cognitive functions are employed to perform these tasks, and other factors such as emotional arousal may be influencing the results, performance of task switching is reliably known to capture the varying levels of cognitive flexibility between individuals.

5.5.4 Creativity Task

Research looking at the brain activity of schizotypal individuals have found that a greater spread of cortical activation is an important factor for creative thought processes (Park, Roberts, Kirk, and Waldie, 2015). This is also consistent with previously mentioned neuroimaging work that has shown diversification of functional networks after psychedelic administration, anecdotal reports of enhanced creative thinking, and increased activation of indirect semantic associations under psilocybin (Spitzer, 1996). Taken together, these findings lend some indirect support for the hypothesis that microdoses of psychedelics may enhance creative thinking by altering the communication of existing neural circuits to generate novel combinations of information.

There are many different conceptualizations of creativity, but they essentially describe the ability for an individual to engage in conceptual and abstract thinking that goes beyond obvious or typical patterns to adopt a novel idea or perspective (Dietrich, 2004). A cognitive neuroscience approach will be used to operationalize this process. Creativity is considered here as a form of cognitive flexibility, constituted by the ability to generate novel and appropriate combinations of information, and is employed in any station where an individual has to adapt to a novel situation, context, or solve a problem (Dietrich, 2004).

Kuypers and colleagues (2016) found that the psychedelic substance, Ayahuasca, enhances divergent cognition, a style of thinking whereby an individual is generating new ideas in a context where more than one solution is correct. This study used the Pattern/Line Meaning Task (PLMT) and the Picture Concept Task (PCT) to measure divergent thinking. The ability to think divergently is highly adaptive, as individuals need to generate a multitude of solutions to select the one that is the most appropriate. It is also important to generate alternative solutions when an existing behavior or thought process has become maladaptive or harmful.

The task selected to assess whether microdosing a psychedelic substance (psilocybin or LSD) enhances creativity is the Alternative Uses Task (Guilford, 1967). This task is one of the classic measures of divergent thinking and is explorative and easy to employ. Participants must generate as many uses as possible for a given item within 45 seconds. Because these tasks will be online, the participant must type out as many uses as possible. Some examples of items include a shoe, snow, a car tire, a brick, a paperclip, a chair, a coffee mug, or any item that has a function but can be used for other purposes.

Assessment techniques are adopted from a previous study and scored based on fluency (number of uses generated), flexibility (number of distinct groups responses could be placed in), appropriateness (1 for appropriate, 0 for inappropriate), originality (comparing each response to the responses of all other participants) (Addis et al., 2014). Because these judgments are done by researchers, it is important to have several raters and run inter-rater reliability checking. Outcomes on these four measures have significant inter-correlations, so it is possible to generate a mean divergent thinking score to compare between groups (Addis et al., 2014).

5.5.5 Perceptual Effects

Psychedelic substances alter the way sensory information is processed and represented in the brain, possibly by altering the excitability of neurons in the visual cortex (Moreau et al., 2010). This alteration in visual processing results in distortions of external stimuli, (objects and their motion, shape, space, and distance) as well as the production of a sensory experience in the absence of external stimuli, which has all of the qualities of real perception, known as hallucinations (Kometer et al., 2013). Other perceptual effects include intensifications of textures, colors, lights, and sounds, as well as a higher level of detail perception, (Kometer & Vollenweider, 2016) and synaesthesia (Ward, 2013).

While microdoses are by definition ‘sub-perceptual’ and will not produce hallucinations or visual distortions, they may have subtle and/or unconscious effects on perceptual processing. Put another way, while microdoses will not alter the way the brain represents physical characteristics of external stimuli (the object itself), anecdotal reports of enhanced awareness to the environment suggest they may alter the ability to detect a stimuli and/or identify subtle changes in a visual scene. Because it is still unclear the exact nature of the disturbances in functional network connectivity, tasks that have already been linked to specific networks would help researchers identify which perceptual mechanisms are effected by LSD or psilocybin.

5.5.6 Perceptual Processing Tasks

Psychedelic users report somewhat paradoxical effects of psychedelics on perceptual processing. In some cases, users report having enhanced detail perception and other reports reflect a more ‘gestalt’ processing of the environment. Therefore, the first task seeks to target these seemingly contradicting reports of changes in perceptual processing. It may be the case that how psychedelics alter processing of a visual scene depends on prior processing style, (Witkin, 1981; Walter & Dassonville, 2011) in which case researchers can investigate the nature of the impact of these substances on processing style with this task as well, or just control for these individual differences.

The Embedded Figures Task (EFT) targets the ability to find a particular shape within a more complex figure composed of many intersecting lines by breaking down the figure into its structural components (Manjaly et al., 2007). Neuroimaging research on this task have shown a recruitment of the frontoparietal network of brain regions (superior parietal cortex, precuneus, and middle frontal gyrus). Significant positive correlations between a portion of the right parietal cortex and processing speed were found, as well as strong correlations between processing speed and activation in the frontal gyrus (Walter & Dassonville, 2011).

This line of research suggests that healthy individuals rely on the integrity of the frontoparietal network is essential for proper EFT performance. Researchers interested in autism spectrum disorder (ASD) find that healthy individuals rely on working memory to suppress contextual information and search for the target shape, while the underconnectivity of frontoparietal regions in ASD cause individuals to rely more heavily on the parietal-occipital system for feature analysis (Ring et al., 1999; Damarla et al., 2010).

Muthukumaraswamy and colleagues (2013) report decreased frontoparietal connectivity after psilocybin administration, which is also consistent with fMRI results (Carhart-Harris et al., 2012). Research on low-dose effects of psychedelics should employ this task in a between samples (grouped by dosage) design in order to identify when these substances begin to exert their effects on this functional network, as well as what processing styles are employed if frontoparietal connectivity is compromised.

While the first task requires a shape be held in the mind and searched for in a complex embedded figure, the second task targets the ability to identify change in a scene with many visual elements. The Change Blindness Task (CBT) is more explorative and naturalistic compared to the EFT, and can perhaps capture more nuanced changes in perceptual processing. Change blindness is the inability to spot a change in a visual scene that is easily seen when pointed out (Hocchauser, Aran, & Grynszpan, 2017). Tasks that target this phenomenon have been classified as a measure of explorative processing, or a controlled and innate type of selective attention (Enns & Trick, 2006).

The task involves the presentation of a visual scene, followed by a blank screen presented for (at least) 100 ms, and then the same scene with a missing (or changed) element. The participants must notice that a change has occurred and identify which element has changed or is missing, an outcome that varies by the degree of interest or relevance of this element within its context (Hocchauser, Aran, & Grynszpan, 2017; Rensink, 2002).

For a CBT on the effects of low-dose psychedelics, it would be important for visual scenes to vary in content. It has been found that psychedelics enhance a sense of connectedness with nature, animals, other people, therefor naturalistic or social scenes may just be of greater interest in general for the psychedelic group compared to the control group. Studies that employ this task should generate a series of visual scenes that vary in content in order to compare the level of change detection across scenes and between groups.

As mentioned in the previous section, psychedelics have been subjectively reported to alter the way perceptual information is processed at both local levels (element and detail oriented) and global levels (holistic and meaning oriented). The CBT will be a particularly interesting task to employ because it is flexible, meaning the researcher can be a bit creative in order to investigate and control for many variables that may explain differences between groups. Research employing CBT should investigate changes in perceptual processing by manipulating the content of the visual scene (natural, social, industrial, etc.), level of relevance and meaning amongst elements (high connection/low connection), as well as the meaning saliency of the target element (high importance/low importance), and see how this correlates with detection rates.

It will not be enough to say increased detection rates means an enhancement local processing. Increased detection rates could result from an enhanced global processing because of a heightened perception to meaning or relevance between elements. If one of the elements changes or goes missing, it can be detected by its “void of meaning” left behind as a function of its level of connection with other meaningful elements. This can be teased apart by systematically manipulating the level of connection between elements in the visual scenes and the level of importance of the changed/missing elements.

Perhaps the type of processing, either local or global, that is employed will depend on the content and narrative of the visual scene itself. It is possible that the influence of psychedelics on perceptual processing may be contingent upon what and how content is presented, guiding the brain to employ the processing style that is most appropriate in a flexible and adaptive way. For example, if a visual scene has a bunch of elements that are not connected by meaning or relevance, perhaps a more local processing is employed to identify change. If a visual scene with high relevance between elements, perhaps a more global processing is employed.

5.6 Discussion and Concluding Remarks

As mentioned previously, psychedelics are molecules that exert extremely widespread effects on the brain, cognitive processing, and behavior. Cognitive tasks may be able to identify critical points for the onset of effects on cognitive functioning, as well as capture the degree and nature of these effects. Ideally, cognitive tasks would also be paired with neuroimaging to identify changes in the functional network activity that underpins these tasks. This is important for explaining observed differences in performance. Subjective reports also have their place in supplementing findings from cognitive and neuroscience methods and should be included in any analysis, especially when there could be individual differences in strategies used.

Although research that seeks to employ these tasks would ideally take place in a controlled, double-blind research setting, these substances remain federally illegal in the United States and most of Europe. Therefore, preliminary research will most-likely be de-identified and online, with the demand of 200+ participants for psychedelic and non-psychedelic groups. Initial studies can be considered preliminary, with the hopes of generating substantial evidence for why these methods should be funded and carried out in a laboratory. It is crucial that this research evolve into controlled, double-blind research designs. While cognitive tasks are considered objective measures, and sample sizes will be large, the lack of control of the dosage and purity of the psychedelic substance is a large confounding variable. This is important for taking into account placebo effects.

Understanding how low-dose use of psychedelics effects cognitive functioning is not just an intriguing research opportunity. Many people across the world report using psychedelics at low-doses fairly often. This research has real-life application for individuals who are going to start microdosing but are unsure as to how it will affect their everyday functioning. It is important that cognitive science takes a leading role in the psychedelic research community, as the documented effects currently take the form of subjective report and neuroimaging data.

5.7 References:

Alonso, J. F., Romero, S., Mananas, M. A., Riba, J. (2015). Serotonergic Psychedelics Temporarily Modify Information Transfer in Humans. International Journal of Neuropsychopharmacology: 1-9

Arlt, J., Yui, A., Eneva, K., Dryman, T. M., Heimberg, R. G., Chen, E. Y. (2016). Contributions of cognitive inflexibility to eating disorder and social anxiety symptoms. Eating Behavior: 30-32

Baddeley, A. (2010). Working Memory. Current Biology, 20(4). DOI: https://doi.org/10.1016/j.cub.2009.12.014

Baggott, M. J. (2015). Psychedelics and creativity: a review of the quantitative literature. PeerJ. PrePrints. doi: 10.7287/peerj.preprints.1202v1

Bouso, J. C., Palhano-Fontes, F., Rodríguez-Fornells, A., Ribeiro, S., Sanches, R., Crippa, J. A. S., et al. (2015). Long-term use of psychedelic drugs is associated with differences in brain structure and personality in humans. European Journal of Neuropsychopharmacology, 25: 483–492. doi: 10.1016/j.euroneuro.2015.01.008

Cañas, J.J. Quesada, J. F., Antolí, A., and Fajardo, I. (2003) Cognitive flexibility and adaptability to environmental changes in dynamic complex problem-solving tasks. Ergonomics, 46(482).

Carhart-Harris RL, Erritzoe D, Williams T, Stone JM, Reed LJ, Colasanti A, Tyacke RJ, Leech R, Malizia AL, Murphy K, Hobden P, Evans J, Feilding A, Wise RG, Nutt DJ. (2012).Neural correlates of the psychedelic state as determined by fMRI studies with psilocybin. Proceedings in the National Academy of Science, USA. 109: 2138-2143.

Carhart-Harris, R. L., Leech, R., Hellyer, P. J., Shanahan, M., Feilding, A., Tagliazucchi, E., Chialvo, D. R., Nutt, D. (2014). The Entropic Brain: a Theory of Conscious States Informed by Neuroimaging Research with Psychedelic Drugs. Frontiers in Human Neuroscience, 8(20).

Carhart-Harris, R. L., Kaelen, M., Bolstridge, M., Williams, T. M., Williams, L. T., Underwood, R., et al. (2016b). The paradoxical psychological effects of lysergic acid diethylamide (LSD). Psychological Medicine. 46, 1379–1390. doi: 10.1017/S0033291715002901

Carhart-Harris, R.L., Erritzoe, D., Haijen, E., Kaelen, M., Watts., R. (2018). Psychedelics and connectedness. Psychopharmacology, 235: 547.https://doi.org/10.1007/s00213-017-4701-y

Carter, O. L., Burr, D. C., Pettigrew, J. D., Wallis, G. M., Hasler, F., and Vollenweider, F. X. (2005). Using psilocybin to investigate the relationship between attention, working memory, and the serotonin 1A and 2A receptors. Journal of Cognitive Neuroscience, 17, 1497–1508. doi: 10.1162/089892905774

Chen Q., Yang, W., Li, W., Wei, D., Li, H., Lei, Q., Zhang, Q., Qiu, J. (2014). Association of creative achievement with cognitive flexibility by a combined voxel-based morphometry and resting-state functional connectivity study. NeuroImage, 102:474–483

Clark, A. (2013). Whatever next? Predictive brains, situated agents, and the future of cognitive science. Behavioral Brain Science, 36: 181–204. doi: 10.1017/S0140525X12000477

Clark, A. (2015). Surfing Uncertainty: Prediction, Action, and the Embodied Mind. Oxford: Oxford University Press.

Damarla, S. R., Keller, T. A., Kana, R. J., Cherkassky, V. L., Williams, D. L., Minshew, N. J., Just, M. A. (2010). Cortical underconnectivity coupled with preserved visuospatial cognition in autism: Evidence from an fMRI study of an embedded figures task. Autism Research, 3(5): 273-279.

Davis, J. C., Marra, C. A., Najafzadeh, M., Liu-Ambrose, T. (2010). The independent contribution of executive functions to health related quality of life in older women. BMC Geriatrics, (10)16.

Dietrich, A. (2004). The Cognitive Neuroscience of Creativity. Psychonomic Bulletin & Review, 11(6): 1011-1026

Addis, D. R., Ling Pan, R., Schacter, D. L., Schacter, M. (2014): Divergent thinking and constructing episodic simulations. Memory, DOI: 10.1080/09658211.2014.985591

Enns, J. T., & Trick, L. M. (2006). Four modes of selection. In Lifespan cognition: Mechanisms of change (pp. 43–56). Oxford: Oxford University Press

Fadiman, J. (2011). The Psychedelic Explorer’s Guide: Safe, Therapeutic, and Sacred Journeys. Inner Traditions/Bear & Company. ISBN-13: 9781594774027

Family, N., Vinson, D., Vigliocco, G., Kaelen, M., Bolstridge, M., Nutt, D. J., et al. (2016). Semantic activation in LSD: evidence from picture naming. Language, Cognition, and Neuroscience. 31, 1320-1327. doi: 10.1080/23273798.2016.1217030

Friston, K. (2010). The free-energy principle: a unified brain theory? National Review Neuroscience. 11, 127–138. doi: 10.1038/nrn2787

Gasser, P., Kirchner, K., Passie, T. (2014). LSD-assisted psychotherapy for anxiety associated with a life-threatening disease: a qualitative study of acute and sustained subjective effects. Journal of Psychopharmacology: 1-12. DOI: 10.1177/0269881114555249

Genet JJ, Siemer M. (2011). Flexible control in processing affective and non-affective material predicts individual differences in trait resilience. Cognition and Emotion, 25:380–388

Gregoire, C. (2017). Everything you Wanted to know about Microdosing (But Were Afraid to Ask): A leading psychedelic researcher explains what’s really behind the trend. Huffington Post, 2017.

Griffiths, R. R., Johnson, M. W., Richards, W. A., Richards, B. D., McCann, U., Jesse, R. (2011). Psilocybin occasioned mystical-type experiences: immediate and persisting dose- related effects. Pharmacology, 218(4): 649-65. doi: 10.1007/s00213-011-2358-5

Guilford, J. P. (1967). The nature of human intelligence. New York, NY: McGraw-Hill.

Halberstadt, A. D. (2015). Recent Advances in the Neuropsychopharmacology of serotonergic Hallucinogens. Behavioral Brain Research, 277: 99-120

Hocchauser, M., Aran, Adi., Grynszpan, O. (2017). How Adolescents with Autism Spectrum Disorder (ASD) Spontaneously Attend to Real-World Scenes: Use of a Change Blindness Paradigm. Journal of Autism and Developmental Disorders. DOI 10.1007/s10803-017-3343-6

Johnstas, P. G. (2018). Powerful Substances in tiny amounts: An interview study pf psychedelic microdosing. Nordic Studies on Alcohol and Drugs, 35(1), 39-51

Kent, J. L. (2010). Psychedelic information theory: Shamanism in the age of reason. PIT Press/Supermassive.

Krebs, T.S., Johansen, P. Lysergic acid diethylamide (LSD) for alcoholism: meta-analysis of randomized control trials. Journal of Psychopharmacology, 26(7): 994-1002

Kuypers, K. P. C., Riba, J., de la Fuente Revenga, M., Barker, S., Theunissen, E. L., and Ramaekers, J. G. (2016). Ayahuasca enhances creative divergent thinking while decreasing conventional convergent thinking. Psychopharmacology 233, 3395–3403. doi: 10.1007/s00213-016-4377-8

Letheby, C. The Philosophy of Psychedelic Transformation. Journal of Consciousness Studies, 22(9-10): 170-193

Letheby, C., Gerrans, P. (2017). Self unbound: ego dissolution in psychedelic experience. Neuroscience of Consciousness, 1(1).

Learner, M., Lyvers, M. (2006). Values and Beliefs of Psychedelic Drug Users: A Cross-Cultural Study. Journal of Psychoactive Drugs, 38(2)

Lebedev, A. V., Kaelen, M., Lövdén, M., Nilsson, J., Feilding, A., Nutt, D. J., Charhart-Harris, R. L. (2016). LSD-Induced Entropic Brain Activity Predicts Subsequent Personality Change. Human Brain Mapping, 37(9): 3203-3213

Liu, H., Fan, N., Rossi, S., Yao, P., Chen, B. (2016). The effect of cognitive flexibity on task switching and language switching. International Journal of Bilingualism, 20(5): 563-579

MacLean, K. A., Johnson, M. W., and Griffiths, R. R. (2011). Mystical experiences occasioned by the hallucinogen psilocybin lead to increases in the personality domain of openness. Journal of Psychopharmacology, 25, 1453–1461. doi: 10.1177/0269881111420188

Manjaly, Z. M., Bruning, N., Neufang, S., Stephan, K. E., Brieber, S., Marshall, J. C. (2007) Neurophysiological correlates of relatively enhanced local visual search in autistic adolescents. NeuroImage, 35(1):283–291

Martin, D. A., Nichols, C. E. (2016). Psychedelics Recruit Multiple Cellular Types and Produce Complex Transcriptional Responses Within the Brain. Elsevier BioMedicine: 262-277 http://dx.doi.org/10.1016/j.ebiom.2016.08.049

Nour, M. M., Evans, L., Carhart-Harris, R. L. B.Sc. (2017): Psychedelics, Personality and Political Perspectives. Journal of Psychoactive Drugs, DOI: 10.1080/02791072.2017.1312643

Meiran, N., Diamond, G. M., Toder, D., Nemets, B. (2011). Cognitive rigidity in unipolar depression and obsessive compulsive disorder: Examination of task switching, Stroop, working memory updating and post-conflict Adaptation. Psychiatry Research, 185(1-2): 149-156 doi:10.1016/j.psychres.2010.04.044

Meule, A. (2017). Reporting and Interpreting Working Memory Performance in n-back Tasks. Frontiers in Psychology, 8(352). DOI: 10.3389/fpsyg.2017.00352

Muthukumaraswamy, S. D., Carhart-Harris, R. L., Moran, R. J., Brookes, M. J., Williams, T. M., Errtizoe, D., Sessa, B., Papadolpoulos, A., Bolstridge, M., Singh, K. D., Feilding, A., Friston, K. J., Nutt, D. J. (2013). Broadband Cortical Desynchronization Underlies the Human Psychedelic State. Journal of Neuroscience, 33(38): 1517-15183

Nour, M. M., Evans, L., Nutt, D., and Carhart-Harris, R. L. (2016). Ego-dissolution and psychedelics: validation of the Ego-Dissolution Inventory (EDI). Frontiers in Human Neuroscience, 10(269) doi: 10.3389/fnhum.2016.00269

Ottaviani, C., Medea, B., Lonigro, A., Tarvainen, M., Couyoumdjian, A. (2015). Cognitive rigidity is mirrored by autonomic inflexibility in daily life perseverative cognition. Biological Psychology, 107: 24-30

Ottaviani, Christina, Watson, David R, Meeten, Frances, Makovac, Elena, Garfinkel, Sarah N and Critchley, Hugo D. (2016). Neurobiological substrates of cognitive rigidity and autonomic inflexibility in generalized anxiety disorder. Biological Psychology, 119: 31-41. ISSN 0301- 0511

Park H, Roberts R, Kirk I and Waldie K (2015). Neural Correlates of Creativity in Schizotypy: an fMRI study. Frontiers in Human Neuroscience. Conference Abstract: XII International Conference on Cognitive Neuroscience (ICON-XII).doi: 10.3389/conf.fnhum.2015.217.00288

Preller, K. H., Vollenweider, F. X. (2016). Phenomenology, Structure, and Dynamics of Psychedelic States. Current Topics in Behavioral Neurosciences Springer, Berlin, Heidelberg. DOI: https://doi.org/10.1007/7854_2016_459

Preller, K. H., Herdener, M., Pokorny, T., Planzer, A., Kraehenmann, R., Stämpfli, P., et al. (2017). The fabric of meaning and subjective effects in LSD induced states depend on serotonin 2A receptor activation. Current Biology, 27: 451–457. doi:10.1016/j.cub.2016.12.030

Rensink, R. A. (2002). Change detection. Annual Review of Psychology, 53(1), 245–277.

Ring, H. A., Baron-Cohen, S., Wheelwright, S., Williams, S. C. R., Brammer, M., Andrew, C. (1999). Cerebral correlates of preserved cognitive skills in autism: A functional MRI study of Embedded Figures Task performance. Brain, 122(7):1305–1315.

Ross, S., Bossis, A., Guss, J., Agin-Liebes, G., Malone, T., Cohen, B., Mennenga, S. E., Belser,A., Kalliontzi, K., Babb, J., Su, Z., Corbey, P., Schmidt, B. L. (2016). Rapid andsustained symptom reduction following psilocybin treatment for anxiety and depression in patients with life-threatening cancer: a randomized controlled trial. Journal of Psychopharmacology, 30(12): 1165-1180

Scarpina, F., Tagini, S. (2017). The Stroop Color and Word Test. Frontiers in Psychology, 8(557). DOI: 10.3389/fpsyg.2017.00557

Simon, J. R., Berbaum, K. (1988): Effect of irrelevant information on retrieval time for relevant information. Acta Psychologica, 67(1):33–57.

Simon, J. R., Berbaum, K. (1990): Effect of conflicting cues on information-processing — the Stroop effect vs the Simon effect. Acta Psychologica, 73:159 –170.

Spitzer, M., Thimm, M., Hermle, L., Holzmann, P., Kovar, K. A., Heirmann, H., Gouzoulis-Mayfrank, E., Kischka, U., Scheider, F. (1996). Increased activation of indirect semantic associations under psilocybin. The Journal of Psychiatric Neuroscience and Therapeutics, 39(12): 1055-1057. DOI: https://doi.org/10.1016/0006-3223(95)00418-1

Stroop, R. J. (1935). Studies of Interference in Serial verbal Reactions. Journal of Experimental Psychology, 18: 643-662

Swanson, L. R. (2018). Unifying Theories of Psychedelic Drug Effects. Frontiers in Pharmacology, 9(172). doi: 10.3389/fphar.2018.00172

Sweat, N. W., Bates, L. W., and Hendricks, P. S. (2016). The associations of naturalistic classic psychedelic use, mystical experience, and creative problem solving. Journal of Psychoactive Drugs, 48, 344–350. doi: 10.1080/02791072.2016.1234090

Tagliazucchi, E., Carhart‐Harris, R., Leech, R., Nutt, D., & Chialvo, D. R. (2014). Enhanced repertoire of brain dynamical states during the psychedelic experience. Human brain mapping, 35(11), 5442-5456.

Tang, Y. Y., Ma, Y., Fan, Y., Feng, H., Wang, J., Feng, S., et al (2009). Central and autonomic nervous system interaction is altered by short-term meditation. Proceedings of the National Academy of Sciences, 106(22), 8865–8870. doi:10.1073/pnas.0904031106.

Vehling, S., Kissane, D. W., Lo, C., Glaesmer, H., Hartung, T. J., Rodin, G., Mehnert, A. (2017). The association of demoralization with mental disorders and suicidal ideation in patients with cancer. Cancer, American Cancer Society,https://doi.org/10.1002/cncr.30749

Vollenweider, F. X., Csomor, P. A., Knappe, B., Geyer, M. A., and Quednow, B. B. (2007). The effects of the preferential 5-HT2A agonist psilocybin on prepulse inhibition of startle in healthy human volunteers depend on interstimulus interval. Neuropsychopharmacology 32, 1876–1887. doi: 10.1038/ sj.npp.1301324

Waldman, A. (2017). A Really Good Day: How Microdosing Made a Mega Difference in My Mood, My Marriage, and My Life. Alfred A. Knopf, Penguin Random House LLC.

Ward, J. (2013). Synesthesia. Annual Review in Psychology, 64: 49–75. doi: 10.1146/annurevpsych-113011-143840

Walter E, Dassonville P (2011) Activation in a Frontoparietal Cortical Network Underlies Individual Differences in the Performance of an Embedded Figures Task. PLoS ONE, 6(7): e20742. https://doi.org/10.1371/journal.pone.0020742

Witkin, H. A., Goodenough, D. R. (1981) Cognitive styles: essence and origins. Field dependence and field independence. Psychological Issues: 1–141

Wittmann, M., Carter, O., Hasler, F., Cahn, B. R., Grimberg, U., Spring, P., Hell, D., Flohr, H., Vollenweider, F. X. (2007). Effects of psilocybin on time perception and temporal control of behaviour in humans. Journal of Psychopharmacology, 21(1): 50-64

Wong, S. (2017). Leading the high life. Journal of Psychopharmacology, 21(1), 50-64

Zeidan, F., & Faust, M. (2008). The effects of brief mindful training on cognitive control. In Southeastern psychological association conference, Charlotte, NC.

Zeytinoglu, S., Calkins, S. D., Leerkes, E. M. (2018). Maternal emotional support but not cognitive support during problem-solving predicts increases in cognitive flexibility in early childhood. International Journal of Behavioral Development.