LSD acutely impairs working memory, executive functions, and cognitive flexibility, but not risk-based decision-making

Pokorny, Thomas; Duerler, Patricia; Seifritz, Erich; Vollenweider, Franz X.; Preller, Katrin H.

doi:10.1017/s0033291719002393

Cited by 74 publications

(72 citation statements)

References 69 publications

(102 reference statements)

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“…It is therefore conceivable that these changes in brain activity during social decision-making are modulated via dopamine rather than 5-HT systems, in particular since previous results have implicated the dopamine system in decision-making processes 51 . Our results are also in line with previous findings showing that decision-making is a cognitive domain not influenced by stimulating the 5-HT 2A receptor 52 . Therefore, social feedback processing and socially influenced decision-making are potentially modulated by two different neurotransmitter systems, i.e.…”

Section: Social Feedback Processing May Depend On the 5-ht 2a Receptosupporting

confidence: 93%

LSD-induced increases in social adaptation to opinions similar to one’s own are associated with stimulation of serotonin receptors

Duerler¹,

Schilbach

Stämpfli

et al. 2020

Sci Rep

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Adapting one's attitudes and behaviors to group norms is essential for successful social interaction and, thus, participation in society. Yet, despite its importance for societal and individual functioning, the underlying neuropharmacology is poorly understood. We therefore investigated its neurochemical and neural correlates in a pharmacological functional magnetic resonance imaging study. Lysergic acid diethylamide (LSD) has been shown to alter social processing and therefore provides the unique opportunity to investigate the role of the 5-HT 2A receptor in social influence processing. Twenty-four healthy human volunteers received either (1) placebo + placebo, (2) placebo + LSD (100 µg), or (3) the 5-HT 2A receptor antagonist ketanserin (40 mg) + LSD (100 µg) at three different occasions in a doubleblind, randomized, counterbalanced, cross-over design. LSD increases social adaptation but only if the opinions of others are similar to the individual's own. these increases were associated with increased activity in the medial prefrontal cortex while participants received social feedback. furthermore, pretreatment with the 5-HT 2A antagonist ketanserin fully blocked LSD-induced changes during feedback processing, indicating a key role of the 5-HT 2A system in social feedback processing. our results highlight the crucial role of the 5-HT-system in social influence and, thus, provide important insight into the neuropharmacological basis of social cognition and behavior. The quality and quantity of individuals' social relationships has been tightly linked to morbidity and mortality 1. Social influence is omnipresent in our everyday life and reacting to the opinions of others is deeply rooted in human nature 2. Every time people interact or communicate, be it in real life or virtually, people are influenced by each other. Social adaptation refers to the act of changing one's attitudes, beliefs, or behaviors to match social norms that are implicitly or explicitly shared by a group of individuals 3. Zaki et al. 4 suggest that exposure to social norms directly influences participants' neural representations of the value they assign to stimuli. Being susceptible to social influence is essential for successful social interaction and communication, and also for the functioning and organization of an entire society. However, it can also have negative consequences if misused 5,6. In recent years, social neuroscience has advanced our understanding of the neural systems underlying social influence processing 7-9. Amongst other brain regions, it has been shown that frontal regions as well as the reward system are strongly implicated in adaptation to group norms 10-12. In particular, when exposed to a mismatch between the own and the group opinion, participants showed a deactivation of the ventral striatum and an

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Section: Social Feedback Processing May Depend On the 5-ht 2a Receptosupporting

confidence: 93%

LSD-induced increases in social adaptation to opinions similar to one’s own are associated with stimulation of serotonin receptors

Duerler¹,

Schilbach

Stämpfli

et al. 2020

Sci Rep

Self Cite

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“…Further, consistent with the notion that psilocybin impairs cognitive focus and control, 5-HT2A agonism has been implicated in an acute decline in convergent thinking, which critically relies on adequate executive functioning (137). In line with this, it was shown that LSD-induced impairment of working memory, executive functions, and cognitive flexibility was mediated by the 5-HT2A receptor (174). Conversely, 5-HT2A agonism is also associated with increased cognitive flexibility and divergent thinking (106,119,127,137,144,175).…”

Section: Executive Functioningsupporting

confidence: 53%

Depression, Mindfulness, and Psilocybin: Possible Complementary Effects of Mindfulness Meditation and Psilocybin in the Treatment of Depression. A Review

Heuschkel

Kuypers

2020

Front. Psychiatry

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Depression is a major public health problem that affects approximately 4.4% of the global population. Since conventional pharmacotherapies and psychotherapies are only partially effective, as demonstrated by the number of patients failing to achieve remission, alternative treatments are needed. Mindfulness meditation (MM) and psilocybin represent two promising novel treatments that might even have complementary therapeutic effects when combined. Since the current literature is limited to theoretical and empirical underpinnings of either treatment alone, the present review aimed to identify possible complementary effects that may be relevant to the treatment of depression. To that end, the individual effects of MM and psilocybin, and their underlying working mechanisms, were compared on a non-exhaustive selection of six prominent psychological and biological processes that are well known to show impairments in patients suffering from major depression disorder, that is mood, executive functioning, social skills, neuroplasticity, core neural networks, and neuroendocrine and neuroimmunological levels. Based on predefined search strings used in two online databases (PubMed and Google Scholar) 1129 articles were identified. After screening title and abstract for relevance related to the question, 82 articles were retained and 11 were added after reference list search, resulting in 93 articles included in the review. Findings show that MM and psilocybin exert similar effects on mood, social skills, and neuroplasticity; different effects were found on executive functioning, neural core networks, and neuroendocrine and neuroimmune system markers. Potential mechanisms of MM's effects are enhanced affective self-regulation through mental strategies, optimization of stress reactivity, and structural and functional adjustments of prefrontal and limbic areas; psilocybin's effects might be established via attenuation of cognitive associations through deep personal insights, cognitive disinhibition, and global neural network disintegration. It is suggested that, when used in combination, MM and psilocybin could exert complementary effects by potentiating or prolonging mutual positive effects, for example, MM potentially facilitating psilocybin-induced peak

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“…It is as yet unclear whether psychedelic microdosing is of therapeutic value for depression due to the limited amount of studies (with small sample sizes) that have been conducted. Nonetheless, the aforementioned effects on selective cognitive processes, resembling in a milder way the effects of full psychedelic doses, 51 , 52 and without impairing cognitive processes, 47 suggest that low doses of psychedelics could play a role in depression. Some underlying cognitive mechanisms of action, deduced from the observed effects, that is, increased divergent thinking and slowed down time perception, could be the induction of respectively increased cognitive flexibility, 31 , 32 and the production of a heightened experience of ‘being more in the present’ or mindful, 33 , 53 which could lead to lessened ruminative thinking and more self-compassion, decreasing depressive symptoms.…”

Section: Discussionmentioning

confidence: 99%

“…The latter two were assessed with tasks sensitive to the effects of full psychedelic doses of a psychedelic. 46,47 While no persisting effects on mood were shown 2 days after administration, it has to be noted that this questionnaire was completed by only 55% of the participants. 37 A low LSD dose led to a statistically significant, though clinically irrelevant, increase in systolic (13, 26 mcg) and diastolic (26 mcg) blood pressure 2 h after LSD administration, compared with placebo.…”

Section: Older Research With Lsdmentioning

confidence: 96%

The therapeutic potential of microdosing psychedelics in depression

Kuypers

2020

Therapeutic Advances in Psychopharmacology

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Microdosing psychedelics is the repeated use of small doses of, for example, lysergic acid diethylamide (LSD) and psilocybin, typically for a few weeks. Despite the popular and scientific attention in recent years, and claims by users that it has therapeutic value in affective disorders like depression, little scientific knowledge is available to back this. The purpose of this review was to investigate whether there are scientific grounds to state that this practice could be helpful in the treatment of affective disorders, and safe to use repeatedly. To that end, the literature (PubMed, MedLine) was searched, looking for (controlled) experimental studies with low doses of LSD and/or psilocybin, in healthy volunteers and patient samples. After a selection process and the addition of relevant articles, 14 experimental studies entered this review. Findings show that both LSD (10–20 mcg) and psilocybin (<1–3 mg) have subtle (positive) effects on cognitive processes (time perception, convergent and divergent thinking) and brain regions involved in affective processes. Besides the pleasant experience, increased anxiety and a cycling pattern of depressive and euphoric mood were also found. With regard to safety, it was demonstrated that low doses are well tolerated (in healthy volunteers) and have no-to-minimal effects on physiological measures. While it is yet unclear whether psychedelic microdosing is of therapeutic value for depression, the aforementioned effects on selective processes suggest that low doses of psychedelics could play a role in depression by inducing some kind of cognitive flexibility, which might lead to decreased rumination. While previous studies were conducted mostly in small samples of healthy volunteers, future placebo-controlled clinical trials in depressed patients are required to understand the therapeutic value of microdosing psychedelics, how this differs from therapy using full psychedelic doses, and whether different psychedelics have different effect patterns. The proposed research will give new insights into the potential of future alternative psychiatric treatment forms that are fiercely needed.

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LSD acutely impairs working memory, executive functions, and cognitive flexibility, but not risk-based decision-making

Cited by 74 publications

References 69 publications

LSD-induced increases in social adaptation to opinions similar to one’s own are associated with stimulation of serotonin receptors

LSD-induced increases in social adaptation to opinions similar to one’s own are associated with stimulation of serotonin receptors

Depression, Mindfulness, and Psilocybin: Possible Complementary Effects of Mindfulness Meditation and Psilocybin in the Treatment of Depression. A Review

The therapeutic potential of microdosing psychedelics in depression

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