Psychedelic drugs: neurobiology and potential for treatment of psychiatric disorders

Vollenweider, Franz X.; Preller, Katrin H.

doi:10.1038/s41583-020-0367-2

Cited by 324 publications

(366 citation statements)

References 180 publications

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“…Various brain-imaging studies have furthermore explored how psychedelics change the functional architecture of the brain when participants are not engaged in any task using different methodological approaches. While some of the results have not yet revealed a consistent pattern (for review, see [138]), one of the most replicated findings is a psychedelic-induced acute decrease in connectivity between nodes of the DMN [139][140][141][142][143][144]. This result is of particular interest, as MD has been associated with increased DMN connectivity (see above).…”

Section: Changes In Neuropsychological Functions and Functional Networkmentioning

confidence: 96%

Classical Psychedelics as Therapeutics in Psychiatry – Current Clinical Evidence and Potential Therapeutic Mechanisms in Substance Use and Mood Disorders

Mertens

Preller

2021

Pharmacopsychiatry

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Classical psychedelics, primarily psilocybin and lysergic acid diethylamide (LSD), have been used and extensively studied in Western medicine as part of substance-assisted psychotherapy in the 1950s and 1960s. Modern clinical research is currently gaining momentum and provides new evidence for the safety and efficacy of classical psychedelics (primarily psilocybin, but also LSD and ayahuasca) in the treatment of different psychiatric conditions, including substance use and mood disorders.In this review article, we outline common pathological mechanisms of substance use disorders (SUD) and unipolar depression. Next, the current literature on the effects of psychedelics is summarized in order to generate hypotheses regarding their potential therapeutic mechanisms of action in treating these psychiatric conditions. Finally, we review and discuss clinical trials published since 2011 investigating the effects of psychedelics in SUD and depression.While results from those modern clinical trials are promising, most of them do not meet the methodological requirements to allow firm conclusions on the clinical efficacy of psychedelics. Larger, blinded, randomized controlled trials (RCT) with clearly defined patient groups and well-defined primary endpoints are needed. Additionally, the therapeutic mechanisms of classical psychedelics are currently unknown. This review presents hypotheses derived from preclinical and human studies that need to be tested in future trials to better understand the clinical potential of psychedelic substances in modern psychiatry.

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Section: Changes In Neuropsychological Functions and Functional Networkmentioning

confidence: 96%

Classical Psychedelics as Therapeutics in Psychiatry – Current Clinical Evidence and Potential Therapeutic Mechanisms in Substance Use and Mood Disorders

Mertens

Preller

2021

Pharmacopsychiatry

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“…Psilocybin is a classical serotonergic psychedelic; a unique class of drugs capable of inducing profound alterations of perception, cognition, and behaviour, commonly characterised as the psychedelic state. A growing body of evidence suggests that, under appropriately controlled conditions, acute psilocybin exposure can promote long-lasting positive effects on mood and psychological well-being, offering a promising new treatment method for affective disorders (Carhart-Harris et al, 2016; Carhart-Harris & Goodwin, 2017; Davis et al, 2020; Vollenweider & Preller, 2020).…”

Section: Introductionmentioning

confidence: 99%

Psilocin acutely disrupts sleep and affects local but not global sleep homeostasis in laboratory mice

Thomas

Blanco‐Duque

Bréant

et al. 2021

Preprint

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Serotonergic psychedelic drugs, such as psilocin (4-hydroxy-N,N-dimethyltryptamine), profoundly alter the quality of consciousness through mechanisms which are incompletely understood. Growing evidence suggests that a single psychedelic experience can positively impact long-term psychological well-being, with relevance for the treatment of psychiatric disorders, including depression. A prominent factor associated with psychiatric disorders is disturbed sleep, and the sleep-wake cycle is implicated in the regulation of neuronal firing and activity homeostasis. It remains unknown to what extent psychedelic agents directly affect sleep, in terms of both acute arousal and homeostatic sleep regulation. Here, chronic in vivo electrophysiological recordings were obtained in mice to track sleep-wake architecture and cortical activity after psilocin injection. Administration of psilocin led to delayed REM sleep onset and reduced NREM sleep maintenance for up to approximately 3 hours after dosing, and the acute EEG response was associated primarily with an enhanced oscillation around 4 Hz. No long-term changes in sleep-wake quantity were found. When combined with sleep deprivation, psilocin did not alter the dynamics of homeostatic sleep rebound during the subsequent recovery period, as reflected in both sleep amount and EEG slow wave activity. However, psilocin decreased the recovery rate of sleep slow wave activity following sleep deprivation in the local field potentials of electrodes targeting medial prefrontal and surrounding cortex. It is concluded that psilocin affects both global vigilance state control and local sleep homeostasis, an effect which may be relevant for its antidepressant efficacy.

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“…Research into lysergic acid diethylamide (LSD) as a potential therapeutic agent in psychiatry has been revitalised in recent years (Nutt and Carhart-Harris 2020; Vollenweider and Preller 2020). Theories on the putative beneficial effects of LSD on mental health centre on its effects on learning and plasticity (Carhart-Harris and Nutt 2017), yet few studies have examined its effect on human behaviour.…”

Section: Introductionmentioning

confidence: 99%

Effect of lysergic acid diethylamide (LSD) on reinforcement learning in humans

Kanen

Luo

Kandroodi

et al. 2020

Preprint

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The non-selective serotonin 2A (5-HT2A) receptor agonist lysergic acid diethylamide (LSD) holds promise as a treatment for some psychiatric disorders. Psychedelic drugs such as LSD have been suggested to have therapeutic actions through their effects on learning. The behavioural effects of LSD in humans, however, remain largely unexplored. Here we examined how LSD affects probabilistic reversal learning in healthy humans. Healthy volunteers received intravenous LSD (75μg in 10 mL saline) or placebo (10mL saline) in a within-subjects design and completed a probabilistic reversal learning task. Participants had to learn through trial and error which of three stimuli was rewarded most of the time, and these contingencies switched in a reversal phase. Computational models of reinforcement learning were fitted to the behavioural data to assess how LSD affected the updating (“learning rates”) and deployment (“reinforcement sensitivity”) of value representations during choice, as well as “stimulus stickiness”, which assays choice repetition irrespective of reinforcement history. Conventional measures assessing sensitivity to immediate feedback (“win-stay” and “lose-shift” probabilities) were unaffected, whereas LSD increased the impact of the strength of initial learning on perseveration. Computational modelling revealed that the most pronounced effect of LSD was enhancement of the reward learning rate. The punishment learning rate was also elevated. Stimulus stickiness was decreased by LSD, reflecting heightened exploratory behaviour, while reinforcement sensitivity was unaffected. Increased reinforcement learning rates suggest LSD induced a state of heightened plasticity. These results indicate a potential mechanism through which revision of maladaptive associations could occur in the clinical application of LSD.Significance statementThe psychedelic (“mind-manifesting”) drug LSD holds promise for the treatment of some psychiatric disorders. Theories have postulated its therapeutic potential centres on enhancing learning and flexible thinking. Here we provide substantiating empirical evidence by examining the computations underlying behaviour as healthy volunteers learned through trial and error under LSD. Viewing choice as based on representations of an action’s value, LSD increased the speed at which value was updated following feedback, which was more pronounced following reward than punishment. Behaviour was also more exploratory under LSD, irrespective of the outcome of actions. These results indicate that LSD impacted a fundamental belief-updating process inherent in the brain which can be leveraged to revise maladaptive associations characteristic of a range of mental disorders.

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Psychedelic drugs: neurobiology and potential for treatment of psychiatric disorders

Cited by 324 publications

References 180 publications

Classical Psychedelics as Therapeutics in Psychiatry – Current Clinical Evidence and Potential Therapeutic Mechanisms in Substance Use and Mood Disorders

Classical Psychedelics as Therapeutics in Psychiatry – Current Clinical Evidence and Potential Therapeutic Mechanisms in Substance Use and Mood Disorders

Psilocin acutely disrupts sleep and affects local but not global sleep homeostasis in laboratory mice

Effect of lysergic acid diethylamide (LSD) on reinforcement learning in humans

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