Psilocybin Induces Time-Dependent Changes in Global Functional Connectivity

Preller, Katrin H.; Duerler, Patricia; Burt, Joshua B.; Ji, Jie Lisa; Adkinson, Brendan; Stämpfli, Philipp; Seifritz, Erich; Repovš, Grega; Krystal, John H.; Murray, John D.; Antičević, Alan; Vollenweider, Franz X.

doi:10.1016/j.biopsych.2019.12.027

Cited by 135 publications

(184 citation statements)

References 46 publications

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“…Although SSRIs are administered chronically, rendering a direct comparison with psychedelics difficult, it is interesting to note that these antidepressants also induce a similar reduction of functional connectivity in the DMN. Furthermore, 2 studies have shown that LSD and psilocybin acutely increase global functional connectivity in sensory brain areas while connectivity is reduced in associative brain regions including the DMN [143,145]. This could point to increased sensory processing and concurrently altered integration of information.…”

Section: Changes In Neuropsychological Functions and Functional Networkmentioning

confidence: 99%

“…These changes in DMN connectivity could enable patients to escape ruminative thinking patterns at least temporarily and pave the way for developing a new perspective on problems during integration work after a psychedelic dose. Furthermore, one study showed that the magnitude of changes in global connectivity induced by psilocybin was correlated with the participants' baseline connectivity [145]. It is therefore possible that global brain connectivity may represent a predictive marker of psilocybin-induced effects that could be relevant to predict treatment success.…”

Section: Changes In Neuropsychological Functions and Functional Networkmentioning

confidence: 99%

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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: 99%

Section: Changes In Neuropsychological Functions and Functional Networkmentioning

confidence: 99%

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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“…In addition to their effects on the DMN, psychedelics have been shown to acutely alter functional connectivity within and between various other brain regions. 86,87,[107][108][109] The ability of psychedelics to alter connectivity between brain regions may bear particular relevance to the treatment of functional movement disorders. In these disorders, while motor symptoms may have the appearance of voluntariness, patients experience movements as outside their volitional control-stated differently, there is an apparent loss of motor agency.…”

Section: The Temporoparietal Junction and Disruptions In The Agencymentioning

confidence: 99%

“…The findings of increased within‐network DMN functional connectivity in patients with FNDs are of particular interest when considering psychedelic therapy as a potential treatment for these disorders. Specifically, the ability of psychedelics to acutely diminish RSFC between nodes of the DMN 72,73,84‐87 could conceivably represent a biological correlate of the amelioration of FND symptoms induced by psychedelic administration. Examples of the latter are outlined in the case reports section.…”

Section: Mechanistic Models Of Fnds and Their Relevance To Psychedelimentioning

confidence: 99%

Psychedelic‐assisted therapy for functional neurological disorders: A theoretical framework and review of prior reports

Stewart

Dean

Koek

et al. 2020

Pharmacology Res & Perspec

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Functional neurological disorders (FNDs), which are sometimes also referred to as psychogenic neurological disorders or conversion disorder, are common disabling neuropsychiatric disorders with limited treatment options. FNDs can present with sensory and/or motor symptoms, and, though they may mimic other neurological conditions, they are thought to occur via mechanisms other than those related to identifiable structural neuropathology and, in many cases, appear to be triggered and sustained by recognizable psychological factors. There is intriguing preliminary evidence to support the use of psychedelic‐assisted therapy in a growing number of psychiatric illnesses, including FNDs. We review the theoretical arguments for and against exploring psychedelic‐assisted therapy as a treatment for FNDs. We also provide an in‐depth discussion of prior published cases detailing the use of psychedelics for psychosomatic conditions, analyzing therapeutic outcomes from a contemporary neuroscientific vantage as informed by several recent neuroimaging studies on psychedelics and FNDs.

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“…During the psychedelic experience, psilocybin produces a reduction in the synchronised BOLD activity of the major hubs of the default mode network (DMN) (Carhart-Harris et al, 2012; Mason et al, 2020), increases between-network RSFC (Roseman et al, 2014) and increases global RSFC across the sensory cortex while decreasing global connectivity in associative regions (Preller et al, 2020). Similarly, LSD increases RSFC between high-level association cortices, which correlates with subjective reports of egodissolution (Tagliazucchi et al, 2016).…”

Section: Introductionmentioning

confidence: 99%

Lasting effects of a single psilocybin dose on resting-state functional connectivity in healthy individuals

McCulloch

Madsen

Stenbæk

et al. 2021

Preprint

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BackgroundPsilocybin is a psychedelic drug that has shown lasting positive effects on clinical symptoms and self-reported well-being following a single dose. There has been little research into the long-term effects of psilocybin on brain connectivity in humans.AimsEvaluate changes in resting-state functional connectivity (RSFC) at one-week and three-months after one psilocybin dose in 10 healthy psychedelic-naïve volunteers and explore associations between change in RSFC and related measures.MethodsParticipants received 0.2-0.3 mg/kg psilocybin in a controlled setting. Participants completed resting-state fMRI scans at baseline, one-week and three-months post-administration and [11C]Cimbi-36 PET scans at baseline and one-week. We examined changes in within-network, between-network and region-to-region RSFC. We explored associations between changes in RSFC and psilocybin-induced phenomenology as well as changes in psychological measures and neocortex serotonin 2A receptor binding.ResultsPsilocybin was well tolerated and produced positive changes in well-being. At one-week only, executive control network (ECN) RSFC was significantly decreased (Cohen’s d=-1.73, pFWE=0.010). We observed no other significant changes in RSFC at one-week or three-months, nor changes in region-to-region RSFC. Exploratory analyses indicated that decreased ECN RSFC at one-week predicted increased mindfulness at three-months (r =-0.65).ConclusionsThese findings in a small cohort indicate that psilocybin affects ECN function within the psychedelic “afterglow” period. Our findings implicate ECN modulation as mediating psilocybin-induced, long-lasting increases in mindfulness. Although our findings implicate a neural pathway mediating lasting psilocybin effects, it is notable that changes in neuroimaging measures at three-months, when personality changes are observed, remain to be identified.

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Psilocybin Induces Time-Dependent Changes in Global Functional Connectivity

Cited by 135 publications

References 46 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

Psychedelic‐assisted therapy for functional neurological disorders: A theoretical framework and review of prior reports

Lasting effects of a single psilocybin dose on resting-state functional connectivity in healthy individuals

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