The effects of psilocybin on cognitive and emotional functions in healthy participants: Results from a phase 1, randomised, placebo-controlled trial involving simultaneous psilocybin administration and preparation

Background: Psilocybin, a psychoactive serotonin receptor partial agonist, has been reported to acutely reduce clinical symptoms of depressive disorders. Psilocybin’s effects on cognitive function have not been widely or systematically studied. Aim: The aim of this study was to explore the safety of simultaneous administration of psilocybin to healthy participants in the largest randomised controlled trial of psilocybin to date. Primary and secondary endpoints assessed the short- and longer-term change in cognitive functioning, as assessed by a Cambridge Neuropsychological Test Automated Battery (CANTAB) Panel, and emotional processing scales. Safety was assessed via endpoints which included cognitive function, assessed by CANTAB global composite score, and treatment-emergent adverse event (TEAE) monitoring. Methods: In this phase 1, randomised, double-blind, placebo-controlled study, healthy participants ( n = 89; mean age 36.1 years; 41 females, 48 males) were randomised to receive a single oral dose of 10 or 25 mg psilocybin, or placebo, administered simultaneously to up to six participants, with one-to-one psychological support – each participant having an assigned, dedicated therapist available throughout the session. Results: In total, 511 TEAEs were reported, with a median duration of 1.0 day; 67% of all TEAEs started and resolved on the day of administration. There were no serious TEAEs, and none led to study withdrawal. There were no clinically relevant between-group differences in CANTAB global composite score, CANTAB cognitive domain scores, or emotional processing scale scores. Conclusions: These results indicate that 10 mg and 25 mg doses of psilocybin were generally well tolerated when given to up to six participants simultaneously and did not have any detrimental short- or long-term effects on cognitive functioning or emotional processing. Clinical Trial Registration: EudraCT ( https://www.clinicaltrialsregister.eu/ ) number: 2018-000978-30.

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Corticosteroids versus clobazam in epileptic encephalopathy with ESES: a European multicentre randomised controlled clinical trial (RESCUE ESES*)

Trials ◽

10.1186/s13063-020-04874-2 ◽

2020 ◽

Vol 21 (1) ◽

Author(s):

Bart van den Munckhof ◽

◽

Alexis Arzimanoglou ◽

Emilio Perucca ◽

Heleen C. van Teeseling ◽

...

Keyword(s):

Cognitive Functioning ◽

Treatment Response ◽

Controlled Trial ◽

Epileptic Encephalopathy ◽

Cognitive Outcome ◽

Controlled Study ◽

Controlled Clinical Trial ◽

Epilepsy Syndrome ◽

Eeg Abnormalities ◽

Randomised Controlled

Abstract Background Epileptic encephalopathy with electrical status epilepticus in sleep (ESES) is an epilepsy syndrome occurring almost exclusively in children, usually at an age between 4 and 12 years. It is characterised by abundant sleep-induced epileptic activity in the electroencephalogram (EEG) and by acquired cognitive and behavioural deficits. The goal of treatment is to prevent further decline or even improve cognitive functioning. Based on mostly small and retrospective studies, corticosteroids and clobazam are regarded by many clinicians as the most effective pharmacological treatments. This European multicentre randomised controlled trial is designed to compare the effects of corticosteroids and clobazam on cognitive functioning after 6 months. Secondary outcomes include cognitive functioning after 18 months, EEG abnormalities in sleep, safety and tolerability, and seizure frequency. We also aimed at investigating whether treatment response in epileptic encephalopathy with ESES can be predicted by measurement of inflammatory mediators and autoantibodies in serum. Methods The pragmatic study will be performed in centres with expertise in the treatment of rare paediatric epilepsy syndromes across Europe. A total of 130 patients, 2 to 12 years of age, with epileptic encephalopathy with ESES will be enrolled and randomised in a 1:1 ratio to receive either corticosteroids (monthly intravenous methylprednisolone pulses or daily oral prednisolone) or oral clobazam for 6 months according to an open-label parallel-group design. Follow-up visits with clinical assessment, EEGs, and neuropsychological testing are scheduled for up to 18 months. Blood samples for cytokine and autoantibody testing are obtained before treatment and 8 months after treatment initiation. Discussion The treatment of epileptic encephalopathy with ESES aims at improving cognitive outcome. This randomised controlled study will compare the most frequently used treatments, i.e. corticosteroids and clobazam. If the study proves superiority of one treatment over the other or identifies biomarkers of treatment response, results will guide clinicians in the early treatment of this severe epilepsy syndrome. Trial registration ISRCTN, ISRCTN42686094. Registered on 24 May 2013.

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Effect of buspirone, a serotonin1A partial agonist, on cognitive function in schizophrenia: A randomized, double-blind, placebo-controlled study

Schizophrenia Research ◽

10.1016/j.schres.2007.06.008 ◽

2007 ◽

Vol 95 (1-3) ◽

pp. 158-168 ◽

Cited By ~ 93

Author(s):

Tomiki Sumiyoshi ◽

Sohee Park ◽

Karu Jayathilake ◽

Ajanta Roy ◽

Aygun Ertugrul ◽

...

Keyword(s):

Cognitive Function ◽

Partial Agonist ◽

Controlled Study ◽

Double Blind ◽

Double Blind Placebo

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Safety and tolerability of ubrogepant following intermittent, high-frequency dosing: Randomized, placebo-controlled trial in healthy adults

Cephalalgia ◽

10.1177/0333102419869918 ◽

2019 ◽

Vol 39 (14) ◽

pp. 1753-1761 ◽

Cited By ~ 14

Author(s):

Peter J Goadsby ◽

Stewart J Tepper ◽

Paul B Watkins ◽

Girma Ayele ◽

Rosa Miceli ◽

...

Keyword(s):

Alanine Aminotransferase ◽

High Frequency ◽

Controlled Trial ◽

Phase 1 ◽

Healthy Adults ◽

Double Blind ◽

Upper Limit ◽

Safety Population ◽

Cgrp Receptor Antagonist ◽

Healthy Participants

Background Ubrogepant is a novel, oral calcitonin gene–related peptide (CGRP) receptor antagonist in development for the acute treatment of migraine. This trial evaluated the safety and tolerability of ubrogepant, focusing on hepatic safety, when administered intermittently with high-frequency dosing to healthy participants. Methods In this phase 1, multicenter, double-blind, parallel-group trial, healthy adults (age 18–50 years) were randomized 1:1 to placebo or ubrogepant. Ubrogepant was dosed at 100 mg (2 × 50 mg tablets) on 2 consecutive days followed by 2 consecutive days of placebo, alternating for 8 weeks. Primary outcome measures were safety and tolerability. Results Of participants randomized (n = 518), 516 were included in the safety population (n = 260 placebo; n = 256 ubrogepant). Treatment-emergent adverse events were reported in 45% of placebo and 44% of ubrogepant participants. The most common was headache (10% placebo; 11% ubrogepant). Overall, seven cases of alanine aminotransferase and/or aspartate aminotransferase levels ≥ 3 × the upper limit of normal (five placebo, two ubrogepant) were reported and adjudicated by a panel of independent liver experts blinded to treatment. Four cases were judged unlikely related to treatment. Two cases (one placebo, one ubrogepant) were judged possibly related, and one (ubrogepant) probably related. Alanine aminotransferase increases to ≥ 3 × the upper limit of normal in the two ubrogepant cases (possibly or probably related) were transient and resolved with continued dosing; both cases were asymptomatic, with no concurrent bilirubin elevation. Conclusion Ubrogepant was well tolerated following intermittent, high-frequency dosing in healthy participants, with no clinically relevant signal of hepatotoxicity. Trial Registration NA.

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Evaluation of titanium mesh cranioplasty and polyetheretherketone cranioplasty: protocol for a multicentre, assessor-blinded, randomised controlled trial

BMJ Open ◽

10.1136/bmjopen-2019-033997 ◽

2019 ◽

Vol 9 (12) ◽

pp. e033997

Author(s):

Jingguo Yang ◽

Tong Sun ◽

Yikai Yuan ◽

Xuepei Li ◽

Hang Yu ◽

...

Keyword(s):

Cognitive Function ◽

Controlled Trial ◽

Haemorrhagic Stroke ◽

Cerebral Hemodynamics ◽

Controlled Study ◽

Complication Rates ◽

Titanium Mesh ◽

Next Of Kin ◽

Implant Materials ◽

Randomised Controlled

IntroductionCranioplasty is a common surgery in neurosurgery department. However, restoring the integrity of skull brings many challenges to surgeons, and the selection of ideal implant materials is throughout the history of cranioplasty. Although titanium mesh was still preferred by many neurosurgeons in cranial reconstruction, the new polyetheretherketone (PEEK) material, for example, is gaining popularity for craniofacial reconstruction today. There remain limited data that compare the outcome of PEEK cranioplasty and titanium mesh cranioplasty. It is necessary to conduct a study to compare outcome of different materials for cranioplasty.Methods/designIn this multicentre, assessor-blinded, randomised controlled study, we will randomise 140 patients in a 1:1 ratio to PEEK cranioplasty versus titanium cranioplasty. Eligible patients are adults who were diagnosed with cranial defect (due to severe traumatic brain injury, ischaemic stroke, haemorrhagic stroke, infiltrative tumour and so on), the defect size is over 25 cm2, and they need to agree to participate in this trial. Instead of standard examinations, the enrolled patients receive neurological, motor, cognitive function and cerebral hemodynamics examinations as well as cosmetic evaluation. The procedures are repeated 3, 6 months after cranioplasty. The primary outcome, defined as infection or implant exposure after surgery, is the implant failure rate within 6 months. Secondary outcomes include postoperative complication rates, neurological outcomes, motor function, cerebral hemodynamics, cosmetic outcome and the total cost over a 6-month period.Ethics and disseminationThis trial protocol has been approved by Biomedical Research Ethics Committee of West China Hospital of Sichuan University. All patients will be fully informed the implant materials, potential complications after surgery, responsibilities during the trial, and they will sign the informed consent before joining in this trial. If the patient’s cognitive function is impaired, the patient’s next of kin would be carefully informed. The results will be disseminated through academic conferences, student theses and will be published in a peer-reviewed journal.Trail registration numberChiCTR1900024625; Pre-results.

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Effects of a 12-week Avocado Randomized-controlled Trial on Cognitive Function and Lutein Status Among Adults with Overweight and Obesity (OR05-01-19)

Current Developments in Nutrition ◽

10.1093/cdn/nzz029.or05-01-19 ◽

2019 ◽

Vol 3 (Supplement_1) ◽

Author(s):

Caitlyn Edwards ◽

Anne Walk ◽

Sharon Thompson ◽

Ginger Reeser ◽

John Erdman ◽

...

Keyword(s):

Cognitive Function ◽

Selective Attention ◽

Flanker Task ◽

Controlled Trial ◽

Intervention Group ◽

Overweight And Obesity ◽

Controlled Study ◽

Control Group ◽

Daily Consumption ◽

Randomized Controlled

Abstract Objectives Overweight and obesity affect over two-thirds of the US population. This is concerning, as excess adiposity increases risk for dementia in later life. Thus, it is important to elucidate dietary approaches that benefit cognition. Lutein is a xanthophyll carotenoid thought to impact cognitive function. Daily consumption of avocado has been shown to improve cognitive function and lutein status but it is not clear whether these benefits extend to populations with overweight and obesity. Thus, we evaluated the influence of daily avocado consumption on cognitive function, serum lutein concentrations, and retinal xanthophyll status among adults with overweight and obesity using a randomized-controlled study. Methods Adults (N = 72, 25–45 years, 31 males) with overweight or obesity (BMI 25 kg/m2) were randomized to an intervention group (N = 38) that received a daily meal with one avocado or a control group (N = 34) that received an isocaloric meal without avocado for 12 weeks. Fasting serum lutein concentrations were evaluated through high-performance liquid chromatography. Macular pigment optical density (MPOD) was assessed through heterochromatic flicker photometry. Selective attention was assessed by a modified Flanker task. Results Group by time interactions were seen for serum lutein concentrations (P = 0.002) and flanker accuracy (P = 0.006) whereby the intervention group exhibited a more substantial increase in serum lutein concentrations (0.04 ug/ml; 95% CI, 0.02 to 0.06) and overall task accuracy (2.4%; 95% CI, 0.4 to 4.5). However, there was no relationship between task performance and changes in serum lutein concentration (P = 0.23), nor changes in MPOD. Conclusions Daily consumption of a meal containing avocado improved selective attention and serum lutein concentrations among adults with overweight and obesity. The cognitive benefits of avocado consumption were apparent even prior to changes in retinal lutein status. Given that avocados are comprised of a variety of nutrients, additional work is necessary to determine non-carotenoid dependent mechanisms by which avocados may impact cognitive function. Funding Sources This work was supported by funds from the Hass Avocado Board, the Department of Kinesiology and Community Health at the University of Illinois, and the USDA National Institute of Food and Agriculture, Hatch project 1009249.

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Improvement in cognitive function in young people with bipolar disorder: Results from participants in an 18-month randomised controlled trial of adjunctive psychotherapy

Australian & New Zealand Journal of Psychiatry ◽

10.1177/0004867419887794 ◽

2019 ◽

Vol 54 (3) ◽

pp. 272-281 ◽

Cited By ~ 2

Author(s):

Richard J Porter ◽

Maree Inder ◽

Katie M Douglas ◽

Stephanie Moor ◽

Janet D Carter ◽

...

Keyword(s):

Bipolar Disorder ◽

Cognitive Function ◽

Young People ◽

Clinical Management ◽

Controlled Trial ◽

Cognitive Testing ◽

Composite Score ◽

Social Rhythm ◽

The Impact

Objective: To examine the effects of 18 months of intensive stabilisation with medication management and Interpersonal and Social Rhythm Therapy or Non-specific Supportive Clinical Management on cognitive function in young people with bipolar disorder. Determinants of change in cognitive function over the 18 months of the trial were also examined. Method: Patients aged 15–36 years with Bipolar I Disorder, Bipolar II Disorder and Bipolar Not Otherwise Specified were recruited. From a battery of cognitive tests, change scores for pre-defined domains of cognitive function were created based on performance at baseline and follow-up. Change was compared between the two therapy groups. Regression analysis was used to determine the impact of a range of clinical variables on change in cognitive performance between baseline and follow-up. Results: One hundred participants were randomised to Interpersonal and Social Rhythm Therapy ( n = 49) or Non-specific Supportive Clinical Management ( n = 51). Seventy-eight patients underwent cognitive testing at baseline and 18 months. Across both groups, there were significant improvements in a Global Cognitive Composite score, Executive Function and Psychomotor Speed domains from baseline to 18 months. Lower scores at baseline on all domains were associated with greater improvement over 18 months. Overall, there was no difference between therapies in change in cognitive function, either in a global composite score or change in domains. Conclusion: While there was no difference between therapy groups, intensive stabilisation with psychological therapy was associated with improved cognitive function, particularly in those patients with poorer cognitive function at baseline. However, this was not compared with treatment as usual so cannot be attributed necessarily to the therapies.

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Corticosteroids versus clobazam in epileptic encephalopathy with ESES: a European multicenter randomized controlled clinical trial (RESCUE ESES*)

10.21203/rs.3.rs-22593/v1 ◽

2020 ◽

Author(s):

Bart van den Munckhof ◽

Alexis Arzimanoglou ◽

Emilio Perucca ◽

Heleen C. van Teeseling ◽

Frans S.S. Leijten ◽

...

Keyword(s):

Cognitive Functioning ◽

Treatment Response ◽

Controlled Trial ◽

Epileptic Encephalopathy ◽

Cognitive Outcome ◽

Controlled Study ◽

Controlled Clinical Trial ◽

Epilepsy Syndrome ◽

Randomized Controlled ◽

Eeg Abnormalities

Abstract Background: Epileptic encephalopathy with electrical status epilepticus in sleep (ESES) is an epilepsy syndrome occurring almost exclusively in children, usually at an age between 4 and 12 years. It is characterized by abundant sleep-induced epileptic activity in the electroencephalogram (EEG) and by acquired cognitive and behavioural deficits. The goal of treatment is to prevent further decline or even improve cognitive functioning. Based on mostly small and retrospective studies, corticosteroids and clobazam are regarded by many clinicians as the most effective pharmacological treatments. This European multicentre randomized controlled trial is designed to compare the effects of corticosteroids and clobazam on cognitive functioning after 6 months. Secondary outcomes include cognitive functioning after 18 months, EEG abnormalities in sleep, safety and tolerability, and seizure frequency. We also aimed at investigating whether treatment response in epileptic encephalopathy with ESES can be predicted by measurement of inflammatory mediators and auto-antibodies in serum.Methods: The pragmatic study will be performed in centres with expertise in the treatment of rare paediatric epilepsy syndromes across Europe. 130 patients, 2 to 12 years of age, with epileptic encephalopathy with ESES will be enrolled and randomized in a 1:1 ratio to receive either corticosteroids (monthly intravenous methylprednisolone pulses or daily oral prednisolone) or oral clobazam for 6 months according to an open-label parallel-group design. Follow-up visits with clinical assessment, EEGs and neuropsychological testing are scheduled for up to 18 months. Blood samples for cytokine and auto-antibody testing are obtained before treatment and after 8 months of treatment.Discussion: The treatment of epileptic encephalopathy with ESES aims at improving cognitive outcome. This randomized controlled study will compare the most frequently used treatments, i.e. corticosteroids and clobazam. If the study proves superiority of one treatment over the other or identifies biomarkers of treatment response, results will guide clinicians in the early treatment of this severe epilepsy syndrome.Trial registration: ISRCTN, ISRCTN42686094, registered 24 May 2013, http://www.isrctn.com/ISRCTN42686094

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