Ignite Creation Date:
2024-10-26 @ 3:35 PM
Last Modification Date:
2024-10-26 @ 3:35 PM
Study NCT ID:
NCT06506019
Status:
RECRUITING
Last Update Posted:
None
First Post:
2024-06-26
Brief Title:
Neurobiological Effects of Psilocybin in Treatment Resistant Bipolar Depression
Sponsor:
None
Organization:
None
Study Overview
Official Title:
Neurobiological Effects of Psilocybin in Treatment Resistant Bipolar Depression An Emotional-Processing fMRI Pilot Study
Status:
RECRUITING
Status Verified Date:
2024-10
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
No
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
Psilo-BD
Brief Summary:
This study is an open-label single-arm proof-of-concept study wherein treatment resistant bipolar depression TRBD participants will receive one 25 mg dose of oral psilocybin accompanied by preparatory monitoring and integration psychotherapy sessions psilocybin-assisted psychotherapy or PAP Using fMRI functional magnetic resonance imaging the findings of this study will provide data on the neurobiological mechanism of psilocybin in TRBD
The primary objective is to understand the dynamic role of amygdala activity by evaluating the neurobiological effects of a single psychedelic dose 25 mg of oral psilocybin in individuals with a moderate to severe major depressive episode and a primary diagnosis of Bipolar II Disorder with 2 or more failed treatment trials ie treatment resistant bipolar depression TRBD Neurobiological effects will be determined by evaluating the association between post-treatment right amygdala activity during the facial affect task determined by fMRI one day after the psilocybin dose and antidepressant effects determined by changes in the Montgomery-Åsberg Depression Rating Scale MADRS scores over time during the one-week period post-psilocybin dose This is a single-arm open-label clinical trial wherein all participants will receive the same study intervention
Hypothesis Increased right amygdala activity on fMRI with emotional stimuli one day after psilocybin treatment will be associated with greater antidepressant effects in the one-week period post-treatment in individuals with TRBD
The primary objective is to understand the dynamic role of amygdala activity by evaluating the neurobiological effects of a single psychedelic dose 25 mg of oral psilocybin in individuals with a moderate to severe major depressive episode and a primary diagnosis of Bipolar II Disorder with 2 or more failed treatment trials ie treatment resistant bipolar depression TRBD Neurobiological effects will be determined by evaluating the association between post-treatment right amygdala activity during the facial affect task determined by fMRI one day after the psilocybin dose and antidepressant effects determined by changes in the Montgomery-Åsberg Depression Rating Scale MADRS scores over time during the one-week period post-psilocybin dose This is a single-arm open-label clinical trial wherein all participants will receive the same study intervention
Hypothesis Increased right amygdala activity on fMRI with emotional stimuli one day after psilocybin treatment will be associated with greater antidepressant effects in the one-week period post-treatment in individuals with TRBD
Detailed Description:
Individuals with bipolar disorder BD spend a third of their lives in the midst of a depressive episode BD is a severe and persistent mental illness with a lifetime prevalence of 2-3 Bipolar depression remains a significant treatment challenge with a paucity of evidence-based treatments Only four pharmacological treatments for acute bipolar depression cariprazine olanzapine-fluoxetine combination quetiapine and lurasidone are approved by the US Food and Drug Administration FDA Other medications often used for the treatment of BD are those primarily used to treat mania or psychosis ie lithium antipsychotics or major depressive disorder MDD ie antidepressants Lamotrigine which is recommended by international guidelines as a maintenance treatment for BD to prevent depressive recurrence has limited efficacy for acute BD Current medication options are also limited by adverse effects including renal and thyroid impairment with long-term lithium therapy and weight gain and metabolic abnormalities with atypical antipsychotics Furthermore treatment outcomes remain poor particularly for depressive episodes with over one-third of patients failing to respond to two or more first-line treatments Hence there is a clear need for novel and efficacious treatments for BD However there is a limited understanding of the neurobiology of BD which poses as a major barrier to identifying truly innovative treatments
Psilocybin is a chemical compound that naturally occurs in certain species of mushrooms for example in the psilocybe genus among others It belongs to a class of drugs referred to as psychedelics Psilocybin is a tryptamine which is chemically similar to the neurotransmitter serotonin and the essential amino acid tryptophan It is considered a 5-hydroxytrptamineric serotonergic psychedelic along with other similar drugs such as dimethyltryptamine DMT and lysergic acid dieythamide LSD Psilocybin is a product for the pharmacologically active ingredient psilocin which readily crosses the blood-brain barrier and acts as a potential partial agonist at serotonin 5HT2A and 5HT2c receptors in the brain Typical effects of psilocybin include significantly altered states of consciousness experienced through visual and auditory effects changes in perception distortions of time and a range of effects including a sense of awe novel perspectives existential and personal insight dramatically heightened empathy and feelings of compassion strong emotions and unitive experience With proper screening and preparation psilocybin has a safe physiological and psychological profile Psilocybin is currently the preferred compound for use in clinical research involving 5-hydroxytrptaminergic psychedelics because it has a shorter duration of action and suffers from less notoriety and stigma than other similar drugs
Two recently completed clinical trials have assessed the effects of psilocybin on TRD in participants with BDII The first study was a non-randomized controlled trial that demonstrated a single 25 mg dose of psilocybin with accompanying PAP led to a decrease in MADRS scores in all study participants n15 at the 3-week primary endpoint The second study was a randomized controlled trial that included participants with both unipolar n27 and bipolar treatment-resistant depression n4 wherein all participants received at least one 25 mg dose of psilocybin with accompanying PAP with the exception of one participant who dropped out of the study before receiving the study intervention Participants had the opportunity to receive up to two additional 25 mg doses of psilocybin with accompanying PAP if they were eligible to receive a repeat dose as per the study protocol Both trials demonstrated that 25 mg of psilocybin resulted in a decrease of depressive symptoms in participants with treatment-resistant bipolar depression without increased incidence of manic or hypomanic symptoms
Beyond the clinical benefits observed psilocybin has provided several new insights into the neurobiology of depression with dozens of additional ongoing mechanistic studies underway Neuroimaging studies evaluating the effects of psilocybin in treatment-resistant unipolar depression TRD have provided surprising neurobiological insights that have called into question several assumptions of mood disorders In an open-label TRD trial evaluating the antidepressant and neurobiological effects of psilocybin increased activity of the right amygdala was observed in response to fearful and happy faces post-treatment Psilocybins antidepressant effects were associated with increased right amygdala responses to negative emotional stimuli an opposite effect to previous findings with selective serotonin reuptake inhibitors SSRIs Wherein SSRIs mitigate negative emotions psilocybin might allow patients to feel confront and work through them These findings also suggest that neurobiological targets and mechanisms required to alleviate TRD may be different from non-resistant depression where SSRIs are often effective by reducing amygdala response to negative stimuli Notably the impact of psilocybin on amygdala function varies inter-individually depending on baseline mood state More specifically in healthy volunteers psilocybin has been shown to decrease amygdala response to emotional stimuli whereas in TRD psilocybin was associated with increased amygdala response Evaluating the effects of psilocybin in TRBD may improve the investigators understanding of the neurobiology of bipolar depression by dynamically evaluating altered amygdala function and associated changes in depressive symptoms over time
Psilocybin is a chemical compound that naturally occurs in certain species of mushrooms for example in the psilocybe genus among others It belongs to a class of drugs referred to as psychedelics Psilocybin is a tryptamine which is chemically similar to the neurotransmitter serotonin and the essential amino acid tryptophan It is considered a 5-hydroxytrptamineric serotonergic psychedelic along with other similar drugs such as dimethyltryptamine DMT and lysergic acid dieythamide LSD Psilocybin is a product for the pharmacologically active ingredient psilocin which readily crosses the blood-brain barrier and acts as a potential partial agonist at serotonin 5HT2A and 5HT2c receptors in the brain Typical effects of psilocybin include significantly altered states of consciousness experienced through visual and auditory effects changes in perception distortions of time and a range of effects including a sense of awe novel perspectives existential and personal insight dramatically heightened empathy and feelings of compassion strong emotions and unitive experience With proper screening and preparation psilocybin has a safe physiological and psychological profile Psilocybin is currently the preferred compound for use in clinical research involving 5-hydroxytrptaminergic psychedelics because it has a shorter duration of action and suffers from less notoriety and stigma than other similar drugs
Two recently completed clinical trials have assessed the effects of psilocybin on TRD in participants with BDII The first study was a non-randomized controlled trial that demonstrated a single 25 mg dose of psilocybin with accompanying PAP led to a decrease in MADRS scores in all study participants n15 at the 3-week primary endpoint The second study was a randomized controlled trial that included participants with both unipolar n27 and bipolar treatment-resistant depression n4 wherein all participants received at least one 25 mg dose of psilocybin with accompanying PAP with the exception of one participant who dropped out of the study before receiving the study intervention Participants had the opportunity to receive up to two additional 25 mg doses of psilocybin with accompanying PAP if they were eligible to receive a repeat dose as per the study protocol Both trials demonstrated that 25 mg of psilocybin resulted in a decrease of depressive symptoms in participants with treatment-resistant bipolar depression without increased incidence of manic or hypomanic symptoms
Beyond the clinical benefits observed psilocybin has provided several new insights into the neurobiology of depression with dozens of additional ongoing mechanistic studies underway Neuroimaging studies evaluating the effects of psilocybin in treatment-resistant unipolar depression TRD have provided surprising neurobiological insights that have called into question several assumptions of mood disorders In an open-label TRD trial evaluating the antidepressant and neurobiological effects of psilocybin increased activity of the right amygdala was observed in response to fearful and happy faces post-treatment Psilocybins antidepressant effects were associated with increased right amygdala responses to negative emotional stimuli an opposite effect to previous findings with selective serotonin reuptake inhibitors SSRIs Wherein SSRIs mitigate negative emotions psilocybin might allow patients to feel confront and work through them These findings also suggest that neurobiological targets and mechanisms required to alleviate TRD may be different from non-resistant depression where SSRIs are often effective by reducing amygdala response to negative stimuli Notably the impact of psilocybin on amygdala function varies inter-individually depending on baseline mood state More specifically in healthy volunteers psilocybin has been shown to decrease amygdala response to emotional stimuli whereas in TRD psilocybin was associated with increased amygdala response Evaluating the effects of psilocybin in TRBD may improve the investigators understanding of the neurobiology of bipolar depression by dynamically evaluating altered amygdala function and associated changes in depressive symptoms over time
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None