Psilocybin for Mild Cognitive Impairment
Recruiting in Palo Alto (17 mi)
Age: 18+
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 2
Recruiting
Sponsor: Centre for Addiction and Mental Health
Must not be taking: Anticonvulsants, Antidepressants, Antipsychotics, others
Disqualifiers: Unstable medical illness, Major depression, Substance dependence, others
Prior Safety Data
Trial Summary
What is the purpose of this trial?The goal of this clinical trial is to investigate the effects of psilocybin on synaptic vesicular density (SVD) as measured by the positron emission tomography (PET) radiotracer, 18F-SynVesT-1, in participants with amnestic Mild Cognitive Impairment (aMCI) and healthy participants. The investigators hypothesize that SVD levels in the brain will be higher following the ingestion of psilocybin in comparison to placebo, and that increases in SVD will be associated with improvements in cognition.
60 participants (30 with aMCI, and 30 sex and age matched healthy volunteers) will:
* Be randomized to receive either:
1. Two 25 mg macrodoses of psilocybin separated by 1 week.
2. Two placebo doses separated by 1 week.
* Receive a baseline 18F-SynVesT-1 PET scan, clinical, and neuropsychological assessments.
* Receive a 18F-SynVesT-1 PET scan one week after the last dose of treatment.
* Receive a third PET scan at any time within 4 weeks of the screening visit to quantify tauopathy with the \[18F\]T807 radiotracer.
* Receive clinical and neuropsychological testing 1, 4, and 12 weeks after the last treatment.
Researchers will compare placebo vs. experimental groups to see if psilocybin will increase SVD, and if increases in SVD are associated with cognitive improvements.
Do I have to stop taking my current medications for the trial?
The trial requires participants to be on a stable dose of medication for at least 2 months and unlikely to change during the study. However, certain medications like anticonvulsants, antidepressants, antipsychotics, mood stabilizers, opioids, benzodiazepines, and some others must be discontinued before participating.
What evidence supports the effectiveness of the drug psilocybin for mild cognitive impairment?
Research shows that psilocybin has been effective in improving mood and mental health, and it has shown promise in treating depression and other psychiatric disorders. While specific studies on mild cognitive impairment are limited, these findings suggest potential benefits for mental health conditions.
12345Is psilocybin generally safe for humans?
Psilocybin, found in 'magic mushrooms,' has been studied for its potential in treating conditions like depression and addiction. While it can cause hallucinations and other effects on the nervous system, recent studies suggest it may be safe in controlled settings, but more research is needed to fully understand its safety profile.
36789How does the drug psilocybin differ from other treatments for mild cognitive impairment?
Psilocybin is unique because it is a psychedelic compound that works by affecting serotonin receptors in the brain, which is different from traditional treatments for cognitive impairment. It has shown promise in treating other conditions like depression and addiction, suggesting it might offer novel benefits for cognitive issues.
3471011Eligibility Criteria
This trial is for people aged 60-75 with mild cognitive impairment who can consent to participate, have a study partner, and are non-smokers. They must not have used psychedelic drugs before or be at risk of exceeding radiation exposure from PET scans. Participants cannot join if they're pregnant, breastfeeding, on certain medications like anticoagulants or antidepressants, or have had recent serious health issues like strokes.Inclusion Criteria
I have been on the same dose of medication for at least 2 months and it's unlikely to change.
You have been diagnosed with Minor Neurocognitive Disorder (MCI) according to specific criteria set by doctors.
I am of any gender and from any racial or ethnic background.
+7 more
Exclusion Criteria
You are currently having thoughts about hurting yourself or someone else.
A close family member has schizophrenia, bipolar disorder, or a psychotic disorder not caused by substances or medical conditions.
I have been diagnosed with major depression, bipolar disorder, intellectual disability, Alzheimer's, or a psychotic disorder.
+16 more
Trial Timeline
Screening
Participants are screened for eligibility to participate in the trial
2-4 weeks
1 visit (in-person)
Baseline Assessment
Participants receive a baseline 18F-SynVesT-1 PET scan, clinical, and neuropsychological assessments
1 week
1 visit (in-person)
Treatment
Participants receive two doses of either psilocybin or placebo, separated by one week
2 weeks
2 visits (in-person)
Post-Treatment Assessment
Participants receive a 18F-SynVesT-1 PET scan one week after the last dose of treatment
1 week
1 visit (in-person)
Follow-up
Participants are monitored for safety and effectiveness after treatment with clinical and neuropsychological testing at 1, 4, and 12 weeks after the last treatment
12 weeks
3 visits (in-person)
Participant Groups
Researchers are testing whether psilocybin (a compound found in magic mushrooms) can increase synaptic vesicular density in the brain compared to a placebo. The study involves two doses of either psilocybin or placebo given one week apart and several PET scans and neuropsychological tests before and after treatment to measure changes.
4Treatment groups
Experimental Treatment
Placebo Group
Group I: Healthy Participants Receiving PsilocybinExperimental Treatment1 Intervention
Receiving 2 doses of 25mg of psilocybin separated by 1 week.
Group II: Amnestic Mild Cognitive Impairment Participants Receiving PsilocybinExperimental Treatment1 Intervention
Receiving 2 doses of 25mg of psilocybin separated by 1 week.
Group III: Healthy Participants Receiving PlaceboPlacebo Group1 Intervention
Receiving 2 doses of placebo separated by 1 week.
Group IV: Amnestic Mild Cognitive Impairment Participants Receiving PlaceboPlacebo Group1 Intervention
Receiving 2 doses of placebo separated by 1 week.
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
Centre for Addiction and Mental HealthToronto, Canada
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Who Is Running the Clinical Trial?
Centre for Addiction and Mental HealthLead Sponsor
References
Psilocybin microdosers demonstrate greater observed improvements in mood and mental health at one month relative to non-microdosing controls. [2022]Psilocybin microdosing involves repeated self-administration of mushrooms containing psilocybin at doses small enough to not impact regular functioning. Microdose practices are diverse and include combining psilocybin with substances such as lion's mane mushrooms (Hericium erinaceus; HE) and niacin (vitamin-B3). Public uptake of microdosing has outpaced evidence, mandating further prospective research. Using a naturalistic, observational design, we followed psilocybin microdosers (n = 953) and non-microdosing comparators (n = 180) for approximately 30 days and identified small- to medium-sized improvements in mood and mental health that were generally consistent across gender, age and presence of mental health concerns, as we all as improvements in psychomotor performance that were specific to older adults. Supplementary analyses indicated that combining psilocybin with HE and B3 did not impact changes in mood and mental health. However, among older microdosers combining psilocybin, HE and B3 was associated with psychomotor improvements relative to psilocybin alone and psilocybin and HE. Our findings of mood and mental health improvements associated with psilocybin microdosing add to previous studies of psychedelic microdosing by using a comparator group and by examining the consistency of effects across age, gender, and mental health. Findings regarding the combination of psilocybin, HE and B3 are novel and highlight the need for further research to confirm and elucidate these apparent effects.
Assessing potential of psilocybin for depressive disorders. [2023]There has been increasing interest in the role psilocybin may play in the treatment of depressive disorders. Several clinical trials have shown psilocybin to have efficacy in reducing symptoms of depression.
Dose-response relationships of psilocybin-induced subjective experiences in humans. [2022]Label="BACKGROUND" NlmCategory="BACKGROUND">Psilocybin is the psychoactive component in Psilocybe mushrooms ('magic mushrooms'). Whether and how the quality of the psilocybin-induced experience might mediate beneficial health outcomes is currently under investigation, for example, in therapeutic applications. However, to date, no meta-analysis has investigated the dose-dependency of subjective experiences across available studies.
Pharmacokinetics of Escalating Doses of Oral Psilocybin in Healthy Adults. [2022]Psilocybin is a psychedelic tryptamine that has shown promise in recent clinical trials for the treatment of depression and substance use disorders. This open-label study of the pharmacokinetics of psilocybin was performed to describe the pharmacokinetics and safety profile of psilocybin in sequential, escalating oral doses of 0.3, 0.45, and 0.6 mg/kg in 12 healthy adults.
[Treatment with psilocybin: applications for patients with psychiatric disorders]. [2021]After a cessation of almost 40 years, there is renewed interest into therapeutic applicationsof the serotonergic psychedelic psilocybin for the treatment of patients with various psychiatric disorders. PubMed was searched for clinical trials into "psilocybin" between 2000 and 2020, complemented by handsearching. Articles were also screened for explanatory models and working mechanisms. Psilocybin has been studied in 9 clinical trials: for the treatment of substance use disorders, depression, end-of-life anxiety, demoralization, and obsessive-compulsive disorder. Results show that psilocybin is well tolerated, with only limited side-effects, while even patients with treatment-resistant disorders sometimes show marked, long-term improvements after one or a few sessions. Initial results are encouraging, but there are several limitations. More research is needed to determine which patient populations can benefit, what role setting and the placebo response play, and how these novel treatments can be optimized.
The pharmacology of psilocybin. [2016]Psilocybin (4-phosphoryloxy-N,N-dimethyltryptamine) is the major psychoactive alkaloid of some species of mushrooms distributed worldwide. These mushrooms represent a growing problem regarding hallucinogenic drug abuse. Despite its experimental medical use in the 1960s, only very few pharmacological data about psilocybin were known until recently. Because of its still growing capacity for abuse and the widely dispersed data this review presents all the available pharmacological data about psilocybin.
DARK Classics in Chemical Neuroscience: Psilocybin. [2019]Psilocybin is found in a family of mushrooms commonly known as "magic mushrooms" that have been used throughout history to induce hallucinations. In the late 1950s Albert Hofmann, of Sandoz Laboratories, identified and synthesized the psychoactive compounds psilocybin and psilocin which are found in psilocybe mushrooms. Psilocybin was marketed by Sandoz as Indocybin for basic psychopharmacological and therapeutic clinical research. Psilocybin saw a rapid rise in popularity during the 1960s and was classed as a Schedule I drug in 1970. This led to a significant decrease in psilocybin research. Recently, however, preliminary studies with psilocybin have shown promise as potential for the treatment of obsessive compulsive disorder, alcohol addiction, tobacco addiction, and major depressive disorder, and the treatment of depression in terminally ill cancer patients. This review describes in detail the synthesis, metabolism, pharmacology, adverse drug reactions, and importance of psilocybin to neuroscience in the past and present.
A Proposal to Study the Safety and Efficacy of Psilocybe cubensis in Preclinical and Clinical Studies as a Therapeutic Alternative for Major Depressive Disorder. [2023]The pharmacological treatment of depression consists of taking antidepressant drugs for prolonged periods; its modest therapeutic effect can often be associated with significant adverse effects, while its discontinuation can lead to relapses. Psilocybin is today a novel and breakthrough therapy for major depression. It is a natural alkaloid in Psilocybe mushrooms, which are endemic to Mexico. Research on a larger scale is lacking in various populations, including the Mexican people. This proposal contemplates the experimental design of a preclinical (toxicity and pharmacological evaluation of an extract in mice) and clinical study by including the chemical analysis of a species of Psilocybe cubensis mushroom to characterize its main constituents. The clinical study will consider the safety evaluation by exploring tolerated doses of Psilocybe cubensis by measuring pharmacokinetic parameters after oral administration in healthy adults and an open trial on a sample of patients with major depressive disorder to assess the safety and efficacy of fully characterized Psilocybe cubensis in a two-single doses treatment, (with assisted psychotherapy), compared with the traditional care model at the Instituto Nacional de Psiquiatría Ramón de la Fuente Muñiz in Mexico City. This report presents the design of a research project with preclinical and clinical experimental components.
[Hallucinogenic mushrooms]. [2018]The group of hallucinogenic mushrooms (species of the genera Conocybe, Gymnopilus, Panaeolus, Pluteus, Psilocybe, and Stropharia) is psilocybin-containing mushrooms. These "magic", psychoactive fungi have the serotonergic hallucinogen psilocybin. Toxicity of these mushrooms is substantial because of the popularity of hallucinogens. Psilocybin and its active metabolite psilocin are similar to lysergic acid diethylamide. These hallucinogens affect the central nervous system rapidly (within 0.5-1 hour after ingestion), producing ataxia, hyperkinesis, and hallucinations. In this review article there are discussed about history of use of hallucinogenic mushrooms and epidemiology; pharmacology, pharmacodynamics, somatic effects and pharmacokinetics of psilocybin, the clinical effects of psilocybin and psilocin, signs and symptoms of ingestion of hallucinogenic mushrooms, treatment and prognosis.
Structure-Activity Relationships for Psilocybin, Baeocystin, Aeruginascin, and Related Analogues to Produce Pharmacological Effects in Mice. [2023]4-Phosphoryloxy-N,N-dimethyltryptamine (psilocybin) is a naturally occurring tertiary amine found in many mushroom species. Psilocybin is a prodrug for 4-hydroxy-N,N-dimethyltryptamine (psilocin), which induces psychedelic effects via agonist activity at the serotonin (5-HT) 2A receptor (5-HT2A). Several other 4-position ring-substituted tryptamines are present in psilocybin-containing mushrooms, including the secondary amine 4-phosphoryloxy-N-methyltryptamine (baeocystin) and the quaternary ammonium 4-phosphoryloxy-N,N,N-trimethyltryptamine (aeruginascin), but these compounds are not well studied. Here, we investigated the structure-activity relationships for psilocybin, baeocystin, and aeruginascin, as compared to their 4-acetoxy and 4-hydroxy analogues, using in vitro and in vivo methods. Broad receptor screening using radioligand binding assays in transfected cells revealed that secondary and tertiary tryptamines with either 4-acetoxy or 4-hydroxy substitutions display nanomolar affinity for most human 5-HT receptor subtypes tested, including the 5-HT2A and the serotonin 1A receptor (5-HT1A). The same compounds displayed affinity for 5-HT2A and 5-HT1A in mouse brain tissue in vitro and exhibited agonist efficacy in assays examining 5-HT2A-mediated calcium mobilization and β-arrestin 2 recruitment. In mouse experiments, only the tertiary amines psilocin, psilocybin, and 4-acetoxy-N,N-dimethyltryptamine (psilacetin) induced head twitch responses (ED50 0.11-0.29 mg/kg) indicative of psychedelic-like activity. Head twitches were blocked by 5-HT2A antagonist pretreatment, supporting 5-HT2A involvement. Both secondary and tertiary amines decreased body temperature and locomotor activity at higher doses, the effects of which were blocked by 5-HT1A antagonist pretreatment. Across all assays, the pharmacological effects of 4-acetoxy and 4-hydroxy compounds were similar, and these compounds were more potent than their 4-phosphoryloxy counterparts. Importantly, psilacetin appears to be a prodrug for psilocin that displays substantial serotonin receptor activities of its own.
Determination of psilocin and 4-hydroxyindole-3-acetic acid in plasma by HPLC-ECD and pharmacokinetic profiles of oral and intravenous psilocybin in man. [2019]In order to investigate the pharmacokinetic properties of psilocybin (PY), the main psychoactive compound of Psilocybe mushrooms, high performance liquid chromatographic procedures with column-switching coupled with electrochemical detection (HPLC-ECD) for reliable quantitative determination of the PY metabolites psilocin (PI) and 4-hydroxyindole-3-acetic acid (4HIAA) in human plasma were established. Sample work-up includes protection of the highly unstable phenolic analytes with ascorbic acid, freeze-drying and in-vitro microdialysis. The data of two controlled clinical studies with healthy volunteers are presented. The subjects (N = 6 for both studies) received single oral PY doses of 0.224 +/- 0.02 mg/kg b.wt. (10-20 mg) and intravenous doses of 1 mg PY, respectively. Peak plasma levels of PI after oral administration of PY were measured after 105 +/- 37 min showing an average concentration of 8.2 +/- 2.8 ng PI/ml plasma. 4HIAA peak concentrations of 150 +/- 61 ng/ml plasma were found 113 +/- 41 min after ingestion of PY. After intravenous administration, a mean PI maximum plasma concentration of 12.9 +/- 5.6 ng/ml plasma was found 1.9 +/- 1.0 min after injection. The maximum plasma levels appearing within a very short period indicate a rapid dephosphorylation of PY also when administered systemically. 4HIAA was not detected after 1 mg of intravenous PY. Estimates for the absolute bioavailability of PI after oral administration of PY were 52.7 +/- 20% (N = 3).