The primary objective is to investigate the effects of repeated small doses of psilocybin and ketamine on affect (self-rated). Secondary objectives are to is to investigate the effects of repeated small doses of psilocybin and ketamine on [1] well-…
ID
Source
Brief title
Condition
- Neurological disorders NEC
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Main study parameter will be a (statistically significant) change in a
subjective parameters (mood) after treatment with low doses of psilocybin and
ketamine compared to placebo treatment.
Secondary outcome
Secondary parameters are to is to investigate the effects of repeated low doses
of psilocybin and ketamine on [1] well-being, [2] (emotional) attention, [3]
neuroplasticity, [4] cognitive performance measures of memory and executive
functioning, known to be impaired in Parkinson*s disease (computer tasks), [5]
emotion regulation, [6] Parkinson*s symptoms, and [7] biological markers of
wellbeing (microbiome, immune system, cortisol).
A tertiary parameter is to investigate the effects of repeated low doses of
psilocybin on and ketamine the endocannabinoid system, by measuring
endocannabinoid concentrations (AEA and 2-AG) in blood plasma.
Background summary
Parkinson's disease is a neurodegenerative disorder with an estimated
prevalence of 2-3% in the population older than 65 years. Treatment is
symptomatic and focused on motor symptoms, while patients also suffer from
non-motor symptoms, including cognitive and emotional problems. Emotional state
has been shown to negatively affect quality of life and levels of stress affect
motor symptoms. The need for alternative drugs with fewer side effects that can
also improve emotional and cognitive processes is clear.
Ketamine and psychedelics, previously shown to improve mental well-being and
mood, have also been shown to positively affect the immune system and enhance
neuroplasticity, the brain's ability to form new neural connections and
neurons. In animal models of Parkinson's disease (PD), enhanced neuroplasticity
(BDNF) has been shown to aid the survival of dopaminergic neurons, resulting in
improved dopaminergic neurotransmission and motor performance.
Recently, we have shown that a low dose of LSD increases BDNF levels up to 6
hours after administration. In addition to increased neuroplasticity, low dose
LSD also increased positive mood, improved connectivity in brain regions
involved in emotional processing, and improved attention performance. Ketamine
has been shown to have a rapid antidepressant effect in patients with
depression. An increase in BDNF is hereby suggested to underlie the positive
effects of psilocybin and ketamine.
Low doses of psilocybin and ketamine are therefore proposed to alleviate
cognitive and emotional disturbances in patients with Parkinson's disease.
Study objective
The primary objective is to investigate the effects of repeated small doses of
psilocybin and ketamine on affect (self-rated).
Secondary objectives are to is to investigate the effects of repeated small
doses of psilocybin and ketamine on [1] well-being (self-rated), [2] emotional
and cognitive attention (computer tasks), [3] biological markers of
neuroplasticity (BDNF in blood samples), [4] cognitive performance measures of
memory and executive functioning, known to be impaired in Parkinson*s disease
(Robbins & Cools, 2014) (computer tasks), [5] emotion regulation (self-rated),
[6] Parkinson*s symptoms, and [7] biological markers of wellbeing (microbiome,
immune system, cortisol). A tertiary objective includes investigating the
effect of repeated low doses of psilocybin and ketamine on the endocannabinoid
concentrations in blood samples.
Study design
The study design will be double-blind, placebo-controlled, randomized
cross-over, with three treatment conditions. Treatments will be psilocybin (5
mg), ketamine (35 mg) and placebo, administered three times, with one day in
between each dose. There will be six possible treatment orders, and
participants will be assigned randomly to one of these orders. Participants
will be assessed on cognitive and emotional skills after the first and third
dose of each drug condition. They will be assessed before and after dosing to
have a baseline measurement and an *acute* treatment effect measurement. On the
dose-less days they will be asked to fill out their diary. There will be one
week wash-out in between the treatment conditions.
Intervention
Psilocybin is a serotonin 2A receptor agonists. Ketamine is a glutamate
receptor (NMDA) antagonist. Effects are expected to last up to 4 hours.
Participants will receive three doses of psilocybin (5 mg), ketamine (35 mg)
and 3 times placebo.
Study burden and risks
The patients will be enrolled for minimally seven weeks. In this period they
will undergo medical screening (blood and urine sample will be taken), a
training (familiarization with procedures, tasks, and questionnaires), and
three treatment periods (psilocybin, ketamine, placebo). During a treatment
period they will receive three doses, with one day in between treatments.
On the first test day of each condition, five blood samples will be taken.
Blood samples will serve to determine markers of immune function,
neuroplasticity, cortisol and endocannabinoid levels. Questionnaires and tests
assessing mood and cognitive functions will be offered during the day.
Potential discomfort will be linked to the blood draw, and the administration
of placebo, in case low doses of psilocybin and ketamine boost their emotional
and cognitive performance, which will not be experienced in the period when
they receive a placebo. Also, standard medication for Parkinson's disease will
be postponed for 7 weeks while being enrolled in the study, this can be
considered a disadvantage for patients who want to take this medication and
would experience benefit from it.
Universiteitssingel 40
Maastricht 6229 ET
NL
Universiteitssingel 40
Maastricht 6229 ET
NL
Listed location countries
Age
Inclusion criteria
- At least 18 years of age
- Being diagnosed with Parkinson*s Disease
- Underwent a DAT scan as part of the diagnostic process
- Being able to provide details about the duration of the disease or provide
medical records
- Free from conventional Parkinson medication (i.e., Levodopa, dopamine
agonist, amantadine, adenosine a2a antagonist, COMT inhibitors, anticholinergic
drugs, MAO inhibitors)
- The participant is, in the opinion of the investigator, generally healthy
based on assessment of medical history, physical examination, vital signs,
electrocardiogram (ECG), and the results of the haematology, clinical
chemistry, urinalysis, serology, and other laboratory tests
- A resting pulse and heart rate (as read on the ECG) *51 bpm and *100 bpm. For
participants in good physical condition, the lower limit is *45 bpm.
- A resting systolic blood pressure *91 mmHg and *140 mmHg and a resting
diastolic blood pressure *51 mmHg and *90 mmHg.
- Clinical laboratory test values within clinical reference ranges at
screening. Borderline values may be accepted if they are, in the opinion of the
investigator, clinically insignificant.
- Normal binocular visual acuity, corrected or uncorrected
- Absence of any major medical, endocrine and neurological condition (apart
from Parkinson*s disease), as determined by the medical history, medical
examination, electrocardiogram and laboratory analyses (haematology, clinical
chemistry, urinalysis, serology).
- Normal weight, body mass index (weight/height2) between 19,5 and 28 kg/m2
- Being able to communicate in Dutch or English
- Written informed consent
Exclusion criteria
- Previous experience of serious side effects to psychedelic drugs (anxiety or
panic attacks)
- Use of conventional Parkinson*s disease medication or other psychiatric
medication (i.e., Levodopa, dopamine agonist, amantadine, adenosine a2a
antagonist, COMT inhibitors, anticholinergic drugs, MAO inhibitors)
- History of drug addiction (determined by the medical questionnaire, drug
questionnaire and medical examination)
- Depression or dementia
- Excessive alcohol consumption (>20 units a week)
- Excessive smoking (>20 cigarettes a week)
- Current or history of psychiatric disorder (determined by the medical
questionnaire and medical examination)
- Hypertension (diastolic >90; systolic >140)
- Liver dysfunction
- History of cardiac dysfunctions (arrhythmia, ischemic heart disease, etc)
- Pregnancy or lactation
- For women of childbearing potential: absence of reliable contraceptive
measures
- Experience with a full dose of a psychedelic within the last three months
Design
Recruitment
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| EudraCT | EUCTR2021-000041-40-NL |
| CCMO | NL76320.068.21 |