Effect of experimental endocannabinoid modulation on brain function in individuals at high risk for psychosis
| ISRCTN | ISRCTN46322781 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN46322781 |
| Secondary identifying numbers | 16975 |
- Submission date
- 14/07/2016
- Registration date
- 12/10/2016
- Last edited
- 08/11/2023
- Recruitment status
- No longer recruiting
- Overall study status
- Completed
- Condition category
- Mental and Behavioural Disorders
Plain English summary of protocol
Background and study aims
The human body has an internal system known as the endocannabinoid system which regulates processes within the body. The purpose of this study is to find out how the endocannabinoid system can affect brain function and symptoms experienced by people in an ‘at-risk mental state’, who may experience psychological problems or difficulties in coping with day-to-day activities. We will do this by assessing the effects of a chemical known as cannabidiol (CBD) on symptoms and brain function using Magnetic Resonance Imaging (MRI) brain scans. Cannabidiol is a cannabinoid that is extracted from the cannabis plant and is known to affect the endocannabinoid system. It is not responsible for the acute effects produced by cannabis, such as ‘feeling high’. Based on published information, it appears that CBD may have certain beneficial psychological effects. We hope that in the future, the knowledge gained from this study will help in a better understanding of the causes of mental health problems and in the development of new treatments.
Who can participate?
Right-handed adults aged 18-35 who are ultra-high risk (UHR) for psychosis.
What does the study involve?
Participants are randomly allocated to one of two groups. Those in the first group are given capsules containing 600mg of cannabidiol to take once a day for 21 days. Those in the second group are given capsules containing a placebo (dummy drug) to take once a day for 21 days. At the start of the study and then again after 21 days, participants in both groups have an MRI scan of their brain and have a sample of blood taken to measure levels of endocannabinoid substances in the body.
What are the possible benefits and risks of participating?
Participants may benefit from an improvement to their mental health problems, however this is not guaranteed. There is a small risk of some mild sleepiness but otherwise no other side effects have been reported from taking the study drug. There is a risk that some participants may feel anxious or claustrophobic during MRI scanning, and there is a small risk of some temporary, mild discomfort and bruising when having blood samples taken.
Where is the study run from?
The study is run from the Department of Psychosis Studies at the Institute of Psychiatry, Psychology and Neuroscience, King’s College, London (UK)
When is the study starting and how long is it expected to run for?
April 2012 to February 2017
Who is funding the study?
Medical Research Council (UK)
Who is the main contact?
Dr Sagnik Bhattacharyya
Contact information
Scientific
Department of Psychosis Studies
Box PO67
Institute of Psychiatry, Psychology and Neuroscience
King’s College London
De Crespigny Park
London
SE5 8AF
United Kingdom
Study information
| Study design | Parallel-group double-blind randomized placebo-controlled trial |
|---|---|
| Primary study design | Interventional |
| Secondary study design | Randomised controlled trial |
| Study setting(s) | Community |
| Study type | Other |
| Participant information sheet | Not available in web format, please use the contact details to request a patient information sheet |
| Scientific title | Acute and long-term effects of endocannabinoid modulation in individuals at high risk for psychosis: an experimental study |
| Study acronym | CANTOP |
| Study objectives | The aim of this study is to: 1. Investigate the precise relationship between dynamic alterations of the endocannabinoid system by administering CBD, an inverse agonist/ antagonist cannabinoid, and the functioning of the neural substrates for learning, salience and emotional processing that may underlie the psychotic and anxiety symptoms experienced by the UHR population 2. Examine whether the acute and short-term treatments of CBD are associated with an effect on plasma endocannabinoid [Anandamide, 2-Arachidonoylglycerol (2-AG), Palmitoyl-ethanolamine (PEA), Oleoyl-ethanolamine (OEA)] levels over the same time period |
| Ethics approval(s) | NRES London – Camberwell St Giles Research Ethics Committee, 08/05/2013, ref: 13/LO/0243 |
| Health condition(s) or problem(s) studied | Ultra high risk for psychosis |
| Intervention | Participants will be randomly allocated to one of the two treatment arms using a blocked randomisation list with a 1:1 allocation ratio. Intervention arm: Participants receive oral administration of a single capsule containing 600mg of cannabidiol, to be taken once in a day in the morning for a total of 21 days. Control arm: Participants receive oral administration of a single matched placebo capsule, to be taken once a day in the morning for 21 days. Final follow-up assessment for all the treatment arms to be carried out on day 21 of the study which is also the final intake of the study drug. |
| Intervention type | Drug |
| Pharmaceutical study type(s) | |
| Phase | Phase I |
| Drug / device / biological / vaccine name(s) | Cannabidiol |
| Primary outcome measure | fMRI BOLD signal in the hippocampus, striatum and amygdala measured during the memory, salience and emotional (fear) processing tasks on day 1 and day 21. |
| Secondary outcome measures | Plasma endocannabinoid (Anandamide, 2-AG, OEA, PEA) levels measured on day 1 (110 minutes following drug administration on day 1) and day 21 (110 minutes following administration of the last dose of the drug). |
| Overall study start date | 23/04/2012 |
| Completion date | 28/02/2017 |
Eligibility
| Participant type(s) | Patient |
|---|---|
| Age group | Adult |
| Lower age limit | 18 Years |
| Upper age limit | 35 Years |
| Sex | Both |
| Target number of participants | 40 |
| Total final enrolment | 33 |
| Key inclusion criteria | 1. Aged 18- 35 years 2. Right-handed 3. Ultra high risk (UHR) for psychosis individuals being supported by OASIS (https://www.oasislondon.com), a large clinical service for this group 4. Have positive psychotic symptoms and anxiety symptoms, as defined using the Positive and Negative syndrome scale (PANSS) and the State-Trait Anxiety Inventory (STAI) 5. Medication naïve |
| Key exclusion criteria | 1. History of previous psychotic disorder or manic episode 2. Current DSM IV diagnosis of substance dependence (except cannabis dependence) 3. Neurological disorders (eg., epilepsy) or severe intercurrent illness that may put the person at risk 4. IQ of less than 70 5. Female subject who is unwilling to use two forms of contraception (one of which must be a barrier contraception), pregnant, lactating or planning pregnancy during the course of the study and 3 months from the date of the last dose and a male subject whose partner is of child-bearing potential and unwilling to use a barrier method of contraception along with their partner |
| Date of first enrolment | 08/05/2013 |
| Date of final enrolment | 09/12/2015 |
Locations
Countries of recruitment
- England
- United Kingdom
Study participating centre
16 De Crespigny Park
London
SE5 8AF
United Kingdom
Sponsor information
University/education
Strand
London
WC2R 2LS
England
United Kingdom
"ROR" |
https://ror.org/0220mzb33 |
|---|
Funders
Funder type
Research council
Government organisation / National government
- Alternative name(s)
- Medical Research Council (United Kingdom), UK Medical Research Council, MRC
- Location
- United Kingdom
Results and Publications
| Intention to publish date | 28/02/2017 |
|---|---|
| Individual participant data (IPD) Intention to share | Yes |
| IPD sharing plan summary | Available on request |
| Publication and dissemination plan | Planned publication in a high-impact peer reviewed journal with intention to publish in February 2017. |
| IPD sharing plan |
Study outputs
| Output type | Details | Date created | Date added | Peer reviewed? | Patient-facing? |
|---|---|---|---|---|---|
| Results article | results | 01/11/2018 | Yes | No | |
| HRA research summary | 28/06/2023 | No | No | ||
| Protocol (other) | 01/11/2018 | 08/11/2023 | No | No | |
| Results article | 13/09/2020 | 08/11/2023 | Yes | No |
Editorial Notes
08/11/2023: Publication reference, protocol and total final enrolment added.
03/09/2018: Publication reference added.
