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
Prospectively registered
Protocol
Statistical analysis plan
Results
Individual participant data

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

Dr Sagnik Bhattacharyya
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 designParallel-group double-blind randomized placebo-controlled trial
Primary study designInterventional
Secondary study designRandomised controlled trial
Study setting(s)Community
Study typeOther
Participant information sheet Not available in web format, please use the contact details to request a patient information sheet
Scientific titleAcute and long-term effects of endocannabinoid modulation in individuals at high risk for psychosis: an experimental study
Study acronymCANTOP
Study objectivesThe 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) studiedUltra high risk for psychosis
InterventionParticipants 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 typeDrug
Pharmaceutical study type(s)
PhasePhase I
Drug / device / biological / vaccine name(s)Cannabidiol
Primary outcome measurefMRI 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 measuresPlasma 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 date23/04/2012
Completion date28/02/2017

Eligibility

Participant type(s)Patient
Age groupAdult
Lower age limit18 Years
Upper age limit35 Years
SexBoth
Target number of participants40
Total final enrolment33
Key inclusion criteria1. 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 criteria1. 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 enrolment08/05/2013
Date of final enrolment09/12/2015

Locations

Countries of recruitment

  • England
  • United Kingdom

Study participating centre

King’s College, London
Institute of Psychiatry, Psychology & Neuroscience
16 De Crespigny Park
London
SE5 8AF
United Kingdom

Sponsor information

King's College London
University/education

Strand
London
WC2R 2LS
England
United Kingdom

ROR logo "ROR" https://ror.org/0220mzb33

Funders

Funder type

Research council

Medical 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 date28/02/2017
Individual participant data (IPD) Intention to shareYes
IPD sharing plan summaryAvailable on request
Publication and dissemination planPlanned 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.