Condition category
Mental and Behavioural Disorders
Date applied
14/07/2016
Date assigned
12/10/2016
Last edited
12/10/2016
Prospective/Retrospective
Retrospectively registered
Overall trial status
Ongoing
Recruitment status
No longer recruiting

Plain English Summary

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

Trial website

Contact information

Type

Scientific

Primary contact

Dr Sagnik Bhattacharyya

ORCID ID

Contact details

Department of Psychosis Studies
Box PO67
Institute of Psychiatry
Psychology and Neuroscience
King’s College London
De Crespigny Park
London
SE5 8AF
United Kingdom

Additional identifiers

EudraCT number

ClinicalTrials.gov number

Protocol/serial number

16975

Study information

Scientific title

Acute and long-term effects of endocannabinoid modulation in individuals at high risk for psychosis: an experimental study

Acronym

CANTOP

Study hypothesis

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

NRES London – Camberwell St Giles Research Ethics Committee, 08/05/2013, ref: 13/LO/0243

Study design

Parallel-group double-blind randomized placebo-controlled trial

Primary study design

Interventional

Secondary study design

Randomised controlled trial

Trial setting

Community

Trial type

Other

Patient information sheet

Not available in web format, please use the contact details below to request a patient information sheet

Condition

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

Phase

Phase I

Drug names

Cannabidiol

Primary outcome measures

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 trial start date

23/04/2012

Overall trial end date

28/02/2017

Reason abandoned

Eligibility

Participant inclusion criteria

1. Aged 18- 35 years
2. Right-handed
3. Ultra high risk (UHR) for psychosis individuals being supported by OASIS (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

Participant type

Patient

Age group

Adult

Gender

Both

Target number of participants

40

Participant 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

Recruitment start date

08/05/2013

Recruitment end date

09/12/2015

Locations

Countries of recruitment

United Kingdom

Trial participating centre

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

Sponsor information

Organisation

King's College London

Sponsor details

Strand
London
WC2R 2LS
United Kingdom

Sponsor type

University/education

Website

Funders

Funder type

Research council

Funder name

Medical Research Council

Alternative name(s)

MRC

Funding Body Type

private sector organisation

Funding Body Subtype

other non-profit

Location

United Kingdom

Results and Publications

Publication and dissemination plan

Planned publication in a high-impact peer reviewed journal with intention to publish in February 2017.

Intention to publish date

28/02/2017

Participant level data

Available on request

Results - basic reporting

Publication summary

Publication citations

Additional files

Editorial Notes