Does cannabidiol treatment lead to recovery of brain structure and function in cannabis users?

ISRCTN	ISRCTN89498802
DOI	https://doi.org/10.1186/ISRCTN89498802
Secondary identifying numbers	CT15/02

Submission date: 13/06/2017
Registration date: 16/06/2017
Last edited: 04/10/2022

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

Background and study aims:
Cannabis is a widely-used illegal drug derived from the cannabis plant. Cannabidiol (CBD) is a constituent of cannabis plant matter that has gain notoriety for its supposed therapeutic, neuroprotective (protecting the nervous system) and antipsychotic properties. CBD has been shown to improve or reverse problems with cognition (mental processes) and psychotic symptoms associated with cannabis use, and preliminary evidence suggests CBD may protect against shrinking of a part of the brain called the hippocampus (which is responsible for memory), which is often seen in cannabis users. Whilst the mechanisms underlying these effects are currently unknown, there is evidence to suggest that CBD may protect against the harms associated with cannabis use and that it may do so by controlling certain pathways in the brain involving natural chemical messengers (neurotransmitters). The aim of this study is to find out whether prolonged CBD treatment in regular cannabis users has an effect on brain structure and to see if this is underpinned by changes in neurotransmitter mechanisms.

Who can participate?
Adults who have been using cannabis at least once a week for at least three years.

What does the study involve?
All participants receive capsules containing CBD to take four times a day for ten weeks. At the start of the study and ten weeks later, participants undergo brain scans to see if there have been any structural changes to the brain or changes in brain activity. Participants also answer questions via telephone about their mental health one month and three months after the end of the study.

What are the possible benefits and risks of participating?
There are no direct benefits or risk involved with participating.

Where is the study run from?
University of Wollongong (Australia)

When is study starting and how long is it expected to run for?
March 2015 to June 2018

Who is funding the study?
Australian Research Council (Australia)

Who is the main contact?
Professor Nadia Solowij
nadia@uow.edu.au

Contact information

Prof Nadia Solowij
Scientific

School of Psychology
University of Wollongong
Wollongong
2522
Australia

ORCID ID	0000-0002-5222-5637
Phone	+61 4221 3732
Email	nadia@uow.edu.au

Study information

Study design	Interventional non-randomised study
Primary study design	Interventional
Secondary study design	Non randomised study
Study setting(s)	Community
Study type	Treatment
Participant information sheet	Not available in web format, please use the contact details below to request a patient information sheet
Scientific title	Does cannabidiol treatment lead to recovery of brain structure and function in cannabis users? A pilot investigation
Study acronym	Prolonged CBD Trial
Study hypothesis	Primary study aim: The aim of this study is to determine whether daily cannabidiol (CBD) administration over a 10 week period will lead to improved brain structure, function, neurochemistry and integrity (via modulation of glutamatergic and GABAergic signalling) in regular cannabis users. Primary hypothesis: Prolonged CBD administration will result in larger volumes of specific hippocampal subfields (such as CA1 and subiculum); elevated markers of hippocampal neuronal integrity (NAA); more normalised glutamate and GABA levels in the hippocampus; and increased MMN amplitude Secondary study aim: The aim of this study is to investigate the potential for CBD administration to reduce cognitive impairment, psychological symptoms and cannabis use in regular cannabis users. Secondary hypotheses: 2. Prolonged CBD administration will result in the following outcomes and in turn these will be associated with the primary outcomes of Hypothesis 1:improved cognitive function; and reduced psychological symptoms 3. Prolonged CBD administration will result in reduced cannabis use
Ethics approval(s)	Joint University of Wollongong and Illawarra and Shoalhaven Local Health District Health and Medical Human Research Ethics committee, 08/07/2015, ref: CT15/02
Condition	Chronic cannabis use
Intervention	All participants receive medical grade cannabidiol (CBD) formulated into capsules for oral administration. Each capsule contained 50mg of 99.9% pure CBD powder solved in corn oil gelatin capsules (BSPG/Trigal Pharmaceuticals, UK). Participants are instructed to take four capsules per day (100mg in the morning and 100mg in the evening, totaling 200mg daily). Participants are clinically and cognitively assessed and EEG and MRI measured obtained at baseline and after 10 weeks of daily CBD administration. They are also followed up by brief telephone assessment one month and three months after the end of the trial.
Intervention type	Drug
Pharmaceutical study type(s)
Phase	Phase II
Drug / device / biological / vaccine name(s)	Cannabidiol.
Primary outcome measure	1. Hippocampal volumetrics (whole hippocampus as well as subfields (e.g. CA1 and subiculum) is assessed by magnetic resonance imaging (MRI) using high resolution T1 weighted images at baseline and following 10 weeks of CBD administration 2. Markers of hippocampal neuronal integrity (NAA), as well as glutamate and GABA levels in the hippocampus, aremeasured using magnetic resonance spectroscopy (MRS) at baseline and following 10 weeks of CBD administration 3. MMN amplitude is recorded via electroencephalography (EEG) at baseline and following 10 weeks of CBD administration
Secondary outcome measures	1. Other EEG and fMRI measures including P50 and resting state EEG/fMRI measured at baseline and following 10 weeks of CBD administration 2. Neuropsychological measures, assessed utilising the Rey Auditory Verbal Learning Test (RAVLT), and the Cambridge Neuropsychological Test Automated Battery (CANTAB) and CogState test batteries at baseline and following 10 weeks of CBD administration 4. Psychological symptomatology, as assessed by the Beck Depression Inventory (BDI); State-Trait Anxiety Index (STAI-I and II); Profile of Mood States (POMS); Community Assessment of Psychic Experiences (CAPE); Schizotypal Personality Questionnaire (SPQ); and Cannabis Experiences Questionnaire (CEQ) at baseline and following 10 weeks of CBD administration. 5. Substance use measures, utilising Timeline Follow Back; Cannabis Withdrawal Scale (CWS), Severity of Dependence Scale; and the Alcohol Use Disorder Identification Test (AUDIT) at baseline and following 10 weeks of CBD administration. 6. Levels of CBD and THC metabolites and neurotransmitter markers in blood and urine weekly throughout the 10 week trial
Overall study start date	01/03/2015
Overall study end date	30/06/2018

Eligibility

Participant type(s)	Healthy volunteer
Age group	Adult
Lower age limit	18 Years
Sex	Both
Target number of participants	22
Participant inclusion criteria	1. Cannabis use at least once per week for a minimum of three years 2. Between 18 and 55 years of age
Participant exclusion criteria	1. Current regular (more than once per month) use of substances other than cannabis, aside from alcohol and tobacco 2. Consumption of more than 28 standard drinks of alcohol per week 3. A history of regular illicit drug use (more than weekly) or dependence on or treatment seeking for any substance other than cannabis 4. Any neurological or psychiatric disorders (assessed by the MINI International Psychiatric Interview Plus) 5. Pregnancy of lack of contraception use for female cannabis users 6. Contraindications for EEG or MRI (e.g. epilepsy, metal implants, claustrophobia)
Recruitment start date	08/07/2015
Recruitment end date	10/06/2016

Locations

Countries of recruitment

Australia

Study participating centres

University of Wollongong

School of Psychology and Illawarra Health and Medical Research Institute
Northfields Avenue
Wollongong
2522
Australia

Liverpool Cancer Therapy Centre and Ingham Institute

Liverpool Hospital (MRI scanner facility)
Campbell Street
Liverpool
NSW 2170
Australia

Sponsor information

University of Wollongong
University/education

Northfields Avenue
Wollongong
2522
Australia

Phone	+61 4221 3732
Email	nadia@uow.edu.au
Website	http://www.uow.edu.au
"ROR"	https://ror.org/00jtmb277

Funders

Funder type

Government

Australian Research Council
Government organisation / Other non-profit organizations

Alternative name(s): arc_gov_au, The Australian Research Council, Australian Government Australian Research Council (ARC), ARC
Location: Australia

Results and Publications

Intention to publish date	31/12/2018
Individual participant data (IPD) Intention to share	No
IPD sharing plan summary	Not provided at time of registration
Publication and dissemination plan	Publications in peer-reviewed journals are planned from 2017-2018.
IPD sharing plan	The current data sharing plans for the current study are unknown and will be made available at a later date.

Study outputs

Output type	Details	Date created	Date added	Peer reviewed?	Patient-facing?
Results article		01/03/2018	04/10/2022	Yes	No
Results article		01/03/2018	04/10/2022	Yes	No

Editorial Notes

04/10/2022: Publication references added.