Vulnerability markers in the association between cannabis and schizophrenia
| ISRCTN | ISRCTN24109245 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN24109245 |
| Secondary identifying numbers | CT12/003 |
- Submission date
- 05/11/2012
- Registration date
- 19/11/2012
- Last edited
- 21/01/2019
- Recruitment status
- No longer recruiting
- Overall study status
- Completed
- Condition category
- Mental and Behavioural Disorders
Plain English summary of protocol
Background and study aims
Cannabis is one of the most widely used illegal drugs across the world. It has been well documented that use of cannabis is linked to people developing mental problems, such as depression or anxiety. A major concern is that heavy use of cannabis is a leading cause of serious mental illnesses such as schizophrenia or psychosis, conditions which cause people to lose touch with reality and find it difficult to cope with day to day life. There are a huge number of chemical compounds present in cannabis, the most dominant of which are tetrahydrocannabinol (THC) and cannabidiol (CBD). It is well known that THC is the main chemical that affects the mind and can trigger psychotic behaviour. CBD however, is thought to reduce these effects and may actually counteract the effects of THC. Both THC and CBD are known to interact with specific receptors in the brain called the glutamate NMDA receptors. Mismatch negativity (MMN), an electrical signal which shows how well these receptors are working, which is often lower than it should be in people with schizophrenia. The aim of this study is to find out how TCH and CBD affect MMN in order to find out why some people can use cannabis frequently without major adverse effects, while others may develop psychosis.
Who can participate?
Adults who have been using cannabis at least 4 times a month for 3 years, and aged matched controls who have used cannabis between 5 and 20 times across their lifetime but not within 3 months prior to enrolment.
What does the study involve?
At the start of the study, all participants take an IQ test, as well as having psychological assessments designed to test how well their brains are functioning. The participants then return to the testing centre five times to be given a different substance through a vaporiser. The following five substances will be given to each participant in a random order: Tetrahydrocannabinol (THC) alone, Cannabidiol (CBD) alone (high dose), THC+ CBD (low dose), THC + CBD (high dose), and a placebo (dummy drug) which will act as a control. At each of these visits, the participants’ brain activity will be recorded using Electroencephalography (EEG), which will measure the MMN.
What are the possible benefits and risks of participating?
There are no noteworthy benefits for participating in the study, other than helping to improve knowledge and understanding of the relationship between chronic cannabis use and psychosis in vulnerable individuals. Possible risks of taking part in the study include mild side effects from taking the drug, such as nausea and increased heart rate. The investigative team will carefully screen participants in order to avoid potential damaging effects such as anxiety or paranoia.
Where is the study run from?
University of Wollongong, School of Psychology (Australia)
When is the study starting and how long is it expected to run for?
November 2012 to March 2014
Who is funding the study?
National Health and Medical Research Council of Australia (NHMRC) (Australia)
Who is the main contact?
Professor Nadia Solowij
nadia@uow.edu.au
Contact information
Scientific
School of Psychology
University of Wollongong
Wollongong
2522
Australia
| Phone | +61 (02) 4221 3732 |
|---|---|
| nadia@uow.edu.au |
Study information
| Study design | Randomised double-blind placebo-controlled crossover study |
|---|---|
| Primary study design | Interventional |
| Secondary study design | Randomised controlled trial |
| Study setting(s) | Other |
| 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 | Vulnerability markers in the association between cannabis and schizophrenia: a randomised controlled trial of acute cannabinoid administration |
| Study objectives | The acute administration of cannabinoids (THC + CBD) will modulate the amplitude of the mismatch negativity (a brain marker of glutamate receptor function) in regular cannabis users versus non-naïve controls. |
| Ethics approval(s) | Joint University of Wollongong and Illawarra and Shoalhaven Local Health Network Health and Medical Human Research Ethics committee, 6 August 2012, Reference number: CT12/003 |
| Health condition(s) or problem(s) studied | Cannabis use and psychosis |
| Intervention | Cannabis user and non-user non-naïve control participants will receive each of the following five conditions in randomised order, administered through a vaporiser 1. Tetrahydrocannabinol (THC) alone 2. Cannabidiol (CBD) alone (high dose) 3. THC+ CBD (low dose) 4. THC + CBD (high dose) 5. Placebo |
| Intervention type | Other |
| Primary outcome measure | The effect of THC and CBD on MMN amplitude recorded immediately following drug administration |
| Secondary outcome measures | The effect of THC and CBD on 1. Other EEG/ERP measures including P50 and resting state EEG 2. Neuropsychological measures including CogState battery of tests 3. Psychotic-like symptoms as indicated on a visual analogue scale, the Psychotomimetic States Inventory and the Clinician Administered Dissociative States Scale. 4. The potential moderating effect of specific genetic polymorphisms on THC and CBD (alone and in combination) effects on the MMN and other EEG/ERP and neuropsychological measures. |
| Overall study start date | 12/11/2012 |
| Completion date | 31/03/2014 |
Eligibility
| Participant type(s) | Patient |
|---|---|
| Age group | Adult |
| Lower age limit | 18 Years |
| Sex | Both |
| Target number of participants | 40 |
| Key inclusion criteria | Cannabis user group 1. Cannabis use for at least 3 years, and at least 4 times a month. 2. All participants must be between 18 and 55 years of age. Control group 1. Cannabis use at least 5 times but less than 20 times in total across lifetime; and for those participants only having used 5-10 times, they must have used at least once in the last 2 years; while for those participants having used between 10 and 20 times, the most recent exposure must not have been more than 10 years ago. No cannabis use in the past 3 months. 2. All participants must be between 18 and 55 years of age. |
| Key exclusion criteria | Cannabis user group 1. Daily cannabis use, or use of any illicit substance more than once a month for a period of six months 2. Head injury resulting in trauma to the brain, prolonged unconsciousness or concussion or required surgery, prolonged hospitalisation or rehabilitation 3. Medical diagnosis that would interfere with EEG testing (epilepsy, stroke, brain tumour, HIV positive, Hepatitis B or C, meningitis, encephalitis, MS, microcephaly), or a medical diagnosis contraindicated for cannabis exposure (e.g. asthma, cardiovascular disease, untreated hypertension). 4. Co-ingestion / concurrent use of medicines or drugs which will interfere with testing or are contraindicated for cannabis exposure (e.g. antipsychotics, antidepressants, benzodiazepines, amphetamines, opioids, alcohol). 5. A Body Mass Index (BMI) of less than 18 kg/m2 or more than 28 kg/m2. 6. A history of anaemia 7. Pregnancy 8. A current diagnosis of a psychotic disorder, or a score of 50 or more on the Community Assessment of Psychic Experiences. A first degree family member with psychotic diagnosis. 9. Use of any illicit substance (other than cannabis) in the 14 days prior to testing. 10. Meets DSM-IV criteria for dependence on alcohol or drugs other than cannabis; history of treatment for substance use problems other than cannabis. Control group 1. Use of any illicit substance more than once a month for a period of six months. 2. Head injury resulting in trauma to the brain, prolonged unconsciousness or concussion or required surgery, prolonged hospitalisation or rehabilitation. 3. Medical diagnosis that would interfere with EEG testing (epilepsy, stroke, brain tumour, HIV positive, Hepatitis B or C, meningitis, encephalitis, MS, microcephaly), or a medical diagnosis contraindicated for cannabis exposure (e.g. asthma, cardiovascular disease, untreated hypertension). 4. Co-ingestion /concurrent use of medicines or drugs which will interfere with testing or are contraindicated for cannabis exposure (e.g. antipsychotics, antidepressants, benzodiazepines, amphetamines, opioids, alcohol). 5. A body Mass Index (BMI) of less than 18 kg/m2 or more than 28 kg/m2. 6. A history of anaemia. 7. Pregnancy 8. A current diagnosis of a psychotic disorder, or a score of 50 or more on the Community Assessment of Psychic Experiences. 9. A first degree family member with psychotic diagnosis. Use of any illicit substance (other than cannabis) in the 14 days prior to testing. 10. Meets DSM-IV criteria for dependence on alcohol or drugs or a history of treatment for substance use problems. |
| Date of first enrolment | 12/11/2012 |
| Date of final enrolment | 31/03/2014 |
Locations
Countries of recruitment
- Australia
Study participating centre
2522
Australia
Sponsor information
University/education
Northfields Avenue
Wollongong
2522
Australia
"ROR" |
https://ror.org/00jtmb277 |
|---|
Funders
Funder type
Research council
No information available
Results and Publications
| Intention to publish date | |
|---|---|
| Individual participant data (IPD) Intention to share | No |
| IPD sharing plan summary | Not provided at time of registration |
| Publication and dissemination plan | |
| IPD sharing plan |
Study outputs
| Output type | Details | Date created | Date added | Peer reviewed? | Patient-facing? |
|---|---|---|---|---|---|
| Results article | results | 16/10/2014 | Yes | No | |
| Results article | results | 01/02/2019 | Yes | No |
Editorial Notes
21/01/2019: Publication reference added.
