Condition category
Mental and Behavioural Disorders
Date applied
10/01/2013
Date assigned
18/03/2013
Last edited
13/06/2016
Prospective/Retrospective
Retrospectively registered
Overall trial status
Completed
Recruitment status
No longer recruiting

Plain English Summary

Background and study aims
The cannabis plant contains the molecules tetrahydrocannabinol (THC) and tetrahydrocannabivarin (THCV). It is thought that THCV prevents the psychological effects of THC. Whilst THC is an agonist (a substance that starts a chemical reaction in the body when combined with a receptor) at CB1 receptors (a type of cannabinoid receptor expressed by cells in various parts of the body), THCV is a neutral antagonist (these compete with agonists to bind to receptors but do not cause the same chemical reaction). Thus THCV can antagonise tissue responses to THC. The effects on mood and behaviour caused by pure THC in humans are well established. However, whether THCV can prevent the effects of THC in man is unknown. The theory we would like to test through a small pilot study is that pure THCV prevents the characteristic psychological and mental processing effects of intravenous (IV) THC (where THC is administered through a vein).

Who can participate?
Males between 21 and 35 and in good health, both physically and mentally, may be able to participate. It is important that participants have not suffered from mental illness, including depression or anxiety in the past. Drug or alcohol addiction rules a person out. However, participants must have taken cannabis recreationally (for enjoyment), at least once in the past and no more than 25 times.

What does the study involve?
There are two separate blocks, one block for THCV and one for the placebo (dummy treatment). Both involve four days dosing followed by a THC session. The blocks will be at least two weeks apart. The following describes what happens within a block. (Note that participants will be asked to complete two blocks, one for placebo and one for THCV). On day 1, participants will be given a tablet containing either THCV 10 mg or placebo. We then ask participants to stay at the Wellcome Clinical Research Facility for four hours, to make sure that they do not have a bad reaction to the drug. We ask them to come back to Denmark Hill on days 2, 3 and 4 for further tablets. There is no requirement to stay for monitoring as on the first day, but we ask carefully about side-effects. We will give participants a travel pass so that they do not run up any costs. A contact number will be provided which can be accessed at any time, should there be a concern. On day 5 you will return to Denmark Hill for the experimental session - this will take place in the Wellcome Clinical Research Facility.

On day 5, participants will receive the final dose of THCV (or placebo) at the Wellcome Clinical Research Facility. Thereafter the THC will be delivered intravenously through an indwelling cannula (a fixed tube) in the forearm. It takes about 5 minutes for the effects of THC to begin. The dose is 1.25 mg. In previous studies the effects wore off after 2 hours. During this time, we will ask participants to complete a number of puzzles to test their mental processes (which take about 40 minutes), and ask them to complete questionnaires that assess mood and thoughts.

What are the possible benefits and risks of participating?
Participants will have the opportunity to take part in an interesting research project studying the effects of cannabinoid molecules under controlled, scientific conditions. The topic of cannabis and mental health is highly topical. Some people find cannabis unpleasant. Others find it relaxing and pleasurable. Some feel suspicious and paranoid. Some people become muddled and find it difficult to keep track of their thoughts. Some may feel they have special powers or a special role. Others report things seeming unreal with different perceptions of time and feeling ‘high’ or ‘anxious’. The effects wear off after 1-2 hours. If a participant has a ‘bad’ reaction to the drug they will be able to stop at any time. The study doctor will provide reassurance until the experience subsides, and rescue drugs (lorazepam tablets) will be made available.

Where is the study run from?
The Denmark Hill Campus of King's College London (Wellcome Clinical Research Facility, King’s College Hospital, UK).

When is the study starting and how long is it expected to run for?
The study will begin in February 2013 and run for approximately one year.

Who is funding the study?
The study is departmentally funded, which includes an unrestricted grant to the principal investigator from GW Pharmaceuticals.

Who is the main contact?
Dr Paul Morrison
paul.morrison@kcl.ac.uk

Trial website

Contact information

Type

Scientific

Primary contact

Dr Paul Morrison

ORCID ID

Contact details

De Crespigny Park
Denmark Hill
London
SE5 8AF
United Kingdom
+44 (0)20 7848 0057
paul.morrison@kcl.ac.uk

Additional identifiers

EudraCT number

ClinicalTrials.gov number

Protocol/serial number

CSA/11/032

Study information

Scientific title

The effect of delta-9-tetrahydrocannabivarin (THCV) on delta-9-tetrahydrocannabinol (THC): a randomised double-blind crossover study

Acronym

ToTS

Study hypothesis

ToTS: Tetrahydrocannabivarin on Tetrahydrocannabinol Study

The hypothesis is that pure delta-9-tetrahydrocannabivarin (THCV) inhibits the characteristic psychological and cognitive effects of intravenous (IV) delta-9-tetrahydrocannabinol (THC).

Ethics approval

NRES Committee London - Camden & Islington, 24/10/2011, ref: 11/LO/1537

Study design

Randomised double-blind crossover study

Primary study design

Interventional

Secondary study design

Randomised cross over trial

Trial setting

Other

Trial type

Other

Patient information sheet

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

Condition

Cannabis elicited psychopathology and cognitive impairment

Intervention

Delta-9-tetrahydrocannabivarin (THCV) 10 mg per day for 5 days or matched placebo.

Intervention type

Drug

Phase

Not Applicable

Drug names

Delta-9-tetrahydrocannabivarin

Primary outcome measures

Scores on the following cognitive tasks:
1. The Hopkins Verbal Learning Task
2. Digit-span
3. The time estimation task

Psychotic symptoms:
1. The Community Assessment of Psychic Experiences (CAPE) scale
2. The Self Assessment Module (SAM) scale

Measures will be taken at baseline, post THCV/placebo and post THC over the course of 5 days

Secondary outcome measures

Scores on the following scales of psychopathology:
1. The Mood Adjective Check List
2. Beck’s Anxiety Inventory
3. Visual Analogue Scales
4. The State Social Paranoia Scale

Measures will be taken at baseline, post THCV/placebo and post THC over the course of 5 days

Overall trial start date

01/03/2013

Overall trial end date

01/03/2014

Reason abandoned

Eligibility

Participant inclusion criteria

Healthy male volunteers aged 21-35 who have used cannabis not more than 25 times

Participant type

Healthy volunteer

Age group

Adult

Gender

Male

Target number of participants

10

Participant exclusion criteria

1. History (or family history) of mental illness (including any psychotic disorder, depression/anxiety)
2. Major physical illness,
3. Previous treatment with psychotropic medicines and drug/alcohol addiction

Recruitment start date

01/03/2013

Recruitment end date

01/03/2014

Locations

Countries of recruitment

United Kingdom

Trial participating centre

King's College London
London
SE5 8AF
United Kingdom

Sponsor information

Organisation

King's College London (UK)

Sponsor details

SLAM/IoP R&D Office
De Crespigny Park
Denmark Hill
London
SE5 8AF
United Kingdom

Sponsor type

University/education

Website

http://www.kcl.ac.uk/iop/research/office/index.aspx

Funders

Funder type

Industry

Funder name

GW Pharmaceuticals (UK) - departmental funds via an unrestricted grant to the principal investigator

Alternative name(s)

Funding Body Type

Funding Body Subtype

Location

Results and Publications

Publication and dissemination plan

Not provided at time of registration

Intention to publish date

Participant level data

Not provided at time of registration

Results - basic reporting

Publication summary

2016 results in: http://www.ncbi.nlm.nih.gov/pubmed/26577065

Publication citations

Additional files

Editorial Notes

13/06/2016: Publication reference added.