What determines an individual's vulnerability to the harmful effects of cannabis?

Lead Research Organisation: University College London
Department Name: Clinical Health and Educational Psych

Abstract

A young person who has ever used cannabis has a 40% increased risk of developing a psychotic disorder like schizophrenia; in those using heavily, the increased risk can be 200%. There are also rapidly growing numbers of young people now seeking treatment for cannabis addiction. The Times recently headlined that in England: ?500 cannabis smokers a week seek medical help? (January 11th, 2008). Further, the effects of cannabis on the brain raise concerns that young people who use this drug may under-achieve in education or work. What we don?t yet understand is why some individuals can use cannabis with few apparent harmful effects whereas others become mentally ill or addicted or have problems concentrating and remembering.

In the first research of its kind, we recently discovered that two main constituents (THC and CBD) in the cannabis that young people smoke influence the psychotic-like effects they experience in everyday life. The proposed research builds on this finding and on our recent large-scale study with 244 young people assessing the effects of cannabis. It aims to determine which cannabis-related and which individual factors make some young people vulnerable to the harmful effects of the drug. The three main harms it addresses are psychotic-like symptoms, addiction and cognitive impairment. The first phase of the study will be naturalistic and involve 600 16-23 year olds who differ in their cannabis use. Some cannabis users will be selected for Phase 2 - a controlled, laboratory study of the effects of two main constituents of cannabis (THC and CBD) both alone and combined. In both Phases, the effects we will assess are psychotic-like, addiction-related and cognitive. We will also investigate young people?s beliefs and views about different strains of cannabis, such as skunk and sinsemilla.

At the time of writing this proposal, the Government is waiting for findings of yet another review of the classification of cannabis. Whether or not this results in it being raised from Class C to B will have negligible impact on cannabis users.

If we show that the harmful effects can be reduced if vulnerable youngsters choose strains with higher CBD content, or if they take CBD supplements, then this could lead to a new era of safer cannabis use. Importantly, it could significantly reduce the numbers of young people in the UK currently diagnosed schizophrenic who would not have become mentally ill if they had not used this drug.

Technical Summary

The current debate on the harmful effects of cannabis centres mainly on psychosis but increasingly on addiction and cognitive impairment. A major unanswered question is: why are some individuals vulnerable and others resilient to these harmful effects? Our very recent finding suggests that one major constituent of cannabis ‘cannabidiol (CBD)‘ protects against the harmful effects of THC, the drug‘s main psychoactive constituent. The present research aims to determine how the CBD and THC content of cannabis interact with vulnerability factors - including an individual?s psychosis-proneness and level of cannabis use - to determine their acute response to this drug, a potential marker of longer-term harm. Phase I will be the first ever large-scale naturalistic study of the acute effects of cannabis and will involve 600 16-23 year olds: 200 daily and 200 recreational users, 100 ex-users and 100 non-using controls. Psychosis-like, dependence-related and cognitive effects will be assessed both whilst users are and are not intoxicated with the drug in a cross-over design. THC and CBD content of cannabis habitually taken will be measured in hair and that taken acutely will be measured in the ‘spliff‘ actually smoked as well as saliva/urine levels. Relevant genetic markers will be assessed. Individuals‘ beliefs about and preferences for different strains of cannabis (e.g. skunk, hash) and intake behaviours (e.g. titration of dose) will also be explored. Phase II will employ the same psychotic-like, dependence-related and cognitive measures in a double-blind, balanced, placebo-controlled comparison of the acute effects of pure CBD and THC, both alone and in combination, in 48 cannabis users carefully selected from Phase I to differ in psychosis-proneness (high versus low) and extent of use (daily versus recreational). An intermediate phase of the study involves a semi-structured interview with subsets of 20 daily, recreational and ex-users to allow detailed exploraons for use, strains of cannabis used and response to information on risk factors (including personal feedback). If, as hypothesised, CBD protects against psychotic-like, cognitive and/or dependence-inducing effects of cannabis, this would have major implications for public health given that 40-50% of young British people use this drug. The potential use of CBD as a protective agent by vulnerable young people could significantly reduce the 14% who are currently diagnosed with a psychotic disorder in the UK who would not have been if they had not consumed cannabis. It could also impact clinically on prevention and treatment of cannabis dependence.

Publications

10 25 50
 
Description All Party Parliamentary Committee on Drug Policy Reform, House of Lords, 'The case for rescheduling cannabis under the medicines act'
Geographic Reach National 
Policy Influence Type Gave evidence to a government review
 
Description All Party Parliamentary Committee on Drug Policy Reform, House of Lords. 'The case for rescheduling cannabis under the medicines act'
Geographic Reach National 
Policy Influence Type Participation in a advisory committee
 
Description DrugScience
Geographic Reach National 
Policy Influence Type Participation in a advisory committee
 
Description Scientific expert - evidence to the All Parliamentary Committee at the House of Lords on Reform of Drug Policy (Baroness Meacher Chair)
Geographic Reach National 
Policy Influence Type Gave evidence to a government review
 
Description BBSRC studentship
Amount £45,000 (GBP)
Organisation Biotechnology and Biological Sciences Research Council (BBSRC) 
Sector Public
Country United Kingdom
Start 01/2013 
End 09/2015
 
Description Beckley Foundation
Amount £10,000 (GBP)
Organisation Beckley Foundation 
Sector Charity/Non Profit
Country United Kingdom
Start 10/2014 
End 11/2015
 
Description British Medical Association Margaret Temple Grant - Developing an endocannabinoid clinical model of schizophrenia: a multimodal pharmacological imaging study
Amount £50,000 (GBP)
Organisation British Medical Association (BMA) 
Sector Learned Society
Country United Kingdom
Start 01/2015 
End 12/2017
 
Description European College of Neuropsychopharmacology Fellowship Award
Amount £1,042 (GBP)
Organisation European College of Neuropsychopharmacology (ECNP) 
Sector Learned Society
Country European Union (EU)
Start 10/2009 
End 10/2010
 
Description MRC ESRC Interdisciplinary Studentships
Amount £69,710 (GBP)
Funding ID G0900207 
Organisation Medical Research Council (MRC) 
Sector Academic/University
Country United Kingdom
Start 10/2009 
End 09/2013
 
Description Sensitivity to acute effects of cannabis: PET and FMRI analysis 
Organisation Medical Research Council (MRC)
Department MRC Clinical Sciences Centre (CSC)
Country United Kingdom 
Sector Academic/University 
PI Contribution Recruitment of participants who are highly sensitive to acute cannabinoid psychotomimetic effects
Collaborator Contribution Brain scanning expertise and use of scanner
Impact There have been two publications (doi: 10.1007/s00213-014-3523-4 and 10.1016/j.biopsych.2013.05.027)
Start Year 2010
 
Description 5th UK Paediatric Neuropsychology International Symposium (London) 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Professional Practitioners
Results and Impact Presentation on Cannabis and Adolescent Mental Health that sparked questions and discussion afterwards
Year(s) Of Engagement Activity 2017
URL http://www.ucl.ac.uk/centre-developmental-cognitive-neuroscience/events/events-2017/paediatric-neuro...
 
Description A new approach to European drug policy for the 21st century 
Form Of Engagement Activity A formal working group, expert panel or dialogue
Part Of Official Scheme? Yes
Geographic Reach International
Primary Audience Policymakers/politicians
Results and Impact Talk sparked questions and discussions afterwards

Talk led to a visit to us in London by Madame Ruth Dreifuss (ex-President of Switzerland; member of the Global Drugs Commission)
Year(s) Of Engagement Activity 2014
URL https://www.youtube.com/watch?v=ldQ53v37Y8U&feature=youtu.be
 
Description ACU & APS Believe in Change Public Lecture - Cannabis: Pleasure, Madness, Medicine? 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Undergraduate students
Results and Impact Presentation on Cannabis: Pleasure, Madness, Medicine? Presentation sparked questions and discussions afterwards
Year(s) Of Engagement Activity 2017
URL https://www.acu.edu.au/connect_with_acu/events/melbourne/acu_And_aps_believe_in_change_public_lectur...
 
Description All Party Parliamentary Committee on Drug Policy Reform (House of Lords, London) 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Policymakers/politicians
Results and Impact All Party Parliamentary Committee on Drug Policy Reform, House of Lords, Feb 10th 2016. Talk on 'The case for rescheduling cannabis under the medicines act'
Year(s) Of Engagement Activity 2016
 
Description American Psychosomatic Society 74th Annual Scientific Meeting (Denver, Colorado) 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact American Psychosomatic Society 74th Annual meeting in Denver, Colorado, USA. Plenary speaker on Cannabinoids and Cannabis Use Disorder. Talk sparked questions and discussion afterwards.
Year(s) Of Engagement Activity 2016
 
Description Article in Nature News: Key ingredient staves off marijuana memory loss (2010) 
Form Of Engagement Activity A magazine, newsletter or online publication
Part Of Official Scheme? No
Type Of Presentation Keynote/Invited Speaker
Geographic Reach International
Primary Audience Public/other audiences
Results and Impact Article was published in Nature News as a result of journal article in British Journal of Psychiatry.

Other media interest derived from this article on the front page of Nature News (eg article in Telegraph)
Year(s) Of Engagement Activity 2010
 
Description Article in Newsweek: How procedural and legal restrictions make studying the effects of medical marijuana difficult (2010) 
Form Of Engagement Activity A magazine, newsletter or online publication
Part Of Official Scheme? No
Type Of Presentation Keynote/Invited Speaker
Geographic Reach International
Primary Audience Public/other audiences
Results and Impact Article was published in Newsweek as a result of publications from MRC grant

N/A
Year(s) Of Engagement Activity 2010
 
Description BBC Radio 4 PM - Talk on Cannabis and CBD trial (London) 
Form Of Engagement Activity A broadcast e.g. TV/radio/film/podcast (other than news/press)
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Public/other audiences
Results and Impact Prof. Val Curran and Dr Tom Freeman talk about cannabis and the CBD clinical trial as part of Cannabis week on BBC Radio 4. http://www.bbc.co.uk/programmes/b05s310m
Year(s) Of Engagement Activity 2015
URL http://www.bbc.co.uk/news/science-environment-31518546
 
Description BBC Three documentary How Drugs work Cannabis (2011) 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Type Of Presentation Keynote/Invited Speaker
Geographic Reach National
Primary Audience Public/other audiences
Results and Impact Documentary showing the effects of Cannabis and one of our cannabinoid experiments

N/A
Year(s) Of Engagement Activity 2011
 
Description British Association for Psychopharmacology Summer Meeting (Brighton, UK) 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact Talk by TF on 'Dissociable effects of cannabinoids on anticipatory and consummatory reward processing' at British Association for Psychopharmacology Summer Meeting, Brighton UK, July 2016. Talk sparked questions and discussion afterwards.
Year(s) Of Engagement Activity 2015,2016
 
Description British Neuroscience Association (Edinburgh, Scotland) 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Professional Practitioners
Results and Impact Presentation by TF on 'Cannabis and addiction: cause, cure or both?' British Neuroscience Association, Edinburgh, April 2015. Talk sparked questions and discussion afterwards.
Year(s) Of Engagement Activity 2015
 
Description Cannabis use disorder and its effects on cognitive function - World Congress of Biological Psychiatry, June 2017 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact Presentation on Cannabis use disorder and its effects on cognitive function at World Congress of Biological Psychiatry, Copenhagen, June 2017. Presentation sparked questions and discussion
Year(s) Of Engagement Activity 2017
URL http://www.cpo-media.net/WFSBP/2017/Final_Programme/#46/z
 
Description Crime Research Centre, Sussex - Intoxication, Addiction and the Criminal Law 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Other audiences
Results and Impact Presentation at Crime Research Centre, Uni of Sussex - NEUROBIOLOGICAL AND COGNITIVE CONSEQUENCES OF ACUTE AND CHRONIC DRUGS: A FOCUS ON CANNABINOIDS. Presentation sparked questions and discussion afterwards.
Year(s) Of Engagement Activity 2018
URL http://www.sussex.ac.uk/crime/newsandevents/intoxication_addiction_criminal_law
 
Description ECNP Junior Scientist Workshop (Nice, France, March 2017) 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Other audiences
Results and Impact Talk by TF on 'Cannabis increases wanting but not liking of music and dampens its rewarding effects on the brain' ECNP Junior Scientist Workshop, Nice, France, March 2017. Talk sparked questions and discussion afterwards.
Year(s) Of Engagement Activity 2017
 
Description Early Phase Clinical Trials Workshop, MRC Clinical Trials Unit (London, November 2015) 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach Local
Primary Audience Other audiences
Results and Impact Talk by TF on 'Risk evaluation: monitoring on a CBD trial' Early Phase Clinical Trials Workshop, MRC Clinical Trials Unit, London, November 2015. Talk sparked questions and discussion afterwards.
Year(s) Of Engagement Activity 2015
 
Description European Monitoring Centre for Drugs and Drug Addiction (Lisbon, Portugul) 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Other audiences
Results and Impact Talk by TF on 'How can we optimise the treatment of people who are cannabis dependent?' European Monitoring Centre for Drugs and Drug Addiction (EMCDDA): Lisbon Addictions 2015.Talk sparked questions and discussion afterwards.
Year(s) Of Engagement Activity 2015
 
Description IEPA Early Intervention in Mental Health (Milan, Italy) 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact Talk by TF on 'Comparing different types of cannabis on cognition, reward and addiction' at Early Intervention in Mental Health International Conference in Milan, Italy, October 2016. Talk sparked questions and discussion afterwards.
Year(s) Of Engagement Activity 2016
 
Description Institute of Psychology Health and Society Departmental Seminar, University of Liverpool ( Liverpool, UK). 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach Local
Primary Audience Other audiences
Results and Impact Presentation by TF on 'Can we reduce the harmful effects of cannabis?' at the Institute of Psychology Health and Society Departmental Seminar, University of Liverpool, UK, May 2014. Talk sparked questions and discussion afterwards
Year(s) Of Engagement Activity 2014
 
Description Invited speaker at 1st conference of the European Monitoring Centre for Drugs and Drug Addiction (Lisbon, Portugal) 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact Invited talk on Purple haze, Northern lightsneurocognitive effects of different strains of cannabis at 1st conference of the European Monitoring Centre for Drugs and Drug Addiction. Talk sparked questions and discussion afterwards
Year(s) Of Engagement Activity 2015
URL http://www.lisbonaddictions.eu/start
 
Description Invited speaker at The London Salon on Cannabis: Medicine, madness and Pleasure (London) 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Public/other audiences
Results and Impact Invited speaker at The London Salon to give talk on Cannabis: Medicine, madness and Pleasure. Talk sparked questions and discussion afterwards.
Year(s) Of Engagement Activity 2015
 
Description Invited speaker, American College of Neuropharmacology (ACNP), How does the THC and CBD content of cannabis influence its effects? (Miami, USA) 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact Invited speaker at American College of Neuropharmacology (ACNP) annual meeting. 1700 members and scientific guests in attendance.
Talk on How does the THC and CBD content of cannabis influence its effects?
Year(s) Of Engagement Activity 2016
URL http://www.acnp.org/default.aspx
 
Description Media interview - Cannabis: Promise, risk and controversy 
Form Of Engagement Activity A press release, press conference or response to a media enquiry/interview
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Public/other audiences
Results and Impact Article on Cannabis: Promise, risk and controversy
Year(s) Of Engagement Activity 2015
URL http://www.bbc.co.uk/news/science-environment-31518546
 
Description Nature article (2012) 
Form Of Engagement Activity A magazine, newsletter or online publication
Part Of Official Scheme? No
Type Of Presentation Keynote/Invited Speaker
Geographic Reach International
Primary Audience Public/other audiences
Results and Impact Response to published manuscript in Nature - 'Drop in IQ linked to heavy teenage cannabis use' in Nature magazine

N/A
Year(s) Of Engagement Activity 2012
 
Description Newcastle University (Newcastle, UK) 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach Local
Primary Audience Other audiences
Results and Impact Talk by HVC at Newcastle University on Cannabis: pleasure, madness, medicine. Talk sparked questions and discussion afterwards.
Year(s) Of Engagement Activity 2016
 
Description Plenary lecture - Pembroke-King's Programme (PKP) 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Undergraduate students
Results and Impact Talk sparked questions and discussion afterwards

N/A - public engagement activity
Year(s) Of Engagement Activity 2014
URL http://pembrokekings.wordpress.com/2014/07/21/pkp-plenary-lectures/
 
Description Presentation at Uni of Hertfordshire (Feb 2017) 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Undergraduate students
Results and Impact Presentation on Cannabis: pleasure, madness and medicine? Presentation sparked questions and discussion afterwards
Year(s) Of Engagement Activity 2017
URL https://www.herts.ac.uk/__data/assets/pdf_file/0020/162911/PSS-ResSeminars-UHweb_16-17.pdf
 
Description Public lecture - Cannabis: pleasure, madness & medicine 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Public/other audiences
Results and Impact Talk sparked questions and discussion afterwards

N/A - public engagement activity
Year(s) Of Engagement Activity 2014
URL http://www.scienceandcocktails.org/2014/Cannabis.html
 
Description Public lecture: The Intoxication Season at Kew Gardens - Cannabis: medicine or madness? 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Public/other audiences
Results and Impact Talk sparked questions and discussion afterwards

Public engagement activity - talk sparked questions and discussion afterwards from members of the public and Kew staff who attended.
Year(s) Of Engagement Activity 2014
URL http://www.kew.org/visit-kew-gardens/whats-on/intoxication-season
 
Description Research Talk - Roehampton University 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach Local
Primary Audience Postgraduate students
Results and Impact Presentation on Cannabis: Pleasure, Madness, Medicine? at Roehampton University
Year(s) Of Engagement Activity 2018
URL https://www.roehampton.ac.uk/psychology/events/
 
Description Synthetic cannabinoids: a growing problem? ECNP, Paris 2017 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact Moderator on Synthetic cannabinoids: a growing problem? panel at ECNP, Paris, 2-5th September 2017
Year(s) Of Engagement Activity 2017
URL https://www.ecnp.eu/~/media/Files/congress/Paris2017/Programme/Congress_programme_booklet.pdf?la=en
 
Description TV documentary for SKY TV (2010) 
Form Of Engagement Activity A press release, press conference or response to a media enquiry/interview
Part Of Official Scheme? No
Type Of Presentation Keynote/Invited Speaker
Geographic Reach National
Primary Audience Public/other audiences
Results and Impact Documentary showing one of our cannabinoid experiments and discussing findings.

N/A
Year(s) Of Engagement Activity 2010
 
Description UCL Institute of Mental Health Clinical Academic Seminar (London) 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach Local
Primary Audience Other audiences
Results and Impact Presentation by HVC at UCL Institute of Mental Health on Cannabis: pleasure, madness, medicine. Talk sparked questions and discussion afterwards.
Year(s) Of Engagement Activity 2017
 
Description UCL Neuroscience Society (London) 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach Local
Primary Audience Other audiences
Results and Impact Presentation by HVC at UCL Neuroscience Society on Cannabis: pleasure, medicine, madness. 18/10/2016. Talk sparked questions and discussion afterwards.
Year(s) Of Engagement Activity 2016
 
Description University College Hospital weekly Accident and Emergency meeting (UK) 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach Local
Primary Audience Professional Practitioners
Results and Impact Presentation by TF on 'Cannabidiol: a novel intervention for cannabis use problems?' University College Hospital weekly Accident and Emergency meeting, UK, June 2014. Talk sparked questions and discussion afterwards
Year(s) Of Engagement Activity 2014
 
Description University of Hertfordshire. Talk on Cannabis and cannabinoids: mental health and medicines (Hertfordshire ) 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach Local
Primary Audience Other audiences
Results and Impact Presentation by HVC at University of Hertfordshire (16/02/2017) on Cannabis and cannabinoids: mental health and medicines. Talk sparked question and discussion afterwards
Year(s) Of Engagement Activity 2017
 
Description Wellcome Trust 'High Society' exhibition (London, 2011) 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Type Of Presentation Keynote/Invited Speaker
Geographic Reach Regional
Primary Audience Public/other audiences
Results and Impact Public talk on 'What is a drug?' as part of Wellcome Trust 'High Society' exhibition

No notable impact as yet
Year(s) Of Engagement Activity 2011