Claire Mokrysz1, Natacha D C Shaban1, Tom P Freeman1,2,3, Will Lawn1, Rebecca A Pope1, Chandni Hindocha1, Abigail Freeman1, Matthew B Wall1,4,5, Michael A P Bloomfield1,6,7,8, Celia J A Morgan1,9, David J Nutt10, H Valerie Curran1. 1. Clinical Psychopharmacology Unit, University College London, London, UK. 2. Addiction and Mental Health Group (AIM), Department of Psychology, University of Bath, Bath, UK. 3. National Addiction Centre, Institute of Psychiatry, Psychology & Neuroscience, King's College London, London, UK. 4. Invicro, Burlington Danes Building, Imperial College London, Hammersmith Hospital, Du Cane Road, London, UK. 5. Division of Brain Sciences, Imperial College London, London, UK. 6. Psychiatric Imaging Group, Medical Research Council Clinical Sciences Centre, Hammersmith Hospital, London, UK. 7. Division of Psychiatry, Translational Psychiatry Research Group, University College London, Maple House, London, UK. 8. NIHR University College London Hospitals Biomedical Research Centre, University College Hospitals NHS Foundation Trust, London, UK. 9. Psychopharmacology and Addiction Research Centre, University of Exeter, Exeter, UK. 10. Neuropsychopharmacology Unit, Division of Experimental Medicine, Imperial College London, Burlington Danes Building, Du Cane Road, London, UK.
Abstract
BACKGROUND: Acute cannabis administration can produce transient psychotic-like effects in healthy individuals. However, the mechanisms through which this occurs and which factors predict vulnerability remain unclear. We investigate whether cannabis inhalation leads to psychotic-like symptoms and speech illusion; and whether cannabidiol (CBD) blunts such effects (study 1) and adolescence heightens such effects (study 2). METHODS: Two double-blind placebo-controlled studies, assessing speech illusion in a white noise task, and psychotic-like symptoms on the Psychotomimetic States Inventory (PSI). Study 1 compared effects of Cann-CBD (cannabis containing Δ-9-tetrahydrocannabinol (THC) and negligible levels of CBD) with Cann+CBD (cannabis containing THC and CBD) in 17 adults. Study 2 compared effects of Cann-CBD in 20 adolescents and 20 adults. All participants were healthy individuals who currently used cannabis. RESULTS: In study 1, relative to placebo, both Cann-CBD and Cann+CBD increased PSI scores but not speech illusion. No differences between Cann-CBD and Cann+CBD emerged. In study 2, relative to placebo, Cann-CBD increased PSI scores and incidence of speech illusion, with the odds of experiencing speech illusion 3.1 (95% CIs 1.3-7.2) times higher after Cann-CBD. No age group differences were found for speech illusion, but adults showed heightened effects on the PSI. CONCLUSIONS: Inhalation of cannabis reliably increases psychotic-like symptoms in healthy cannabis users and may increase the incidence of speech illusion. CBD did not influence psychotic-like effects of cannabis. Adolescents may be less vulnerable to acute psychotic-like effects of cannabis than adults.
RCT Entities:
BACKGROUND: Acute cannabis administration can produce transient psychotic-like effects in healthy individuals. However, the mechanisms through which this occurs and which factors predict vulnerability remain unclear. We investigate whether cannabis inhalation leads to psychotic-like symptoms and speech illusion; and whether cannabidiol (CBD) blunts such effects (study 1) and adolescence heightens such effects (study 2). METHODS: Two double-blind placebo-controlled studies, assessing speech illusion in a white noise task, and psychotic-like symptoms on the Psychotomimetic States Inventory (PSI). Study 1 compared effects of Cann-CBD (cannabis containing Δ-9-tetrahydrocannabinol (THC) and negligible levels of CBD) with Cann+CBD (cannabis containing THC and CBD) in 17 adults. Study 2 compared effects of Cann-CBD in 20 adolescents and 20 adults. All participants were healthy individuals who currently used cannabis. RESULTS: In study 1, relative to placebo, both Cann-CBD and Cann+CBD increased PSI scores but not speech illusion. No differences between Cann-CBD and Cann+CBD emerged. In study 2, relative to placebo, Cann-CBD increased PSI scores and incidence of speech illusion, with the odds of experiencing speech illusion 3.1 (95% CIs 1.3-7.2) times higher after Cann-CBD. No age group differences were found for speech illusion, but adults showed heightened effects on the PSI. CONCLUSIONS: Inhalation of cannabis reliably increases psychotic-like symptoms in healthy cannabis users and may increase the incidence of speech illusion. CBD did not influence psychotic-like effects of cannabis. Adolescents may be less vulnerable to acute psychotic-like effects of cannabis than adults.
Authors: Matthew B Wall; Tom P Freeman; Chandni Hindocha; Lysia Demetriou; Natalie Ertl; Abigail M Freeman; Augustus Pm Jones; Will Lawn; Rebecca Pope; Claire Mokrysz; Daniel Solomons; Ben Statton; Hannah R Walker; Yumeya Yamamori; Zixu Yang; Jocelyn Ll Yim; David J Nutt; Oliver D Howes; H Valerie Curran; Michael Ap Bloomfield Journal: J Psychopharmacol Date: 2022-05-20 Impact factor: 4.562