How cannabis causes paranoia: using the intravenous administration of ∆9-tetrahydrocannabinol (THC) to identify key cognitive mechanisms leading to paranoia.
Daniel Freeman, Graham Dunn, Robin Murray, Nicole Evans, Rachel Lister, Angus Antley, Mel Slater, Beata Godlewska, Robert Cornish, Jonathan Williams, Martina Di Simplicio, Artemis Igoumenou, Rudolf Brenneisen, Elizabeth M Tunbridge, Paul J Harrison, Catherine J Harmer, Philip J. Cowen, Paul D. Morrison
Schizophrenia Bulletin March 2015 DOI: 10.1093/schbul/sbu098 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Randomized controlled trial Placebo-controlled Peer reviewed |
|---|---|
| Sample size | 121 |
| Population | Individuals with paranoid ideation |
| Interventions | THC cognitive awareness condition |
| Topics | Cannabis |
| Keywords | Cognitive Delusions Paranoia |
| Key findings | Intravenous THC increased paranoia in individuals with paranoid ideation. The increase in negative affect and anomalous experiences fully accounted for the increase in paranoia, whereas working memory changes did not. The authors conclude that THC triggers paranoid thoughts in vulnerable individuals, most likely through negative affect and anomalous experiences. |
Abstract
Paranoia is receiving increasing attention in its own right, since it is a central experience of psychotic disorders and a marker of the health of a society. Paranoia is associated with use of the most commonly taken illicit drug, cannabis. The objective was to determine whether the principal psychoactive ingredient of cannabis-∆(9)-tetrahydrocannabinol (THC)-causes paranoia and to use the drug as a probe to identify key cognitive mechanisms underlying paranoia. A randomized, placebo-controlled, between-groups test of the effects of intravenous THC was conducted. A total of 121 individuals with paranoid ideation were randomized to receive placebo, THC, or THC preceded by a cognitive awareness condition. Paranoia was assessed extensively via a real social situation, an immersive virtual reality experiment, and standard self-report and interviewer measures. Putative causal factors were assessed. Principal components analysis was used to create a composite paranoia score and composite causal variables to be tested in a mediation analysis. THC significantly increased paranoia, negative affect (anxiety, worry, depression, negative thoughts about the self), and a range of anomalous experiences, and reduced working memory capacity. The increase in negative affect and in anomalous experiences fully accounted for the increase in paranoia. Working memory changes did not lead to paranoia. Making participants aware of the effects of THC had little impact. In this largest study of intravenous THC, it was definitively demonstrated that the drug triggers paranoid thoughts in vulnerable individuals. The most likely mechanism of action causing paranoia was the generation of negative affect and anomalous experiences.
Comparable studies
Other randomized controlled trials on cannabis, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| Cannabidiol inhibits THC-elicited paranoid symptoms and hippocampal-dependent memory impairment Healthy participants | 2012 | Randomized controlled trial | n = 48 |
| Distinct Effects of Δ9-Tetrahydrocannabinol and Cannabidiol on Neural Activation During Emotional Processing Healthy, English-native, right-handed men who had used cannabis 15 times or less in... | 2009 | Double-blind, randomized, placebo-controlled crossover trial | n = 15 |
| Acute Effects of a Single, Oral dose of d9-tetrahydrocannabinol (THC) and Cannabidiol (CBD) Administration in Healthy Volunteers Healthy male subjects | 2012 | Randomized controlled trial | n = 16 |
| Modulation of Mediotemporal and Ventrostriatal Function in Humans by Δ9-Tetrahydrocannabinol Healthy, native English-speaking, right-handed men of white race/ethnicity who had used... | 2009 | Randomized controlled trial | n = 15 |
| Cannabidiol (CBD) content in vaporized cannabis does not prevent tetrahydrocannabinol (THC)-induced impairment of driving and cognition Healthy volunteers with a history of light cannabis use | 2019 | Randomized, double-blind, within-subjects crossover | n = 14 |
Citations in the library
Cited by 25
- The Challenging Experience Questionnaire: Characterization of challenging experiences with psilocybin mushrooms Journal of Psychopharmacology November 18, 2016
- Traditional marijuana, high‐potency cannabis and synthetic cannabinoids: increasing risk for psychosis World Psychiatry September 22, 2016
- The neuropsychopharmacology of cannabis: A review of human imaging studies Pharmacology & Therapeutics October 20, 2018
- Human Laboratory Studies on Cannabinoids and Psychosis. Biological Psychiatry April 1, 2016
- Cognitive mechanisms in cannabis-related paranoia; Initial testing and model proposal Psychosis May 13, 2020
and 20 more in the library
Cites 7
- Psychosis as a state of aberrant salience: a framework linking biology, phenomenology, and pharmacology in schizophrenia. American Journal of Psychiatry 2003
- Opposite effects of delta-9-tetrahydrocannabinol and cannabidiol on human brain function and psychopathology. Neuropsychopharmacology November 18, 2009
- The acute effects of synthetic intravenous Delta9-tetrahydrocannabinol on psychosis, mood and cognitive functioning. Psychological Medicine October 2009
- Effects of haloperidol on the behavioral, subjective, cognitive, motor, and neuroendocrine effects of Delta-9-tetrahydrocannabinol in humans. Psychopharmacology July 2008
- The Cardiff Anomalous Perceptions Scale (CAPS): a new validated measure of anomalous perceptual experience. Schizophrenia Bulletin October 19, 2005
and 2 more in the library