Induction of psychosis by Δ9-tetrahydrocannabinol reflects modulation of prefrontal and striatal function during attentional salience processing.
Sagnik Bhattacharyya, José Alexandre S. Crippa, Paul Allen, Rocío Martín‐Santos, Stefan Borgwardt, Paolo Fusar‐poli, Katya Rubia, Joseph P. Kambeitz, Colin O'Carroll, Marc L. Seal, Vincent Giampietro, Michael J Brammer, Antônio Waldo Zuardi, Zerrin Atakan, Philip Mcguire
Archives of General Psychiatry January 2012 DOI: 10.1001/archgenpsychiatry.2011.161 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Randomized, placebo-controlled, within-subject pharmacological fMRI experiment Peer reviewed |
|---|---|
| Sample size | 15 |
| Population | Healthy men with minimal previous cannabis use |
| Interventions | Δ9-tetrahydrocannabinol (Δ9-THC) cannabidiol (CBD) placebo |
| Topics | Cannabis |
| Key findings | Δ9-THC and CBD differentially modulated brain activation during attentional salience processing: Δ9-THC attenuated right caudate and augmented right prefrontal activation, while CBD showed the opposite pattern, augmenting left caudate and hippocampal activation and attenuating right prefrontal activation. The right caudate effect of Δ9-THC correlated negatively with the severity of psychotic symptoms it induced and with its effect on response latency. The authors propose these effects may contribute to cannabis's impact on psychotic symptoms and psychosis risk. |
Abstract
The aberrant processing of salience is thought to be a fundamental factor underlying psychosis. Cannabis can induce acute psychotic symptoms, and its chronic use may increase the risk of schizophrenia. We investigated whether its psychotic effects are mediated through an influence on attentional salience processing. To examine the effects of Δ9-tetrahydrocannabinol (Δ9-THC) and cannabidiol (CBD) on regional brain function during salience processing. Volunteers were studied using event-related functional magnetic resonance imaging on 3 occasions after administration of Δ9-THC, CBD, or placebo while performing a visual oddball detection paradigm that involved allocation of attention to infrequent (oddball) stimuli within a string of frequent (standard) stimuli. University center. Fifteen healthy men with minimal previous cannabis use. Symptom ratings, task performance, and regional brain activation. During the processing of oddball stimuli, relative to placebo, Δ9-THC attenuated activation in the right caudate but augmented it in the right prefrontal cortex. Δ9-Tetrahydrocannabinol also reduced the response latency to standard relative to oddball stimuli. The effect of Δ9-THC in the right caudate was negatively correlated with the severity of the psychotic symptoms it induced and its effect on response latency. The effects of CBD on task-related activation were in the opposite direction of those of Δ9-THC; relative to placebo, CBD augmented left caudate and hippocampal activation but attenuated right prefrontal activation. Δ9-Tetrahydrocannabinol and CBD differentially modulate prefrontal, striatal, and hippocampal function during attentional salience processing. These effects may contribute to the effects of cannabis on psychotic symptoms and on the risk of psychotic disorders.
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 48
- Cannabidiol inhibits THC-elicited paranoid symptoms and hippocampal-dependent memory impairment Journal of Psychopharmacology October 5, 2012
- Translational Investigation of the Therapeutic Potential of Cannabidiol (CBD): Toward a New Age Frontiers in Immunology September 21, 2018
- Gone to Pot – A Review of the Association between Cannabis and Psychosis Frontiers in Psychiatry May 22, 2014
- 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
and 43 more in the library
Cites 18
- Psychosis as a state of aberrant salience: a framework linking biology, phenomenology, and pharmacology in schizophrenia. American Journal of Psychiatry 2003
- From dopamine to salience to psychosis--linking biology, pharmacology and phenomenology of psychosis. Schizophrenia Research November 1, 2005
- Distinct Effects of Δ9-Tetrahydrocannabinol and Cannabidiol on Neural Activation During Emotional Processing Archives of General Psychiatry 2009
- Cannabidiol, a Cannabis sativa constituent, as an antipsychotic drug Brazilian Journal of Medical and Biological Research April 1, 2006
- Modulation of Mediotemporal and Ventrostriatal Function in Humans by Δ9-Tetrahydrocannabinol Archives of General Psychiatry April 1, 2009
and 13 more in the library