Previous cannabis exposure modulates the acute effects of delta-9-tetrahydrocannabinol on attentional salience and fear processing.
Marco Colizzi, Philip Mcguire, Vincent Giampietro, Steve C. R. Williams, Mick Brammer, Sagnik Bhattacharyya
Experimental and Clinical Psychopharmacology December 2018 DOI: 10.1037/pha0000221 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Double-blind, randomized, placebo-controlled, repeated-measures, within-subject Δ9-THC challenge study using fMRI Peer reviewed |
|---|---|
| Sample size | 24 |
| Population | Healthy men: 12 nonusers (<5 lifetime cannabis joints smoked) and 12 abstinent-modest cannabis users (24.5 ± 9 lifetime cannabis joints smoked) |
| Intervention | Δ9-THC |
| Topics | Cannabis |
| Key points | Δ9-THC disrupted attentional salience and emotional-processing brain activity and induced transient anxiety and psychotic symptoms, but these acute symptomatic, behavioral, and neurophysiological effects were more pronounced in nonusers than in abstinent-modest cannabis users. Cannabis users showed residual effects of prior exposure yet more blunted responses to the acute challenge in an exposure-dependent manner. |
Abstract
Cannabis can induce transient psychotic and anxiety symptoms and long-lasting disorders. The acute psychoactive effects of its main active ingredient, (-)-trans-Δ9-tetrahydrocannabinol (Δ9-THC), may be modulated by previous cannabis exposure. Secondary data analyses tested whether modest previous cannabis exposure modulated the acute effects of Δ9-THC on attentional salience and emotional processing and their neurophysiological substrates. Twenty-four healthy men participated in a double-blind, randomized, placebo-controlled, repeated-measures, within-subject, Δ9-THC challenge study using fMRI. Compared with nonusers (NUs; n = 12; <5 lifetime cannabis joints smoked), abstinent-modest cannabis users (CUs; n = 12; 24.5 ± 9 lifetime cannabis joints smoked) showed less efficient attentional salience processing and recruited different/additional brain areas to process attentional salient and emotional stimuli (all ps ≤ .01). The Δ9-THC challenge disrupted attentional salience and emotional-processing-related brain activity and induced transient anxiety and psychotic symptoms (all ps ≤ .02). However, Δ9-THC-induced psychotic symptoms and attentional salience behavioral impairment were more pronounced in NUs compared with CUs (all ps ≤ .04). Also, NUs under Δ9-THC shifted toward recruitment of other brain areas to perform the tasks. Conversely, CUs were less affected by the acute challenge in an exposure-dependent manner, showing a neurophysiological pattern similar to that of NUs under placebo. Only in NUs, Δ9-THC-induced psychotic symptom and cognitive impairment severity was associated with a more pronounced neurophysiological alteration (all ps ≤ .048). In conclusion, CUs displayed residual effects of cannabis exposure but more blunted responses to the acute symptomatic, behavioral, and neurophysiological effects of Δ9-THC, which were more marked in NUs. (PsycINFO Database Record (c) 2018 APA, all rights reserved).
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 14
- Unraveling the Intoxicating and Therapeutic Effects of Cannabis Ingredients on Psychosis and Cognition Frontiers in Psychology May 14, 2020
- High-Concentration Delta-9-Tetrahydrocannabinol Cannabis Products and Mental Health Outcomes : A Systematic Review. Annals of Internal Medicine October 1, 2025
- Dose-related reductions in prefrontal recruitment during cognitive reappraisal following oral delta-9-tetrahydrocannabinol in posttraumatic stress disorder. Neuropsychopharmacology July 16, 2026
- Potential Risks from Cannabis- Infused Beverages: A Critical Review Cannabis November 26, 2024
- Effects of Cannabis Use on Neurocognition: A Scoping Review of MRI Studies Journal of Psychoactive Drugs June 29, 2024
and 9 more in the library