Significant decreases in frontal and temporal [11C]-raclopride binding after THC challenge.
Paul R A Stokes, Alice Egerton, Ben Watson, Alistair Reid, Gerome Breen, Anne Lingford‐hughes, David Nutt, Mitul A. Mehta
Neuroimage May 6, 2010 DOI: 10.1016/j.neuroimage.2010.04.274 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Within-subject crossover PET imaging study Peer reviewed |
|---|---|
| Sample size | 13 |
| Population | Healthy volunteers |
| Intervention | Delta9-tetrahydrocannabinol (THC) |
| Dose | 10 mg oral |
| Measures | [11C]-raclopride binding potential (BP(ND)), simplified reference tissue model R1 |
| Topics | Cannabis |
| Keywords | Frontal lobe Temporal lobe Humans Raclopride Dopamine Psychotropic drugs Radiopharmaceuticals Radionuclide imaging Tissue distribution Adult Female Dronabinol |
| Key points | Oral THC (10 mg) decreased [11C]-raclopride binding potential in bilateral frontopolar cortex and left superior temporal gyrus, with reductions exceeding test-retest variability. The authors interpret this as evidence of increased cortical dopamine release, though they discuss alternative explanations including blood flow effects. |
Abstract
Delta9-tetrahydrocannabinol (THC) increases prefrontal cortical dopamine release in animals, but this is yet to be examined in humans. In man, striatal dopamine release can be indexed using [11C]-raclopride positron emission tomography (PET), and recent reports suggest that cortical [11C]-raclopride binding may also be sensitive to dopaminergic challenges. Using an existing dataset we examined whether THC alters [11C]-raclopride binding potential (BP(ND)) in cortical regions. Thirteen healthy volunteers underwent two [11C]-raclopride PET scans following either oral 10 mg THC or placebo. Significant areas of decreased cortical [11C]-raclopride BP(ND) were identified using whole brain voxel-wise analysis and quantified using a region of interest (ROI) ratio analysis. Effect of blood flow on binding was estimated using a simplified reference tissue model analysis. Results were compared to [11C]-raclopride test-retest reliability in the ROIs identified using a separate cohort of volunteers. Voxel-wise analysis identified three significant clusters of decreased [11C]-raclopride BP(ND) after THC in the right middle frontal gyrus, left superior frontal gyrus and left superior temporal gyrus. Decreases in [11C]-raclopride BPND following THC were greater than test-retest variability in these ROIs. R1, an estimate of blood flow, significantly decreased in the left superior frontal gyrus in the THC condition but was unchanged in the other ROIs. Decreased frontal binding significantly correlated to catechol-o-methyl transferase (COMT) val108 status. We have demonstrated for the first time significant decreases in bilateral frontopolar cortical and left superior temporal gyrus [11C]-raclopride binding after THC. The interpretation of these findings in relation to prefrontal dopamine release is discussed.
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 10
- Drug-Induced Psychosis: How to Avoid Star Gazing in Schizophrenia Research by Looking at More Obvious Sources of Light Frontiers in Behavioral Neuroscience 2011
- History of cannabis use is not associated with alterations in striatal dopamine D 2 /D 3 receptor availability Journal of Psychopharmacology September 2, 2011
- Investigation of the COMT Val158Met variant association with age of onset of psychosis, adjusting for cannabis use Brain and Behavior October 6, 2017
- Cannabis Use and Neuroadaptation: A Call for Δ9-Tetrahydrocannabinol Challenge Studies Frontiers in Psychiatry April 14, 2022
- Cross cultural studies on adolescent cannabis use and psychosis 2011
and 5 more in the library
Cites 8
- Delta 9-tetrahydrocannabinol induces dopamine release in the human striatum. Neuropsychopharmacology February 2009
- Neural basis of Delta-9-tetrahydrocannabinol and cannabidiol: effects during response inhibition. Biological Psychiatry December 1, 2008
- The psychotomimetic states inventory (PSI): measuring psychotic-type experiences from ketamine and cannabis. Schizophrenia Research August 2008
- Effects of haloperidol on the behavioral, subjective, cognitive, motor, and neuroendocrine effects of Delta-9-tetrahydrocannabinol in humans. Psychopharmacology July 2008
- Effects of smoking marijuana on focal attention and brain blood flow. Human psychopharmacology April 2007
and 3 more in the library