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Manipulating brain connectivity with δ⁹-tetrahydrocannabinol: a pharmacological resting state FMRI study.

Linda E. Klumpers, David M. Cole, Najmeh Khalili-Mahani, Roelof P Soeter, Erik T Te Beek, Serge A.r.b. Rombouts, Joop van Gerven

Neuroimage November 15, 2012 DOI: 10.1016/j.neuroimage.2012.07.051 (opens in new tab)

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Study at a glance

AI-extracted from the abstract
Characteristics Randomized, double-blind, crossover trial Peer reviewed
Sample size 12
Population Healthy volunteers (9 male, 3 female)
Intervention THC
Dose 2, 6 and 6 mg THC or placebo with 90-minute intervals
Duration Three occasions with 90-minute dosing intervals; eight 8-minute RS-FMRI scans per occasion
Measures visual analog scale, resting-state functional magnetic resonance imaging (RS-FMRI)
Topics Cannabis
Key findings THC administration increased functional connectivity in the sensorimotor network and was associated with dissociable lateralized connectivity changes in the right and left dorsal visual stream networks, including the cerebellum and dorsal frontal cortical regions. THC also increased feeling high, external perception, heart rate, and cortisol while decreasing prolactin. The authors report both increases and, to a lesser extent, decreases in connectivity, mainly in regions with high CB1-receptor densities.

Abstract

Resting state-functional magnetic resonance imaging (RS-FMRI) is a neuroimaging technique that allows repeated assessments of functional connectivity in resting state. While task-related FMRI is limited to indirectly measured drug effects in areas affected by the task, resting state can show direct CNS effects across all brain networks. Hence, RS-FMRI could be an objective measure for compounds affecting the CNS. Several studies on the effects of cannabinoid receptor type 1 (CB(1))-receptor agonist δ(9)-tetrahydrocannabinol (THC) on task-dependent FMRI have been performed. However, no studies on the effects of cannabinoids on resting state networks using RS-FMRI have been published. Therefore, we investigated the effects of THC on functional brain connectivity using RS-FMRI. Twelve healthy volunteers (9 male, 3 female) inhaled 2, 6 and 6 mg THC or placebo with 90-minute intervals in a randomized, double blind, cross-over trial. Eight RS-FMRI scans of 8 min were obtained per occasion. Subjects rated subjective psychedelic effects on a visual analog scale after each scan, as pharmacodynamic effect measures. Drug-induced effects on functional connectivity were examined using dual regression with FSL software (FMRIB Analysis Group, Oxford). Eight maps of voxel-wise connectivity throughout the entire brain were provided per RS-FMRI series with eight predefined resting-state networks of interest. These maps were used in a mixed effects model group analysis to determine brain regions with a statistically significant drug-by-time interaction. Statistical images were cluster-corrected, and results were Bonferroni-corrected across multiple contrasts. THC administration increased functional connectivity in the sensorimotor network, and was associated with dissociable lateralized connectivity changes in the right and left dorsal visual stream networks. The brain regions showing connectivity changes included the cerebellum and dorsal frontal cortical regions. Clear increases were found for feeling high, external perception, heart rate and cortisol, whereas prolactin decreased. This study shows that THC induces both increases and (to a lesser extent) decreases in functional brain connectivity, mainly in brain regions with high densities of CB(1)-receptors. Some of the involved regions could be functionally related to robust THC-induced CNS-effects that have been found in previous studies (Zuurman et al., 2008), such as postural stability, feeling high and altered time perception.

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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

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