title: Brain Mapping-Based Model of Δ(9)-Tetrahydrocannabinol Effects on Connectivity in the Pain Matrix.
abstract: Cannabinoids receive increasing interest as analgesic treatments. However, the clinical use of Δ(9)-tetrahydrocannabinol (Δ(9)-THC) has progressed with justified caution, which also owes to the incomplete mechanistic understanding of its analgesic effects, in particular its interference with the processing of sensory or affective components of pain. The present placebo-controlled crossover study therefore focused on the effects of 20 mg oral THC on the connectivity between brain areas of the pain matrix following experimental stimulation of trigeminal nocisensors in 15 non-addicted healthy volunteers. A general linear model (GLM) analysis identified reduced activations in the hippocampus and the anterior insula following THC administration. However, assessment of psychophysiological interaction (PPI) revealed that the effects of THC first consisted in a weakening of the interaction between the thalamus and the secondary somatosensory cortex (S2). From there, dynamic causal modeling (DCM) was employed to infer that THC attenuated the connections to the hippocampus and to the anterior insula, suggesting that the reduced activations in these regions are secondary to a reduction of the connectivity from somatosensory regions by THC. These findings may have consequences for the way THC effects are currently interpreted: as cannabinoids are increasingly considered in pain treatment, present results provide relevant information about how THC interferes with the affective component of pain. Specifically, the present experiment suggests that THC does not selectively affect limbic regions, but rather interferes with sensory processing which in turn reduces sensory-limbic connectivity, leading to deactivation of affective regions.
authors.affiliation: Institute of Clinical Pharmacology, Goethe University, Frankfurt am Main, Germany.
authors.forename: Carmen
authors.initials: C
authors.lastname: Walter
authors.affiliation: Institute of Clinical Pharmacology, Goethe University, Frankfurt am Main, Germany.
authors.forename: Bruno G
authors.initials: BG
authors.lastname: Oertel
authors.affiliation: Institute of Clinical Pharmacology, Goethe University, Frankfurt am Main, Germany.
authors.forename: Lisa
authors.initials: L
authors.lastname: Felden
authors.affiliation: Brain Imaging Center, Goethe University, Frankfurt am Main, Germany.|Department of Neurology, Goethe University, Frankfurt am Main, Germany.
authors.forename: Christian A
authors.initials: CA
authors.lastname: Kell
authors.affiliation: Brain Imaging Center, Goethe University, Frankfurt am Main, Germany.
authors.forename: Ulrike
authors.initials: U
authors.lastname: Nöth
authors.affiliation: Institute of Clinical Pharmacology, Goethe University, Frankfurt am Main, Germany.
authors.forename: Johannes
authors.initials: J
authors.lastname: Vermehren
authors.affiliation: Institute of Medical Psychology, Goethe University, Frankfurt am Main, Germany.
authors.forename: Jochen
authors.initials: J
authors.lastname: Kaiser
authors.affiliation: Brain Imaging Center, Goethe University, Frankfurt am Main, Germany.
authors.forename: Ralf
authors.initials: R
authors.lastname: Deichmann
authors.affiliation: Institute of Clinical Pharmacology, Goethe University, Frankfurt am Main, Germany.
authors.forename: Jörn
authors.initials: J
authors.lastname: Lötsch
mesh_terms: D000328:Adult; D000700:Analgesics / Q000494:pharmacology*; D001921:Brain / Q000000981:diagnostic imaging / Q000187:drug effects* / Q000503:physiopathology; D001931:Brain Mapping; D018592:Cross-Over Studies; D004311:Double-Blind Method; D013759:Dronabinol / Q000494:pharmacology*; D005260:Female; D059907:Functional Neuroimaging; D006624:Hippocampus / Q000000981:diagnostic imaging / Q000187:drug effects / Q000503:physiopathology; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008959:Models, Neurological; D009434:Neural Pathways / Q000000981:diagnostic imaging / Q000187:drug effects* / Q000503:physiopathology; D010146:Pain / Q000188:drug therapy* / Q000503:physiopathology; D013003:Somatosensory Cortex / Q000000981:diagnostic imaging / Q000187:drug effects / Q000503:physiopathology; D013788:Thalamus / Q000000981:diagnostic imaging / Q000187:drug effects / Q000503:physiopathology; D055815:Young Adult
chemical_list: D000700:Analgesics; D013759:Dronabinol