title: Amygdala activity contributes to the dissociative effect of cannabis on pain perception.
abstract: Cannabis is reported to be remarkably effective for the relief of otherwise intractable pain. However, the bases for pain relief afforded by this psychotropic agent are debatable. Nonetheless, the frontal-limbic distribution of cannabinoid receptors in the brain suggests that cannabis may target preferentially the affective qualities of pain. This central mechanism of action may be relevant to cannabinoid analgesia in humans, but has yet to be demonstrated. Here, we employed functional magnetic resonance imaging to investigate the effects of delta-9-tetrahydrocannabinol (THC), a naturally occurring cannabinoid, on brain activity related to cutaneous ongoing pain and hyperalgesia that were temporarily induced by capsaicin in healthy volunteers. On average, THC reduced the reported unpleasantness, but not the intensity of ongoing pain and hyperalgesia: the specific analgesic effect on hyperalgesia was substantiated by diminished activity in the anterior mid cingulate cortex. In individuals, the drug-induced reduction in the unpleasantness of hyperalgesia was positively correlated with right amygdala activity. THC also reduced functional connectivity between the amygdala and primary sensorimotor areas during the ongoing-pain state. Critically, the reduction in sensory-limbic functional connectivity was positively correlated with the difference in drug effects on the unpleasantness and the intensity of ongoing pain. Peripheral mechanisms alone cannot account for the dissociative effects of THC on the pain that was observed. Instead, the data reveal that amygdala activity contributes to interindividual response to cannabinoid analgesia, and suggest that dissociative effects of THC in the brain are relevant to pain relief in humans.
authors.affiliation: Centre for Functional MRI of the Brain (FMRIB), Department of Clinical Neurology and Nuffield Department of Clinical Neurosciences, Division of Anaesthesia, University of Oxford, Oxford, UK Department of Neurology, Technische Universtität München, Munich, Germany NeuroImage Nord, Department of Neurology, University Medical Center, Hamburg-Eppendorf, Germany Department of Medicine, Division of Anaesthesia, University of Cambridge, Cambridge, UK.
authors.forename: Michael C
authors.initials: MC
authors.lastname: Lee
authors.forename: Markus
authors.initials: M
authors.lastname: Ploner
authors.forename: Katja
authors.initials: K
authors.lastname: Wiech
authors.forename: Ulrike
authors.initials: U
authors.lastname: Bingel
authors.forename: Vishvarani
authors.initials: V
authors.lastname: Wanigasekera
authors.forename: Jonathan
authors.initials: J
authors.lastname: Brooks
authors.forename: David K
authors.initials: DK
authors.lastname: Menon
authors.forename: Irene
authors.initials: I
authors.lastname: Tracey
mesh_terms: D000328:Adult; D000679:Amygdala / Q000187:drug effects* / Q000502:physiology; D018712:Analgesics, Non-Narcotic / Q000627:therapeutic use*; D000956:Antigens, Viral; D002211:Capsaicin / Q000009:adverse effects; D018592:Cross-Over Studies; D004213:Dissociative Disorders / Q000139:chemically induced* / Q000523:psychology; D004311:Double-Blind Method; D013759:Dronabinol / Q000627:therapeutic use*; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D006930:Hyperalgesia / Q000139:chemically induced / Q000188:drug therapy* / Q000523:psychology; D008297:Male; D058748:Pain Perception / Q000187:drug effects*; D010919:Placebos; D011597:Psychomotor Performance / Q000187:drug effects; D018689:Sensory System Agents / Q000009:adverse effects; D055815:Young Adult
chemical_list: D018712:Analgesics, Non-Narcotic; D000956:Antigens, Viral; C030663:FMR antigen; D010919:Placebos; D018689:Sensory System Agents; D013759:Dronabinol; D002211:Capsaicin