Amygdala activity contributes to the dissociative effect of cannabis on pain perception

TY - JOUR

T1 - Amygdala activity contributes to the dissociative effect of cannabis on pain perception

AU - Lee, Michael C

AU - Ploner, Markus

AU - Wiech, Katja

AU - Bingel, Ulrike

AU - Wanigasekera, Vishvarani

AU - Brooks, Jonathan

AU - Menon, David K

AU - Tracey, Irene

N1 - Copyright © 2012 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved.

PY - 2013/1/1

Y1 - 2013/1/1

N2 - 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.

AB - 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.

KW - Adult

KW - Amygdala

KW - Analgesics, Non-Narcotic

KW - Antigens, Viral

KW - Capsaicin

KW - Cross-Over Studies

KW - Dissociative Disorders

KW - Double-Blind Method

KW - Dronabinol

KW - Heart Rate

KW - Humans

KW - Hyperalgesia

KW - Male

KW - Pain Perception

KW - Placebos

KW - Psychomotor Performance

KW - Sensory System Agents

KW - Young Adult

U2 - 10.1016/j.pain.2012.09.017

DO - 10.1016/j.pain.2012.09.017

M3 - SCORING: Journal article

C2 - 23273106

VL - 154

SP - 124

EP - 134

JO - PAIN

JF - PAIN

SN - 0304-3959

IS - 1

ER -