Amygdala activity contributes to the dissociative effect of cannabis on pain perception
Michael Lee, M. Ploner, K. Wiech, U. Bingel, Vishvarani Wanigasekera, J. Brooks, D. Menon, Irene Tracey
Pain 2013 DOI: 10.1016/j.pain.2012.09.017 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Experimental study with functional magnetic resonance imaging Peer reviewed |
|---|---|
| Population | Healthy volunteers |
| Topics | Cannabis |
| Key findings | THC reduced the unpleasantness but not the intensity of ongoing pain and hyperalgesia, with effects linked to altered amygdala activity and connectivity. |
Abstract
Summary fMRI evidence suggests that delta‐9‐tetrahydrocannabinol, the psychoactive component of cannabis, targets the affective aspects of pain in humans by altering the activity and functional connections of the amygdala. 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.
Comparable studies
Other experimental studies on cannabis, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| Smoked Cannabis' Psychomotor and Neurocognitive Effects in Occasional and Frequent Smokers Occasional (<2x/week) and frequent (≥4x/week) cannabis smokers | 2015 | Controlled within-subjects study | n = 25 |
| Dissociable effects of cannabis with and without cannabidiol on the human brain’s resting-state functional connectivity Healthy volunteers experienced with cannabis but not regular users | 2019 | Within-subjects experimental design | n = 17 |
| Which biological and self-report measures of cannabis use predict cannabis dependency and acute psychotic-like effects? Young cannabis users | 2018 | Observational study (naturalistic, within-subject counterbalanced design) | n = 410 |
| Cannabis Essential Oil: A Preliminary Study for the Evaluation of the Brain Effects Healthy volunteers | 2018 | Experimental study | n = 5 |
| Coming off cannabis: a cognitive and magnetic resonance imaging study in patients with multiple sclerosis Patients with multiple sclerosis who began using cannabis after disease onset, used it... | 2019 | Quasi-experimental study with odd-even allocation | n = 40 |
Citations in the library
Cited by 10
- Cannabinoid Modulation of Amygdala Subregion Functional Connectivity to Social Signals of Threat The International Journal of Neuropsychopharmacology December 28, 2014
- Cannabinoids and Vanilloids in Schizophrenia: Neurophysiological Evidence and Directions for Basic Research Frontiers in Pharmacology June 21, 2017
- Cannabidiol Increases Psychotropic Effects and Plasma Concentrations of Δ9-Tetrahydrocannabinol Without Improving Its Analgesic Properties. Clinical Pharmacology & Therapeutics November 1, 2024
- Dissociative-like Neurotoxicity Following Analytically Confirmed Exposure To Hexahydrocannabinol (HHC). Journal of Medical Toxicology 2026
- Task-independent acute effects of delta-9-tetrahydrocannabinol on human brain function and its relationship with cannabinoid receptor gene expression: a neuroimaging meta-regression analysis bioRxiv (Cold Spring Harbor Laboratory) November 3, 2021
and 5 more in the library