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

Lee, Michael C.; Ploner, Markus; Wiech, Katja; Bingel, Ulrike; Wanigasekera, Vishvarani; Brooks, Jonathan; Menon, David; Tracey, Irene

doi:10.1016/j.pain.2012.09.017

Cited by 116 publications

(114 citation statements)

References 70 publications

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“…amygdala and primary somatosensory cortex (Lee et al, 2013). The observation of deactivated limbic regions is in line with the observation that THC predominantly influences affective rather than sensory processing of nociceptive information.…”

Section: Discussionsupporting

confidence: 85%

“…An additional analysis performed solely to accommodate a previous finding (Lee et al, 2013) verified a reduced connectivity also between the amygdala and primary somatosensory cortex (see Supplementary Materials).…”

Section: Roi In Functional Imagingmentioning

confidence: 61%

“…Following prior evidence (Lee et al, 2013), we focused on the relationship between the limbic and the somatosensory components of the pain matrix. DCM was applied to the time courses extracted from four ROIs identified during GLM and PPI analyses, ie, the right ventral thalamus, secondary somatosensory cortex (S2), the hippocampus, and the anterior insula.…”

Section: Discussionmentioning

confidence: 99%

“…As recently shown, THC reduces functional connectivity between the amygdala and the primary somatosensory cortex (S1) during pain processing, but it is not clear whether this effect results from reduced limbic output or reduced sensory input into the amygdala (Lee et al, 2013). Thus, the present study investigated effective connectivity of the pain matrix that is modulated by THC by applying dynamic causal modeling (DCM) and Bayesian model selection (BMS) to functional magnetic resonance imaging (fMRI) data collected during experimental pain stimulation.…”

Section: Introductionmentioning

confidence: 99%

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Brain Mapping-Based Model of Δ9-Tetrahydrocannabinol Effects on Connectivity in the Pain Matrix

Walter

Oertel

Felden

et al. 2015

Neuropsychopharmacol

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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.

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Section: Discussionsupporting

confidence: 85%

Section: Roi In Functional Imagingmentioning

confidence: 61%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Brain Mapping-Based Model of Δ9-Tetrahydrocannabinol Effects on Connectivity in the Pain Matrix

Walter

Oertel

Felden

et al. 2015

Neuropsychopharmacol

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“…In addition, endocannabinoids are indispensable in the development of acute stress induced analgesia (Morena et al 2016), and the downregulation of endocannabinoid signalling is an important mechanism in the development of chronic stress induced hyperalgesia (Jennings et al 2015; Lomazzo et al 2015; Rea et al 2014). However, more and more evidence suggests that endocannabinoids mainly influence the affective component of pain, in which amygdala activity has a pivotal role, compared to the sensory aspects (Lee et al 2013). As such, the strength of life stress × CNR1 gene interaction on headache with nausea would be expected to decrease after controlling for depression and anxiety related phenotypes, but this was not the case.…”

Section: Discussionmentioning

confidence: 99%

Variants in the CNR1 gene predispose to headache with nausea in the presence of life stress

Juhász

Csépány

Magyar

et al. 2016

Genes Brain and Behavior

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One of the main effects of the endocannabinoid system in the brain is stress adaptation with presynaptic endocannabinoid receptor 1 (CB1 receptors) playing a major role. In the present study, we investigated whether the effect of the CB1 receptor coding CNR1 gene on migraine and its symptoms is conditional on life stress. In a cross‐sectional European population (n = 2426), recruited from Manchester and Budapest, we used the ID‐Migraine questionnaire for migraine screening, the Life Threatening Experiences questionnaire to measure recent negative life events (RLE), and covered the CNR1 gene with 11 SNPs. The main genetic effects and the CNR1 × RLE interaction with age and sex as covariates were tested. None of the SNPs showed main genetic effects on possible migraine or its symptoms, but 5 SNPs showed nominally significant interaction with RLE on headache with nausea using logistic regression models. The effect of rs806366 remained significant after correction for multiple testing and replicated in the subpopulations. This effect was independent from depression‐ and anxiety‐related phenotypes. In addition, a Bayesian systems‐based analysis demonstrated that in the development of headache with nausea all SNPs were more relevant with higher a posteriori probability in those who experienced recent life stress. In summary, the CNR1 gene in interaction with life stress increased the risk of headache with nausea suggesting a specific pathological mechanism to develop migraine, and indicating that a subgroup of migraine patients, who suffer from life stress triggered migraine with frequent nausea, may benefit from therapies that increase the endocannabinoid tone.

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Cannabinoids for Symptoms of Multiple Sclerosis

Slaven

Levine

2018

JAMA Netw Open

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Despite the facts that millions of people are affected by multiple sclerosis (MS), and that in some countries medicinal cannabinoids have been approved for the treatment of MS symptoms, evidence for the efficacy of cannabinoids for MS symptoms is limited. Torres-Moreno et al 1 conducted a meta-analysis in which 4 different medicinal cannabinoids were evaluated for MS-associated symptoms of spasticity, pain, and bladder spasms. They identified 17 studies involving 3161 patients

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

Abstract: SummaryfMRI 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.

Cited by 116 publications

References 70 publications

Brain Mapping-Based Model of Δ9-Tetrahydrocannabinol Effects on Connectivity in the Pain Matrix

Brain Mapping-Based Model of Δ9-Tetrahydrocannabinol Effects on Connectivity in the Pain Matrix

Variants in the CNR1 gene predispose to headache with nausea in the presence of life stress

Cannabinoids for Symptoms of Multiple Sclerosis

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