Cannabidiol modulates serotonergic transmission and reverses both allodynia and anxiety-like behavior in a model of neuropathic pain

Gregorio, Danilo De; McLaughlin, Ryan J.; Posa, Luca; Ochoa‐Sanchez, Rafael; Enns, Justine P; Lopez‐Canul, Martha; Aboud, Matthew Kaba; Maione, Sabatino; Comai, Stefano; Gobbi, Gabriella

doi:10.1097/j.pain.0000000000001386

Cited by 280 publications

(227 citation statements)

References 89 publications

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“…Its efficacy with migraines and mood disorders has been consistently noted in the literature as well [17][18][19]. A recent preclinical study demonstrated effective neuropathic pain and comorbid anxiety and depression reduction through its interaction with the serotonin 5-HT 1A receptor [20]. It is speculated that this might be the physiological model responsible for the noted improvement in the case study.…”

Section: Discussionmentioning

confidence: 61%

Cannabidiol (CBD) for Treatment of Neurofibromatosis-related Pain and Concomitant Mood Disorder: A Case Report

Hegazy¹,

Platnick²

2019

Cureus

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Neurofibromatosis type 1 (NF1) is a common genetic disorder. Pain is a major symptom of this disease which can be secondary to the development of plexiform and subcutaneous neurofibromas, musculoskeletal symptoms (such as scoliosis and pseudoarthrosis), and headaches. Visible neurofibromas add significant psychosocial distress for NF1 patients. Along with the chronic pain, psychosocial distress contributes to associated mood disorders, such as depression and anxiety. Cannabis has been the focus of many studies for treating multiple conditions, including epilepsy, multiple sclerosis, Parkinsonism disease, and many chronic pain conditions. Cannabidiol (CBD) is the major non-psychotropic component of cannabis. CBD has shown anti-inflammatory and analgesic properties, as well as having mood stabilizer and anxiolytic effects. In this report, we present the use of cannabidiol (CBD) for the management of chronic pain and concomitant mood disorder in an NF1 patient.

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Section: Discussionmentioning

confidence: 61%

Cannabidiol (CBD) for Treatment of Neurofibromatosis-related Pain and Concomitant Mood Disorder: A Case Report

Hegazy¹,

Platnick²

2019

Cureus

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“…The participation of the 5-HT system in similar behaviors across the animal kingdom suggests that its function is conserved in most animal phyla. It can be also observed in functions that have not been covered in this review such as pain [213][214][215][216]. Moreover, in several behavioral responses, several 5-HTRs can be involved implying tight 5-HT regulatory mechanisms in responses to various stimuli.…”

Section: Discussionmentioning

confidence: 87%

Serotonin in Animal Cognition and Behavior

Bacqué-Cazenave

Bharatiya

Barrière

et al. 2020

IJMS

207

111

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Serotonin (5-hydroxytryptamine, 5-HT) is acknowledged as a major neuromodulator of nervous systems in both invertebrates and vertebrates. It has been proposed for several decades that it impacts animal cognition and behavior. In spite of a completely distinct organization of the 5-HT systems across the animal kingdom, several lines of evidence suggest that the influences of 5-HT on behavior and cognition are evolutionary conserved. In this review, we have selected some behaviors classically evoked when addressing the roles of 5-HT on nervous system functions.In particular, we focus on the motor activity, arousal, sleep and circadian rhythm, feeding, social interactions and aggressiveness, anxiety, mood, learning and memory, or impulsive/compulsive dimension and behavioral flexibility. The roles of 5-HT, illustrated in both invertebrates and vertebrates, show that it is more able to potentiate or mitigate the neuronal responses necessary for the fine-tuning of most behaviors, rather than to trigger or halt a specific behavior. 5-HT is, therefore, the prototypical neuromodulator fundamentally involved in the adaptation of all organisms across the animal kingdom.The organization of the 5-HT systems is completely different between species ranging from a limited number of cells in Aplysia or Drosophila (100 5-HT immunoreactive cells) to several thousand neurons in vertebrates. The variety and the heterogeneity of 5-HT neurons have been highlighted in vertebrates [7] as well as in invertebrates [8]. In general, the 5-HT systems in animals comprise 5-HT neurons, which share a particular shape made of thousands of varicosities, leading to the concept of volume transmission [9], and several 5-HT receptors (5-HTRs). In vertebrates, 5-HT neurons are localized in the midbrain raphe nuclei described as the B1-B9 cell groups [1,10]. The raphe pallidus, obscurus, and pontis form a caudal cluster (B1-B5), whereas the dorsal raphe and median raphe form a rostral cluster in the pons (B6-B9) [11]. The caudal raphe group projects to the spinal cord and the rostral group to the forebrain via an extensive and diffuse innervation. The dorsal raphe nucleus contains the highest number of 5-HT neurons and its anatomical sub-regions display some degrees of specific innervation of the forebrain [12][13][14]. The median and dorsal raphe nuclei receive excitatory and inhibitory inputs from most brain areas [15]. In crustaceans or insects, 5-HT neurons are widely present in each of the ventral cord ganglia, display large local ramifications that act in multiple neuropil areas, and some axonal branches form three pairs of rostrocaudal fibers [16][17][18][19]. Presumably, two of those fibers would project anteriorly and one posteriorly to the entire nervous system [20]. 5-HT neurons are often localized close to sensory integration input area in the brain of arthropods and some 5-HT cells in the abdominal ganglia of crayfish nerve cord are sensitive to the mechanical stimulation of abdominal segmental fringe hairs [21]. In cnidarians, 5-HT cells ...

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“…This is consistent with reports of anxiolytic effects of CBD in a chronic unpredicted stress model in mice using both elevated plus maze and novelty supressed feeding test (Campos et al, ; Campos & Guimarães, ; Fogaca, Campos, Coelho, Duman, & Guimaraes, ) where an action of CBD to inhibit TRPV1, CB 1 and CB 2 was implicated respectively. Anxiolytic effects of CBD have also been observed in a mouse model of neuropathic pain where inhibition of 5‐HT 1A receptors was implicated (De Gregorio et al, ).…”

Section: Discussionmentioning

confidence: 99%

Cannabidiol improves survival and behavioural co‐morbidities of Dravet syndrome in mice

Patra

Serafeimidou‐Pouliou

Bazelot

et al. 2020

British J Pharmacology

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Background and Purpose: Dravet syndrome is a severe, genetic form of paediatric epilepsy associated with premature mortality and co-morbidities such as anxiety, depression, autism, motor dysfunction and memory deficits. Cannabidiol is an approved anticonvulsive drug in the United States and Europe for seizures associated with Dravet syndrome in patients 2 years of age and older. We investigated its potential to prevent premature mortality and improve associated co-morbidities. Experimental Approach:The efficacy of sub-chronic cannabidiol administration in two mouse models of Dravet syndrome was investigated. The effect of cannabidiol on neonatal welfare and survival was studied using Scn1a −/− mice. We then used a hybrid, heterozygote Scn1a +/− mouse model to study the effect of cannabidiol on survival and behavioural co-morbidities: motor deficits (rotarod and static-beam test), gait abnormality (gait test), social anxiety (social interaction test), anxiety-like (elevated plus maze) and depressive-like behaviours (sucrose preference test) and cognitive impairment (radial arm maze test). Key Results:In Scn1a −/− mice, cannabidiol increased survival and delayed worsening of neonatal welfare. In Scn1a +/− mice, chronic cannabidiol administration did not show any adverse effect on motor function and gait, reduced premature mortality, improved social behaviour and memory function, and reduced anxiety-like and depressive-like behaviours. Conclusion and Implications:We are the first to demonstrate a potential diseasemodifying effect of cannabidiol in animal models of Dravet syndrome. Cannabidiol treatment reduced premature mortality and improved several behavioural comorbidities in Dravet syndrome mice. These crucial findings may be translated into human therapy to address behavioural co-morbidities associated with Dravet syndrome.

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Cannabidiol modulates serotonergic transmission and reverses both allodynia and anxiety-like behavior in a model of neuropathic pain

Cited by 280 publications

References 89 publications

Cannabidiol (CBD) for Treatment of Neurofibromatosis-related Pain and Concomitant Mood Disorder: A Case Report

Cannabidiol (CBD) for Treatment of Neurofibromatosis-related Pain and Concomitant Mood Disorder: A Case Report

Serotonin in Animal Cognition and Behavior

Cannabidiol improves survival and behavioural co‐morbidities of Dravet syndrome in mice

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