CB1 is the main cannabinoid receptor in the brain but is also found in other tissues. CB1 is a G protein-coupled receptor which inhibits adenylyl cyclase and consequently reduces cAMP upon activation. This in turn regulates many second messenger pathways.

Chemical Name: 
cannabinoid receptor type 1
IUPHAR entry: 
Wikipedia entry: 
Distribution: 

CB1 is the main cannabinoid receptor in the brain and shows particularly strong expression in hippocampus, neocortex, cerebellum, basal ganglia and spinal cord. In the rest of the body, CB1 is expressed in fat, muscle and liver cells and in the digestive tract.

Phytocannabinoids: 
Literature Discussion: 

Addiction

CB1 is the most abundant G-protein coupled receptor in the parts of the brain that are most involved in addictive behavior, suggesting a link. At least one genetic variation/polymorphism in CB1 is linked to increased receptor binding and increased CB1-mediated neuronal activation in the prefrontal cortex (Hutchison et al., 2008).

Post-mortem research suggests that although expression is unaffected, CB1 receptors are hyperactive in the caudate nucleus and hypoactive in the cerebellum of alcoholics (Erdozain et al., 2015).

Blocking the reward signal with CB1 antagonists blocks dopaminergic signaling in the nucleus accumbens and decreases alcohol craving and consumption (Hutchison et al., 2008).

ADHD

In a rat study it was found that the therapeutic effect of amphetamins actually requires CB1 activation (Kleijn et al., 2012)

A genetics study pointed out that ADHD is tightly linked to small variations/mutations (single nucleotide polymorphisms) in the CB1 gene (CNR1)(Lu et al., 2008).

Alzheimer´s

There is controversy about CB1 expression in AD but CB2 is significantly increased in AD patients, probably due to microglial activation around senile plaques (reviewed in: Aso and Ferrer, 2014).

In cultured astrocytes, Aβ1-42 reduced cell viability and PPARγ expression and increased cellular inflammation and anti-oxidant capacity. Specific CB1 stimulation (with WIN55,212-2, a synthetic analog of THC) prevented all these effects and increased cellular viability (Aguirre-Rueda et al., 2015).

Exercise has been shown to be beneficial in neurological disorders like Alzheimer’s disease and depression. Exercise increases the production of new neurons in the hippocampus in rats. In addition, Anandamide levels (and to a lesser degree 2AG levels) and CB1 receptor availability are increased in the hippocampus (but not in the prefrontal cortex). Blocking the endocannabinoid system prevents the production of new neurons suggesting a role for cannabinoids in this process (Hill et al., 2010).

Anorexia

CB1 receptors are upregulated in brains of Anorexia patients and in some brain regions of bulimia patients (Gérard et al., 2011).

CB1 receptors may be upregulated in an attempt to compensate for reduced endocannabinoid signaling. In line with this, mutations in CB1 (the major cannabinoid receptor) and FAAH (the major endocannabinoid degrading enzyme) were found to be associated with Anorexia and bulimia (Monteleone et al., 2009)

Autism

One study in healthy humans linked CB1 polymorphisms (small variations in a gene that are not directly linked to any particular deficit) to variations in the time people spent looking at happy faces (Chakrabarti and Baron-Cohen, 2011).

Interestingly, in another genetic mouse model of mental retardation and Autism (FMR1 knockout), blockade of CB1 normalized cognitive defects (Busquets-Garcia et al., 2013), suggesting CB1 may be a therapeutic target for Autism treatment.

cancer

Bladder Cancer

Until now, we know that human bladder cells express the cannabinoid receptors CB1CB2 and GPR55 (Bakali et al., 2014).

Bone Cancer

Research shows that bone cancer cells express CB1 receptors (Kawamata et al., 2010)

Breast Cancer

cannabinoids as THC and CBD have shown anti cancer properties in several studies through CB1 and CB2 receptors (Caffarel et al., 2008; Massi et al., 2013).

Cervical Cancer

cannabinoid receptors CB1CB2 and TRPV1 are expressed in the cervix. Anandamide bind to those receptors and has multiple functions on them (Ayakannu et al., 2015).

Glioblastoma

CBD modulates Id-1 gene and targets receptors CB1, CB2, TRPV-1 and TRPV-2 (Solinas et al., 2013; Soroceanu et al., 2013).

Leukemia

Leukemia cells express functional CB1 and CB2 receptors (Moaddel et al., 2011). Also, other CB1/2 agonists showed Leukemia cell growth and proliferation inhibition (Gallotta et al., 2010; Yrjölä et al., 2015).

Bulimia

CB1 receptors are upregulated in brains of Anorexia patients and in some brain regions of bulimia patients (Gérard et al., 2011).

CB1 receptors may be upregulated in an attempt to compensate for reduced endocannabinoid signaling. In line with this, mutations in CB1 (the major cannabinoid receptor) and FAAH (the major endocannabinoid degrading enzyme) were found to be associated with Anorexia and bulimia (Monteleone et al., 2009). 

COPD

THC reduced bronchoconstriction, inflammation and coughing in guinea pigs through activation of CB1 and CB2 receptors (Makwana et al., 2015).

Functional Gastro-Intestinal Disorders

Polymorphisms (small, single nucleotide mutations) in the CB1 gene/receptor are linked to the susceptibility to develop Crohn’s Disease, suggesting the involvement of the endocannabinoid system in Crohn’s Disease (Storr et al., 2010). cannabinoid-mediated reduction in gastro-intestinal motility appears to be mediated by CB1 but not CB2 (Aviello et al., 2008). CB1 and TRPV1 signaling are both required for the development of stress-induced visceral hyperalgesia and TRPV4 and TRPA1 may also be involved (Lin et al., 2013).

Cystitis

Another rat study found that endocannabinoid PEA and CB1 were upregulated, PPARα was downregulated and CB2 was unchanged upon induction of Cystitis (Pessina et al., 2014). PEA attenuated pain and bladder voiding. This effect was blocked by CB1 and PPARα antagonists.

Depression

CBG can activate α2 receptors and block CB1 and 5-HT1A receptors (Cascio et al., 2010), suggesting CBG does have therapeutic potential in the treatment of Depression. Exercise has been shown to be beneficial in neurological disorders like Alzheimer’s disease and Depression. Exercise increases the production of new neurons in the hippocampus in rats. In addition, Anandamide levels (and to a lesser degree 2AG levels) and CB1 receptor availability are increased in the hippocampus (but not in the prefrontal cortex). Blocking the endocannabinoid system prevents the production of new neurons suggesting a role for cannabinoids in this process (Hill et al., 2010)

Diabetes

Anandamide and CB1, CB2 and GPR55 receptors are implicated in the pathophysiology of Diabetes type 2 (Jenkin et al., 2014; Jourdan et al., 2014; Troy-Fioramonti et al., 2014).

Eczema

PEA enhances AEA activity at CB1, CB2 and TRPV1 receptors and protects against keratinocyte inflammation in a TRPV1-, but not CB1, CB2 or PPARα-dependent way (Petrosino et al., 2010). In mice CB1 and CB2 suppressed inflammation in allergic contact dermatitis (Karsak et al., 2007).

Epilepsy

In rats, THC and other synthetic CB1 agonists, reduces synchronous firing of hippocampal principal neurons, suggesting a direct role for THC in seizure prevention (Goonawardena et al., 2011). Similarly, CB1 activation decreases synchrony in cortical neurons (Sales-Carbonell et al., 2013). In mice, stimulating CB1 receptors (ACEA) or blocking TRPV1 receptors (capsazepine) protected against PTZ-induced seizures (Naderi et al., 2015). In rats, the synthetic CB1 agonist WIN 55-212-2 was protective against the development of Epilepsy when administered after an episode of status epilepticus (induced by pilocarpine)(Di Maio et al., 2014).

References:

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