The orphan receptor GPR55 is a novel cannabinoid receptor

Posted on August 18, 2017 by David Worrell

“Preparations of Cannabis sativa have been used for medicinal and recreational purposes for at least 4000 years and extracts of C. sativa contain over 60 different pharmacologically active components the most prominent being Δ⁹-tetrahydrocannabinol (Δ⁹-THC) and cannabidiol Ligands such as cannabidiol and abnormal cannabidiol which exhibit no CB₁or CB₂ activity and are believed to function at a novel cannabinoid receptor, also showed activity at GPR55.

These data suggest that GPR55 is a novel cannabinoid receptor, and its ligand profile with respect to CB₁and CB₂ described here will permit delineation of its physiological function(s).”

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2095107/

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GPR55: A therapeutic target for Parkinson's disease?

Posted on August 18, 2017 by David Worrell

“The GPR55 receptor is expressed abundantly in the brain, especially in the striatum, suggesting it might fulfill a role in motor function. Indeed, motor behavior is impaired in mice lacking GPR55, which also display dampened inflammatory responses. Abnormal-cannabidiol (Abn-CBD), a synthetic cannabidiol (CBD) isomer, is a GPR55 agonist that may serve as a therapeutic agent in the treatment of inflammatory diseases. In this study, we explored whether modulating GPR55 could also represent a therapeutic approach for the treatment of Parkinson’s disease (PD). These results demonstrate for the first time that activation of GPR55 might be beneficial in combating PD.” https://www.ncbi.nlm.nih.gov/pubmed/28807673 http://www.sciencedirect.com/science/article/pii/S0028390817303842

“The orphan receptor GPR55 is a novel cannabinoid receptor” https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2095107/

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GPR55: A therapeutic target for Parkinson’s disease?

Posted on August 18, 2017 by David Worrell

Cover image

Abnormal-cannabidiol (Abn-CBD), a synthetic cannabidiol (CBD) isomer, is a GPR55 agonist that may serve as a therapeutic agent in the treatment of inflammatory diseases.

In this study, we explored whether modulating GPR55 could also represent a therapeutic approach for the treatment of Parkinson’s disease (PD).

These results demonstrate for the first time that activation of GPR55 might be beneficial in combating PD.”

https://www.ncbi.nlm.nih.gov/pubmed/28807673

http://www.sciencedirect.com/science/article/pii/S0028390817303842

“The orphan receptor GPR55 is a novel cannabinoid receptor” https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2095107/

The novel cannabinoid receptor GPR55 mediates anxiolytic-like effects in the medial orbital cortex of mice with acute stress.

Posted on August 13, 2017 by David Worrell

“The G protein-coupled receptor 55 (GPR55) is a novel cannabinoid receptor, whose exact role in anxiety remains unknown. The present study was conducted to explore the possible mechanisms by which GPR55 regulates anxiety and to evaluate the effectiveness of O-1602 in the treatment of anxiety-like symptoms. Mice were exposed to two types of acute stressors: restraint and forced swimming. Anxiety behavior was evaluated using the elevated plus maze and the open field test. We found that O-1602 alleviated anxiety-like behavior in acutely stressed mice. We used lentiviral shRNA to selective ly knockdown GPR55 in the medial orbital cortex and found that knockdown of GPR55 abolished the anxiolytic effect of O-1602. We also used Y-27632, a specific inhibitor of ROCK, and U73122, an inhibitor of PLC, and found that both inhibitors attenuated the effectiveness of O-1602. Western blot analysis revealed that O-1602 downregulated the expression of GluA1 and GluN2A in mice. Taken together, these results suggest that GPR55 plays an important role in anxiety and O-1602 may have therapeutic potential in treating anxiety-like symptoms.”

https://www.ncbi.nlm.nih.gov/pubmed/28800762

https://molecularbrain.biomedcentral.com/articles/10.1186/s13041-017-0318-7

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A Review of the Therapeutic Antitumor Potential of Cannabinoids.

Posted on August 12, 2017 by David Worrell

“The aim of this review is to discuss cannabinoids from a preclinical and clinical oncological perspective and provide the audience with a concise, retrospective overview of the most significant findings concerning the potential use of cannabinoids in cancer treatment.

RESULTS:

Cannabis sativa is a plant rich in more than 100 types of cannabinoids. Besides exogenous plant cannabinoids, mammalian endocannabinoids and synthetic cannabinoid analogues have been identified. Cannabinoid receptors type 1 (CB1) and type 2 (CB2) have been isolated and characterized from mammalian cells. Through cannabinoid receptor and non-receptor signaling pathways, cannabinoids show specific cytotoxicity against tumor cells, while protecting healthy tissue from apoptosis. The dual antiproliferative and proapoptotic effects of cannabinoids and associated signaling pathways have been investigated on a large panel of cancer cell lines. Cannabinoids also display potent anticancer activity against tumor xenografts, including tumors that express high resistance to standard chemotherapeutics. Few studies have investigated the possible synergistic effects of cannabinoids with standard oncology therapies, and are based on the preclinically confirmed concept of “cannabinoid sensitizers.” Also, clinical trials aimed to confirm the antineoplastic activity of cannabinoids have only been evaluated on a small number of subjects, with no consensus conclusions regarding their effectiveness.

CONCLUSIONS:

A large number of cannabinoid compounds have been discovered, developed, and used to study the effects of cannabinoids on cancers in model systems. However, few clinical trials have been conducted on the use of cannabinoids in the treatment of cancers in humans. Further studies require extensive monitoring of the effects of cannabinoids alone or in combination with standard anticancer strategies. With such knowledge, cannabinoids could become a therapy of choice in contemporary oncology.”

https://www.ncbi.nlm.nih.gov/pubmed/28799775

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Neuroprotective activity of cannabinoid receptor-2 against oxidative stress and apoptosis in rat pups having experimentally-induced congenital hypothyroidism.

Posted on August 12, 2017 by David Worrell

“In this study, it was aimed to show the cannabinoid receptor-2 (CB2) role, which is a part of neuroprotective endocannabinoidal system, against increasing nitric oxide synthetase (iNOS, eNOS) levels and the apoptotic activity (caspase-3, caspase-9 and DNA in situ fragmentation) within the postnatal critical period in pups of pregnant rats with artificially induced maternal thyroid hormone (TH) deficiency. In conclusion, apoptosis was triggered via oxidative stress in hypothyroid pups. Accordingly, neuroprotective activity of CB2 receptors were motivated spontaneously to resist to CNS lesions during the first 3 weeks of postnatal period.” https://www.ncbi.nlm.nih.gov/pubmed/28799288]]>

Modulation of Astrocyte Activity by Cannabidiol, a Nonpsychoactive Cannabinoid.

Posted on August 10, 2017 by David Worrell

“The astrocytes have gained in recent decades an enormous interest as a potential target for neurotherapies, due to their essential and pleiotropic roles in brain physiology and pathology. Their precise regulation is still far from understood, although several candidate molecules/systems arise as promising targets for astrocyte-mediated neuroregulation and/or neuroprotection. The cannabinoid system and its ligands have been shown to interact and affect activities of astrocytes. Cannabidiol (CBD) is the main non-psychotomimetic cannabinoid derived from Cannabis. CBD is devoid of direct CB1 and CB2 receptor activity, but exerts a number of important effects in the brain. Here, we attempt to sum up the current findings on the effects of CBD on astrocyte activity, and in this way on central nervous system (CNS) functions, across various tested models and neuropathologies. The collected data shows that increased astrocyte activity is suppressed in the presence of CBD in models of ischemia, Alzheimer-like and Multiple-Sclerosis-like neurodegenerations, sciatic nerve injury, epilepsy, and schizophrenia. Moreover, CBD has been shown to decrease proinflammatory functions and signaling in astrocytes.” https://www.ncbi.nlm.nih.gov/pubmed/28788104 http://www.mdpi.com/1422-0067/18/8/1669]]>

Cannabinoid receptor 2-63 RR variant is independently associated with severe necroinflammation in HIV/HCV coinfected patients.

Posted on August 5, 2017 by David Worrell

“This is the first study to analyze the impact of the rs35761398 variant of the CNR2 gene leading to the substitution of GLN (Q) of codon 63 of the cannabinoid receptor 2 (CB2) with ARG (R) on the clinical presentation of chronic hepatitis in HIV/HCV coinfected patients.

This study shows interesting interplay between the CB2-RR variant and liver necroinflammation in chronic hepatitis patients with HIV/HCV coinfection, an observation of clinical value that coincides with the interest in the use of the CB2 agonists and antagonists in clinical practice emerging from the literature.”

https://www.ncbi.nlm.nih.gov/pubmed/28759568

http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0181890

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Could Cannabidiol be a Treatment Option for Intractable Childhood and Adolescent Epilepsy?

Posted on August 5, 2017 by David Worrell

“Epilepsy is an important disease that affects brain function, particularly in those under 3 years old. Uncontrolled seizures can affect cognitive function and quality of life. For these reasons, many trials have been conducted to investigate treatments for pediatric epilepsy. Currently, many antiepileptic drugs are available for the treatment of epilepsy, but cases of intractable epilepsy continue to exist. In the past, cannabis has been tested as a potential treatment of intractable epilepsy. Since 2013, 10 epilepsy centers in America have conducted research regarding the efficacy of cannabis to treat epilepsy. Cannabis has many components, including cannabidiol (CBD) and Δ⁹-tetrahydrocannabinol (THC). THC has psychoactive properties exerted through its binding of the cannabinoid receptor (CBR) whereas CBD is a CBR antagonist. The inhibition of epilepsy by CBD may therefore be caused by various mechanisms, although the detailed mechanisms of CBD actions have not yet been well defined. In most studies, trial doses of CBD were 2-5 mg/kg/day. Several such studies have shown that CBD does have efficacy for treatment of epilepsy. Reported adverse effects of CBD were mostly mild, including drowsiness, diarrhea, and decreased appetite. Severe adverse reactions requiring treatment, such as status epilepticus, have also been reported but it is not clear that this is related to CBD. Furthermore, many previous studies have been limited by an open-label or survey design. In future, double-blind, controlled trials are required and the use of CBD to treat other neurological problems should also be investigated.” https://www.ncbi.nlm.nih.gov/pubmed/28775950 “Most studies suggest anticonvulsant effects of CBD, and consider most adverse effects to be mild. It must be borne in mind that CBD is still illegal in many contexts. However, it has the potential to treat various neurological problems, including epilepsy.” http://www.j-epilepsy.org/journal/view.php?doi=10.14581/jer.17003

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“The endocannabinoid system plays a role in regulating bone mass and bone cell activity and inactivation of the type 1 (Cnr1) or type 2 (Cnr2) cannabinoid receptors influences peak bone mass and age-related bone loss. As the Cnr1 and Cnr2 receptors have limited homology and are activated by different ligands, we have evaluated the effects of combined deficiency of Cnr1 and 2 receptors (Cnr1/2^-/- ) on bone development from birth to old age and studied ovariectomy induced bone loss in female mice. The Cnr1/2^-/- mice had accelerated bone accrual at birth when compared with wild type littermates, and by 3 months of age, they had higher trabecular bone mass. They were also significantly protected against ovariectomy-induced bone loss due to a reduction in osteoclast number. The Cnr1/2^-/- mice had reduced age-related bone loss when compared with wild-type due to a reduction in osteoclast number. Although bone formation was reduced and bone marrow adiposity increased in Cnr1/2^-/- mice, the osteoclast defect outweighed the reduction in bone formation causing preservation of bone mass with aging. This contrasts with the situation previously reported in mice with inactivation of the Cnr1 or Cnr2 receptors individually where aged-related bone loss was greater than in wild-type. We conclude that the Cnr1 and Cnr2 receptors have overlapping but nonredundant roles in regulating osteoclast and osteoblast activities. These observations indicate that combined inhibition of Cnr1 and Cnr2 receptors may be beneficial in preventing age-related bone loss, whereas blockade of individual receptors may be detrimental.” https://www.ncbi.nlm.nih.gov/pubmed/28752643 http://onlinelibrary.wiley.com/doi/10.1111/acel.12638/abstract]]>

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Tag Archives: cannabinoid receptors

The orphan receptor GPR55 is a novel cannabinoid receptor

GPR55: A therapeutic target for Parkinson's disease?

“The orphan receptor GPR55 is a novel cannabinoid receptor” https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2095107/

GPR55: A therapeutic target for Parkinson’s disease?

“The orphan receptor GPR55 is a novel cannabinoid receptor” https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2095107/

The novel cannabinoid receptor GPR55 mediates anxiolytic-like effects in the medial orbital cortex of mice with acute stress.

A Review of the Therapeutic Antitumor Potential of Cannabinoids.

RESULTS:

CONCLUSIONS:

Neuroprotective activity of cannabinoid receptor-2 against oxidative stress and apoptosis in rat pups having experimentally-induced congenital hypothyroidism.

Modulation of Astrocyte Activity by Cannabidiol, a Nonpsychoactive Cannabinoid.

Cannabinoid receptor 2-63 RR variant is independently associated with severe necroinflammation in HIV/HCV coinfected patients.

Could Cannabidiol be a Treatment Option for Intractable Childhood and Adolescent Epilepsy?

Combined deficiency of the Cnr1 and Cnr2 receptors protects against age-related bone loss by osteoclast inhibition.