Studies Investigating the Benefits of CB2 Receptor Activation

CB2 is one of the two main receptors of the ECS. There are numerous benefits to activating this receptor without activating the CB1 receptor. The following is a small list of studies illustrating the benefits of CB2 activation.

Pain & Inflammation:

• The CB2 receptor and its role as a regulator of inflammation (Cell Mol Life Sci. 2016; 73(23): 4449-70.)
• Targeting CB2 receptors and the endocannabinoid system for the treatment of pain (Brain Res Rev. 2009 Apr; 60(1): 255-266.)
• Cannabinoid CB2 receptors: a therapeutic target for the treatment of inflammatory and neuropathic pain (Br J Pharmacol. 2008 Jan; 153(2): 319–334.)
• The central cannabinoid receptor type-2 (CB2) and chronic pain (Int J Neurosci. 2017 Sep;127(9):812-823.)
• A CB2 receptor agonist attenuates bone cancer-induced pain and bone loss (Life Sci. 2010 Apr 24; 86(17-18): 646–653.)

Anxiety

• Anxious behavior induces elevated hippocampal CB2 expression (Neuroscience. 2017 Jun 3;352:273-284.)
• Regulatory role of the CB2 receptor in stress-induced neuroinflammation (Br J Pharmacol. 2014 Jun;171(11):2814-26.)

Degenerative neurological conditions:

• Targeting cannabinoid CB2 receptors in the central nervous system. Medicinal chemistry approaches with focus on neurodegenerative disorders (Front Neurosci. 2016; 10: 406.)
• Central CB2 receptors in inflammation-driven neurodegeneration: dysregulation and therapeutic potential (Neural Regen Res. 2016 Sep; 11(9): 1409–1410.)
• CB2 receptor: Potential role in immunomodulation and neuroinflammation (J Neuroimmune Pharmacol. 2013 Jun; 8(3): 608-620.)
• Cannabinoid CB2 receptors in human brain inflammation (Br J Pharmacol. 2008 Jan; 153(2): 277–285.)
• The Cannabinoid CB2 Receptor as a Target for Inflammation-Dependent Neurodegeneration (Curr Neuropharmacol. 2007 Jun; 5(2): 73–80.)
• Regulatory role of the cannabinoid CB2 receptor in stress-induced neuroinflammation in mice (Br J Pharmacol. 2014 Jun;171(11):2814-26.)

Multiple Sclerosis:

• CB2 receptors as an emerging target for demyelinating diseases: from neuroimmune interactions to cell replacement strategies (Br J Pharmacol. 2008 Jan; 153(2): 216–225.)
• Potent immunomodulatory activity of a highly selective cannabinoid CB2 agonist on immune cells from healthy subjects and patients with multiple sclerosis. (J Neuroimmunol. 2017 Feb 15;303:66-74.)
• Regulatory role of the cannabinoid CB2 receptor in stress-induced neuroinflammation in mice (Br J Pharmacol. 2014 Jun;171(11):2814-26.)

Alzheimer's Disease

• CB2 cannabinoid receptor as potential target against Alzheimer’s Disease (Front Neurosci. 2016; 10: 243.)
• Activation of CB2 receptor system restores cognitive capacity and hippocampal Sox2 expression in a transgenic mouse model of Alzheimer's disease (Eur J Pharmacol. 2017 Sep 15;811:12-20.)
• Activation of CB2 receptors stimulates beta-amyloid removal by human macrophages (Brain Res. 2009 Aug 4;1283:148-54.)

Parkinson's Disease

• Cannabinoid type 2 (CB2) receptors activation protects against oxidative stress and neuroinflammation associated dopaminergic neurodegeneration in rotenone model of Parkinson’s Disease (Front Neurosci. 2016; 10: 321.)
• CB2 receptor activation prevents glial-derived neurotoxic mediator production, BBB leakage and peripheral immune cell infiltration and rescues dopamine neurons in the MPTP model of Parkinson’s disease (Exp Mol Med. 2016 Jan; 48(1): e205.)

Osteoarthritis:

• Cannabinoid CB2 receptors regulate central sensitization and pain responses associated with osteoarthritis of the knee joint (PLoS One. 2013; 8(11): e80440.)
• Expression of cannabinoid receptors in human osteoarthritic cartilage: Implications for future therapies (Cannabis Cannabinoid Res. 2016 Jan 1;1(1):3-15)

Rheumatoid arthritis:

• CB2 as a potential therapeutic target in rheumatoid arthritis (Musculoskeletal Disorders. 2014; 15: 275.)
• Expression of CB2 and its inhibitory effects on synovial fibroblasts in rheumatoid arthritis (Rheumatology. 2014; 53(5): 802-809.)
• Role of CB2 in mediating inflammation in rheumatoid arthritis synovial fibroblasts (Clin Exp Rheumatol. 2019 Nov-Dec;37(6):1026-1035.)

Musculo-Skeletal System (e.g,. osteoporosis):

• A CB2 receptor agonist attenuates bone cancer-induced pain and bone loss (Life Sci. 2010 Apr 24; 86(17-18): 646–653.)
• Disease Modification of Breast Cancer–Induced Bone Remodeling by CB2 Receptor Agonists (J Bone Miner Res. 2013 Jan; 28(1): 92–107.)
• Cannabinoid CB2 receptor stimulation delays rubrospinal mitochondrial-dependent degeneration and improves functional recovery after spinal cord injury (Cell Death Dis. 2014 Sep 4;5(9):e1404.)
• Delayed Systemic Treatment with CB2 Agonist Mitigates Spinal Cord Injury-Induced Osteoporosis More Than Acute Treatment Directly after Injury (2021 Jun 22;2(1):270-284.) 

Immune system modulation:

• CB2: Potential role in immunomodulation and neuroinflammation (J Neuroimmune Pharmacol 2013 Jun; 8(3): 608-620.)
• Emerging role of the CB2 cannabinoid receptor in immune regulation and therapeutic prospects (Expert Rev Mol Med. 2009 Jan 20; 11: e3.)

Cardiovascular:

• CB2 drives neurogenesis and improves functional outcome after stroke (Stroke. 2017 Jan;(48)1:204-212.)
• Prospects for creation of cardioprotective drugs based on cannabinoid receptor agonists (J Cardiovasc Pharmacol Ther. 2016 May;21(3):262-72.)
• CB2 in atherosclerosis and acute cardiovascular diseases (Curr Med Chem. 2014;(21)35:4046-58.)
• CB2 receptor stimulation attenuates the initiation and progression of atherosclerosis (Am J Physiol Heart Circ Physiol. 2007 Oct;293(4):H2210-8.)
• Time-Dependent Protection of CB2 Receptor Agonist in Stroke (PLoS One. 2015 Jul 17;10(7):e0132487.)
• Selective Modulator of CB2 Reduces Memory Impairment and Infarct Size During Cerebral Hypoperfusion and Vascular Dementia (Curr Neurovasc Res. 2016;13(4):289-302.)
• The Endocannabinoid System and Heart Disease: The Role of CB2 (Cardiovasc Hematol Disord Drug Targets. 2018;18(1):34-51.)
• Selective CB2 Receptor Stimulation Reduces Tubular Epithelial Cell Damage after Renal Ischemia-Reperfusion Injury (J Pharmacol Exp Ther. 2018 Feb;364(2):287-299.)

Diabetes, Obesity, & Other Metabolic Disorders:

• CB2 receptor agonist improves systemic sensitivity to insulin (Cell Physiol Biochem. 2016;40(5):1175-1185.)
• Therapeutic potential of CB2 in the treatment of diabetes mellitus and its complications (Eur J Pharmacol. 2019 Nov 5;862:172628.)
• Anti-Obesity Effect of a CB2 Receptor Agonist in Diet-Induced Obese Mice (PLoS One. 2015 Nov 20;10(11):e0140592.)
• CB2 as Antiobesity Target: Inflammation, Fat Storage, and Browning Modulation (J Clin Endocrinol Metab. 2016 Sep;101(9):3469-78.)
• CB2 receptors regulate Ca(2+) signals and insulin secretion in pancreatic beta-cell (Cell Calcium. 2006 Feb;39(2):155-62.)

Digestive Disorders:

• The CB2 receptor: a good friend in the gut (Neurogastroenterol. Motil. 2007 Sept;19(9):704-8.)
• CB2 receptor-induced relief of hypermotility in a rat model of the irritable bowel syndrome (Neurogastroenterol Motil. 2019 Jun;31(6):e13613.)
• Cannabinoids and intestinal motility: welcome to CB2 receptors (Br J Pharmacol. 2004 Aug;142(8):1201-2.)
• CB2 receptors in the gastrointestinal tract: a regulatory system in states of inflammation (Br J Pharmacol. 2008 Jan;153(2):263-70.)
• Activation of CB2 receptor relieves colonic hypermotility in a rat model of irritable bowel syndrome (Neurogastroenterol. Motil. 2019 Jun;31(6):e13555.)

Migraine:

• Activation of CB2 receptors as a potential therapeutic target for migraine: evaluation in an animal model (J Headache Pain. 2014; 15(1): 14.)

Eye Health

• Inflammation and CB2 signaling drive novel changes in the ocular lipidome and regulate immune cell activity in the eye (Prostaglandins Other Lipid Mediat. 2018 Nov;139:54-62.)
• CB2 receptors are upregulated with corneal injury and regulate the course of corneal wound healing (Exp Eye Res. 2019 May;182:74-84.)
• Activation of CB2 by selective agonists regulates the deposition and remodelling of the extracellular matrix (Biomed Pharmacother. 2017 Nov;95:1704-1709.)
• CB2 receptor is a novel anti-inflammatory target in experimental proliferative vitreoretinopathy (Neuropharmacology. 2017 Feb;113(Pt B):627-638.)
• CB2 receptor activation reduces leukocyte adhesion and improves capillary perfusion in the iridial microvasculature during systemic inflammation (Clin Hemorheol Microcirc. 2015;61(2):237-49.)

Skin Health:

• CB2 exerts antifibrotic effects in experimental dermal fibrosis (Arthritis Rheum. 2009 Apr;60(4):1129-36.)

Liver Health:

• Antifibrogenic role of the cannabinoid receptor CB2 in the liver (Gastroenterology. 2005 Mar;128(3):742-55.)
• CB2 Receptor Agonist Attenuates Inflammation, Apoptosis and Stimulate Progenitor Cells in Bile Duct Ligated Rat (Open Access Maced J Med Sci. 2019 Mar 29;7(6):925-936.)
• A new CB2 agonist attenuates oxidative stress, inflammation and cell death associated with hepatic ischaemia/reperfusion injury (Br J Pharmacol. 2012 Apr;165(8):2462-78.

Kidney & Bladder Health:

• Selective CB2 Receptor Stimulation Reduces Tubular Epithelial Cell Damage after Renal Ischemia-Reperfusion Injury (J Pharmacol Exp Ther. 2018 Feb;364(2):287-299.)
• Activation of CB2 inhibits experimental cystitis (Am J Physiol Regul Integr Comp Physiol. 2013 May 15;304(10):R846-53.)

Pancreatic Health:

• Activation of CB2 reduces inflammation in acute experimental pancreatitis (AM J Physiol Gastrointest Liver Physiol. 2013 Jan 15;304(2):G181-92.)
• The role of CB2 receptors in acute pancreatitis (Pancreas. 2008 Nov;37(4):493-494.
• CB2 receptors regulate Ca(2+) signals and insulin secretion in pancreatic beta-cell (Cell Calcium. 2006 Feb;39(2):155-62.)
• Therapeutic potential of CB2 in the treatment of diabetes mellitus and its complications (Eur J Pharmacol. 2019 Nov 5;862:172628.)
• CB2 agonist attenuates pain related behavior in rats with chronic alcohol/high fat diet induced pancreatitis (Mol Pain. 2014 Nov 17;10:66.)

Respiratory Health:

• CB2 agonist prevents nicotine induced lung fibrosis (Exp Lung Res. 2018 Sep;44(7):344-351.)
• CB2 receptors regulate natural killer cells that limit allergic airway inflammation in a murine model of asthma (Allergy. 2017 Jun;72(6):937-947.)

Addictions & Substance Use Disorders:

• CB2 receptor involvement in the treatment of substance use disorders (Biomolecules. 2021 Nov; 11(11): 1556.)
• Role of cannabinoid CB2 receptor in the reinforcing actions of ethanol (Addict Biol. Jan;20(1):43-55.)
• Role of CB2 cannabinoid receptors in the rewarding reinforcing and physical effects of nicotine (Neuropsychopharmacology. 2013 Nov; 38(12): 2515–2524.)

Opioid Crisis:

• Cannabinoid CB2 Receptor Activation Attenuates Fentanyl-Induced Respiratory Depression. (Cannabis Cannabinoid Res. 2020 Oct 21.)