The nonpsychotropic cannabinoid cannabidiol modulates and directly activates alpha-1 and alpha-1-Beta glycine receptor function.
Loss of inhibitory synaptic transmission within the dorsal horn of the spinal cord plays a key role in the development of chronic pain following inflammation or nerve injury. Inhibitory postsynaptic transmission in the adult spinal cord involves mainly glycine. Cannabidiol is a nonpsychotropic plant constituent of Cannabis sativa. As we hypothesized that non-CB receptor mechanisms of cannabidiol might contribute to its anti-inflammatory and neuroprotective effects, we investigated the interaction of cannabidiol with strychnine-sensitive alpha(1 )and alpha(1)beta glycine receptors by using the whole-cell patch clamp technique. Cannabidiol showed a positive allosteric modulating effect in a low micromolar concentration range (EC(50) values: alpha(1) = 12.3 +/- 3.8 micromol/l and alpha(1)beta = 18.1 +/- 6.2 micromol/l). Direct activation of glycine receptors was observed at higher concentrations above 100 micromol/l (EC(50) values: alpha(1) = 132.4 +/- 12.3 micromol/l and alpha(1)beta = 144.3 +/- 22.7 micromol/l). These in vitro results suggest that strychnine-sensitive glycine receptors may be a target for cannabidiol mediating some of its anti-inflammatory and neuroprotective properties.
Ahrens
Jörg
J
Clinic for Anaesthesia and Critical Care Medicine, OE 8050, Hannover, Germany. ahrens.j@mh-hannover.de
Demir
Reyhan
R
Leuwer
Martin
M
de la Roche
Jeanne
J
Krampfl
Klaus
K
Foadi
Nilufar
N
Karst
Matthias
M
Haeseler
Gertrud
G
D002185:Cannabidiol / Q000494:pharmacology*; D002186:Cannabinoids / Q000494:pharmacology*; D002461:Cell Line, Transformed; D002478:Cells, Cultured; D053595:Embryonic Stem Cells; D005998:Glycine / Q000494:pharmacology; D006801:Humans; D066298:In Vitro Techniques; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D018009:Receptors, Glycine / Q000819:agonists* / Q000235:genetics; D014162:Transfection
D002186:Cannabinoids; C114561:GLRB protein, human; D018009:Receptors, Glycine; D002185:Cannabidiol; D005998:Glycine