Cannabidiol is an allosteric modulator at mu- and delta-opioid receptors

  title={Cannabidiol is an allosteric modulator at mu- and delta-opioid receptors},
  author={Markus Kathmann and Karsten Flau and Agnes Redmer and Christian Tr{\"a}nkle and E Schlicker},
  journal={Naunyn-Schmiedeberg's Archives of Pharmacology},
The mechanism of action of cannabidiol, one of the major constituents of cannabis, is not well understood but a noncompetitive interaction with mu opioid receptors has been suggested on the basis of saturation binding experiments. The aim of the present study was to examine whether cannabidiol is an allosteric modulator at this receptor, using kinetic binding studies, which are particularly sensitive for the measurement of allosteric interactions at G protein-coupled receptors. In addition, we… 

The cannabinoid receptor agonists, anandamide and WIN 55,212-2, do not directly affect mu opioid receptors expressed in Xenopus oocytes

It is concluded that neither anandamide nor WIN 55,212-2 directly activate or modulate mu opioid receptor function in oocytes and that interactions of cannabinoids with mu opioid receptors are likely to be indirect.

Binding and Signaling Studies Disclose a Potential Allosteric Site for Cannabidiol in Cannabinoid CB2 Receptors

It is confirmed that CBD does not bind with high affinity to the orthosteric site of the human CB2R where the synthetic cannabinoid, [3H]-WIN 55,212-2, binds, and CBD was, however, able to produce minor but consistent reduction in the homogeneous binding assays in living cells using the fluorophore-conjugatedCB2R-selective compound, CM-157.

Dimerization with Cannabinoid Receptors Allosterically Modulates Delta Opioid Receptor Activity during Neuropathic Pain

An important role for CB1R-DOR heteromers in altered cortical function of DOR during neuropathic pain is demonstrated and the possibility that a novel heteromer-directed therapeutic strategy for enhancing DOR activity, could potentially be employed to reduce anxiety associated with chronic pain is suggested.

Exploring the first Rimonabant analog-opioid peptide hybrid compound, as bivalent ligand for CB1 and opioid receptors

From a small series of new Rimonabant analogs one CB1R reverse agonist to be conjugated to the opioid fragment Tyr-D-Ala-Gly-Phe-NH2, the bivalent compound has been used for in vitro binding assays, for in vivo antinociception models and in vitro hypothalamic perfusion test, to evaluate the neurotransmitters release.



Modulation of rat brain opioid receptors by cannabinoids.

Delta 9-THC inhibited the binding of [3H]etorphine (potent opioid agonist) to solubilized, partially purified opioid receptors with a Ki value similar to that observed for the membrane-bound receptors, indicating that the allosteric modulation of the opioid receptor by delta 9- THC is the result of a direct interaction with the receptor protein or with a specific protein-lipid complex.

Pharmacology of cannabinoid receptor ligands.

  • R. Pertwee
  • Biology, Chemistry
    Current medicinal chemistry
  • 1999
This review summarizes current knowledge about the in vitro pharmacological properties of important CB1 and CB2 receptor ligands and pays particular attention to the binding properties of these ligands, to the efficacies of cannabinoid receptor agonists, as determined using cyclic AMP or [35S]GTPgammaS binding assays, and to selected examples of how these pharmacological Properties can be influenced by chemical structure.

The effects of cannabinoids on the brain

  • A. Ameri
  • Biology
    Progress in Neurobiology
  • 1999

International Union of Pharmacology. XXVII. Classification of Cannabinoid Receptors

It is considered premature to rename cannabinoid receptors after an endogenous agonist as is recommended by the International Union of Pharmacology Committee on Receptor Nomenclature and Drug Classification, because pharmacological evidence for the existence of additional types of cannabinoid receptor is emerging and other kinds of supporting evidence are still lacking.

Modulation of transmitter release via presynaptic cannabinoid receptors.

[3H]naltrindole: a potent and selective ligand for labeling delta-opioid receptors.

It is demonstrated that [3H]NTI is a potent and selective radioligand for delta-opioid receptors in rat brain preparations and was not significantly inhibited by mu- or kappa-OPioid ligands or by nonopIOid compounds.

Modulation of brain α2-adrenoceptor and μ-opioid receptor densities during morphine dependence and spontaneous withdrawal in rats

Modulation of hypothalamic α2-adrenoceptor density during morphine withdrawal is a relevant physiological mechanism by which the opiate abstinence syndrome is counteracted.

(-)-Cannabidiol antagonizes cannabinoid receptor agonists and noradrenaline in the mouse vas deferens.

Tetrahydroaminoacridine and other allosteric antagonists of hippocampal M1 muscarine receptors.

The present results indicate that compounds that can act allosterically may compete with acetylcholine for primary receptor sites but that allosteric effects of these drugs on muscarine receptors are not likely to be important clinically.