But further research by cannabinoid researchers shows that the issue is not quite that simple. What is usually referred to when talking about binding to a receptor is the orthosteric receptor. Binding at the orthosteric receptor is what causes the downstream response. If a molecule binds elsewhere on the protein surface it can perturb the the protein surface atoms, with the perturbation propagating in a wave like fashion until it reaches the orthosteric binding site. This is called allosteric binding since the Greek root allo refers to other and steric to site.
This would be of no interest save for the fact that the perturbation can change the conformational coupling at the binding site, in this case CB1. This is called affinity modulation . Positive allosteric modulators, when an appropriate molecule has bound to the orthosteric receptor, enhance the natural physiological activity of the receptor, allowing the modulator to exert its effects while leaving normal physiological signaling patterns unaffected. Negative allosteric modulators reduce the physiological activity of the receptor.
So, to put it simply, CBD does not really bind at the CB1 receptor, rather it binds elsewhere and affects the efficiency of whatever does happen to bind at the CB1 receptor, possibly reducing or potentiating the effect.
By George Bennet,