In addition to these CB1-associated proteins, the cannabinoid receptor associated protein 1a (CRIP1a) has been implicated in modulating the function of CB1 in response to antagonists. Notably, over-expression of CRIP1a with CB1 reduces the increased Ca2+ conductance observed when SR is applied to cells where only CB1 is expressed (Niehaus et al., 2007). Furthermore, over-expression of CRIP1a in cultured cortical neurons reveals a neuroprotective effect of SR treatment in response to glutamate excitotoxicity (Brower, 2001). As a consequence, an understanding of CRIP1a modulation of CB1 may help to clarify the conflicting results regarding the effect of cannabinoid pharmacotherapies on withdrawal severity. However, few studies have followed up on the original report, and much work still needs to be done to fully characterize the involvement of CRIP1a-regulation of CB1 signaling.
