CB2: a cannabinoid receptor with an identity crisis

Area of Science:

• Neuroscience
• Immunology
• Pharmacology

Background:

• Cannabinoid receptor 2 (CB2) was initially termed the 'peripheral cannabinoid receptor' due to its presumed absence in the central nervous system (CNS).
• Recent findings indicate CB2 expression in the CNS, particularly in microglia during neuroinflammation, prompting re-evaluation of its distribution.
• The presence and extent of CB2 expression in CNS neurons remain a subject of ongoing debate and conflicting research.

Purpose of the Study:

• To review the reported tissue distribution of CB2, with a specific focus on its presence in CNS neurons.
• To discuss the implications of CB2 expression in neurons for drug discovery and therapeutic applications.
• To provide recommendations for the interpretation of existing data and guide future research on CB2 in the CNS.

Main Methods:

• Literature review of studies reporting CB2 expression in various tissues, emphasizing neuronal expression in the CNS.
• Analysis of conflicting data regarding the extent of CB2 expression in neurons.
• Synthesis of findings to address the controversy surrounding CB2's neuronal localization.

Main Results:

• Evidence suggests CB2 is present in the CNS, notably in microglia during neuroinflammation.
• The extent of CB2 expression within neurons, particularly in the CNS, is highly controversial, with studies reporting a wide range from complete absence to widespread presence.
• The precise localization of CB2 in neurons significantly impacts its potential as a therapeutic target.

Conclusions:

• The presence of CB2 in CNS neurons requires careful consideration and cautious interpretation of current research.
• Further rigorous investigation is essential to definitively establish the distribution and role of CB2 in neurons.
• Clarifying neuronal CB2 expression is crucial for advancing drug discovery for conditions treatable by CB2 modulation without psychoactivity.