We now know that many effects of
endocannabinoids are not mediated through
either the CB1 or CB2 receptor. These include
health-related effects on blood pressure,
inflammation, pain, and cancer cell growth. In
fact, endocannabinoids can directly bind to at
least eight different receptors beyond CB1
and CB2.
Below, I will give an overview of the different
receptors that are either part of the
endocannabinoid system, or are part of a
different signalling system, yet are still
modulated by endocannabinoids.
Cannabinoid CB1 Receptor
The CB1 receptor is hands down the most
famous of the endocannabinoid system. This
receptor, like the next 4 that I describe, are
part of a class of receptors called G protein-
coupled receptors (GPCRs). These receptors
sit within the cell membrane and upon
activation, start a signalling cascade within
the cell that leads to specific effects. The two
most common endocannabinoids to activate
CB1 are anandamide and 2-AG.
The highest levels of CB1 expression are in
the central nervous system (CNS). In fact,
there are more CB1 receptors in the brain than
any other type of GPCR.
However, despite descriptions as the “brain
receptor” it is also found throughout the body
in many different tissues: cardiovascular,
reproductive, immune, gastrointestinal, and
peripheral nerves to name a few important
ones.
Given the wide distribution of the CB1
receptor, it is not surprising that it seems to be
involved in, well, just about everything. I can
only give a high level summary, as any one of
these points could be an entire article in itself.
• Regulates learning and memory
• Neuronal development & synaptic
plasticity
• Regulates reward and addiction
• Reduces pain
• Reduces neuroinflammation and
degeneration
• Regulates metabolism & food intake
• Regulates bone mass
• Cardiovascular effects
Cannabinoid CB2 Receptor
The CB2 receptor is located primarily in the
periphery instead of the CNS.
It is mainly expressed in immune cells, giving
it an important role in inflammation.
However, we now know that CB2 is
expressed in a variety of cells, including those
in the CNS, liver, and bone. CB1 is no longer
considered to be the only cannabinoid
receptor that affects memory and cognition.
The amino acid sequence of the CB2 receptor
is relatively similar to the CB1 receptor. So
not surprisingly, the CB2 receptor is activated
by similar cannabinoids as the CB1 receptor,
including anandamide and 2-AG.
• Allergic
and
autoimmune
inflammatory diseases
• Osteoporosis (loss of bone mass)
• Neurodegenerative diseases
• Ischemic injury from stroke or heart
attack
• Chronic pain
• Hepatic (liver) injury and disease
• Alcohol and nicotine addiction
• Weight gain
• Stress responses
There is no guarantee that activation of CB2
receptors will help these conditions in
humans.
For many of
these conditions,
there is
additional
Supportive
nonclinical and
clinical
evidence, but
that is out of the
scope of this
article.