The Leaf THE LEAF November-December 2017 | Page 13

TRP Channels
The transient receptor potential (TRP)
channels are ion channels involved in
temperature, pressure, and pain sensation.
There are three different subfamilies of this
class that cannabinoids can modulate:
vanilloid (TRPV), ankyrin (TRPA), and
melastatin (TRPM). were both potent antagonists of the TRPM8
channel (EC50s=160 nM/ 60 nM).
TRPV1, expressed in sensory neurons and the
brain, mediates pain and temperature
sensation. It is famous for being activated by
capsaicin (the molecule that makes chilis taste
spicy). CBD (EC50=1 μM) is an agonist of
TRPV1. Nuclear Receptors
Peroxisome proliferator-activated receptors
(PPARs) are nuclear receptors that regulate
gene expression. Activation of PPARs is
associated with some of the neuroprotective,
pain-blocking,
anti-cancer,
anti-
inflammatory, and metabolism-improving
properties of cannabinoids.
But wait, isn’t it bad to activate a receptor that
causes a burning pain? Actually, TRPV1
agonists can also cause a prolonged period of
receptor desensitization. For this reason,
topical capsaicin is used to treat neuropathic
pain. At least one model of inflammatory pain
showed that the pain-blocking effects of CBD
were due to actions at TRPV1.
The list of related TRP channels acted on by
phytocannabinoids is long. THC and CBD
both activate TRPV2 (EC50s=650 nm/ 1.25
μM), TRPV3 (EC50s=9.5 μM/ 3.7 μM), and
TRPV4 (EC50s=8.5 μM/ 800 nM). The
potency at TRPA1 is especially low (EC50s=
230 nM/ 110 nM). Finally, THC and CBD
We still do not fully understand the role of
each of these channels for the effects of
phytocannabinoids. I would keep a close eye
on research in this area for the treatment of
different types of chronic pain.
Although endocannabinoids can activate the
PPARα isoform, evidence for direct
activation of PPARα by Phytocannabinoids is
weak. Activation by THC or CBD may occur
indirectly through other receptors.
On the other hand, both THC and CBD are
potent and direct activators of the PPARγ
isoform. Although an EC50 has not been
calculated, PPARγ activation was seen with
just 100 nM of THC or CBD.
http://profofpot.com/endocannabinoid-
receptors/