Endocannabinoid Receptors – More Than Just CB1 and CB2 (Part 3)
THC & CBD – Promiscuous Partners with many Receptors
and CBD will engage.
Did you think that THC and CBD could only
So for example, if you smoke a bit of low-
interact with just the CB1 and CB2 receptors?
CBD cannabis, the CBD levels in your body
Think again!
will be too low to engage many of the targets
(or maybe none at all). If you take a very high
Both tetrahydrocannabinol (THC) and
dose of purified CBD oil, levels in your body
cannabidiol (CBD) are highly promiscuous.
could be high enough to engage many of
Yes, this is an actual term in pharmacology! It
them. The potency of other targets may be so
means that they hit multiple pharmacologic
low that engagement can only be shown in the
targets within the cell instead of just one.
lab and has no real significance. In a follow-
There are many different targets, including
up article, I will estimate what doses are
cell surface receptors, nuclear receptors,
needed to engage different targets.
uptake transporters, and cannabinoid binding
proteins.
Below, are the targets of THC and CBD that
How common are promiscuous drugs?
You see them less and less. Pharmaceutical
drugs these days are optimised to have very
high potency at one intended target.
Molecules are chosen for their selectivity –
the ability to hit just one target without
touching others.
However, many older drugs (especially
psychiatric ones like antidepressants and
antipsychotics) do bind multiple targets.
This can both contribute to their efficacy and
their side effects.
Potency is an important concept that cannot
be overlooked. Contrary to how it is
informally used, it does not mean how strong
the effect of a drug is. Rather, it refers to what
concentration or dose the effect is achieved at.
Potency can be expressed as an EC50 – the
concentration that produces half the maximal
effect, or an IC50 – the concentration that
produces
half
the
maximal inhibition
of an effect.
THC and CBD
have
different
potencies
at
different
targets.
The importance of
this is that the
higher the dose, the
more targets THC
have been discovered (so far).
I won’t cite every individual study, but here is
a recent review on the topic
[Here is an explanation of the different types
of receptor ligands (agonists, antagonists,
allosteric modulators, etc.)