The quick take home is that variation may be driven by a spectrum of largely undetected variations on THC. It certainly confirms that the most basic science is still underway for cannabis.
Determining their values will remain a sought after goal but at least the work is well underway.
Empirical work over thousands of years has produced a small handful of truly active plants along with thousands of plants with indications as well. that data is only now been recovered and it is also only now that we have the tools able to ferret out multiple aspects of these plants. So this is an indicator of just how much we have to do..
THCP: A newly discovered, potentially more potent, cannabis compound
By Rich Haridy
January 14, 2020
Italian scientists have identified two new cannabinoids, including a compound called THCP that could be significantly stronger than traditional THC
https://newatlas.com/science/thcp-cdbp-new-cannabinoid-cannabis-chemical/
A recently published article in the journal Scientific Reports
has described the remarkable discovery of a previously unknown
cannabinoid. Dubbed THCP, the molecule has been shown to be
significantly more potent that its well-known counterpart THC, however,
it’s still unclear how psychoactive it is in humans or how present it is
in popular cannabis varieties.
Although
humans have been utilizing the intoxicating properties of cannabis for
thousands of years, it is only incredibly recently that scientists began
to understand exactly how the plant confers its psychoactive affects.
In the late 1980s scientists discovered a new type of brain receptor
that seemed to respond directly to compounds in cannabis. A few years
later a second similar receptor was discovered, and the two receptors
were labeled CB1 and CB2.
These two kinds of receptors, found in
significant volumes across the entire human body, are strongly activated
by tetrahydrocannabinol (THC), perhaps the most well-known psychoactive
compound in cannabis. A number of naturally produced neurotransmitters,
called endocannabinoids, also interact with CB1 and CB2 receptors.
The ability for chemicals found in cannabis to bind
with CB1 and CB2 receptors is primarily determined by its side chain.
THC, as shown above, has a five-link side chain. No naturally occurring
compound in cannabis has been found to have more than five links in this
side chain, however, synthetic cannabinoids with more side chain links
have been created by scientists.
The new study, from a team of
Italian scientists, has for the first time discovered two naturally
occurring cannabinoids with seven link side chains. The researchers have
named the cannabinoids tetrahydrocannabiphorol (THCP) and
cannabidiphorol (CBDP).
Richard Haridy
The
subsequent pharmacological tests revealed THCP seems to be over 30
times more potent in its ability to bind to CB1 receptors, compared to
THC.
What does this mean? Is THCP 30 times stronger than THC? Not exactly.
“THCP
was tested in vitro on CB1 and CB2 receptors proving to have a 33-fold
affinity for CB1 compared to the data on THC reported in the
literature,” explains corresponding author Guiseppe Cannazza in an email
to New Atlas. “This does not mean that it is active in vivo. Therefore,
Dr. L. Luongo tested THCP on mice to evaluate its cannabimimetic
activity. The results suggest that THCP acts similarly to THC but at
lower doses (about half dose).”
Cannazza is clear the team’s
animal studies so far do demonstrate THCP is substantially more
psychoactive than THC. However, what this means for human intoxication
is at this stage entirely unknown. It is also unclear whether different
strains of cannabis contain varying levels of THCP.
“The Italian
Ministry of Health gave us the authorization to study the FM2 cannabis
variety, which is produced by the Military Chemical Pharmaceutical
Institute of Florence,” says Cannazza. “The concentration [of THCP]
present in this variety is extremely low and probably it does not reach
the effective dose to produce a pharmacological effect. It should not be
ruled out though that the concentration of THCP might be higher in
other cannabis variety, since this compound has never been searched in
the plant.”
The researchers do hypothesize THCP, and other
yet-to-be-discovered compounds, could explain the dramatic variability
in subjective responses to cannabis. A number of trials have been
conducted using cannabis with uniform THC volumes yet individuals often
report broadly different psychotropic effects. As THCP has never
previously been detected, or measured, in cannabis strains, the study
does suggest this potentially psychoactive cannabinoid may account for
some of these different effects.
“In our opinion, this compound should be included in the list of the
main phytocannabinoids to be determined for a correct evaluation of the
pharmacological effect of the cannabis extracts administered to
patients,” the researchers conclude in the recently published study. “In
fact, we believe that the discovery of an extremely potent THC-like
phytocannabinoid may shed light on several pharmacological effects not
ascribable solely to THC.”
CBDP, the newly discovered seven link
side chain homolog of CBD, another well known, yet significantly less
psychoactive, compound found in cannabis, is even more of a mystery than
THCP. While a form of CBD has recently been approved by the FDA to treat certain kinds of epilepsy, its mechanism of action is still incredibly unclear.
Cannazza
says that since CBD is not known to strongly act on CB1 or CB2
receptors, his team’s research primarily focused on exploring the
psychoactive effects of THCP. So, whether or not CBDP is more potent
than CBD, or more therapeutically effective, is another mystery yet to
be investigated.
“No biological test was performed on CBDP,”
explains Cannazza. “Its activity is completely unknown. Indeed, CBD
itself has poor affinity for CB receptors and its mechanism of action is
still not completely clear. We cannot state that CBDP is more or less
potent than CBD since it seems not to act through CB receptors. Its
biological activity is all to be evaluated.”
Essentially, this
remarkable work highlights how much there is to still learn about the
properties of cannabis. Technical advancements in mass spectrometry and
the relaxing of legal regulations relating to cannabis are only now
allowing scientists to fully explore exactly what novel compounds can be
found in this iconic plant.
Cannazza and his team are initially
focusing on simply characterizing the many unknown compounds in
cannabis. It will then be up to other scientists to find out whether
these substances have any therapeutic value.
“We are going on with our research to study the chemical composition
of different cannabis varieties,” concludes Cannazza in an email to New
Atlas. “We started with CBDB and THCB, the corresponding derivatives
with a four-term alkyl chain, published in the Journal of Natural Products,
then we studied CBDP and THCP. We are now looking for CBGB, CBGP, CBCB,
CBCP, and so on. There is still a long way to accomplish a
comprehensive characterization of cannabinoids in a cannabis variety,
but our work will pave the way to pharmacologists, toxicologists, and
clinicians for the correlation of the observed biological effects with
the chemical composition of the different cannabis varieties employed.”
The new study was published in the journal Scientific Reports.
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