It's the information age, lmgtfy while you gfafb.
ACDC 22:1 @ CB3
Alternative Cannabinoid Dietary Cannabis
22%CBDA:1%THCA acting at GPR55 Alias CB3
William L. Courtney, MD, AACM
American Academy of Cannabinoid Medicine
drcourtney@cannabisinternational.org For over a decade Guanine Nucleotide-Binding Protein-Coupled Receptor 55 / GPR55 has been
fondly known as the ‘Orphan’ receptor. While it
was known that yso hosphatidyl nositol /LPI binds at
this pro-inflammatory site, it was the discovery that the
phyto-cannabinoid acids are also potent ligands at
GPR55 that argues that we now rename the ‘Orphan’
receptor, the Third Cannabinoid Binding receptor or
CB3.
Raphael Mechoulam’s 80th birthday celebration was
held at the Israeli Institute for Advanced Studies in
Jerusalem this last November. At the concurrent conference
Cannabinoids In Biology and Medicine, Dr. Ruth
Ross of Aberdeen Scotland gave, from my perspective,
one of the most seminal presentations of the last decade.
Thinking outside of the box, Dr. Ross tested CBDAcid
and CBGAcid to see if they might be the missing exogenous
ligands of GPR55. She reported that CBDA and
CBGA are 2-4 fold more effective antagonists than CBD
which is patented as an anti-inflammatory, a copy of
which is available at CannabisInternational.org.
Despite my 6 year long fascination with CBD, a fascination
that bordered on an obsession, it was my patients
continued reporting of their strong response to the
dietary use of raw cannabis bud and leaf, that kept pushing
me to understand the relationship between CBD and
CBDA. Despite the massive amount of research on CBD
there has been very little on CBDA, a delicate molecule
with a poor shelf life i.e. minimal market value or financial
upside, the promise of which determines the investment
of research dollars. With Dr. Ross’s research, the
gauntlet has now been thrown and the synthetic chemists
are now focused on that carboxyl moiety.
My interest in unheated cannabis began in 2006 and initially
focused on dried leaf. In June 2007 I switched from
dry leaf to juiced fresh leaf to preserve the terpenes that
act as allosteric modulators of cannabinoid receptors,
antibiotics, anti-inflammatories and in numerous other
physiologic and pathophysiologic modalities . Raw
mature bud was added to the fresh leaf in October
of 2009 following the International Cannabis
as Medicine conference in Koln Germany.
Kristen Peskuski, my partner in Cannabis
International.org, was asked to present on
the patient panel. After her presentation we
were given an article and foreign patent that
issued in the US Oct 5, 2010. This US Patent
on MEDICINAL ACIDIC CANNABINOIDS
7,807,711, can be found on the patent page at
CannabisInternational.org. The article behind the patent
noted that the concentration of THCA to THC was
14,500μg THCA/ml : 90 μg THC/ml. Since the typical
dose of THC is 10mg or 10,000 μg, clearly the 90 μg/ml
found in unheated flower / bud would be insufficient to
be psychoactive.
Despite marked trepidation, consumption proved that
raw flower was in fact non-psychoactive. The immature
flower was almost palatable but as it matured the acidic
content dramatically increased. The fully mature flower
was quite caustic on the back of the throat. There is a
strong urge to wash the masticated flower down with the
closest available liquid. The critically point worth reiterating
is that raw cannabis / THCA is not psychoactive,
even at doses 60 to 100 times greater than the traditional
psychoactive dose!
Once it was confirmed that fully mature bud was not
psychoactive it cleared the way for a dramatic increase of
dosing. For the last 10,000 years the use of heat to chemically
modify non-psychoactive THCA into THC, inadvertently
resulted in the voluntary reduction of dose from
1,000mg to 10 mg! By 20 mg THC euphoria is replaced
dysphoria, ataxia, slurring. If the THC dose is accidentally
increased to 30mg, dysphoria is replaced by psychtoxicity
and one becomes ‘unable or unwilling to assume
the erect position’. As noted repeatedly in US patent6,630,507, it is the absence of psychoactivity that allows the increases
in dose required for the cannabinoid acids to act as an anti-oxidant,
neuroprotectant and anti-inflammatory. It is this
dramatic increase in dose from 10 mg of
psychoactive THC to the 500-1,000
mg of non-psychoactive THCA /
CBDA / CBGA ….. that comprises
the primary difference between traditional
‘Medical Marijuana’ and
Alternative Cannabinoid Dietary
Cannabis. Curiously it is the US
Department of Health and Human Services
patent, 6,630,507 issued in 2003, that teaches
the ‘Effective human dosage schedule’ for nonpsychoactive
use. This dosage schedule comports
with numerous other research articles and issued
patents, see CannabisInternational.org.
Sharing the cover of Treating Yourself, Issue 24 was
an article I had written entitled, Cannabis as a
Unique Functional Food and an article about the
strain Cannatonic by Resin Seeds. When that
article was written I was unaware of
Cannatonic, but a patient who knew of my
interest in high CBD plants brought the strain to
my attention. I went to Barcelona to meet the
principal of Resin Seeds. Over the summer of 2010
I had described to thousands of patients that feminized
seeds were similar to a clone. The use of
stress, either light or chemical, to lean upon
cannabis’ inherent ability to
forego it’s dioecious preference is
well known. The hermaphorditic
conversion that results in the
production of pollen by the
female plant can occur
spontaneously as
well as in response to
exogenous stress. Regardless
of the cause, this conversion
of dioecious to monoecious,
subserves the annual
plant’s drive to produce
the seed required to survive the winter.
With no new DNA introduced
through this process it was assumed
that the feminized seed would be very similar to the
parent plant profile. Recently I was told that 1 in 4
plants grown for feminized Cannatonic seeds would
express an increased CBD chemotype.
34 million years of evolution lead to this dominant presentation
of cannabinoid acids. Sadly our headlong pursuit
of THC has resulted in the near extinction of the
vast majority of the cannabinoids. In 2009 ElSohly in
Biologically Active Cannabinoids from High-Potency
Cannabis sativa reports discovering another 9 cannabinoids.
Why did it take 30 years to find them? Because
we had effectively eliminated them from the plant! Turns
out that these vestigial cannabinoids provide very
important antibiotic support against the intracellular
pathogens that would take opportunistic advantage of
the animal that was consuming cannabis on a dietary basis. Dietary use provides remarkable antioxidant benefits,
but one of the side effects of cannabis that I include
in every medical evaluation I conduct, is the warning
that regular use of cannabis requires attention to
Legionairres, Leishmaniasis and TB. The white blood
cells of the immune system intentionally secrete superoxides
in their effort to destroy the tissue harboring the
intracellular pathogens. CBD / CBDA neutralizes those
superoxides thereby hampering the immune system.
Because we have driven these cannabinoids out of the
plant they no longer provide potent antimicrobial protection
from these intracellular pathogens.
There are several reasons why I chose the strain name,
Alternative Cannabinoid Dietary Cannabis / ACDC
CBDA:THCA. ACDC 22:1 for example identifies the
amount of CBDA first, then THCA second, contrary to
every other nomenclature which begins with the amount
of THC. In part this forces individuals to begin the arduous
task of realizing that in the non-psychoactive realm,
THCA is but one of many cannabinoid acids. Quite
possibly THCA is less significant than the other 79 (and
counting) cannabinoids. ACDC is also a nod to the
AK47 / Train Wreck crowd, in that if you heat an ACDC
strain you will decarboxylate the THCA, that is you will
generate THC euphoria. Yes, if you make a baked good
and eat one to many you will create a state of dysphoria.
True to the Dr. Jekyll / Mr. Hyde analogy, if you eat
5 or 6 brownies made for an ACDC strain you will
become psychotoxic. Finally with any heated application
your dose of CBDA will go to near zero and the
amount of CBD will be physiologically negligible as an
antioxidant. That is THC will limit your dose of CBD to
1-20mg which is 599-580mg short of the target dose,
600mg. If you happened to be using ACDC 22:1,
because of the dearth of THCA you would have a significant
amount of decarboxylated CBDA that is you
would have a significant amount of CBD which is 2-4
fold less effective at antagonizing the pro-inflammatory
CB3 / GPR55. All told, heat devastates cannabis as a
dietary essential but you do get some CB1 receptor stimulation
in the Faustian Bargin.
CBDA is the first Alternative Cannabinoid ACDC will
eventually include an acronym soup of known and
unknown cannabinoid and cannabinoid-like substances.
The journey of Dietary Cannabis is not one of 10,000 miles but one of 10,000 years. As we begin this journey
of 10,000 years our curiosity grows as we try to imagine
what this plant looked like before 10,000 years of
selective hybridization. Over the last 10,000 years we
have created a plant in which 95% of the cannabinoid
content is dominated by a single cannabinoid, THCA.
The other 79 known cannabinoids are left to divvy up
the remaining 5 % of cannabinoid content. Hopefully
cannabis can help heal itself and thereby restore a more
balanced profile of cannabinoids.
As cannabis heals, we heal. As we disseminate the
incontrovertible science that describes the interface
between the Endogenous Cannabinoid System and the
Phytocannabinoids found in cannabis, Treaty One will
be amended to remove cannabis freeing it up for access
as a raw leafy green vegetable that is ideally suited to
prevent illness. Used as the dietary essential that it is,
there is no need to call it a medicine. For those of us
who embrace the FDA dose of CBD at 600 mg/day in
divided doses, we are forced to grow the plant ourselves
because in the 10 mg market, the price of a glass of juice
with 600 mg is staggering! Many of my patients in
Mendocino and Humboldt are refining the succession
grow in which one plant, either seed and or clone of
cannabis, is started every day or two. Every day one
plant becomes fully mature and it’s leaves and flowers /
buds are juiced, diluted and taken in 5 divided doses
across the day because of the rapid clearance.
With the advent of testing facilities, tremendous
progress has been made in the last year. It is important
to keep the plant alive if you plan to analyze for
cannabinoids, terpenes or other constituents.
As we recognize that cannabis is a dietary essential for 7 billion people, we can employ the CO2 fixation capacity of billions of acres of cannabis to heal the earth while it provides the individual with the finest dietary support for our small and shrinking planet.