yes, there’s more to it than meets the eye;
way more than HomoSociopathis can comprehend,
and our High Society wants to admit.
Here, numb-nuts-science is just getting a glimpse of the bigger picture,
a sweet taste of the real world out there.

Welcome to a reality where economy begins with ecology,
where life & death belong together
and the world runs on synergy and not on power.

This is real Life, were you & me are connected, and completely entangled with the rest of creation,
but also utterly clueless how to respond to it and/or correspond with all of this.

The Entourage Effect from Insights on Vimeo.

Maybe we should have called it Life Beyond THC.com

By Fred Gardner fred@plebesite.com.
has been an editor of Scientific American and public information officer for the District Attorney of San Francisco.

The chemical structure of tetrahyrdocannabinol (THC) was determined in 1964 by R. Mechoulam & Y. Gaoni.
For more than three decades thereafter, its blatant psycho-activity induced scientists
to define THC as the active ingredient in the plant.

Experienced marijuana smokers who tried the drug Marinol (pure, synthetic THC) when it became
prescribeable in the mid-1980s, reported that the effects were noticeably dissimilar.
But it wasn’t until the late 1990s that the research establishment acknowledged that another compound,
cannabidiol (CBD), was exerting significant effects, too.

In 1999 a British start-up, G.W. Pharmaceuticals, began clinical trials of a plant extract
containing equal amounts of THC and CBD. Multiple Sclerosis patients found the combination
more effective in reducing pain & spasticity than a THC extract, and less psychoactive.
The THC-CBD combo, ‘Sativex‘, has now been approved for use by MS patients in England,
Canada, New Zealand, and a growing list of European countries.

Several of the so-called ‘minor cannabinoids’ —notably tetrahydrocannabavarin (THCV),
cannabigerol (CBG) & cannabichromene (CBC) — also show therapeutic promise,
and plants with high levels of each have been grown out in G.W.’s glasshouses for research purposes.

Now scientists are formally acknowledging something else that Cannabis consumers
have long taken for granted:aroma is associated with effect.

Plant cannabinoids, —21-carbon molecules found only in Cannabis, are odorless.
It’s the terpenoids —components of the plant’s “essential oils”— that create the fragrance.
Terpenoids contain repeating units of a 5-carbon molecule called isoprene, and are prevalent
in smelly herbs such as mints & sage, citrus peel, some flowers, aromatic barks and woods.
The aroma of a given plant depends on which terpenoids predominate.
They tend to be volatile molecules that readily evaporate, and they’re very potent
—all it takes is a few reaching the nose to announce their presence.
The cannabinoid content of a trichome might be 10 times heavier than the terpenoid content.

Evidence that ‘phytocannabinoid-terpenoid interactions’ enhance the therapeutic effects of cannabis
was presented by Ethan Russo, MD, at a conference in Israel last fall and is about to be published
in the British Journal of Pharmacology. Russo, a neurologist and ethnobotanist,
is senior medical adviser at G.W. Pharmaceuticals.

Terpenoids and cannabinoids are both secreted inside the Cannabis plant’s glandular trichomes
and they have a parent compound in common (geranyl pyrophosphate).
More than 100 terpenoids have been identified in Cannabis.
The most common and most studied include limonene, myrcene, alpha-pinene,
linalool, beta-caryophyllene, caryophyllene oxide, nerolidol and phytol.
Anecdotal evidence suggests that alpha-pinene is alerting,
limonene is ‘sunshine-y‘, and beta-myrcene is sedating.

As the names suggest, pinene is abundant in pine needles and limonene in lemons.
Myrcene is found in hops (Humulus), the only other member of the Cannabicae plant family.

The fact that most terpenoid compounds are common components of the human diet and ‘generally recognized
as safe‘ by the Food and Drug Administration has made research possible, and scientists
employed by flavors & fragrances manufacturers have investigated their properties over the years.
But the terpenoids ‘remain understudied’ in terms of therapeutic potential, according to Russo.

His paper mustered all the evidence, —proof in some cases, mere hints in others— that a
cannabinoid-terpenoid synergy is involved when Cannabis abates the symptoms of various conditions.
He listed “pain, inflammation, depression, anxiety, addiction, epilepsy, cancer, fungal & bacterial
infections (including methicillin-resistant Staphylococcus aureus).”

For example, as an indication that some terpenoids may, like CBD, be ‘antidotes to the
intoxicating effects of THC‘, Russo noted that traditional responses to Cannabis overdose
include limonene-rich citrus and pinene-rich black pepper.

Jeffrey Hergenrather, MD, president of the Society of Cannabis Clinicians, who attended
Russo’s talk in Israel, expects its publication to “generate great interest in terpenes among
medical cannabis users as well as physicians.” The SCC recently began collecting data on patients’ responses
to CBD-rich Cannabis. Future surveys will seek to document which terpenoids are having which effects.

Phytocannabinoid & cannabis terpenoid biosynthesis →

Synergy research: approaching a new generation of phytopharmaceuticals →

The ‘Entourage Effect’

The conference at which Russo presented his paper was held at Hebrew University, Jerusalem,
where Raphael Mechoulam directs a lab, in honor of Mechoulam’s 80th birthday.

In 1998 Mechoulam co-authored a paper with Shimon Ben-Shabat suggesting that cannabinoids,
made in the body, work by means of an ‘entourage effect’. →
They had found that the endocannabinoid 2-AG (2-arachidonoylglycerol), tested by itself, did not bind
very strongly to the cannabinoid receptors or exert pronounced behavioral effect on mice.
But when administered with two related compounds, it did both.

To pharmacologists who customarily designed experiments aimed at finding the active ingredient,
this had heavy implications. Mechoulam spelled them out: “Biochemically active natural products,
from either plant or animal origin, are in many instances accompanied by chemically related
though biologically inactive constituents. Very seldom is the biological activity of
the active constituent assayed together with inactive ‘entourage’ compounds.
Investigations of the effect of the active component in the presence of its ‘entourage’ compounds
may lead to results that differ from those observed with the active component only.”

In 2001 John McPartland and Russo published a paper in the Journal of Cannabis Therapeutics applying
the ‘entourage‘ concept to the plant itself. “Good evidence shows that secondary compounds in cannabis
may enhance the beneficial effects of THC… and reduce THC-induced anxiety, cholinergic deficits,
and immunosuppresion,” they wrote. “Cannabis terpenoids and flavonoids may also increase cerebral blood flow,
enhance cortical activity, kill respiratory pathogens, and provide anti-inflammatory activity.”

Talking Terpenoids