Is CBD pure better? A ground-breaking study has demonstrated that CBD-rich cannabis extract from the full plant has superior medicinal benefits compared to CBD molecules isolated from the plant.

Compared to single-molecule cannabidiol, whole-plant CBD-rich cannabis extract possesses superior medicinal benefits, according to a ground-breaking study from Israel (CBD).

Published in the journal Pharmacology & Pharmacy in February 2015, the paper directly confronts one of Big Pharma’s and the medical-industrial complex’s sacred cows: the assumption that “crude” botanical preparations are fundamentally inferior and less effective than pure, single-molecule chemicals.

The article, titled “Overcoming the Bell-Shaped Dose-Response of Cannabidiol by Using Cannabis Extract Enriched in Cannabidiol,” is notable because co-author Lumir Hanus was instrumental in the discovery of anandamide, the endogenous cannabinoid compound first identified in the mammalian brain in 1992.

Hanus and two Israeli colleagues from Hebrew University of Jerusalem reviewed the scientific literature and found that numerous preclinical studies had focused on the anti-inflammatory effects of pure, single-molecule CBD in animal models of various pathologies, such as rheumatoid arthritis, inflammatory bowel disease, multiple sclerosis, and diabetes, over the past fifteen years. (See preclinical evidence regarding CBD.)

These experiments demonstrated that delivery of pure, single-molecule CBD resulted in a dose-response curve shaped like a bell, indicating that when the amount of CBD exceeded a particular threshold, its therapeutic efficacy diminished drastically. “Healing was only evident when CBD was administered within a very narrow dose range, but neither lower nor larger doses produced any positive effects,” the investigators noted. This property of single-molecule CBD, which manifests as a bell-shaped dosage response, imposes significant constraints that limit its clinical utility.

The Israeli researchers wanted to investigate if the administration of a CBD-rich whole-plant extract would also produce a bell-shaped dose-response curve in mice. Or, would CBD derived from CBD-rich cannabis eliminate this liability? The authors said that the purpose of this work was to identify a CBD source that could abolish the bell-shaped dose-response of pure CBD.

The CBD-rich “Avidekel” variety was obtained from Tikkun Olam, an Israeli medical marijuana manufacturer. Avidekel, referred to as “clone 202” in this study, contains very little THC and is hence not psychoactive. Avidekel can be traced back to Spain, where breeders created numerous variants of “Cannatonic” (as in “cannabis tonic”), including a strain with close to 20 percent CBD by dry weight and nearly no psychoactive compounds. In California, the same high-yielding CBD-dominant variety is known as “ACDC.”

From clone 202, the Israeli researchers isolated an oil rich in CBD. Mice were administered an extract containing 17.9 percent CBD, 1.1 percent THC, 1.1 percent cannabichromene (CBC), 0.2 percent cannabigerol (CBG), and “traces” of cannabinol (CBN) and cannabivarol (CBDV) to evaluate its anti-inflammatory and analgesic properties.

The researchers supplied pure CBD to a second set of mice and evaluated its anti-inflammatory and analgesic qualities for comparison purposes. In addition, they evaluated the amount to which single-molecule CBD and CBD extracted from the complete plant suppressed the production of tumor necrosis factor alpha (TNFa), a systemic inflammatory signaling molecule. Several disorders, such as cancer, Alzheimer’s, clinical depression, and irritable bowel syndrome, have been linked to the dysregulation of TNF-alpha production.

The experiments on pure CBD confirmed the results of previous preclinical research. Again, delivery of a single molecule of CBD produced a bell-shaped dose-response curve with a narrow therapeutic window.

When clone 202 extract was fed to mice, however, a distinct dose-response pattern was identified. In lieu of a bell-shaped curve, where a therapeutic effect could only be produced at a certain concentration of pure CBD, the CBD-rich extract of the whole plant generated a dose-dependent, direct decrease of pain, inflammation, and TNF production. “In striking contrast to purified CBD,” the Israeli scientists stated, “the clone extract…provided a clear link between anti-inflammatory and anti-nociceptive reactions and dose, with rising responses with increasing doses, making this plant medicine appropriate for clinical applications.”

In addition, the Israeli researchers discovered that a modest amount of CBD in the clone extract was sufficient to provide significant pain relief, whereas a far larger amount of pure CBD was necessary to have the same analgesic effect. And whereas a “overdose” of pure, single-molecule CBD caused a severe reduction in efficacy, a “overdose” of whole plant CBD-rich extract did not diminish its therapeutic efficiency. When more than the ideal dose of clone 202 oil was supplied, its efficacy plateaued, indicating that a therapeutic plateau had been reached.

According to the Israeli study, Cannabis clone 202 extract is superior to CBD for treating inflammatory disorders. CBD’s additive or synergistic interactions with dozens of minor phytocannabinoids and hundreds of non-cannabinoid plant components may account for the enhanced efficacy of the whole plant extract. “It is possible that other components in the extract interact synergistically with CBD to provide the desired anti-inflammatory effect, which may contribute to overcoming the bell-shaped dose-response of pure CBD,” the Israeli researchers hypothesized.

The scientists deemed it essential to compare the CBD-rich cannabis extract to commercial painkillers and anti-inflammatory medications. Both pure CBD and the clone 202 extract displayed stronger anti-inflammatory effectiveness than aspirin, the researchers discovered. Aspirin, but not tramadol, had a small inhibitory effect on TNFa production, which was insignificant compared to the potent inhibitory effect of pure CBD and clone 202.

Recent results confirming the anti-proliferative action of cannabidiol on tumor cells and the inhibiting effect of CBD on bladder contractility reinforce the main conclusion that CBD in the presence of other Cannabis components increases the dose-response.

The Israeli team stated, “Much study has been conducted to separate and analyze isolated single ingredients of traditional herbal medicine to determine their reason for therapeutic usage.” “However, our data and those of others provide justification for the introduction of a new generation of phytopharmaceuticals to treat diseases that were previously treated exclusively with synthetic medications. The therapeutic synergy observed with plant extracts necessitates a smaller amount of active components, resulting in fewer side effects.”

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