In the pharmaceutical field, experts often look down on unrefined botanical preparations. They are treated as low grade and ineffective forms of the plant compared to pure compounds extracted from a single molecule. When it comes to cannabis, this accepted truth has been proven to be inaccurate.
A study published by Israeli scientists in the journal Pharmacology & Pharmacy showed that whole plant CBD-rich extracts are far superior to single-molecule cannabidiol in terms of therapeutic properties.
One of the authors of the February 2015 study is the legendary Lumir Hanus – a Czech analytic chemist who, together with William Anthony Devane, discovered the first endogenous cannabinoid in mammals back in 1992. They named the compound anandamide, the Sanskrit word for joy or bliss.
"Overcoming the Bell-Shaped Dose-Response of Cannabidiol by Using Cannabis Extract Enriched in Cannabidiol"
In their documented research, Hanus and his two Israeli colleagues from Hebrew University of Jerusalem surveyed scientific evidence over the past 15 years. They noted that most preclinical studies had focused on the anti-inflammatory effects of pure, single-molecule CBD on animal diseases such as multiple sclerosis, rheumatoid arthritis, bowel disease, and diabetes.
The most startling result of their review is that the therapeutic impact of pure, single-molecule CBD had a dramatic decline after the amount of CBD administered had reached a certain point. This phenomenon is called a bell-shaped dose response. CBD was only effective within a very limited dose range and showed no healing effect at low or high doses. According to the authors, the bell-shaped dose-response curve of single-molecule CBD severely limits its usefulness in a clinical context.
Following this observation, the research team proceeded to determine whether whole plant CBD would generate the same bell-shaped dose response when administered to mice. The goal of the experiment was to find an alternative source that eliminates the bell-shaped dose-response of purified CBD.
Tikkun Olam, a medical producer in Israel, supplied the CBD extract for the study. Its CBD-rich strain called "Avidekel" had insignificant levels of THC – the psychoactive chemical in marijuana.
Referred to as "Clone 202" in the study, Avidekel traces its origin from Spanish breeders who had developed a cannabis strain measuring close to 20 percent CBD in dry weight. This is the same high-yielding CBD-rich strain known as "ACDC" in California which is known to contain zero intoxicating ingredients.
The extracted oil from Clone 202 contained the following:
- 9 percent CBD
- 1 percent THC
- 1 percent cannabichromene (CBC)
- 2 percent cannabigerol (CBG)
- Traces of cannabinol (CBN) and cannabivarol (CBDV)
For comparative analysis, one group of mice was given pure CBD and another group of mice was administered with the Clone 202 oil. Both groups were later evaluated for anti-inflammatory and analgesic effects. The scientists also analyzed how single-molecule CBD and whole plant CBD slowed down the production of tumor necrosis factor alpha (TNFa), a systemic inflammatory signaling molecule. The dysregulation of TNFa production has been associated with cancer, irritable bowel syndrome, clinical depression, Alzheimer's, and other diseases.
Confirming the findings of earlier preclinical research, pure single-molecule CBD generated a bell-shaped dose-response curve where a therapeutic effect could only be achieved from a concentration of pure CBD.
In stark contrast, whole plant CBD-rich extract did not have a limited therapeutic window. The Clone 202 oil caused a direct, dose-dependent inhibition of pain, inflammation, and TNFa production – making it a more ideal plant medicine for clinical purposes.
The study also revealed that only a small amount of Clone 202 CBD was needed for effective pain relief while pure CBD required a much larger dose to achieve the same analgesic effect.
Another significant finding was that pure, single-molecule CBD caused a dramatic drop in efficacy if a higher dosage was administered. On the other hand, overdosing on whole plant CBD-rich extract did not compromise its therapeutic potency.
Comparing cannabis extracts to commercial painkillers and anti-inflammatory drugs, the scientists found that pure CBD and Clone 202 extracts were both more potent than aspirin in treating inflammatory conditions. Clone 202 and pure CBD also exhibited more powerful inhibitory effect on TNFa production compared to aspirin.
The Israeli research team concluded that Clone 202, or whole plant cannabis-rich extract, is superior over pure single-molecule CBD in treating inflammatory diseases. One probable explanation is that the addition of minor phytocannabinoids and hundreds of non-cannabinoid elements in the plant and their synergistic interactions with pure CBD contribute to the greater efficiency of the whole plant extract. This synergy between cannabis compounds also helps eliminate the bell-shaped dose-response of purified CBD.
The team's key finding is supported by recent studies that have documented how cannabidiol is able to help stop the proliferation of tumor cells and slow down bladder contractility.
While a lot of research has been made to isolate single constituents of traditional herbal medicine, scientific data from the Clone 202 study proves that the synergy of multiple compounds in whole plant extracts improves potency, reduces bell-shaped dose response, and requires even less amount of the active components to achieve optimal therapeutic effects.