Whole Plant Extract CBD Compared to Isolate
There is clear evidence that CBD has significant anti-inflammatory effects but there is some controversy as to the effective anti-inflammatory and analgesic dose for CBD. THC also has significant inflammatory effects but for this example, we will focus on CBD.
An Israeli study in 2015 titled “Overcoming the Bell-shaped Dose Response of Cannabidiol by Using Cannabis Extract Enriched in Cannabidiol,” shed some very interesting light on this question. In this study, researchers evaluated the effectiveness of CBD on pain and inflammation compared to a purified CBD isolate and a whole plant extract. They also compared the cannabinoid results to aspirin and tramadol and measured the TNF-α levels in order to assess effects on inflammation. For reference, all the statistical values presented in the paper were statistically significant with a p < 0.05.
In the study, they use the well-studied zymosan-induced paw swelling and pain model for inflammation and pain response in mice. For pain measurement, they used the von Frey nociceptive filament assay to measure pain reflex response quantitatively. After zymosan was injected into the paws of mice and the inflammatory response begun, swelling was measured at 2, 6, and 24 hour intervals. The researchers then injected CBD isolate intraperitoneally at 1 mg/kg, 5 mg/kg, 25 mg/kg, and 50 mg/kg doses. They injected ethanol whole plant extract of clone 202, which produces high amounts of CBD at the same mg/kg doses except they included 150 mg/kg as well for the extract due to its linear effects. The researchers also had negative control and positive control mice and they also compared the results to mice given aspirin orally (OS) at 50 mg/kg and those given tramadol intraperitoneally (IP).
The results were quite interesting in that the CBD isolate showed a Bell-shaped curve result in that 1 mg/kg was ineffective, 5 mg/kg showed maximal results, and 25 and 50 mg/kg showed worse pain and inflammation response than 5 mg/kg. For equivalence, 5 mg/kg IP is equivalent to 25 mg/kg orally. The maximal response at 5 mg/kg was a 50% reduction in inflammation at 2 hours and 57% reduction at 6 and 24 hours. The 25 and 50 mg/kg doses showed only a 20-25% reduction in inflammation at 2 hours and 14-28% reduction at 6 and 24 hours.
The whole plant CBD extract from clone 202, however, showed a linear dose-dependent response that showed maximum benefits at 50 and 150 mg/kg, showing a much higher pain and inflammation response. At 50 mg/kg of the extract, the absolute CBD dose was 10mg/kg, showing that CBD in the whole plant extract was effective at much lower doses as compared to the isolate. The whole plant extract at 25 mg/kg showed a 43% reduction in inflammation at 24 hours and the 50 mg/kg dose showed a 64% reduction at 24 hours. Overall, this showed that the whole plant extract was significantly more effective than CBD isolate alone for pain and inflammation.
This same effect was noted for the effects on TNF-α, wherein the CBD isolate showed a Bell-shaped curve again, showing diminishing and reversing returns with increased dose while the clone 202 extract showed a linear dosing response. The CBD isolate showed no effect at reducing TNF-α at 1 mg/kg, 25 mg/kg, or 50 mg/kg but did show a significant inhibitory effect (43% reduction) at 5 mg/kg. The whole plant extract, however, showed significant reductions in TNF-α production at 5, 25, and 50 mg/kg doses (39%, 46%, and 57% respectively) in a linear dose response. For reference 25 mg/kg extract IP is equivalent to 5 mg/kg CBD.
This was repeated with oral administration for both the CBD isolate and the whole plant extract and the results were very similar to the IP results and showed the same dosing curves. When compared to aspirin at 50 mg/kg oral, both the CBD isolate and the whole plant extract produced better results for pain, inflammation (swelling thickness), and TNF-α production. Tramadol reduced pain but had almost no effect on inflammation.
What is truly interesting about this article is that it compares a CBD isolate, a whole plant extract, aspirin, and tramadol in a whole-animal pain and inflammation model that measures several quantitative responses, including swelling, pain response, and TNF-α production. All results showed a bell-curve result for the CBD isolate that had maximal benefit at 5 mg/kg IP which is equivalent to 25 mg/kg orally. Higher and lower doses of a CBD did not improve responses at all but diminished them. On the other hand, an ethanol-extracted whole plant mixture showed a linear dose-dependent response that was greater than CBD alone and did not show diminishing returns until near plateau at 150 mg/kg. In the extract, the overall CBD dose was also lower. This clearly demonstrates you get more benefit from CBD as a whole plant extract and are also able to lower the overall CBD dose. For example, by using an isolate as compared to a whole plant extract, you would need 25 mg/kg CBD orally for an effective isolate dose while the same effectiveness absolute CBD dose in the whole plant extract is only 10 mg/kg.
This model is a superb example of good science comparing cannabinoid isolates vs whole plant extracts. I hope the authors should extend this research by evaluating THC and CBD as either isolates and whole plant extracts in a murine pain and inflammation model. Israel is still leading the world when it comes to good basic science into cannabinoid pharmacology in all of its interesting complexity. The US should consider changing laws and encouraging similar research into cannabinoid pharmacology or else it could lose its position as a world leader in the next half-century of medicine.