Whole Plant vs. Isolate, Cannabis vs. Cannabinoid

By Stacey Marie Kerr MD, Hawaiian Ethos Medical Advisor

What works?

Recently I consulted a patient with hyperemesis gravidarum, a severe form of morning sickness that occurs for some pregnant women. Wanting the purest form of medicine possible and being cautious with her pregnancy, she had tried a purified THC:CBD 1:1 ratio medicine.

Surprisingly, it gave her no relief. When given whole plant medicine, she had immediate results with a smaller dose and was able to eat normally. An N-of-1 observation that begs the question: Which is better medicine?

Sophisticated meds

Whole plant or isolates? Whole plant medicine includes juicing leaves, utilizing tinctures, oils, extracts, and other products that are made from whole plant material rather than chemically separated constituents.  To use the whole plant and all it has to offer, or to isolate the known active ingredients and package them as medicine? 

This is becoming a valid question as the medical cannabis industry grows. As we learn more about which cannabinoids may help with specific medical conditions, the interest in creating calibrated medicine has surged. Well-funded labs are isolating cannabinoids, then mixing them back together in exact ratios for patient delivery. Need some terpenes? Buy those in bulk – limonene from lemons, linalool from lavender – and add them back in with care and specificity.

“Artisanal medicine” – created for each patient, each medical condition. It has a nice ring. Medicine customized for the patient, removed from the reefer that caused madness, clean and quality controlled. A far cry from smoking a joint!

From herb to pill, then back again?

The question we ask as clinicians is whether isolates work as well as whole plant medicine. Certainly, isolated THC in Marinol (dronabinol) did not work as well; many patients reverted to smoking their favorite herb for better relief than the legal capsule provided.

But that was several years ago and we have improved our isolation techniques and knowledge base since then.  We can now add in other constituents that we have learned are essential. Add some CBD to the THC to make it easier to tolerate and more effective. Include some terpenes to enhance the needed effects. Create designer cannabis-derived medicine.

Ethan Russo, in his 2011 well-referenced and oft-quoted article “Taming THC” [1] states the following: 

“...synergism may play a role in the widely held (but not experimentally based) view that in some cases plants are better drugs than the natural products isolated from them. Support derives from studies in which cannabis extracts demonstrated effects two to four times greater than THC (Carlini et al., 1974); unidentified THC antagonists and synergists were claimed (Fairbairn and Pickens, 1981), anticonvulsant activity was observed beyond the cannabinoid fraction (Wilkinson et al., 2003), and extracts of THC and CBD modulated effects in hippocampal neurons distinctly from pure compounds (Ryan et al., 2006). Older literature also presented refutations: no observed differences were noted by humans ingesting or smoking pure THC versus herbal cannabis. (Wachtel et al., 2002)”  

This last reference to ‘older literature’ refuting the entourage effect simply points out the need for research that clearly addresses the issue.

CBD

Epidiolex, a CBD investigational isolate produced by GW Pharmaceuticals, seems to work well in trials on seizure disorders. However, many patients already using whole-plant cannabis oil are resistant to change and say they would not switch to the isolate when and if it becomes available in the US. They do not want to change from something that is working well to a product than may or may not be effective for their needs.

A 2015 article published in the journal Pharmacology and Pharmacy [2] looked at the bell-shaped dose response seen in purified CBD extracts. The abstract states:

“In stark contrast to purified CBD, the clone 202 extract (standardized plant extracts derived from Cannabis sativa), when given either intraperitoneally or orally, provided a clear correlation between the anti‐inflammatory and anti‐nociceptive responses. The dose, with increasing responses upon increasing doses, makes this plant medicine ideal for clinical uses. It is likely that other components in the extract synergize with CBD to achieve the desired anti‐inflammatory action that may contribute to overcoming the bell‐shaped dose‐response of purified CBD. We therefore propose that Cannabis clone 202 extract is superior over CBD for the treatment of inflammatory conditions.”

cultural bias, and the intelligence of nature

We still do not know all the medicinal ingredients or qualities of the cannabis plant. Essential synergy and small-but-powerful chemicals yet unidentified may significantly affect therapeutic qualities.

Meanwhile, a cultural bias exists. Long-time cannabis users are generally faithful to whole plant medicine, while patients previously naïve to cannabis may prefer isolates in more traditional medication formulations such as capsules and tinctures.

What we need are controlled studies that compare the two philosophies of producing medicine from the cannabis plant. We may find that some conditions do respond to whole-plant medicine more effectively than isolates while others may be treated well with purified forms of cannabinoids. Again, patient response may vary from one formulation to another, creating even more variables to take into account.