Medical Cannabis: Whole Plant vs. Pharma/Isolates

There are three different forms of medical cannabis currently available in select regions:

• Pharmaceutical cannabis products: Plant-derived or synthetic isolates that have passed through clinical trials and received FDA-approval.

• Cannabis isolates: Cannabis-derived isolates that have not been FDA-approved.

• Whole plant cannabis extracts: Cannabis-derived extracts that contain a variety of compounds from the plant.

Some people object to the use of medical cannabis altogether because they believe it’s dangerous and/or more research needs to be done to better understand its effects on the body.

Some approve of pharmaceutical forms of cannabis because these have passed through FDA scrutiny. At the same time, however, many advocates of pharma forms of cannabis do not approve of (either non-FDA approved isolates or) whole plant forms of cannabis, because they believe they’re too risky.

Still others not only approve of whole plant cannabis, but they advocate its use over pharma/isolate forms of cannabis, claiming whole plant cannabis is actually less risky than cannabis isolates (whether or not they’re FDA-approved).

So who’s right? Is medical cannabis risky? Is whole plant cannabis more or less risky than pharma/isolates? This analysis addresses these questions.

Reframing the Question

Is medical cannabis risky?

Few actions in life contain no risk. Yes, medical cannabis is risky. In fact, all medications are generally risky. If nonzero risk was the criterion for whether or not we should use a particular medication, then the answer would generally be no, we should not take that medication, because it’s risky.

However, that’s not the question we should be asking. The appropriate question is actually twofold. First, do the benefits of medical cannabis outweigh the costs? And second, what are the alternatives to medical cannabis? That is, is cannabis risky, as compared with what?

As an aside, many doctors and scientist believe cannabis is too risky to advocate its use for medical patients. To these doctors and scientists, I would ask, “what alternatives do patients face?” I expect that in 10 years, scientists will have achieved a much better understanding of how cannabis works in our bodies, and technologists will have created much safer and more effective means of using medical cannabis. However, that doesn’t help current patients who are faced with medical problems they want to treat right now. For these patients, doctors and scientists (not to mention the patients themselves) must consider the alternatives to medical cannabis that are currently available to help treat these patients’ healthcare problems.

Each option, whole plant and isolate, offers a very different bundle of benefits and costs. Since patients vary in their individual circumstances, it would make sense to discover that some people will find whole plant cannabis offers a more favorable overall experience, while others will find the experience associated with pharmaceutical cannabis preferable. Let’s see how different aspects of the whole plant and pharma/isolate forms of cannabis compare with each other.

Factors to Consider

1. Consistency in Formulations

Do profiles of active ingredients vary from one sample of cannabis to the next?

Whole Plant: Profiles of whole plant cannabis flower or extract are generally not identical from sample to sample, due to natural variation in plant makeups.

Isolates/Pharma: Profiles of isolates or pharma products do not vary from sample to sample. Processes ensure each dose is identical to the next.

Advocates of isolates insist that consistency from dose to dose is crucial for medical users. Whole plant advocates argue that benefits achieved from interactions of different compounds in the cannabis plant (i.e., the entourage effect) outweigh the disadvantages of dose-to-dose variations in formulations.

As an aside, pharmaceutical regulations allow some small batch-to-batch variations in quantities of active ingredients (“acceptable levels of variance”[1]). I have been unable to find the exact variances allowed. This begs the question: Are acceptable levels of variance in pharma products actually that much smaller than plant-to-plant variations in whole plant products?

2. Consistency in Dosing

Do the quantities of active ingredients vary from one cannabis dose to the next?

Whole Plant:

Traditional methods for smoking and vaping cannabis provide inconsistent doses from one inhalation to the next, due to such differences as: the amount of side stream smoke/vapor generated, the extent to which cannabis compounds are burned in process, the duration of draws, and the depth at which vapor is held in the lungs. Newer metering technologies in smoking and vaping devices claim to improve the consistency of dosing. However, metering technologies presumably cannot address dose-to-dose variations in depth and duration of inhalation.

Tinctures and capsules provide consistent means of dosing cannabis extracts.

Doses of cannabis edibles may vary to the extent that (i) edibles are not homogenized during the manufacturing process, and (ii) users consume less than an entire edible (say, half a cookie).

Isolates/Pharma: Doses of pharma products do not vary from sample to sample.

3. Guidance

Are patients provided guidance in their use of medical cannabis, regarding, for example, which formulations to use, how much to take, and risks of drug interactions?

Isolates/Whole Plant: Medical users of whole plant cannabis run the gamut from using cannabis on their own without any guidance from healthcare providers, to having budtenders (with whatever knowledge of medical cannabis they may have) recommend cannabis products, to using cannabis under the strict guidance of knowledgeable cannabis providers. My sense is that the majority of medical cannabis users do not have the guidance they would like.

Pharma: Pharma cannabis products are prescribed by healthcare providers. Presumably, healthcare prescribers of cannabis use information provided by the FDA to guide patients in their cannabis use.

4. Accessibility

Are patients likely to find their same cannabis product formulation on the dispensary shelf when they refill their medication?

Isolates/Whole Plant: The extent to which consumers are able to find particular cannabis products on store shelves is jointly determined by several factors, such as:

• The availability of cannabis products from growers: Consumers may have a hard time finding products provided by small growers who don’t have the capacity to supply large quantities of products.

• The variability of growing methods employed: Consumers may have a hard time finding products that are consistent from one batch to the next if many different growers or manufacturers use different cultivation or processing methods to supply the “same” product.

• A product’s popularity with consumers: Consumers may have a hard time finding products for which consumer demand is low. In these cases, dispensaries may find it more profitable to devote scarce shelf space to more profitable products.

• The availability of a dispensary’s shelf space: Consumers may have a hard time finding products in dispensaries with less shelf space, which can’t supply the variety of products found in larger dispensaries.

Pharma: Pharma products are standardized, so one package is the same as the next. Pharma cannabis products can generally be found in pharmacies.

5. Efficacy

How well do formulations treat the conditions for which patients use medical cannabis?

Whole plant medicine is based on the idea that many different elements of a medicinal plant work together in our bodies to create beneficial outcomes. That is, the interactions of different compounds create an entourage effect or synergy, where joint outcomes generated by the plant as a whole are better than outcomes achieved using isolated ingredients from the plant. Studies show that various compounds in cannabis combine to achieve pharmacokinetic and pharmacodynamic benefits for users, and researchers have found that users of whole plant cannabis achieve better outcomes with fewer negative effects, and at lower doses than users of cannabis isolates (for more detailed information see Understanding Cannabis’s Entourage Effects).

6. Variety of Forms and Formulations

Are there a variety of forms available for the patient to choose from?

Whole Plant: Whole plant cannabis comes in a large variety of forms: flower, oil, capsules or tablets, tinctures, topicals, or edibles. Cannabis can be smoked; inhaled; absorbed through nasal, buccal, or mucus membranes; absorbed through the skin; taken orally; or taken as suppositories.

Isolates/Pharma: Pharma products come in natural (plant-derived) and synthetic forms, either in oral solutions, oromucosal sprays, or capsules/tablets.

Are there a variety of formulations available for the patient to choose from?

Whole Plant: Whole plant cannabis comes in a virtually unlimited number of different combinations of cannabinoids and terpenes.

Isolates/Pharma: Pharma products come in a limited number of formulations: THC, CBD, or fixed ratios of CBD to THC.

7. Therapeutic Window

How wide is the therapeutic window for an individual’s cannabis medication?

Wikipedia defines therapeutic window[2] as follows:

The therapeutic window (or pharmaceutical window) of a drug is the range of drug dosages which can treat disease effectively without having toxic effects. Medication with a small therapeutic window must be administered with care and control, frequently measuring blood concentration of the drug, to avoid harm.

A study by the Lautenberg Center for Immunology and Cancer Research[3] examined the effectiveness of CBD isolate compared to full-plant extract. The study found that purified CBD had a narrow range in dosing for which patients could achieve benefits from CBD. Whole plant extract CBD, on the other hand, achieved a dose-dependent response, that is, effects increased with dosage. The authors of the study concluded, “Thus the limitation with purified CBD could be overcome when presented together with other natural components of the plant.” The authors also indicated that other studies generated similar outcomes.

8. Side Effects

Are patients likely to experience unwanted side effects from their cannabis medications?

Studies show that whole plant cannabis extracts generate fewer negative side effects than do cannabis isolates. For example,[4]

CBD decreased psychotic symptoms, post-THC paranoia, and memory impairments compared to THC alone

CBD … attenuated effects of …THC including tachycardia, disturbed time tasks, and strong psychological reactions.

CBD changed THC symptoms in such a way that the subjects receiving the mixtures showed less anxiety and panic but reported more pleasurable effects.

9. Price of Product

What is the price of cannabis medication?

Prices for pharmaceutical and whole plant cannabis are provided in Figure 1.

Figure 1

As is typical with most pharmaceuticals, prices tend to be high. Yet, some healthcare insurance plans reimburse patients for the costs of cannabis pharmaceuticals. Cannabis flower is moderately priced, while whole plant extracts run the gamut from low-priced to expensive.

10. Price of MD/Card

What is the price of a medical card and healthcare provider office visit?

Whole Plant: Patients who use whole plant extracts must see a healthcare provider to obtain a note enabling the patient to receive a medical card from the state. The price of an office visit varies with patients’ healthcare insurance plans. If not covered by insurance, medical marijuana consultations reportedly range from $80 - $200. The price of a state medical card varies from $25 - $200, which must be renewed regularly as per state regulations, generally annually or bi-annually.[5]

Pharma: Patients who use pharmaceuticals must see a doctor to obtain a prescription. The price of an office visit varies with patients’ healthcare insurance plans.

Conclusions

Figure 2 presents a summary of these points of comparison between whole plant and pharma forms of medical cannabis. The summary figure makes it clear that the decision is not a case of one-size-fits-all. Rather, whether a patient prefers whole plant cannabis or pharma cannabis depends on that patient’s overall situation. Specifically, patients for whom consistency in formulations and dosing, guidance in use, and accessibility to particular products are more important than efficacy, variety, size of therapeutic window, or side effects will probably do better with pharma or isolate forms of cannabis. Those patients for whom the reverse is true will probably do better with whole plant form of cannabis.

Figure 2

References

[1] FDA’s Policy on Declaring Small Amounts of Nutrients and Dietary Ingredients on Nutrition Labels: Guidance for Industry (2016, Jul). U.S. Department of Health and Human Services, Food and Drug Administration. Retrieved from https://www.fda.gov/media/98834/download

[2] Wikipedia contributors. (2020, June27). Therapeutic index. Wikipedia, The Free Encyclopedia. Retrieved from https://en.wikipedia.org/w/index.php?title=Therapeutic_index&oldid=964710062

[3] Gallily, R.; Yekhtin, Z.; and Hanuš, L. (2015, Feb 10). Overcoming the Bell‐Shaped Dose‐Response of Cannabidiol by Using Cannabis Extract Enriched in Cannabidiol. Pharmacology & Pharmacy. Retrieved from https://file.scirp.org/pdf/PP_2015021016351567.pdf

[4] Black, E.; Hocum, B.; Black, K. (2018, Jan 1). Ethics and Science, Cannabinoids and Healthcare. Primary Care Reports. Retrieved from https://www.reliasmedia.com/articles/141970-ethics-and-science-cannabinoids-and-healthcare

[5] Medical Marijuana Card Cost. CostHelper. Retrieved from https://health.costhelper.com/medical-marijuana-cards.html