Dosing Cannabis as Medicine

 

By Stacey Marie Kerr, MD


what does the science say?

There is no scientifically defined dose of cannabis for any medical condition, as individual patients and their responses to medical cannabis are unique for most health conditions. Medicinal cannabis is unique because dosing is patient-centered, self-titrated, and takes time for patients to find the right dose where therapeutic effects are maximized while adverse effects minimized.


the perfect dose for me, the perfect dose for you?

The perfect dose of cannabis to manage nausea for one patient may make the next patient paranoid and uncomfortable, and may not make a dent in the chronic pain of yet another individual. Because patients use cannabis for different conditions and respond to it uniquely, there is no standard dose that guarantees effective treatment or a manageable level of intoxication for all.


what are we dosing, anyway?

There are several phytocannabinoids in each strain of cannabis plants, all containing varying amounts depending on plant genetics and growing conditions. Tetrahydrocannabinol (THC), cannabidiol (CBD), tetrahydrocannabivarin (THCV), and cannabigerol (CBG) are all medically active and occur in varying amounts in each ‘strain’ of cannabis. Terpenes, the chemicals in cannabis that are responsible for aroma, are also active compounds that have significant medical value. The interaction of all these components in the cannabis plant is more effective than any component taken alone. This is called the ‘entourage effect’ – a phenomena that makes cannabis more complex than other medications.


start low, go slow

To mitigate the occurrence and strength of undesired side effects, patients are encouraged to start with a very low dose, slowly increase the dose, and stop increasing intake when effective relief or undesired effects occur. This is especially true for patients who are inexperienced using cannabis, though it is also true for experienced patients trying a new product or formulation. Therefore, the mantra for starting medical cannabis is “Start Low, Go Slow.”


standard dose, overdose?

Self-titration of cannabis dosing is safe, considering the low toxicity of cannabis. This recommendation is not unique to cannabis, as there are other drugs with low toxicity and high dosing limits, gabapentin being a well-known example, titrated to best effects with tolerable side effects. Patients are also familiar with titrating non-prescription medicines like aspirin, acetaminophen, and caffeine.

Still, we try to define a standard dose of medicinal cannabis. In Colorado and Washington State, 10 mg of THC has become the official “standard dose.” The amount of THC is regulated, but what is the effective THC dose for individual patients? How do we accommodate individual differences, minimize adverse effects and maximize therapeutic benefits? In addition, the effect of cannabinoids taken in combination is often different than the effects of the same dose of cannabinoids in isolation. A common example is CBD mitigating the intoxicating effect of THC.


Problems with Strain Names

Strain names are not only of little use in medical cannabis, but may be cause for concern. A patient may purchase “Sour Diesel” expecting it to be the same everywhere, only to find different purchases do not have identical results. This can be due to erroneous labeling, to shifting plant constituents from one crop to the next, or even time of harvest. 

Because patients cannot depend on strain names for consistent therapeutic effects they must rely on accurate lab testing for cannabinoids and terpenes. With more reliable lab analysis (product testing and quality assurance) and ongoing patient data and feedback, we can provide better guidance regarding effective cannabis chemotypes for specific needs.


Problems with Current Available Research

Although medical cannabis research has been growing and accelerating in recent years, there remains a gap between the medical cannabis tested in clinical studies and the cannabis that patients are actually using. Many factors affect outcome. Differences in cannabinoid source, the amount and quantity of phytocannabinoids and terpenes in each dose, the perceived “potency,” dosing and delivery methods (smoking, vaporing, sublingual, enteric, and transdermal) all affect outcome – not to mention co-use of prescription and other non-prescription medications.

Lab analysis is not yet as reliable as we would expect. The equipment for full and accurate testing is expensive and not all labs have adequate facilities. Tiny samples from different parts of the plant, the method of sample preparation, mathematical errors, and calibrated testing equipment all affect the final results.  The same medicine can be submitted to several different labs and different analyses will result. Which can be trusted? Lab standards must be developed -  samples of each chemical constituent with a precisely known composition, which can then be used to calibrate laboratory instruments and validate test protocols. These and quality control guidelines must be put in place before we can completely trust labs’ test results.

Clinical trials use synthetic or purified phytocannabinoid compounds, derivatives from undescribed cannabis strains, or plant material with incomplete chemotype descriptions. This  confounds the literature as does anecdotal evidence from patients using dispensary and home-grown botanical medicine.

Both anecdotal and referenced evidence describes purified phytocannabinoid medication as less effective than botanical extracts. How do we begin to reconcile these seemingly disparate results? Or are they disparate? Should we acknowledge we are working with a botanical with many active compounds synergizing positively and perhaps, at times, negatively?

While the studies are providing valuable information about the validity of cannabis as medicine, many of them may not be providing information that directly applies to patients. To further complicate matters, much of the anecdotal evidence come from patients who do get their medicine at dispensaries, where there are natural variations in batches and strains as well as unreliable availability. This puts the responsibility on dispensaries to provide patients with consistent medicine backed by accurate lab analyses. Responsibility then shifts to the patient to provide accurate feedback to the dispensary on varieties, amounts, and methods of administration for each medical problem being treated.


clinical studies

  • All federally approved studies done in the U.S. with dried flowers come from one federally approved cultivation site. These flowers test between 1-8% THC.
  • Many clinical studies use FDA-approved single compound, synthetic THC drugs such as dronabinol (Marinol) and nabilone (Cesamet). Sativex is one exception as it is plant-derived and contains CBD as well as THC, however it is yet to be approved for use in the U.S.
  • Clinical studies that use dried flowers generally have patients smoke joints, tracking how many “puffs” a patient takes. These joints can range from 30-140 mg of THC, but patients are often not required to smoke the entire joint. 

  • A common dose for synthetic THC in studies is 2-5 mg. 

market anecdotal evidence

  • The average dried flowers available in dispensaries today test at 18% THC and are grown locally throughout the country in varying indoor and outdoor conditions.
  • These drugs are pharmaceuticals and are not available at medical cannabis dispensaries. Patients who get their medicine at dispensaries are using whole plant medicine—extracts that are made from the whole cannabis plant and that therefore have a more complex cannabinoid profile.

  • Patients are being discouraged from smoking, however for those patients who choose to smoke there are many more options including vaporizing, pipes, joints, and dabs (smoking extracts) for which there is little research on actual cannabinoid delivery.

  • Most cannabis products have a minimum dose of 5 mg THC, however products that include other cannabinoids (mainly CBD) may be better tolerated than pure THC.

 

* This data focuses on THC (tetrahydrocannabinol) and do not consider other phytocannabinoids, such as cannabidiol (CBD). CBD doses are best documented in treating epilepsy, with doses ranging from 2 to 11 mg CBD per pound of body weight. This means the dose for a 150 pound man would range between 300 mg to 1650 mg, which contrasts with a “standard” 10 mg THC dose.


Dosing and Delivery Method

Dosing is directly related to delivery method, to chemotype and concentration, and to potency. For example, the potency of one gram of a concentrate differs drastically from the potency of one gram of dried flower.


Smoking

Smoking has been the most common form of delivery for many years. Absorption through the lungs is effective and rapid. Studies done on smoked THC have reported the bioavailability from 2-56%, a wide range due to patients’ variability in smoking behaviors. Up to 40% of the available THC may be lost by combustion in the process of smoking and through side-stream smoke(smoke that passes into the air rather than into the smoker’s lungs), and therefore not biologically available. While each inhalation delivers a discrete dose of cannabinoids to the body, the inhalation volume changes with time and experience. Heavy users could absorb as much as 27% of available THC, maybe twice as much as infrequent users.

The effects from smoking are felt rapidly, within minutes of inhalation. Blood levels fall quickly, and an hour later they are at 5-10% of peak levels. This is not due to metabolism, but to redistribution to other body tissues.  With 40% of active ingredients lost in combustion, and a maximum of 27% of the remaining active ingredients actually absorbed, the maximum THC absorbed by a patient using 2 grams of cannabis containing 10% THC would be 16.3 mg (higher than a 10 mg “standard” dose). (Carter GT, Weydt P, Kyashna-Tocha M, Abrams DI. Medical marijuana: rational guidelines for dosing. IDrugs. 2004;7:464–470.)

Vaporizing loses less through combustion and side stream smoke, so more of the cannabinoids and terpenes are available to the patient. Vaporizing herbal medicine, while not allowed under Hawaii’s medical cannabis regulations, is a better method of inhaling cannabis that provides rapid relief with short acting effects, is easier to titrate, and less likely to cause airway inflammation.


Edibles

Hawaii does not allow the sale of edibles. This raises the question: Is 10 mg of THC in an edible form the same dose as 10 mg of THC in an oil extract? In dried flowers? In a sublingual tincture? In a swallowed pill, capsule, or tablet? Probably not. However, ingesting cannabis has become increasingly popular among patients who can make their own edibles.

The onset of action and titration of dosing is more difficult with orally ingested medicine (edibles) since the effects take longer to be experienced and longer to dissipate. This mode of delivery is quite variable, with physiologic factors such as different absorption rates, different rates of metabolism, and different rates of excretion all affecting blood levels. Edible ingredients also affect absorption. Maximum THC and other cannabinoid levels are reached 1-6 hours after an oral dose, and the half-life (the time it takes for half the substance to be cleared) is 20-30 hours. Furthermore, THC is metabolized in the liver to 11-hydroxy-THC which has potent intoxicating effects. While this increases the risk for unpleasant side effects, the oral route could be beneficial to the patient requiring long-acting medicine for chronic needs. First pass THC metabolism through the liver changes its medicinal qualities, and therefore dosing requirements.


Topicals

Topical (transdermal) use of cannabis is another route that may be beneficial to patients. This delivery route bypasses the liver and hence first-pass metabolism. Cannabinoids applied topically are slow to reach the brain, so intoxicating side effects are not significant. Applying a transdermal patch a few hours before chemotherapy and wearing it for a few days could be an effective way to treat the side effects of chemotherapy.


Tinctures

Tinctures and whole plant extracts made for sublingual delivery are placed under the tongue to be absorbed directly into the bloodstream. This is an effective method of dosing if the medicine is in a titratable liquid form, and the clinical effects are rapid-acting.  However, there remain patient variables. Sucking on a lollipop or lozenge is a new favorite, easy-to-titrate method of sublingual/oromucosal dosing, but if the lollipop is chewed instead of simply allowed to dissolve, the dosing will change from direct absorption to gastrointestinal (enteric) ingestion.


Product Benefit Delivery Method Beginning Dose Suggestion
Capsule Long acting Oral/Ingestion 5 mg THC
Lozenge Titratable Sublingual or Enteric 5 mg THC
Tincture Titratable, Ease of use Sublingual or Topical Sublingual: 5 mg THC, Topical: Refer to packaging
Skin Cream /Ointment Limited Side Effects Topical Refer to packaging
Inhaler Rapid Response Inhalation 1 inhalation, 2 mg THC
Oil Extract Concentrated Oral/Ingestion or Topical Oral/Ingestion: 5 mg THC, Topical: Refer to packaging
Transdermal Patch Long Acting Topical 1 patch
Dried Flower Rapid Response Inhalation (Smoked or Vaporized) 1 inhalation

The Significance of THC and THCA

THC is the most abundant cannabinoid, currently considered the most active intoxicating compound producing medical benefits. While the lethal dose for THC is beyond what anyone could feasibly consume in one sitting, regulation makes it possible for patients to control and track of how much THC they are consuming.

In considering dosing and packaging guidelines, it is important to consider THCA, which occurs in greater abundance in raw cannabis material than THC. THCA turns into intoxicating THC by drying and heating. Dried flowers typically contain anywhere from 10-30% THC. This percentage, however, is somewhat misleading, as dried flowers usually have more THCA than THC. THCA turns into THC when heated, so flowers that have low THC but high THCA content will be quite potent when vaporized, smoked, or used for cooking. These three methods represent the most common uses for dried flowers, suggesting clarity about THC and THCA is a real concern. Currently Hawaii regulations call for labeling of THC and “total THC and activated THCA” content. Is ‘activated THCA’ the same as THC or is ‘activated THCA’ simply THCA capable of being decarboxylated to become THC?  Dosing and packaging restrictions are only for THC. THCA is an active compound in and of itself with medicinal benefits.

Depending on the cannabinoid profile and the method of delivery, a patient may well be receiving a different dose of THC than what is on the package label. The motivation to regulate THC content is sound, but determining how much THC a patient receives is a complex process that we still do not fully understand. Individual patient characteristics, methods of administration, and different varieties of cannabis all confuse the one-dose-fits-all expectation when attempting to regulate cannabis as medicine. What IS a 10mg dose of THC? Does it make sense to identify a ‘standard dose’ of cannabis medicine? This question needs to be answered.