COMMENTARY

Medical Marijuana: The State of the Science

Michael E. Schatman, PhD

Disclosures

February 06, 2015

In This Article

The Dosing Dilemma With CBD

How to dose CBD is a common question among practitioners. Indeed, preclinical and clinical research indicates an extremely wide range of doses that have been used. Although we are far from knowing what doses are ideal, taking into account pharmacogenomic variance among individuals is critical.

Studies often refer to "high-dose" and "low-dose" CBD, although a review of the literature indicates considerable variability in how these are defined. For example, Zhornitsky and Potvin[103] defined "high-dose" oral CBD as 150-600 mg/day.

In addition to set daily doses, weight-based dosing has also been used. Some investigators have extrapolated findings on weight-based doses from animal studies to humans, which is problematic, as demonstrated by the significant variance in bioavailability among rats and mice.[163]

Bioavailability also varies greatly depending on route of administration of CBD. Studies have demonstrated bioavailability of the administered dose of 34%-46% for intranasal administration[164] and 40% for vaporization.[165] In contrast, the bioavailability of oral CBD is thought to be as low as 6%, owing to significant first-pass metabolism.[166]

Whereas the bioavailability of oromucosal nabiximols has been found to be over 90%, with rapid onset of action,[167] the published literature indicates that the bioavailability of oromucosal CBD has not yet been assessed. However, the available data on oromucosal administration of nabiximols have been extrapolated to CBD, with many providers recommending oromucosal administration. Given the absence of evidence supporting oromucosal administration of CBD, there is a clear need for future research to confirm that this is the optimal route of administration.

Cannabinoid medicine is still in its infancy; thus, dosing is not necessarily scientifically based, and confusion is common among healthcare providers. However, unlike marijuana and THC, the risks associated with CBD are extremely low, with not a single case report of CBD overdose in the literature.

Regardless, the dose of CBD should be titrated to effect, emphasizing the adage "start low, go slow." Before the dangers of so-called medical marijuana were understood, experts recommended titrating it to effect.[168] However, as we have learned more about the dangers of the progressively stronger and more toxic marijuana that is marketed as "medical," this recommendation is inappropriate.

Until we begin to see emergency department visits associated with CBD increase (which, in fact, has been empirically associated with "legalized" marijuana[169]), titrating doses to effect is probably the most sound strategy. At present, "CBD products are not produced under the guidance of good manufacturing practices (GMP) and are not subject to regulations governing labeling, purity, and reliability. In other words, currently, there is no guarantee of consistency between products, or even differing lots produced by the same manufacturer."[170]

Some experts recommend that we wait until the US Food and Drug Administration approves CBD and other cannabinoid-based medicines, so that the approved products are subject to standardization and we have better understanding of bioavailability to inform dosing.[171] Numerous others, however, suggest that the safety data of CBD are so compelling (particularly compared with whole-plant cannabis products) that there is probably little harm in considering it for treatment-resistant conditions.

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