Journal of the California Cannabis Research Medical
Listening to Marinol:
Rational Guidelines for Dosing
By Gregory T. Carter, MD; Patrick Weydt, MD;
Muraco Kyashna-Tocha, PhD; and Donald I. Abrams, MD
DRONABINOL is synthetic
THC in sesame-oil capsules. It was marketed as Marinol by
Roxane Laboratories in 1987. By comparing rates at which
THC from drobabinol and smoked natural cannabis are absorbed
into the bloodstream, the authors calculated equivalent doses.
The FDA originally approved Marinol as a treatment for nausea
and subsequently approved it as an appetite stimulant. After
years on Schedule II it was moved to Schedule III by the
DEA in 1999.
Typically, cannabis is smoked as a cigarette weighing between 0.5 and 1.0 g.
After combustion and inhalation, peak venous blood levels of 75 to 150 nanograms
per milliliter of plasma appear about the time smoking is finished.
The main advantage of smoking is rapid onset of effect and easy dose titration.
When cannabis is smoked, cannabinoids in the form of an aerosol in the inhaled
smoke are absorbed and delivered to the brain rapidly as would be expected of
a highly lipid-soluble drug.
A person’s smoking behavior during an experiment
is difficult for a researcher to control and smoking behavior is not
easily standardized, although
protocols for standardization of smoking have been developed. An experienced
cannabis smoker can titrate and regulate dose to obtain the desired acute
effects and to minimize undesired effects.
Each puff delivers a discrete dose of cannabinoids to the body. Puff and inhalation
volume changes with phase of smoking, tending to be highest at the beginning
and lowest at the end of smoking a cigarette.
Heavy users could absorb as much as 27% of available THC, which may
be twice as much as an infrequent user may absorb.
Some studies found frequent users to have higher puff volumes than
did less frequent cannabis users. Heavy users could absorb as much
as 27% of available THC, which may be twice as much as an infrequent
user may absorb.
During smoking, as the cigarette length shortens, the concentration
of THC in the remaining cannabis increases. Thus, each successive puff
contains an increasing concentration of THC. However, up to 40% of
the available THC may be completely combusted in the process of smoking
and not be biologically available.
Post smoking assay of cannabinoids in blood or urine can partially
quantify dose actually absorbed after smoking, but the analytic procedures
are methodologically demanding.
The only form of cannabinoid that is available by a formal, dose specific,
prescription is dronabinol. There are too many variables in the published
clinical trials and case series with raw cannabis to use those studies
as a basis for deriving dosages. Thus we will use the dronabinol prescription
guidelines as published by the manufacturer and accepted by United
States Food and Drug Administration (FDA) as the basis for formulating
our dosing recommendations for natural cannabis.
It is critical to note that dronabinol is an oral preparation and contains
only THC. Most medicinal cannabis patients use smoking as the route
of delivery. As noted, there are significant differences in pharmacokinetics
between oral consumption and smoking. There are varying physiological
effects when other cannabiods are present, as is the case with cannabis
It is also not clear how the original dosing construct for dronabinol
was arrived at, although we assume it was done through clinical testing
for therapeutic benefit versus side effects. Despite these inherent
limitations, these calculations do provide approximate dose equivalents
by weight and are useful as long as one recognizes these limitations.
By directly applying these figures to the recommended dronabinol dosing
model of 30-90 mg per day, we arrive at the dosages shown in table
2 (assuming negligible amounts of cannabidiol present in the cannabis)
Our derived figures lie very closely within the range of reported amounts.
In informal surveys from patients in Washington and California, the
average reported consumption of cannabis by medicinal users typically
ranges between 10 - 20 g per week, or approximately 1.42 to 2.86g per
If the mean strength of the medical cannabis is 19% THC (negligible
CBD), and the average strength is 15% THC as reported by Geiringer,
then the amount of cannabis needed to absorb a 30mg THC dose is .88-1.23g,
and the amount needed for 90mg of THC is 2.65-3.69g. of cannabis. These
figures all share a strikingly similar range.
Our recommended dosages are reinforced by two of the only studies that
utilized smoked cannabis in a dosing regime (Chang, 1975, and Vinciguerra,
1988). These dosages are also within the medical cannabis guidelines
allowed in the Canadian medical system. (The Canadian medical allowance
is for 1-12 g a day with less than 5 g being the mean.)
Thus, despite all of the noted variables, there is remarkable consistency
among the derived and reported doses noted here. The biggest limitations
of our dosing model is that it is based on THC concentrations, despite
growing evidence that THC may not even be the most clinically useful
cannabinoid. However, given the current state of the known, published
pharmacology of cannabis, this is the best dosing model that can be
An issue that warrants discussion is physiological tolerance, which
plays a role in dosing cannabis. With regard to treating chronic,
intractable pain, physicians will often prescribe increasingly larger
doses of long-acting opioids as patients develop tolerance. These
patients are also generally given prescriptions of fast-onset, short-acting
opioids for “breakthrough pain.” This is accepted practice,
despite the fact that opioids, even in an opioid-dependent patient,
still have the capacity to suppress breathing to the extent of inducing
Long-term cannabis users can develop tolerance but there is essentially
no risk for overdose. Thus, it is conceivable that a long-term cannabis
user may require significantly larger amounts of cannabis to achieve
a therapeutic effect. In addition, those who use cannabis by ingestion
may also require significantly higher amounts. Until more refined and
purified cannabinoid preparations are available, it will not be possible
to derive a more specific or exact dosing schedule. It is therefore
critical that legal authorities consult with medical experts before
arriving at any conclusions at to the appropriateness of the amount
We have outlined reasonable guidelines for dosing of medical cannabis,
based on the known pharmacology. However, because of the complexities
of the cannabis plant, the chemistry of the various forms of cannabinoids,
patient tolerance, differing routes of intake and delivery systems,
there are inherent limitations to these guidelines.
Recognizing this, we recommend that an individual, patient-controlled,
self-titration dosing model be used. The guidelines we have described
provide a dosing construct for patients and physicians to do this.
These guidelines also provide legal authorities some reference points
as to what would be considered a reasonable amount of cannabis to use
for medicinal purposes.
Gregory Carter is with the Department of Rehabilitation Medicine and
Patrick Weydt with Department of Neurology at the University of Washington
School of Medicine in Seattle. Muraco Kyashna-Tocha is with the Cyber
Anthropology Institute, Seattle. Donald I. Abrams is with the Division
of Hematology/Oncology, Department of Medicine, San Francisco General
This paper, excerpted from CannabisMD.org, was supported by a grant
from the National Institute on Disability and Rehabilitation Research,
Washington, D.C., USA. It can be read in its entirety, with ample footnotes,