Request for Information: Standard Unit Dose of THC

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Input Invited on the Establishment and Implementation of a Standard Unit Dose of Δ-9-tetrahydrocannabinol (THC) for Cannabis Research

Today, NIDA issued a Request for Information (RFI) from the research community and any other interested parties regarding the establishment of a standard unit dose of THC, the main psychoactive compound in cannabis, in order to facilitate research on cannabis.

Image of marijuana being added to a test tube with tweezers
©iStock/ Moussa81

As States legalize medical and adult-use marijuana and dispensaries create greater access to cannabis, there is increased urgency to study its effects—both adverse and potentially therapeutic—in a systematic fashion. This is especially needed with the widening variety of cannabis products, such as edibles and extracts, as well as the increasing potency of cannabis available on the street and in dispensaries. One hindrance to conducting such research is the lack of a standardized measure of the THC in various cannabis products, making it hard to compare the results of different studies.

In 2017, the National Advisory Council on Drug Abuse established a Cannabis Policy Research Workgroup, which released a report in 2018 that included a recommendation that NIDA “explore the possibility of constructing a standardized dose similar to that for alcohol (the standard drink), tobacco (a cigarette), or opioids (morphine milligram equivalents) for researchers to employ in analyzing use and for users to understand their consumption.” As it now stands, measures of “joints” or “joint years,” sometimes used in research studies are not meaningful, given the wide variability in size and potency in cannabis plant material from different sources, and the current lack of standardization makes much of the experimental data on cannabis use and effects hard to interpret.

We recognize that the cannabis plant contains multiple cannabinoids and other components that may influence its overall effect, and that other factors, including route of administration, are also important. Still, THC is the major contributor to the psychoactive effects of cannabis and thus a good proxy for a standardized unit dose.  Some states have instituted standard serving sizes for edible cannabis products, based on the amount of THC contained in them; however, these are not consistent in all states. 

If a standard unit dose can be established, for it to be maximally useful for research and public health, the research community will need to incorporate it in their measures of use, industry will need to adopt it for labeling, and consumers will need to be educated about what the standard dose means. Indeed, establishment of such a standard would have the greatest impact if universally adopted for commercial product labeling, allowing for more direct comparison across products and a reliable metric by which consumers can understand and accurately report their use. This may influence the way consumers think about cannabis, giving them a reliable unit to track intake—the same way people monitoring their alcohol use may count the number of drinks they have consumed on a given evening.

A standard dose is in some ways arbitrary, especially for this drug, given the shifting potency of cannabis plants, the wide variability in products, and the ways individuals use them. Designating a standard unit dose simply sets an easy-to-follow standard. Designing experiments around a standard amount of THC in whatever form it is administered or consumed (as well as increments or multiples of that amount) will greatly facilitate gathering rigorous data and comparing data across studies. It would improve our ability to assess outcomes in relation to exposure—for instance, effects on brain development in longitudinal studies like the Adolescent Brain Cognitive Development study. This could, in turn, help inform prevention strategies and policies. It would also facilitate comparing the effects of different products and different modes of ingestion in different users.

Last October in Addiction, Tom P. Freeman and Valentina Lorenzetti proposed a dose of 5 milligrams THC as optimal for research purposes. This is a dose that generally produces noticeable psychotropic effects (the high) in both naïve and experienced users, but it is low enough that it seldom produces acute adverse reactions. In a commentary last month, my NIDA colleague Susan Weiss and I concurred with those authors and their reasoning at arriving at a 5 milligram dose. But the decision about a standard unit dose should not be made unilaterally, which is why we want to hear from the research community, the public, and other stakeholders before recommending that researchers settle on any particular milligram amount for their standard, and before NIDA requires use of such a standard in NIDA-funded cannabis research.

The RFI is open through May 1st, and all researchers, stakeholders, and members of the public are encouraged to weigh in. The specific topics to address include whether 5 milligrams is indeed the best amount of THC for a standard dose; how a standard dose can optimize comparability across studies and comparability between current research and past datasets; how to implement the standard dose across various types of cannabis research, from laboratory and clinical studies to observational and epidemiological studies; and any other topic that contributors feel is relevant.

Get more information on the RFI and how to weigh in on these important questions.