Compromised External Validity: Federally Produced Cannabis Does Not Reflect Legal Markets

Authors: Daniela Vergara1 *, L. Cinnamon Bidwell2 , Reggie Gaudino3 , Anthony Torres3 , Gary Du3 , Travis C. Ruthenburg3 †, Kymron deCesare3 , Donald P. Land3 , Kent E. Hutchison4 and Nolan C. Kane1 * Affiliations: 1 University of Colorado Boulder, Department of Ecology and Evolutionary Biology. 2 University of Colorado Boulder, Institute of Cognitive Science. 3 Steep Hill Labs Inc. 1005 Parker Street, Berkeley, CA 94710. 4 University of Colorado Boulder, Department of Psychology and Neuroscience. *Correspondence to: or University of Colorado Boulder 1900 Pleasant Street Boulder, CO 80309 †Current address: SC Laboratories Inc. 4000 Airport Way South, Seattle, WA 98108.


As the most widely used illicit drug, the basis of the fastest growing major industry in the US, and as a source of numerous under-studied psychoactive compounds, understanding the psychological and physiological effects of Cannabis is essential. The National Institute on Drug Abuse (NIDA) is designated as the sole legal producer of Cannabis for use in US research studies. We sought to compare the chemical profiles of Cannabis varieties that are available to consumers in states that have state-legalized use versus what is available to researchers interested in studying the plant and its effects.

Our results demonstrate that the federally produced Cannabis has significantly less variety and lower concentrations of cannabinoids. Current research, which has focused on material that is far less diverse and less potent than that used by the public, limits our understanding of the plant’s chemical, biological, psychological, medical, and pharmacological properties. Investigation is urgently needed on the diverse forms of Cannabis used by the public in state-legal markets.


The United States has witnessed enormous changes concerning public acceptance of marijuana. Use has more than doubled since 2002, across all genders, ethnicities and socioeconomic status

Considering changes on the cultural, political, and legal fronts, research on the effects of Cannabis products that are consumed though legal outlets in states that have legalized is urgently needed. The Cannabis plant is unique in producing a diversity of cannabinoids, a terpenoid chemical compound that interacts with the endocannabinoid system in the brain and nervous system

One of the primary cannabinoids produced, Δ-9-tetrahydrocannabinolic acid (THCA), is converted to the neutral form Δ-9-tetrahydrocannabinol (THC) when heated, e.g. by smoking. THC interacts with the endocannabinoid system producing a wide range of physiological and neurological effects. Studies have found that marijuana’s effects on mood, reward, and cognitive dysfunction appear to follow a dose dependent function based on the THC content

Due to this and other purported psychotropic effects, THCA has been actively selected for by the Cannabis industry and varieties containing more than 30% THCA by weight have been cultivated  In addition to THC, marijuana’s effects are likely related to a number of other compounds including nearly 74 different cannabinoids present at varying ratios across strains. For example, another cannabinoid produced by the plant, is converted to cannabidiol (CBD) when heated. CBD may mitigate the effects of THC and may have other beneficial effects

Demand for high CBDA plants has increased, due to potential therapeutic uses for cancer 19 and  epilepsy.    Other important cannabinoids produced by the plant include cannabigerol (CBG cannabichrome (CBC)  and Δ-9-tetrahydocannabivarin (THCV)

Because research universities across the nation have national grants and must verify compliance with federal law, scientists at these institutions are restricted to research with the only federally legal source of Cannabis. Our current understanding of the effects of marijuana in humans (e.g. on mood, cognition, or pain) has therefore relied exclusively on government-grown marijuana, often administered in a laboratory setting,

Thus, nearly all published US laboratory studies have used Cannabis material obtained from the National Institutes of Health/National Institute on Drug Abuse (NIDA) supply, the only federally legal source for Cannabis plant material. At the same time, dispensary-grade Cannabis available to consumers in state-regulated markets is becoming increasingly potent and diverse. Strains differ substantially in potency and cannabinoid content, and hence, are likely to differ in terms of their effects .

Strains bred for high THCA content are thought to result in greater levels of intoxication as well as differing psychological and physiological effects compared to strains bred for high CBDA content. Accordingly, NIDA has recently developed plant material with varying levels of cannabinoids for research purposes, but the extent to which government cannabis is consistent with cannabis produced in the private market is not clear. To address the critical question of whether the potency and variety of NIDA-provided cannabis reflects products available to consumers through state-regulated markets, we compared the cannabinoid variation and potency from plants from four different cities in the US where peer-reviewed cannabis is legal for medical or recreational reasons (Denver, Oakland, Sacramento, and Seattle; cannabinoid data provided by Steep Hill Labs Inc.) to the cannabinoid content of plants supplied for research purposes by NIDA, using the data publicly available on their website 28.


NIDA differs from all other locations except Seattle in production of CBD (fig. 1A), and differs significantly from all other locations in production of THC. NIDA has the lowest CBD and THC percent with a mean and s.d. of 6.16 ± 2.43%, and 5.15 ± 2.60% respectively.

Sacramento has the highest percent CBD with 12.83 ± 4.73% and Seattle has the highest percent THC with 19.04 ± 4.43%. There are significant differences between the percent of both CBD and THC between US city locations, in addition to differences with NIDA (fig. 1A). CBG production does not differ in any location.

Cannabis plants grown in all locations produce very little CBG, particularly NIDA with only a single sample producing more than 1% CBG (fig. 1B). THC-V is also produced in low quantities in all locations. The only statistically significant difference is between Denver, whose mean and s.d is 1.12 ± 0.13%, and Oakland 2.35 ± 0.68%


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