The objective of this research was to determine whether Cannabis produced and sanctioned by the United States federal government for research purposes reflects the Cannabis that is widely available in state regulated markets. The data demonstrate that Cannabis plants currently grown for NIDA are not representative of plants consumed by recreational and medicinal users through state-legalized markets across the nation. Cannabis flower available from dispensaries appears to be more potent and diverse in cannabinoid content.

The illicit Cannabis contains a higher percent of THC compared to NIDA, but lower compared to the legal markets. However, the black market’s CBD is lower than both NIDA and the private market5. Furthermore, our results suggest that the private markets also store their Cannabis in conditions that avoid degradation of THC to CBN32,33,34. However, the black market’s CBN percentage appears to be higher than NIDA’s5. These CBN measurements could be elevated due to storage time and conditions if the measurements were not done immediately after seizure. Thus, the black market material that is illicitly consumed might have lower CBN than what has been reported5.

The cannabinoid levels in NIDA and the state markets differ in several ways. Indeed, THC levels on average in NIDA were 27–35% of those in the state markets, while CBN levels are 11–23 times higher. Studies that have examined the impact of Cannabis potency have suggested linear dose dependent effects of THC on outcomes such as impaired driving and cognitive abilities, even at much lower potencies than those reported here35,36. Other data suggest that the effects of particular cannabinoids (e.g. THC) differ depending on which other cannabinoids (e.g. CBD) are present in the variety consumed12. Thus, the effects of Cannabis differ by the potency and variety of Cannabis tested. Our findings of different cannabinoid profiles in NIDA vs legal market varieties underscore the importance of assessing the impact of Cannabis as it is used in the real world on outcomes of high importance to public health4.

This underrepresentation of cannabinoid variation and potency in the NIDA’s cultivars should be considered for US investigation in several areas, including chemistry, biochemistry, genomics, biology, psychology, but particularly for medical research. These data suggest that the NIDA varieties underrepresent the variation of cultivars with higher cannabinoid levels and the variation that is found in state-legalized markets37,38.

Medical research using only a limited number of varieties can be misleading, because variation in the amounts and ratios of cannabinoids may have a significant impact on the outcomes of the studies. Particularly as cannabinoids can have dramatic opposing effects and complex interactions with each other11,12,14,15,16,17,18,19,20,21, investigations that only use one source of material may hinder our understanding of pharmacological and therapeutic effects of Cannabis. Given that the effects of Cannabis may vary depending upon the dose39,40, where both the chemotype and the dose are important in the medical effects41,42, and the potential harmful effects12, it is crucial for scientific and medical investigations to access the varieties used by patients and recreational users.

Studies reporting on effects of Cannabis using NIDA varieties will continue to suffer in terms of external validity, possibly underestimating the effects of more potent varieties that are widely available. Compounding this issue is the fact that the public availability of high-potency Cannabis has increased in recent years1,5. Given our data and recent reviews that have suggested that the greater potency of today’s Cannabis, compared to earlier decades4, may lead to significantly greater levels of intoxication and possibility of harm, it is important for research to begin understanding consequences and impact of using the publicly available Cannabis.

The knowledge gap between what we know from studies using government grown Cannabis and what we should know about the effects of Cannabis in the real world could continue to widen with the progressive decriminalization and accessibility of high-potency, dispensary-grade Cannabis. This problem can only be addressed by establishing legal methods for US scientists to access Cannabis more similar to what is sold and consumed in state-regulated markets.

Despite this being one of the most complete cannabinoid analyses to date, it has a number of limitations. First, data analyzed in this study were collected by separate facilities, NIDA and Steep Hill, which may introduce biases. Inter-laboratory comparative analysis between different methods of testing Cannabis products (e.g., different equipment used for this comparison and the various other facilities that offer chemotype testing) has been limited. This limitation is largely imposed by federal laws that prevent third parties (e.g., universities) from conducting such studies. Lastly, Steep Hill data only includes varieties tested at their locations and are not necessarily representative of all Cannabis available to consumers. However, with 2980 samples tested, common varieties are well represented. Similarly, our analysis includes the potential current pool of varieties listed as available by the government for research purposes; however the Cannabis varieties produced historically by NIDA (and used in NIDA-funded studies published prior to 2012, when these additional NIDA varieties became available) are far less potent. Thus, while our analysis focuses on currently available varieties, the discrepancy between publicly-available Cannabis and that used in most existing research is even greater than what we report here.

Moreover, this analysis is limited to the six cannabinoids reported for the NIDA varieties, while additional compounds are known to be important2,8,9. Chemical analyses of Cannabis in commercial testing labs include numerous cannabinoids and terpenoids, which vary between lineages43 and have important physiological effects2,8,9. Compounds not reported for the NIDA varieties may represent additional important differences between the federally approved cultivars and more widely-used material. However, it is worth noting that the cultivars available through NIDA may compare favorably to individual dispensaries in terms of diversity of cannabinoid levels and ratios of THC to CBD.

Additionally, Cannabis flower is one form of Cannabis available in state regulated markets, with concentrates and edibles also widely used. It is critical to note that as of May 2016 on the federal website, there is no source of concentrates or edibles for research. Therefore, there is almost no research on the effects of cannabinoids in extract or edible form, even though in Colorado alone, approximately 650,000 edible units are sold each month. It may be a challenge for the federal government to produce Cannabis in a way that reflects the diversity of products used by the public in states where it is legal.

In conclusion, this study offers a comparison between six cannabinoids from Cannabis produced in four cities in the US and the NIDA supply farm. The data demonstrate that Cannabis produced by NIDA is both less diverse in variety and less potent in the amount of cannabinoids. Because most federally approved research requires the use of government produced Cannabis, this mismatch between what the public is using and what is available to researchers limits scientific study on the potential harms or benefits. In recent years, federal sources have pursued diversification of their varieties with a goal of increasing the diversity and potency of research Cannabis. The research presented here provides concrete data that can inform further changes, so that Cannabis available to researchers in the future can better reflect the types of products widely-used by the public.