Summary of Request for Information (RFI) Regarding Varieties of Marijuana and Marijuana Products for Research
Revised November 2016
The National Institute on Drug Abuse (NIDA) supports the production of research grade marijuana and marijuana products (i.e. extracts, purified cannabinoids, etc.) for research on behalf of the U.S. Government. While there are a number of varieties of marijuana with differing constituent profiles currently available (primarily varying ratios of delta -9-THC and cannabidiol (CBD), but also several other cannabinoids; see Marijuana Plant Material Available from the NIDA Drug Supply Program), NIDA was interested in gathering information on whether other specific marijuana varieties or marijuana-derived products are of interest to the research community.
Consequently, on July 7, 2016 NIDA released a Request for Information (RFI) in order to gather information on several related topics from the research community, including:
- The specific marijuana varieties, strains, or constituent chemotypes that are of research interest;
- The marijuana constituents, products and/or preparations that are of research interest; and,
- The particular research questions that could or would be addressed with such products.
The RFI was originally set to expire on September 15th but was held open until October 15th for additional comments. Fifty-four comments were received, and while some were non-responsive, there were many thoughtful and instructive submissions. NIDA and its partner NIH Institutes and other relevant Federal agencies will use the information obtained to guide efforts to expand production of marijuana and marijuana products for research. Following is a brief summary of the comments received.
Recommendations regarding varieties of marijuana:
- The most consistent recommendation was to provide marijuana strains and products that reflect the diversity of products available in state dispensaries.
- Increase the ‘potency’ of marijuana available: several responders noted that the most potent marijuana available from the NIDA Drug Supply Program (as expressed in %THC by weight), is less potent than the marijuana available through medical and recreational programs in States which have authorized them. The recommendation is to produce and provide marijuana with higher THC content, more reflective of what is found in State programs (up to ~30% THC).
- Increase the number and variety of marijuana chemotypes to include not only a range of THC concentrations, but also other cannabinoids (eg CBD, CBG, CBN, CBC, and THCV), terpenes, and flavonoids.
- This included specific recommendations to provide strains rich in each of the cannabinoids listed above – especially CBD.
- Other recommendations included providing strains with similar cannabinoid chemistries but with varying (low and high) quantities of terpenes (linalool, terpinolene, nerolidiol, myrcene, etc.).
- Provide well characterized, common strains, including those characterized as "indica", “sativa", and “hybrid”.
- Improve the quality of placebo marijuana. Multiple responders noted that the currently available placebo marijuana does not smell, taste, or look like regular marijuana and thus does not serve as an effective placebo.
- Currently the process for manufacturing placebo marijuana removes not only THC but many other compounds, including other cannabinoids as well as volatile compounds (terpenes) that contribute to the color and olfactory characteristics.*
- Explore low pathogen production techniques such as indoor growing.
* NIDA is exploring using different extraction techniques and manufacturing processes to better approximate the color and other characteristics of ‘active’ marijuana
Recommendations regarding marijuana products:
- Several researchers recommended that marijuana-derived products developed under FDA current Good Manufacturing Practices (cGMP) guidelines, including pure THC, CBD, CBG, CBN, CBC, and THCV be made available.
- Placebo crude extract (i.e., zero percent THC, zero percent CBD, but other cannabinoids present in the preparation) are also needed for research. Responders also expressed interest in non-cannabinoid constituents of marijuana that may contribute to its effects. It was recommended that purified cGMP terpenoids (limonene, pinene, myrcene, beta-caraophyllene, linalool, bisabolool, humulene, etc) be made available for research.
- It was recommended that these various extracts be produced with both hot and cold ethanol extractions (for inhalation studies), with oil extractions (for ingestion studies), and using CO2 based extractions.
- Continue to provide and expand formulations to reflect what is available in state dispensaries:
- Marijuana should continue to be provided in standardized cigarette form as well as in bulk.
- Both cigarettes and bulk marijuana should contain flowers only to minimize variability.
- Formulations for oral, sublingual, respiratory, rectal, and dermal delivery of purified and whole plant extracts along with matching placebo formulations should be made available.
- Edibles, hash oil, budder, wax, shatter, etc. equivalent to what is available in Colorado should also be made available.
- Marijuana should continue to be provided in standardized cigarette form as well as in bulk.
- Expand the number and variety of marijuana extracts available, both GMP and non-GMP, initially to examine a range of THC and CBD contents but also their combination in varying proportions.
- Multiple responders noted that the discrepancy between federal and state laws that prevents them from being able to access and conduct research on marijuana strains and products available in state dispensaries. “We are in a rather untenable position of having a multitude of products on the market that are freely available and readily purchased and used by the lay public and yet, scientists with proper and valid Schedule I licenses are barred from utilizing these products in clinical trials. This would seem counterintuitive to the mission of our governmental agencies, who strive to keep the nation safe. A mechanism for clinical researchers to acquire safety and efficacy data on products already in the marketplace is critical and has serious public policy implications.”
- Recommendations included identifying solutions to allow researchers to transport state-legal retail cannabis products across state lines for forensic testing at Schedule I approved testing laboratories.
- Create legal pathways for researchers to study products available in state dispensaries and industrial hemp derived compounds that are widely available and widely consumed,
- Facilitate international research and collaborations in order to take advantage of the advanced state of the science in this area abroad and hasten scientific discovery relevant to the US.
- Develop an investigators brochure to assist researchers with IND applications to FDA.
- It was noted that there is a need to label specific strains to support consistent and reproducible dosing in experiments; recommended that NIDA report the chemical variability of available strains and publish on the Drug Supply Program website.
- There is a need to shorten the timeline for processing cannabinoid extract requests.
- There is a need for a clear pathway from the marijuana products available for research to FDA drug approval and commercial sale of medications. The efforts by the DEA to expand manufacturers providing marijuana for researchers could help address this issue.
- Full quantitative cannabinoid and terpene analyses should be provided for each strain.
Responders expressed interest in conducting research on a wide array of topics including:
- How route of administration and potency influences abuse-liability, risk for cannabis use disorder, cognitive impairments, risk for psychosis, and motor-vehicle impairment.
- The therapeutic effects of cannabinoids for pain, epilepsy, cancer, multiple sclerosis, Tourette syndrome, essential tremor, Alzheimer’s Disease, migraine, behavioral management in dementia, PTSD and other psychiatric applications, palliative care, chemotherapy induced peripheral neuropathy, anorexia, nausea and vomiting, cancer related anxiety and depression, diabetes, etc.
- Effects of smoking and vaping both the marijuana plant and extracts on lung health.
- Adverse effects in specific patient populations including geriatric and HIV-1 infected patients.
- Basic research on:
- Effects of prenatal and adolescent cannabis exposure on brain development and on brain function.
- The effects of cannabinoids on peripheral nerve injury.
- Biology of the cannabis plant.
- Side effects of different MJ products.
- Interactions of marijuana and specific extracts with other drugs.
- Observational research on the safety and efficacy of medical marijuana.
- Combinatorial and synergistic effects of cannabinoids and terpenes.
- Basic pharmacology and safety data on extracts and new formulations.
NIDA would like to thank the respondents for their comprehensive and thoughtful comments. These recommendations will help guide efforts across the federal government to expand access to diverse marijuana strains and products for research purposes.
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