April 8, 2026
By: Don Stanford
Assistant Director, Research Institute of Pharmaceutical Sciences (RIPS)
School of Pharmacy
University of Mississippi
Main Points
• Simplifying the research process: Moving cannabis from Schedule I to Schedule III will significantly streamline the DEA registration process, eliminating the requirement for researchers to submit and wait for approval on detailed study protocols.
• Impact on clinical studies: Rescheduling is expected to reduce major barriers for clinical research, making test materials more accessible and allowing interventional studies to proceed under standard Schedule III registrations commonly used in clinics and pharmacies.
• Manufacturing and distribution changes: While the move to Schedule III will remove manufacturing quota requirements for many materials, the single agency distribution requirement mandated by international treaty will likely remain in place for botanical cannabis.
• Evolution of record-keeping: Researchers will see a shift in logistical requirements, such as the transition from the mandatory DEA Form 222 for material transfers to more standard commercial invoices and receipts
Introduction
Over the past four years the federal government has moved forward in the rescheduling of marijuana from its current Schedule-I (C-I) status to Schedule-III (C-III). Current references are readily available that provide pertinent information on the impact of rescheduling on matters of business, law, and society, [1] but little information is readily available to prepare DEA-licensed cannabis researchers for the change.
This commentary elucidates likely regulatory scenarios based on experiences of researchers working with Dr. Mahmoud ElSohly and others at NCNPR in a cannabis research and materials supply program that began before the Controlled Substance Act (CSA) [2] was even enacted. They experienced firsthand the evolution of regulatory perspectives in cannabis science.
Although the term “marijuana” is the proper term for the dried botanical material prepared from drug-type varieties of cannabis plants the term “cannabis” will be used here to refer to all research materials that are currently handled under US Drug Enforcement Administration (DEA) C-I regulations, such as living plants, dried plant materials, cigarettes, extracts, and purified cannabinoids. For this discussion, the synthetic versions of naturally occurring cannabinoids as research materials are also considered to be rescheduled to C-III.
“The area of cannabis research that will be most affected by rescheduling is clinical research, as it is widely known that the current C-I schedule greatly impedes the design and execution of clinical studies.”
Background
When Congress enacted the CSA in 1970 at a time when cannabis science was in its infancy, practically all cannabis materials became strictly controlled. Eventually, scientists involved in cannabis research in the US obtained DEA C-I Researcher or C-I Analytical registrations to conduct their studies. By the mid-1970s scientists could obtain purified cannabinoids such as THC and CBD from commercial sources or from the National Institute on Drug Abuse, Drug Supply Program (NIDA DSP), but they could not cultivate their own Cannabis sativa plants for research, they could only obtain plant material and cigarettes from the NIDA DSP.
Cultivation of plants and distribution of plant materials is controlled by the treaty agreement of the Single Convention on Narcotic Drugs that specifies very restrictive controls on marijuana (or marihuana) and opium that are different than the controls for other C-I materials for research. The treaty requires that only a “single agency” of a nation may distribute marijuana plant material to researchers. For decades the single agency in the US was NIDA. Today, after the implementation of CFR Part 1318 “Controls to Satisfy the Requirements of the Act Applicable to the Manufacturing of Marihuana” [3] the single agency is DEA who serves as the broker between cultivators and researchers to provide a distribution system that allows for additional sources for plant material other than NIDA.
The term “industrial hemp” arose in 2009 when the state of Oregon began issuing licenses to cultivate fiber-type cannabis plants within the state. Hemp production in the US was at odds with federal law until the passage of the 2014 Agricultural Improvement Act (or Farm Bil) that legitimized industrial hemp research, [4] but it was not until passage of the 2018 Farm Bill that hemp was removed from the list of DEA controlled substances. [5] In 2020 DEA published the notice of interim final rule (IFR) “Implementation of the Agricultural Improvement Act of 2018” [6] which specified that many naturally occurring cannabinoids, such as CBD would no longer be regulated as DEA controlled substances.
The movement to reschedule cannabis began decades ago, shortly after the CSA was enacted when advocates of medicinal cannabis first filed a petition with DEA. More legal petitions followed, state medical cannabis laws were enacted, and scientific data began to support the medical value of cannabis therapies. [7] In October 2022 President Joe Biden formally initiated a rescheduling review by the US Department of Health and Human Services (HHS) and the US Department of Justice (DOJ) which led to a recommendation to move cannabis to C-III and to begin the DEA rulemaking process to accomplish that. [8]
In 2024 DEA published the notice of proposed rulemaking (NPRM) “Schedules of Controlled Substances: Rescheduling of Marijuana” [9] to solicit public comments on the matter. On December 18, 2025, Executive Order 14370, “Increasing Medical Marijuana and Cannabidiol Research,” directed the DOJ to complete the rulemaking process to reschedule marijuana to C-III, and HHS to initiate research that will improve access to hemp-derived cannabinoids. [10]
The 2024 NPRM and the current DEA regulations (21 CFR Parts 1301, 1308 & 1318) [11] are referenced here to demonstrate how rescheduling from C-I to C-III will impact researchers. These regulations are explained in detail in DEA’s comprehensive guide for researchers working with all schedules of controlled substances through their 2022 edition of the Researcher’s Manual, “An Information Outline of the Controlled Substance Act.” [12]
Advancing Research by Reducing Barriers
Those who understand the impact of rescheduling cannabis from C-I to C-III all seem to agree that reducing the barriers inherent in activities involving controlled substances will advance cannabis science and, thus, cannabis-based product development.
The area of cannabis research that will be most affected by rescheduling is clinical research, as it is widely known that the current C-I schedule greatly impedes the design and execution of clinical studies. For instance, an interventional study that requires the clinical site to handle and store test articles will be able to proceed under a DEA C-III registration, which is commonplace in clinics and pharmacies. Additionally, C-III clinical research materials will become more widely available and less expensive for researchers.
Activities Allowed for Researchers
Although research may be conducted under several different categories of DEA registrations, the most common are Researcher and Analytical registrations. A good example of research readily conducted under an Analytical registration is the Potency Monitoring Project that NCNPR carried out for many years to gather statistical data on the cannabinoid levels of illicit cannabis specimens that were confiscated by law enforcement agencies. [13]
One great impact of the rescheduling for researchers is that application requirements for a DEA C-III Researcher registration is much simpler than C-I. In addition to completing the application itself, a C-I researcher must file and receive approval for a research protocol. The protocol must include complete details of each study, including its purpose, procedures, security provisions, as well as names, quantities, and sources of controlled substances. The application along with the protocol and the researcher’s CV goes to both DEA and to FDA for review. A DEA Field Office will arrange for a site visit to verify the security provisions. If all goes well, the DEA will issue the registration that allows research activities as described in the protocol. A registrant may later send an email request for a change in the quantities or may submit a supplemental protocol for procedural changes.
A C-III Researcher registration, however, does not require a protocol to be submitted to DEA. Of course, a competent researcher will have their own written protocol describing the procedures to be used in a study to provide a valid plan for each study. A formal protocol may be required by their institution or in the case of a clinical study by FDA and their IRB.
Please refer to §1301.13 which includes a summary of registration requirements and limitations for “business activities” for all categories of registrations and all schedules. Activities allowed under C-I and C-III Researcher and Analytical registrations are listed as follows:
| RESEARCHER C-I A researcher may manufacture or import the basic class of substance or substances for which registration was issued, provided that such manufacture or import is set forth in the protocol required in §1301.18 and to distribute such class to persons registered or authorized to conduct research with such class of substance or registered or authorized to conduct chemical analysis with controlled substances. |
| RESEARCHER C-III May conduct chemical analysis with controlled substances in those schedules for which registration was issued; manufacture such substances if and to the extent that such manufacture is set forth in a statement filed with the application for registration or reregistration and provided that the manufacture is not for the purposes of dosage form development; import such substances for research purposes; distribute such substances to persons registered or authorized to conduct chemical analysis, instructional activities or research with such substances, and to persons exempted from registration pursuant to §1301.24; and conduct instructional activities with controlled substances. |
| ANALYTICAL C-I and C-III May manufacture and import controlled substances for analytical or instructional activities; may distribute such substances to persons registered or authorized to conduct chemical analysis, instructional activities, or research with such substances and to persons exempted from registration pursuant to §1301.24; may export such substances to persons in other countries performing chemical analysis or enforcing laws related to controlled substances or drugs in those countries; and may conduct instructional activities with controlled substances. |
Manufacturing vs Research
Regarding a Researcher registration approved for cannabis research, the use of the term “manufacture” in the CFR applies to research in a limited context. For example, a study may require a scientist to prepare solutions of cannabinoids, isolate compounds, or synthesize cannabinoids in a lab. A C-I researcher must describe those specific activities in their protocol, while a C-III researcher has much more flexibility to alter their activities as their research progresses.
Under an Analytical registration, manufacturing activities are limited to processes that are reasonably associated with analytical work, such as preparing solutions for their own lab or to be transferred to a researcher.
Please note a common misconception in cannabis circles that when a researcher prepares a diluted cannabinoid solution to be used as a standard or to be injected into animals, the control status changes. In fact, a dilution of a controlled substance solution is still a DEA controlled substance. However, cannabinoid solutions that are DEA exempt are commercially available because the vendor has registered specific products with DEA to make them available to more researchers (§1310.12). This regulation applies to both C-I and C-III controlled substances.
“Manufacture,” however, does not mean that a researcher can grow drug-type Cannabis sativa plants in a greenhouse, as §1301.33 specifically prohibits cultivation of marijuana plants under a Researcher registration. Cultivation of marijuana is only allowed under a Bulk Manufacturer registration as described in Part 1318. The current regulatory scheme, therefore, prohibits the cultivation of plants for studies that do not result in the “manufacture” of marijuana, such as agronomic studies that focus on plant development prior to harvest. Due to the obligations of the Single Convention Treaty the prohibition of cultivation for research will not likely change by rescheduling.
Take note that manufacturing activities allowed under a Researcher registration is limited strictly to research and is not intended for commercial product development. A successful cannabis researcher will likely be associated with new therapies and technologies that may move beyond the scope of research and become product development. It is the responsibility of a researcher to be aware of the registration requirements if their work advances beyond bench-type research to scale-up and development. However, increased interest in new cannabis-based drugs due to rescheduling will foster R&D activities that can readily be accomplished under C-III Manufacturing registrations maintained by institutions or companies.
Regulations for DEA Manufacturer registrations will not likely change due to rescheduling, but the manufacturing of certain cannabis-based materials will be significantly easier under the C-III status. A DEA Bulk Manufacture registration is required for large-scale production of active pharmaceutical ingredients (API) and raw materials that contain C-I or C-II controlled substances. To prepare extracts from cannabis plants or to isolate purified cannabinoids under a C-I Bulk Manufacturer registration, during the calendar year prior to the year of production the registrant must submit to DEA an application for a quota to do so. Similarly, if a manufacturer wants to procure C-I raw materials, such as cannabis extract for isolation of THC, the registrant must apply for a procurement quota.
Manufacturing activities under a C-III Manufacturer registration, however, do not require quotas. Therefore, rescheduling cannabis to C-III will certainly streamline manufacturing operations, such as preparing dosage forms. Activities allowed under a C-III Manufacturer registration, as listed in §1301.13, include chemical analysis and pre-clinical research.
As discussed earlier, cultivation of drug-type cannabis plants for production of marijuana can only be carried out under a Bulk Manufacturer registration as described in Part 1318. Section VIII of DEA’s 2024 NPRM clearly explains that the special requirements for cannabis production required by the Single Convention treaty may be satisfied through additional controls that are not required for other C-III controlled substances. Presumably, the rules that require manufacturing quotas and distribution by a single agency will not change under C-III status.
“One great impact of the rescheduling for researchers is that application requirements for a DEA C-III Researcher registration is much simpler than C-I.”
Logistics and Record-Keeping for Researchers
While cannabis research spans a wide spectrum of disciplines, from molecular biology to public policy, only a researcher who handles and stores any of the controlled substances listed in Part 1308 is required to hold a DEA registration. Although some types of studies many be conducted without a DEA registration, researchers involved in studies that do require a registration, such as laboratory work and interventional clinical studies, should be aware of potential changes in the logistics and recordkeeping for their studies.
Another significant impact of the rescheduling for researchers will be the changes in acquisition and transfer of materials. A DEA Form 222 is required for the transfer of a C-I controlled substance from one C-I registrant to another, such as a researcher purchasing a C-I item from a vendor. The purchaser must prepare and execute the form, either an old-fashioned paper form or the electronic equivalent. The vendor will receive the form with the order and will document the items and quantities shipped to the purchaser. Upon receipt of the items, the purchaser must document the quantities and date received. The Form 222 process is an effective means to prevent diversion of C-I controlled substances during the time that a package is handled by non-registrants, such as couriers.
The same process is required for the transfer of C-I materials between researchers who have DEA registrations for facilities in different physical locations. In addition to the Form 222 documentation, the controlled substances must be recorded in the registrants’ inventories. The person supplying the material should record in their inventory the date and quantity transferred to the recipient. Likewise, the recipient should record the addition to their inventory as well as the source.
The transfer of C-III controlled substances between C-III registrants does not require a Form 222, however, DEA regulations do require that a researcher keep a receipt (invoice or packing slip) of each commercial order. Although the transfer of C-III materials will be evident by examination of the inventories maintained by the two researchers exchanging materials, the requirement for a “receipt” also applies to a non-commercial transfer. Additionally, it is the responsibility of the registrants to report to DEA the loss of any materials in transit.
DEA security requirements for researchers are virtually the same for C-I and C-III controlled substances: The materials must be stored in a securely locked, substantially constructed, cabinet. The only difference in storage requirements is that C-III materials may be stored in the same cabinet with C-IV and C-V materials, while C-I and C-II materials must be segregated.
Like security requirements, inventories and records for C-I items must be maintained separately from the records for C-III items, while C-III records may be kept together with C-IV and C-V records. Little else will change: records for inventory, dispensing, and disposal are required. As with C-I materials, a “biennial inventory” is required for C-III materials as a physical, hands-on, inventory verification and separate record to verify the accuracy of a running inventory record.
Conclusion
Most researchers agree that the findings determined during the rescheduling review by HHS are cause for rescheduling cannabis, with C-III being the most appropriate schedule that will allow research and product development efforts to move forward. The change will certainly reduce many barriers for researchers and enable them to better conduct studies, obtain research materials, and to secure funding from federal agencies and industry. However, cannabis materials will still be DEA controlled substances that must be handled responsibly.
The rescheduling action will bring us one step closer to completion of the necessary research on safety and efficacy to inform doctors and patients of both the benefits and hazards of cannabis as a medicine.
REFERENCES
1. The Cannabis Regulators Association: Overview of the Implications if Marijuana is Rescheduled to Schedule III under the U.S. Controlled Substances Act, December 2025. https://static1.squarespace.com/static/5f7e577e23ad7c718c269776/t/694053c9bc9a3a491b4ed20d/1765823433355/CANNRA+Briefing+on+Schedule+III_December+2025.pdf
2. The Controlled Substances Act (CSA): A Legal Overview for the 119th Congress; CRS Report R45948, Library of Congress; 2025.
3. Controls to Satisfy the Requirements of the Act Applicable to the Manufacturing of Marihuana,
Title 21, US Code of Federal Regulations, Part 1318.
4. Grim R, Ferner M: DEA Seizes Kentucky’s Hemp Seeds Despite Congressional Legalization; HuffPost May 14, 2014.
5. H.R.5485–To amend the Agricultural Marketing Act of 1946 to provide for State and Tribal regulation of hemp production, and for other purposes; 115th Congress (2017–2018); https://www.congress.gov/bill/115th-congress/house-bill/5485/all-info
6. US Drug Enforcement Administration: Interim Final Rule, Implementation of the Agricultural Improvement Act of 2018; Federal Reg 85:51639; 2020.
7. The health effects of cannabis and cannabinoids: The current state of evidence and recommendations for research; National Academies of Sciences, Engineering, and Medicine; National Academies Press.
8. Timeline of Federal Marijuana Rescheduling 2022-2025; Drug Enforcement and Policy Center, The Ohio State University, Moritz Law Center.
9. US Drug Enforcement Administration: Notice of Proposed Rulemaking, Schedules of Controlled Substances: Rescheduling of Marijuana; Federal Reg 89:44597; 2024.
10. Executive Order 14370 of December 18, 2025, Increasing Medical Marijuana and Cannabidiol Research; Federal Reg 90:60541; 2025.
11. Drug Enforcement Administration, Department of Justice, Title 21, US Code of Federal Regulations, Parts 1300-1321.
12. Researcher’s Manual, An Information Outline of the Controlled Substance Act; US Drug Enforcement Administration, 2022.
13. ElSohly MA, Majumdar CG, Chandra S, Radwan MM: A Ten-Year Trend in Cannabis Potency (2013 to 2022) in Different Geographical Regions of The United States of America; Frontiers in Public Health, 12:1442522; 2024.
Insightful piece! Thanks to Don Stanford for his contribution!