The Effect of Controlled Substances Scheduling on Marijuana Research

(Although not discussed at the meeting, this section is provided as background regarding research with Schedule I substances.)

In addition to the requirements of the U.S. Food and Drug Administration (FDA) and sponsoring organizations such as the National Institutes of Health (NIH) concerning the conduct of clinical research, U.S. investigators are subject to specific FDA and Drug Enforcement Agency (DEA) regulations concerning research with controlled substances. Under the Controlled Substances Act (21 USC 822 (a)(1)) and implementing DEA regulations, persons conducting clinical research with any controlled substance must register with the DEA, keep specific types of records, and periodically report to the DEA. Marijuana is currently classified at the highest (most restrictive) level as a Schedule I drug (no accepted medical use, high potential for abuse). Attempts by various petitioners to have marijuana rescheduled have not been successful.

Therefore, there is at least one extra layer (many States have their own laws modeled after the Controlled Substances Act (CSA), which add further complexity) for any investigator undertaking clinical trials with controlled substances. In the case of research conducted under an Investigational New Drug Application (IND), recordkeeping requirements are exempt from the CSA but must be kept in accordance with the Food, Drug and Cosmetic Act (FDCA). Under the FDCA, a sponsor or investigator must make its records concerning shipment, delivery, receipt, and disposition available for inspection and copying at DEA's request. Additionally, FDA regulations require that sponsors and investigators conducting clinical trials take special precautions to prevent diversion, including storage in a secure place with limited access. In the case of some investigator sites, this may require acquisition of a safe and/or other physical space changes and/or procedures to insure security and accountability of the substance.

The CSA also mandates reporting procedures when conducting research with controlled substances. A DEA registration for controlled substances also authorizes (within specified limits) the manufacture and distribution of the substances. If a researcher engages in manufacture or distribution, then he or she is held to the reporting standard of manufacturers and distributors. Presumably, the manufacturer/distributor reporting requirements would not apply in most studies, as the source of marijuana would be the National Institute on Drug Abuse (NIDA) and most studies would not be using the plant material to manufacture other forms or products.

Where research studies of Schedule I substances are not conducted under an IND, the DEA requires a copy of the research protocol be submitted for approval and identify in the registration applications the extent to which the research will involve manufacture or importation. Where research is conducted under an IND, however, the sponsor need only provide the DEA with a copy of the IND and a statement of security precautions. The FDA has ultimate authority to decide whether the research may proceed either under its jurisdiction over INDs (FDCA) or in the case of non-IND research, under the CSA (21CFR1301.42). Where non-IND research is undertaken, the FDA must consult with the DEA concerning the adequacy of the applicant's diversion control procedures. If a researcher desires to increase the amount of Schedule I material it has previously received permission to use, it must apply to the DEA for the increase, and the DEA will forward the request to the FDA for approval/denial, taking into account DEA comments on the adequacy of the researcher's security against diversion control.

Some States may have their own registration requirements for Schedule I substances above and beyond the Federal requirements. Each researcher must check his or her own State authorities to see if other regulatory requirements need to be met. Given the small amounts of research material used by researchers in comparison to the additional regulatory burden and time delays, many researchers have been discouraged from pursuing research with these substances. Indeed, one of the recommendations of the Institute of Medicine Report entitled The Development of Medications for the Treatment of Opiate and Cocaine Addictions: Issues for the Government and Private Sector (National Academy Press, Washington, DC 1995, pp. 168-171) was that the current regulatory system be modified to remove barriers to undertaking clinical research with controlled substances.

state laws and penalties