On September 19, 2024, MAPS received the response from the Office of Neuroscience to the Formal Dispute Resolution Request (FDRR) submitted by MAPS on August 23, 2024. The FDRR was submitted in response to an FDA Clinical Hold letter received in December 2023, which rejected the study of smoked marijuana and vaporized marijuana. Although the Office of Neuroscience denied the appeal, indicating that the study would remain on clinical hold, MAPS successfully achieved agreement on three key issues.
While MAPS initially submitted the clinical study protocol for MJP2 on March 9, 2021, over the three years that followed, the FDA Division of Psychiatry Products (DPP) issued five Partial Clinical Hold letters repeatedly raising concerns about potential risks associated with the proposed dosing and administration of cannabis flower (see Study Timeline).
The fifth Clinical Hold Letter reiterated four previously raised concerns regarding 1) the safety of the proposed dose of THC (which was designed to mirror the real-world use of cannabis), 2) the safety of smoking cannabis flower as an administration method, 3) the safety of vaporization of cannabis flower as an administrative method, and 4) the inclusion of cannabis naive participants.
Given that DPP did not meaningfully address MAPS’ prior Complete Response in the 5th Clinical Hold letter, MAPS submitted an FDRR. The FDRR served an appeal to the DPP’s overseeing Office of Neuroscience to request a thorough review of the data submitted to the FDA. The FDRR reviewed the regulatory history and the previously presented safety data on cannabis and vaporization devices with respect to the proposed study population and treatment conditions.
On September 19, 2024, MAPS received an Appeal Denied Letter from the Office of Neuroscience in response to the FDRR. Despite the fact that the FDA denied MAPS’ appeal to remove the clinical hold, the letter revealed significant changes to the FDA’s previously held positions on cannabis research which would now permit key features of MJP2’s real-world study design.
The letter indicated that the DPP now agreed that the proposed dose of THC was acceptable provided additional safety information regarding the proposed dosage was added to the Informed Consent. DPP also now agreed that smoking and vaporization of cannabis flower does not represent an unreasonable risk in a patient population with a serious condition like PTSD, provided that the risks of both administration methods are adequately documented in the informed consent form. On the final issue, the Office of Neuroscience agreed with the DPP that it is unacceptable to enroll cannabis naive participants who do not have prior experience inhaling smoked or vaporized cannabis.
The proposed Study MJP2 is intended to bolster the cannabis safety literature and contribute to a better understanding of the safety and effectiveness of real-world cannabis consumption by modeling commonly used routes of administration, dose, and % THC content. This response letter indicates that the FDA will allow cannabis research that models real-world consumption provided that the risks of study participation do not outweigh the possible benefits of treatment and that the risks are adequately explained to the study participants.
Following the FDRR response, MAPS intends to submit a sixth Complete Response to the Clinical Hold that incorporates the FDA’s advice and concerns. Given the updated thinking FDA expressed through the FDRR process and the clarity of the remaining concerns, MAPS is confident that the sixth Complete Response will be sufficient to remove the extended clinical hold.