Frequently Asked Questions for RFA-AG-25-004: Safety and Early Efficacy Studies of Psychedelic-Assisted Therapy for Chronic Pain in Older Adults

Whom should I contact if I have questions that are not addressed in the NOFO or by these FAQs?

Please send ALL questions to NIAPsychedelicResearch@nih.gov .

Are letters of intent required? When are they due?

Although a letter of intent is not required, is not binding, and does not enter into the review of a subsequent application, the information that it contains will allow NIH staff to estimate the potential review workload and plan the review.

We ask that prospective applicants submit a letter of intent via email to NIAPsychedelicResearch@nih.gov by September 10, 2024 that includes the following information:

• Descriptive title of proposed activity
• Name(s), email address(es), and telephone number(s) of the PD(s)/PI(s)
• Names of other key personnel
• Participating institution(s)
• Subject line: “[LAST NAME OF CONTACT PI] RFA-AG-25-004 Letter of Intent”

When are applications due?

There is a single receipt date. All applications are due October 10, 2024.

How many awards will be funded?

NIA and partner Institutes/Centers intend to fund one award pending the receipt of meritorious applications and the availability of funds.

Are foreign institutions eligible to apply?

Foreign institutions are not eligible to apply; however, a U.S. institution as the primary applicant can include foreign component(s) as defined in the NIH Grants Policy Statement. Please see Section III. Eligibility Information in the NOFO.

Can my organization submit more than one application?

Yes. Applicant organizations may submit more than one application, provided that each application is scientifically distinct. However, NIH will not accept duplicate or highly overlapping applications for this NOFO per NIH Grants Policy Statement.

How should the consortium be organized?

Applicants are free to organize the study consortium that best fits the aims, personnel, and budget of their application. A Coordinating Center should be included in the consortium, and applicants may choose to consolidate clinical, data, and other coordinating functions at one institution or to distribute these functions among multiple institutions. It is expected that the consortium will be geographically diverse.

What is the award budget?

Application budgets are limited to $3,400,000 per year in total costs (i.e., direct + indirect costs) in years one and two (FY2025 and FY2026), and $5,000,000 per year in total costs in years three to five (FY2027 – FY2029). The budget request should be adequately justified and reflect the actual needs of the proposed project.

How do you define “older adult”?

Biological or physiological factors may be more relevant to understanding aging than chronological age. However, for simplicity in this RFA, older adults are defined as individuals 65 years and older. Note that, in both phases, participants across a broad range of ages must be included, with particular attention to strata at the upper age range (i.e., 75-80 years, and 80+ years old).

How do you define “healthy older adult” in the UG3 phase?

Having one or more co-existing conditions is common among older adults. For this RFA, healthy older adults are individuals in the older age range who have either no pre-existing conditions or one or more existing conditions that would not be expected to confer additional physical and/or psychological risks or adverse effects after administration of psychedelic agents.

The RFA lists examples of chronic pain conditions to be included in the second phase of the award. Should all of these conditions be included, and can others also be included?

The pain conditions identified in the RFA were listed because of their prevalence in older adult populations. It is not required to address all pain conditions, and other conditions not included in the list of examples may also be proposed. Applicants should justify their selection of chronic pain conditions particularly with regard to significance and public health impact.

Can studies in the UH3 phase involve multiple co-occurring pain conditions?

To ensure sufficient scientific rigor, applicants are encouraged to propose in the UH3 phase at least some studies involving different single pain conditions. However, as multiple co-occurring pain conditions are common in older adults, and generalizability of findings is also an important goal of this RFA, there is no requirement that all studies in the UH3 phase involve only single pain conditions. Applicants should justify which co-occurring conditions will be studied and describe adequate plans for study design and analysis to maintain rigor.

Is a particular dose of psychedelic agent required? Is microdosing permitted?

Applicants are encouraged to conduct dose ranging studies in the first phase of the award to evaluate optimal dosing in older adult populations. Dose ranging may also continue in the second phase of the award. An intervention arm that includes microdosing – that is, repeated administration of psychedelic agents at sub-perceptible doses without a psychotherapeutic or behavioral complement to psychedelic dosing – would be considered non-responsive. However, administration of sub-perceptible dose(s) of a psychedelic agent coupled with psychotherapeutic or behavioral component may be used as an active control.

Should an application focus on a single psychedelic agent?

Not necessarily. Applicants are free to test as few or as many agents from among the acceptable psychedelic agents for this RFA (psilocybin, LSD, DMT, mescaline, MDMA, and their analogs). Applicants should consider significance, use in practice settings, and study budget in determining which agent(s) to study. Applications that focus on cannabis, ketamine, or their related compounds would be considered non-responsive.

What is envisioned for pharmacokinetic and pharmacodynamic (PK/PD) studies during the UG3 phase?

Applicants should propose and justify studies of their choosing that enhance knowledge on the absorption, distribution, metabolism, and excretion of psychedelic agents as well as their physiologic and clinical effects in older adult populations. In designing PK/PD studies, applicants are encouraged to consider potential future submissions for regulatory approval.

The RFA is clear that ketamine and related compounds are considered non-responsive. However, can ketamine be included as a comparator agent?

Ketamine or related compounds may not be included in studies supported by this RFA regardless of trial arm. The limited resources for this RFA are intended to focus on one or more of the psychedelic agents specified in the RFA (psilocybin, DMT, LSD, mescaline, MDMA, and their analogs).

How many individual studies should be included in the first (UG3) phase of the award?

While there is no prescribed number of studies, we expect that multiple studies will be conducted during the limited 2-year duration of the UG3 phase in order to generate sufficient data and experience to merit transition to the UH3 phase. Investigators should collect adequate safety and preliminary efficacy data in sufficient numbers of healthy older adults to achieve their UG3-phase milestones. Given the extensive regulatory approvals needed for studies involving psychedelics, investigators are encouraged to plan proactively for the multiple studies proposed in the UG3 phase.

Is a psychotherapeutic or behavioral component required for all studies supported by this RFA?

Yes, studies that do not involve a psychotherapeutic or behavioral component will render the application non-responsive. This is because a psycho-behavioral component is expected to enhance both safety and efficacy. However, applicants may propose and justify the type and intensity of psychotherapy or behavioral therapy surrounding psychedelic administration. In addition, applicants may choose to propose studies that compare higher vs. lower intensity of psychotherapy or behavioral therapy, which could help to inform accessibility and cost-effectiveness of psychedelic-assisted therapy in future practice settings.

Should applications focus on several smaller safety and efficacy studies across multiple pain conditions, or a few larger trials in a limited number of pain conditions?

NIH has not set a specific number of trials for each phase. However, applicants should design trials in each phase that best achieve the goal of the RFA: to provide a strong evidence base for safety and efficacy of psychedelic-assisted therapy in older adults with chronic pain. Studies should be proposed with sufficient rigor and statistical power to inform if and how this therapeutic approach may be studied in larger effectiveness trials in the future.

Must all studies be multi-site, and must all sites of the consortium conduct the same studies?

Not every trial must necessarily be a multi-site study, nor must all sites in the consortium necessarily conduct the same studies. Applicants may determine that it is advantageous for different sites to carry out different studies in some cases. However, applicants should consider how their selection of study sites will affect recruitment rates and diversity of enrolled participants. Investigators are generally more likely to achieve their recruitment goals with adequate power and sufficiently diverse populations in the time available for each phase by conducting the same protocols across multiple sites. In all cases, applicants should justify how their plans will contribute to the overall aims of the project.

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