A top federal health agency is soliciting proposals for a series of research initiatives meant to explore how psychedelics could be used to treat drug addiction, with plans to provide $1.5 million in funding to support relevant studies.
As public interest in the therapeutic potential of psychedelics continues to grow, the National Institute on Drug Abuse (NIDA) this week published three notices of funding opportunities (NOFOs) for research projects to better understand how drugs like psilocybin and ayahuasca could help people with substance use disorders (SUDs).
While all three notices focus on the same overall objective, one would focus on the mechanisms of psychedelics, while the others would need to involve clinical trials with human subjects.
“While broad theoretical frameworks for the mechanisms of psychedelic-induced neurobiological and behavioral changes have been recently posited, empirical tests and refinements of these overarching theoretical frameworks are necessary to move the field forward,” NIDA said in a notice for one of the clinical trial opportunities.
The agency is “particularly interested in a better understanding of the types of neurobiological and network changes that yield improved cognitive and emotional regulation and sustained behavioral change associated with the administration of psychedelics.”
NIDA emphasized that, for this type of research, it would be necessary to utilize “modern neuroimaging and behavioral analytic tools” to illustrate the “changes are elicited by psychedelics.”
With that kind of information, “the field would be better equipped both to identify the key neuroplastic adaptations that signal symptom improvements and to design effective future psychedelic therapies.”
Because of the complexities of carrying out clinical trials of this nature, NIDA cautioned that studies “may involve considerable risk of failure.”
However, they “may lead to a breakthrough in a particular area, or to the development of novel techniques, agents, methodologies, models, or applications that could have a major impact on SUD research involving psychedelics.”
NIDA offered examples of questions that it hoped to answer with such research:
- What specific cognitive constructs relevant to SUD treatment (e.g., cognitive control, social/affective processing, predictive/sensory processing, interoception) are modulated by psychedelics?
- What, if any, core changes to neurobiology do these compounds facilitate that account for their wide-ranging clinical potential?
- How do the underlying network connectivity and task evoked activation scale with and/or predict the magnitude and duration of the observed effects of psychedelics?
- What are the roles of psychedelic compounds in altering the dynamics of large-scale brain networks and specific circuits? What is the relationship of these changes to behavior relevant to SUD?
- What are the temporal trajectories of neurobiological, cognitive, and behavioral effects of psychedelics and the relevant dose-response relationships?
- What are the effects of these compounds both within the canonical 5HT2 receptor pathway and on additional signaling pathways (e.g., dopaminergic)?
- Are the neuroplastic effects of psychedelics observed in animal studies replicable in humans? Are these changes responsible for the long-lasting symptom improvements seen in clinical studies?
For the non-clinical trial research opportunity, NIDA said that the “overarching goal” is to “elucidate and validate the molecular, cellular, circuitry and structural mechanisms and pathways that underly the pharmacology of psychedelic compounds for treating substance use disorders (SUDs) and related psychiatric and neurological co-morbidities.”
The research funding will also “support the design and synthesis of chemical probes to provide mechanistic insights on biological targets modulated by psychedelics, and on common targets/pathways in the context of SUD.”
In simpler terms, the agency wants to learn exactly how psychedelics work on a mechanistic level. Studies have shown that substances like psilocybin hold significant potential in treating addiction—and there are ongoing clinical trials to further substantiate that—but there are “knowledge gaps” in that more fundamental question of how.
NIDA explained that while “classic psychedelics” are known to activate serotonin, different entheogens play on different biological targets.
For example, “psilocin (the active metabolite of psilocybin), LSD and DMT show considerable heterogeneity in signaling dominated by actions at multiple biogenic amine receptors that are themselves coupled to multiple signaling pathways.”
“Ayahuasca, as a multi-component substance exhibits a more promiscuous pharmacology that includes additional interactions with glutamatergic and endocannabinoid systems, sigma-1 receptor, and several accessory proteins involved in monoaminergic neurotransmission,” NIDA said.
“There is insufficient data available on the biological mechanisms by which psychedelics affect brain function and there is a need for understanding which of their multiple targets are important for therapeutic efficacy and which are responsible for adverse effects, if any. The design of chemical biology tools and probes with well-defined selectivity metrics should aid in the systematic investigation of target function and elucidation of mechanisms of action of psychedelic compounds on specific and/or interacting neural targets. Ultimately, the information is necessary for the rational development of psychedelics as therapeutics.”
NIDA said it plans to distribute four awards totaling in $1.5 million in funding collectively in the 2024 Fiscal Year.
Eligible applicants include universities, non-profit organizations, for-profit businesses, state and local governments and federal agencies.
At a Senate committee hearing earlier this month, NIDA Director Nora Volkow told members that there’s emerging evidence that psychedelics carry “significant potential” as therapeutic treatments for certain mental health conditions, and it’s a topic of “great interest” for researchers.
Last year, Sens. Brian Schatz (D-HI) and Cory Booker (D-NJ) pushed top federal officials to provide an update on research into the therapeutic potential of psychedelics, arguing that ongoing federal prohibition has stymied studies.
NIDA responded to the inquiry by saying that federal prohibition makes it more difficult to study the benefits of psychedelics, requiring researchers to jump through additional regulatory hoops. Volkow previously said that she personally hesitates to study Schedule I drugs because of those complications.
The director told Marijuana Moment in 2021 that researchers need to prioritize psychedelics research, as more people are likely to use them as they’re exposed to studies showing the therapeutic potential of the substances.
Congress has started to take notice of psychedelics policy amid renewed research and reform efforts. In March, for example, bipartisan and bicameral congressional lawmakers filed an updated version of a bill to streamline the federal rescheduling of “breakthrough therapies” like psilocybin and MDMA in order to promote research and drug development.
Booker, along with Sen. Rand Paul (R-KY) and Rep. Nancy Mace (R-SC) also led a separate bill last year that was designed to clarify that federal “Right to Try” (RTT) laws give seriously ill patients access to Schedule I drugs, including marijuana and psychedelics like psilocybin and MDMA. It was not enacted by the end of the session, however.
The introduction of the bipartisan psychedelics bill this session roughly coincided with the re-launch of a congressional caucus focused on promoting research into the therapeutic potential of entheogenic substances. (Full Story)