STACKD summary
EmergingDihexa and 5-Amino-1MQ: single-target research chemicals with zero human data
Two mechanistically unrelated compounds, one for cognition and one for fat metabolism, that share the exact same evidence gap.
Plain-language summary
Dihexa and 5-Amino-1MQ don't share a mechanism, dihexa is a small molecule derived from angiotensin IV proposed to boost synapse formation via HGF/c-Met signaling, while 5-Amino-1MQ is a small molecule that inhibits an enzyme (NNMT) involved in fat-cell energy metabolism. What they share is a research-chemical-market status and an identical evidence problem: real, published animal biology, and literally no human trial of any kind, safety or efficacy. Dihexa carries an extra caveat: the 2013 paper establishing much of its core pharmacology has received a formal Notice of Concern from the publishing journal.
What was studied
For dihexa: cell-culture studies of synapse formation in hippocampal tissue, and rodent memory-task studies in scopolamine-impaired, naturally aged, and Alzheimer's-model (APP/PS1) mice. For 5-Amino-1MQ: diet-induced-obese mouse studies measuring fat mass, food intake, and insulin sensitivity after NNMT inhibition, plus a follow-up study combining NNMT inhibition with calorie restriction.
Key takeaways
- Dihexa's foundational 2013 paper, describing its synaptogenic potency and behavioral effects in rats, has received a formal journal Notice of Concern, a flag that doesn't necessarily mean the findings are wrong but does mean they warrant extra scrutiny.
- A separate, more recent 2021 study reported dihexa improved cognitive performance in an Alzheimer's-model mouse, offering some independent support beyond the flagged 2013 paper.
- 5-Amino-1MQ reduced fat mass and improved insulin sensitivity in obese mice without changing food intake, a mechanistically distinct, appetite-independent approach compared with GLP-1 peptides.
- As of this review, a targeted search finds zero published human trials of any kind for 5-Amino-1MQ, despite it being actively marketed for human weight loss.
Limitations & what we don't know
- Neither compound has any published human safety or dosing data; both are sold exclusively as unregulated research chemicals.
- Species differences in the relevant biology (synaptic signaling for dihexa, NNMT/SAM metabolism for 5-Amino-1MQ) mean mouse results cannot be assumed to translate directly to people.
- NNMT and SAM sit at the intersection of many methylation reactions throughout the body, so long-term effects of sustained NNMT inhibition beyond fat-cell metabolism are unexplored.
- The Notice of Concern on dihexa's foundational paper is not disclosed in most online write-ups promoting the compound.
Sources
Primary citations behind this summary. External links are provided for verification, read them yourself before drawing conclusions.