Dihexa

PNB-0408 (small molecule) · F-tier (Dr. Alex Tatem) · Preclinical evidence

Promoted as a brain-regenerating nootropic for Alzheimer’s, but the research foundation was undermined by image-manipulation findings and retractions.

Dr. Tatem’s take

F tier: the published research “had to be retracted,” leaving “no quality data… just a really big promise.” Save it for the scientists for now.

In Dr. Tatem’s tier list

• Not a peptide but a small molecule derived from one; a nootropic aimed at actual neuro-regeneration, not just a cognitive bump like alpha-GPC.
• Supposedly acts like hepatocyte growth factor (HGF) on its receptor, c-Met.
• Was a darling Alzheimer’s candidate in the late 2010s — then much of the research was proven fraudulent and articles were retracted. “Whenever you have a formal retraction like this, that’s a big deal.”
• Verdict: F tier. Nootropics especially need double-blind placebo-controlled trials.

History & background

Dihexa was developed at Washington State University by Joseph Harding and Jay Wright as a stable, brain-penetrant fragment of angiotensin IV, and licensed to the company that became Athira Pharma. Mechanism papers were published in 2012–2014.

In 2021 journals flagged four of the group’s papers for possible image manipulation, and an Athira board investigation found the company’s CEO (a former graduate student on the work) had altered images; she resigned. Key papers were later retracted, and Athira’s follow-on drug failed in 2024.

Benefits

• In animal studies it was reported to form new synapses and improve memory — though some of that work has been retracted.

Risks

• No human safety data.
• Acts on the HGF/c-Met pathway, which is also involved in cancer growth (theoretical tumor risk).
• Underlying research partly retracted.

Dosing protocols (informational, labeled by evidence)

• Community (bro science): Preclinical reference — 2 mg/kg/day (rats), Oral gavage, Daily, 2–4 wk
• Community (bro science): Community human use — Commonly cited ~10–20 mg/day oral/transdermal (unverified), Oral or transdermal, Daily, Short cycles

Status: Not approved. Removed from FDA’s Category 2 list in April 2026; slated for a future advisory meeting. Several key papers have been retracted.

Grade and commentary: Dr. Alex Tatem. Watch: Truth About Popular Peptides Tier List (What Works, What’s Overhyped) | Pt. 3. Subscribe: @DrAlexTatem.