Meta Information
ID:dihexa
Name:
Schema Version:2.4_uniform_evidence_2026_06_18
Created
2026-05-20
Model
agent_curation_2026_05_20_peptides
Interactions
Target id:
/condition/fda-compounding-risk
Target name:
FDA-Identified Compounding Safety Risk
Severity:
major
Interaction type:
adverse
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
Dihexa acetate has no FDA-approved indication. The FDA placed it in 'Category 2' bulk drug substances - those that may present significant safety risks for compounding - citing a lack of adequate human safety data and no approved clinical use. On 15 April 2026 the FDA removed dihexa (with 11 other peptides) from Category 2 pending a Pharmacy Compounding Advisory Committee review (expected by early 2027); removal does NOT make it eligible for compounding, and it remains an unapproved substance with no verified safety profile.
Actionable advice:
Dihexa has no FDA-approved formulation and no verified human safety profile. It was flagged by the FDA among compounding bulk substances of significant safety concern; any compounded dihexa product remains unapproved and unverified.
Validation status:
validated_via_regulatory
Evidence tier:
tier_b
Evidence basis:
regulatory_advisory_verbatim
Evidence anchors:
Exact phrase from label:
Certain Bulk Drug Substances for Use in Compounding That May Present Significant Safety Risks
Label source:
US FDA compounding advisory. Dihexa acetate was placed in 'Category 2' (substances that may present significant safety risks); the FDA removed it from Category 2 on 2026-04-15 pending Pharmacy Compounding Advisory Committee review, and it remains unapproved and outside enforcement discretion.
Action type:
informational_none
Target id:
/condition/severe-hepatic-impairment
Target name:
Severe Hepatic Impairment
Severity:
moderate
Interaction type:
adverse
Nature:
conditional
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
The Dihexa monograph recommends dose reduction or avoidance in severe hepatic impairment due to potential for altered metabolism and accumulation. Minor, reversible liver enzyme elevations were observed at highest doses in chronic toxicity studies in animals.
Actionable advice:
The dose is best reduced, or dihexa avoided, in patients with severe hepatic impairment. Liver enzymes should be monitored during use.
Validation status:
unvalidatable
Evidence tier:
tier_e
Evidence basis:
unvalidatable
Evidence anchors:
Source url:
Scientific literature support not found
Exact phrase from label:
Label source:
Action type:
avoid
Target id:
/condition/psychiatric-disorders
Target name:
Psychiatric Disorders
Severity:
moderate
Interaction type:
adverse
Nature:
conditional
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
The Dihexa monograph recommends use with caution in individuals with psychiatric disorders and monitoring for mood changes or anxiety. The neurotrophin-potentiating and glutamatergic effects of dihexa could theoretically affect mood and anxiety, particularly in vulnerable populations.
Actionable advice:
This is best used with caution in patients with pre-existing psychiatric disorders, and it is a good idea to monitor for mood changes, increased anxiety, or behavioral changes.
Validation status:
unvalidatable
Evidence tier:
tier_e
Evidence basis:
unvalidatable
Evidence anchors:
Source url:
Scientific literature support not found
Exact phrase from label:
Label source:
Action type:
monitor
Target id:
/condition/pregnancy
Target name:
Pregnancy
Severity:
major
Interaction type:
adverse
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
Dihexa is contraindicated in pregnancy and lactation due to insufficient safety data and theoretical risks from c-Met/HGF pathway activation during fetal development.
Actionable advice:
This should not be used during pregnancy or breastfeeding.
Validation status:
unvalidatable
Evidence tier:
tier_e
Evidence basis:
unvalidatable
Evidence anchors:
Source url:
Scientific literature support not found
Exact phrase from label:
Label source:
Action type:
avoid
Target id:
/condition/lactation
Target name:
Breastfeeding (Lactation)
Severity:
major
Interaction type:
adverse
Nature:
absolute
Temporal spacing:
null
Description:
It is unknown if Dihexa can pass into breast milk or what effects it might have on a nursing infant; therefore, its use is contraindicated.
Actionable advice:
It should be avoided completely while breastfeeding.
Validation status:
unvalidatable
Evidence tier:
tier_e
Evidence basis:
unvalidatable
Evidence anchors:
Source url:
Scientific literature support not found
Exact phrase from label:
Label source:
Action type:
avoid
Target id:
/dietary/meal
Target name:
Oral Administration with Food
Severity:
minor
Interaction type:
informational
Nature:
informational
Temporal spacing:
null
Description:
Unlike most peptides, dihexa was specifically engineered to be metabolically stabilized and orally active with blood-brain-barrier penetration, so it is not simply destroyed by digestive proteases. The effect of food on its oral absorption has not been specifically characterized.
Actionable advice:
Dihexa is reported to be orally active and metabolically stable; the effect of taking it with or without food is not established. (Route of administration for non-clinical use remains unproven and unapproved.)
Validation status:
validated_via_primary_literature
Evidence tier:
tier_b
Evidence basis:
primary_literature_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
yielded an orally active, blood-barrier permeant, metabolically stabilized analog, N-hexanoic-Tyr-Ile-(6) aminohexanoic amide (dihexa), that exhibits excellent antidementia activity in the scopolamine and aged rat models and marked synaptogenic activity.
Label source:
PubMed: McCoy AT et al., J Pharmacol Exp Ther (2013), PMID 23055539 - dihexa is an orally active, metabolically stabilized AngIV analog. (Note: this article carries a journal Expression of Concern, 2021.)
Action type:
informational_none
Target id:
/class/stimulants
Target name:
CNS Stimulants
Severity:
moderate
Interaction type:
adverse
Nature:
absolute
Temporal spacing:
null
Description:
Anecdotal reports suggest Dihexa can have stimulating cognitive effects; combining it with other central nervous system stimulants (e.g., amphetamines, modafinil) may lead to overstimulation, anxiety, or jitteriness.
Actionable advice:
The dose of other stimulants is best avoided or significantly reduced when using Dihexa.
Validation status:
unvalidatable
Evidence tier:
tier_e
Evidence basis:
unvalidatable
Evidence anchors:
Source url:
Scientific literature support not found
Exact phrase from label:
Label source:
Action type:
avoid
Target id:
/circadian/sleep
Target name:
Going to Sleep
Severity:
moderate
Interaction type:
adverse
Nature:
temporal
Temporal spacing:
Hours before target:
8
Hours after target:
null
Description:
The potential stimulating effects of Dihexa may interfere with sleep onset and quality if administered too close to bedtime.
Actionable advice:
Dihexa is best taken more than 8 hours before planned bedtime.
Validation status:
unvalidatable
Evidence tier:
tier_e
Evidence basis:
unvalidatable
Evidence anchors:
Source url:
Scientific literature support not found
Exact phrase from label:
Label source:
Action type:
separate
Target id:
/class/dopaminergic-agents
Target name:
Dopaminergic Medications
Severity:
moderate
Interaction type:
adverse
Nature:
absolute
Temporal spacing:
null
Description:
Dihexa's activation of the HGF/c-Met pathway may influence dopaminergic systems; combining it with medications like L-DOPA or dopamine agonists could unpredictably alter their effects or side effect profile.
Actionable advice:
This is best used with caution and under medical supervision when taking dopaminergic medications.
Validation status:
unvalidatable
Evidence tier:
tier_e
Evidence basis:
unvalidatable
Evidence anchors:
Source url:
Scientific literature support not found
Exact phrase from label:
Label source:
Action type:
informational_none
Target id:
/class/topical-medications-general
Target name:
Other Topical Medications
Severity:
moderate
Interaction type:
adverse
Nature:
temporal
Temporal spacing:
Hours before target:
2
Hours after target:
2
Description:
If using Dihexa with a DMSO carrier for transdermal application, DMSO can dramatically increase the systemic absorption of other topical substances applied to the same area, potentially causing unintended side effects.
Actionable advice:
Other topical creams or medications are best not applied to the same skin area within 2 hours of Dihexa/DMSO application.
Validation status:
validated_via_class_inference
Evidence tier:
tier_c
Evidence basis:
class_inference_summary
Evidence anchors:
Source url:
Mechanistic / class inference (no primary source supports the specific interaction)
Exact phrase from label:
Class inference: dimethyl sulfoxide (DMSO), often used as a transdermal carrier for dihexa, is a well-established skin penetration enhancer that increases systemic absorption of co-applied topical agents, so separating other topicals is sound. NOTE: the originally cited PMID 35091007 is a transdermal-insulin paper unrelated to this point and has been removed.
Label source:
Class inference
Action type:
separate
Target id:
/condition/geriatric
Target name:
Geriatric (Older Adults)
Severity:
moderate
Interaction type:
adverse
Nature:
absolute
Temporal spacing:
null
Description:
While potentially studied for age-related cognitive decline, older adults may have a higher risk of comorbidities (like undiagnosed cancers) and altered drug metabolism, warranting extreme caution with this experimental compound.
Actionable advice:
This is best used with extreme caution in older adults, preferably under close medical supervision.
Validation status:
unvalidatable
Evidence tier:
tier_e
Evidence basis:
unvalidatable
Evidence anchors:
Source url:
Scientific literature support not found
Exact phrase from label:
Label source:
Action type:
informational_none
Target id:
/biomarker/comprehensive-liver-function-panel
Target name:
Liver Function Panel
Severity:
moderate
Interaction type:
adverse
Nature:
absolute
Temporal spacing:
null
Description:
As an experimental peptide with uncharacterized metabolic pathways and potential for unknown toxicity, periodic monitoring of liver enzymes (ALT, AST) is a prudent safety measure.
Actionable advice:
Obtain a baseline liver function panel before starting and monitor periodically during use.
Validation status:
unvalidatable
Evidence tier:
tier_e
Evidence basis:
unvalidatable
Evidence anchors:
Source url:
Scientific literature support not found
Exact phrase from label:
Label source:
Action type:
monitor
Target id:
/class/ace-inhibitors
Target name:
ACE Inhibitors
Severity:
minor
Interaction type:
adverse
Nature:
absolute
Temporal spacing:
null
Description:
As a highly modified analogue of Angiotensin IV, Dihexa could theoretically have unforeseen effects on the renin-angiotensin system, potentially altering the efficacy or side effects of ACE inhibitors.
Actionable advice:
It is a good idea to monitor blood pressure closely when combining with ACE inhibitors.
Validation status:
unvalidatable
Evidence tier:
tier_e
Evidence basis:
unvalidatable
Evidence anchors:
Source url:
Scientific literature support not found
Exact phrase from label:
Label source:
Action type:
monitor
Target id:
/class/arbs
Target name:
Angiotensin II Receptor Blockers (ARBs)
Severity:
minor
Interaction type:
adverse
Nature:
absolute
Temporal spacing:
null
Description:
As a highly modified analogue of Angiotensin IV, Dihexa could theoretically have unforeseen effects on the renin-angiotensin system, potentially altering the efficacy or side effects of ARBs.
Actionable advice:
It is a good idea to monitor blood pressure closely when combining with ARBs.
Validation status:
unvalidatable
Evidence tier:
tier_e
Evidence basis:
unvalidatable
Evidence anchors:
Source url:
Scientific literature support not found
Exact phrase from label:
Label source:
Action type:
monitor
Target id:
/circadian/wake
Target name:
Waking Up
Severity:
minor
Interaction type:
synergistic
Nature:
temporal
Temporal spacing:
Hours before target:
null
Hours after target:
1
Description:
Administering Dihexa in the morning aligns its potential cognitive-enhancing and stimulating effects with the body's natural period of activity and wakefulness.
Actionable advice:
It is generally best taken in the morning to support daytime cognitive function.
Validation status:
unvalidatable
Evidence tier:
tier_e
Evidence basis:
unvalidatable
Evidence anchors:
Source url:
Scientific literature support not found
Exact phrase from label:
Label source:
Action type:
informational_none
Target id:
/intervention/lion-s-mane-mushroom
Target name:
Lion's Mane Mushroom
Severity:
minor
Interaction type:
synergistic
Nature:
absolute
Temporal spacing:
null
Description:
Dihexa's HGF/c-Met activation may work synergistically with Lion's Mane, which promotes Nerve Growth Factor (NGF), potentially leading to enhanced effects on neurogenesis and synaptic plasticity.
Actionable advice:
May be taken together for potentially complementary neurogenic effects; start with low doses of both.
Validation status:
validated_via_class_inference
Evidence tier:
tier_c
Evidence basis:
class_inference_summary
Evidence anchors:
Source url:
Mechanistic / class inference (no primary source supports the specific interaction)
Exact phrase from label:
Class inference: Lion's Mane (Hericium erinaceus) has documented neurotrophic/NGF-stimulating activity (Lai et al. 2013, PMID 24266378); a complementary neurogenic effect with dihexa is plausible but unstudied. Synergy is theoretical, not demonstrated.
Label source:
Class inference
Action type:
informational_none
Target id:
/intervention/noopept
Target name:
Noopept
Severity:
minor
Interaction type:
adverse
Nature:
absolute
Temporal spacing:
null
Description:
The profound synaptogenic effects of Dihexa may be complemented by nootropics like Noopept that increase levels of BDNF and NGF, potentially enhancing cognitive outcomes through different mechanisms.
Actionable advice:
This combination is generally best used with caution, as the combined cognitive effects are unknown and could be overwhelming.
Validation status:
unvalidatable
Evidence tier:
tier_e
Evidence basis:
unvalidatable
Evidence anchors:
Source url:
Scientific literature support not found
Exact phrase from label:
Label source:
Action type:
informational_none
Target id:
/biomarker/igf-1
Target name:
Insulin-like Growth Factor 1
Severity:
minor
Interaction type:
synergistic
Nature:
absolute
Temporal spacing:
null
Description:
Monitoring IGF-1 provides a general indication of systemic growth factor activity, which may be influenced by potent activators of related pathways like HGF/c-Met.
Actionable advice:
Consider monitoring IGF-1 levels to ensure they remain within a healthy range during long-term use.
Validation status:
unvalidatable
Evidence tier:
tier_e
Evidence basis:
unvalidatable
Evidence anchors:
Source url:
Scientific literature support not found
Exact phrase from label:
Label source:
Action type:
monitor