STUDresearch · Peptide
PE-22-28
Also known as
Mini-Spadin · PE 22-28 · PE2228 · PE-2228 · PE22-28 · Spadin-related peptide (residues 22–28) · Spadin analog PE 22-28 · GVSWGLR peptide · Gly-Val-Ser-Trp-Gly-Leu-Arg · Sortilin propeptide fragment PE 22-28 · NTSR3/Sortilin-related TREK-1 ligand (spadin-lineage)
Community talk. May be wrong. Not medical advice. Not a protocol. Not for human or animal use.
Peptide
Some talk
Systemic
Nasal / SubQ
Cognitive / nootropic peptides
Systemic CNS focus — TREK-1 potassium-channel block and mood/serotonergic excitability, not a local tissue-repair peptide.
What people say
PE-22-28, or Mini-Spadin, is a seven-amino-acid TREK-1 blocker studied in cells and mice. It is distinct from parent spadin and modified G/A or biotinylated analogs; human mood benefits remain self-reports rather than controlled treatment evidence.
Doses people talk about
Nasal totals, per-nostril claims and SubQ amounts are not interchangeable. The full notes retain 8–16-week chart steps and high nasal outliers as reported context, not instructions. Mouse 3–4 and 32–40 mcg/kg figures concern specified experimental compounds and cannot be scaled into human doses.
How it may feel
Reports range from easier task initiation and improved mood around days 3–4 to no effect or worsening. Irritability, restless sleep and headache also appear. One positive user changed amounts and used other peptides; a separate 500 mcg SubQ user felt worse after nearly 3 weeks.
Inspected SubQ exchange200 mcg each morning
The author described little response at 100 mcg and irritability/restless sleep at 300 mcg, then a two-day break before returning to 200 mcg and noticing effects around days 3–4. Other peptides confounded attribution.
Separate SubQ worsening report500 mcg SubQ
A different participant reported no benefit or feeling worse after nearly 3 weeks. This is not the positive author's later outcome.
Lower SubQ chart family50–200 mcg/day
Once-daily education charts over 8–16 weeks; the full record retains 50, 100, 150 and 200 mcg steps as historical chart detail, not a proposed escalation.
Higher SubQ chart family250–500 mcg once daily
Often described for 4–8 weeks in clinic/vendor blogs. Wider per-administration summaries span 50–500 mcg and label 600 mcg–1 mg as higher territory.
Nasal practitioner discussion~400 mcg in the morning
A preserved practitioner anecdote contrasts 400 mcg with lethargy around 800 mcg; other spray reports mean 400 mcg per nostril, a different total.
Higher nasal marketing500 mcg–1 mg per nostril; 1–2 mg total
Some pages describe this total once or twice daily for 4–8 weeks. These aggressive marketing amounts conflict with lower charts and are not validated human standards.
Half-life & effect duration
- Half-life in the body
- Unmodified PE-22-28No settled estimate
- Felt duration people report
- Positive accountMood changes around days 3–4 and during continued use
- Other accountsNo effect, headaches, restless sleep or worsening around week 3
Cycles people discuss
Reported courses include 2–4, 4–8 and 8–16 weeks. One inspected author later described about 8 weeks on/2 off; other breaks range from days to weeks. These calendars do not establish a safe chronic cycle or necessary washout.
Timing
Morning use is favored in the notes to observe daytime mood and avoid late stimulation or sleep disruption. Once- or twice-daily patterns are community conventions; mouse analog responses do not validate human coverage.
Stacks
Selank, Semax and other mood/cognitive peptides recur in stacks, including a reported 500 mcg nasal PE-22-28 plus 300 mcg nasal Selank pairing. Effects and adverse reactions cannot be assigned cleanly to one compound; prescription interactions remain uncharted.
Watch for
Human safety gap (primary caution): No public Phase 1 program or controlled human side-effect rates; population risk is unknown.
Tap a line to jump into the full notes. Research only — may be wrong.
Timing context & sources
Half-life in the body
Human PE-22-28 parent half-life is not established; 23 hours is not that measurement.
Djillani Results/Figure 7 report forced-swim half-effect in modified analogs: G/A 3.2/32 mcg/kg yielded roughly 14/21 hours; biotinylated G/A 4/40 mcg/kg yielded 17/23 hours. These are mouse behavioral effects, not unmodified peptide concentration decay.
The reported comparison with roughly 7-hour spadin activity is also behavioral. Neither the cell potency nor analog response duration validates a human daily schedule, nasal exposure or parent elimination value.
- Djillani et al. — Shortened Spadin Analogs Display Better TREK-1 Inhibition, In Vivo Stability and Antidepressant Activity (opens in a new tab)2017;8:643, DOI 10.3389/fphar.2017.00643. Abstract, Figures 3/5/6 and Action duration / Figure 7. Exact Figure 7 mapping: G/A analog 3.2/32 mcg/kg → 14/21 h; biotinylated G/A 4/40 mcg/kg → 17/23 h forced-swim half-effect.Primary cell/mouse study; 23 h is a modified-analog behavioral half-effect, not parent plasma PK or an unmodified PE-22-28 human interval. IP efficacy arms and cell IC50 cannot be translated into human nasal/SubQ amounts. Full text accessed at publisher after PMC challenge. Results/Figure 7 give the mapping retained here; the Discussion reverses the high-dose 21/23-hour assignment. Results compare with a 6-hour spadin half-effect, while the abstract uses roughly 7-hour activity.
Felt duration people report
Some describe mood changes around days 3–4 and across weeks; others describe no effect, worsening or headache. A dependable per-dose duration is not established.
The positive OP reported little at 100 mcg and irritability/restless sleep at 300 mcg, then a two-day break before returning to 200 mcg morning SubQ and noticing effects around days 3–4; the author later clarified 8 weeks on/2 off. Another participant reported worsening around 3 weeks at 500 mcg SubQ; an older user reported no discernible effect.
The OP's changing amounts, GLPs and CJC/Ipamorelin are confounders. Supplier-linked subreddit context raises promotional risk. A self-chosen cycle is not evidence of safe chronic use or measured washout.
- My PE-22-28 Experience — positive report, adverse contrasts and OP calendar clarification (opens in a new tab)South_Return5422 OP and same-author replies: 200 mcg daily AM, confirms SubQ; 100 mcg little effect / 300 mcg irritability and restless sleep / two days off before returning to 200 mcg and noticing effects on days 3–4 (same-author reply, opened lines 108–113). cyntre13 separately reports 500 mcg SubQ for nearly 3 weeks, feeling worse. OP later says 60 days, then 8 weeks on/2 off. kayleeeeebop reports headache, then a retry without headache.Anonymous unverified products, depression/anxiety history, GLP and later CJC/Ipamorelin co-use; no validated safety or response rates. Subreddit links approved suppliers and OP offers sourcing DMs, so promotional risk is explicit. Interaction reassurance and suggested titration in replies are not adopted.
- Has Anyone Tried the Peptide PE-22-28? — nonresponse reply (opens in a new tab)baronjpetor reply: never felt anything while using PE-22-28 (opened lines114–119). Other ordering/update branches were read but remain collapsed/deleted at their outcomes.No route, amount or course was supplied for nonresponse. Do not generalize the author's claim of no positive feedback to the wider community; the visible older ordering branch does not prove a later result.
What people say
- Mood anecdotes (human, sparse): Lighter affect, less emotional flatness/anhedonia, “easier to get through the day,” situational depression bridge while waiting for life circumstances to settle — heavily confounded by expectancy and concurrent care. forum
- Clinic podcast lore (Yurth / SuperHuman Radio ecosystem): Framed as a short-course “rescue” for time-limited situational depression (job loss, grief window) because animal onset is fast and users can stop when the situation resolves — not a controlled trial claim. anecdote
- Clarity / mild nootropic claims: Some pair mood lift with focus or less brain fog; others say cognition only improves secondary to mood. No controlled human cognition data. anecdote
- Sleep secondary claims: Occasional better sleep once anxiety/mood settles; not a primary hypnotic like DSIP. Late dosing can disrupt sleep in some logs. forum
- Null / non-responders: Common. Purity, route, dose-band chaos, and expectancy explain much of the forum split. forum
- Stack confound: Often co-logged with Selank, Semax, DSIP, sleep changes, therapy, or exercise — single-agent credit is weak. forum
- Antidepressant-like (mice): Reduced immobility in forced-swim test; faster food-pellet latency in novelty-suppressed feeding after short subchronic treatment (classically ~4 days). animal
- Onset narrative vs SSRIs: Rodent multi-day behavioral change vs classic SSRI weeks-long clinical onset is the main marketing differentiator; human onset unproven. animal
- Neurogenesis / proliferation: ~4-day mouse protocols report increased hippocampal BrdU-positive cells and synaptogenesis markers; secondary write-ups often say roughly doubling BrdU+ counts in cited arms — model-specific. animal
- Synaptic markers: Higher PSD-95, synapsin, and related synapse-density talk in hippocampal work; rapid BDNF mRNA/protein up in hippocampus in secondary summaries of the same program. animal
- TREK-1 potency: ~0.12 nM IC50 — far stronger than parent spadin in the same assay line. lab
- Duration vs spadin: The shortened-analog paper's ~23-hour mouse figure is a forced-swim half-effect for a modified, biotinylated G/A analog after one injection, not measured unmodified PE-22-28 clearance. The ~7-hour spadin comparison describes prior behavioral activity. animal
- Post-stroke / ischemia models: Chronic spadin or PE-22-28 improved recovery measures (motor coordination, Morris water maze learning talk, reduced FST/NSF depression-like scores) with neurogenesis still detectable weeks after trauma in conference/paper summaries; reduced mortality/weight-loss language appears in secondary French-group write-ups. animal
- Post-stroke depression (PSD) angle: TREK-1 overexpression talk in PSD biology; PE-22-28/spadin-line inhibitors discussed as faster and cleaner-feeling than SSRIs in those mouse models — still animal only. animal
- Parent spadin safety narrative (borrowed): Spadin papers claim no interference with pain, epilepsy, ischemia infarct size, hERG/IKr-IKs cardiac currents, systolic BP/heart rate, or glycemia at studied exposures — forums project this onto PE-22-28 by analogy, not PE-22-28-specific multi-species tox. animal
- Selectivity talk: Spadin-line peptides framed as sparing other K2P channels (TREK-2, TRAAK, TASK, TRESK class claims in parent work) better than non-selective TREK drugs. animal
- Stress resilience (clinic blogs): Better tolerance of stressors without benzo-style sedation — serotonergic-upstream framing rather than GABA. forum
Doses people talk about
- Dose culture is split (important): Educational “conservative subQ” charts cluster ~50–200 mcg/day, while clinic/podcast/IN culture often clusters ~400 mcg IN or ~250–500 mcg subQ, and some vendor pages push ~500 mcg–1 mg+. Treat these as competing conventions, not a single ladder. forum
- Conservative subQ educational chart (10 mg vial style): Once-daily subQ 50–200 mcg with gradual titration over 8–16 weeks (example ladder: weeks 1–2 50 mcg → weeks 3–8 100 mcg → optional weeks 9–12 150 mcg → optional weeks 13–16 200 mcg). Many such charts say 100–150 mcg is “enough” given high potency. forum
- Higher subQ clinic/vendor bands: ~250 mcg conservative start AM → ~500 mcg “standard” once daily for 4–8 weeks appears on multiple protocol blogs. In an actual forum exchange, one author reported little response at 100 mcg and irritability/restless sleep at 300 mcg, then a two-day break before returning to 200 mcg morning SubQ and noticing effects around days 3–4; a separate user reported worsening at 500 mcg SubQ after nearly 3 weeks. Those are conflicting self-reports, not a titration recommendation. forumanecdote
- Broad research-chem mcg window: Roundups often list ~50–500 mcg per administration; low band ~100–250 mcg for mild mood/stress goals; moderate ~300–500 mcg; short-term higher ~600 mcg–1 mg in more aggressive write-ups. forum
- Yurth / Jay Campbell–cited IN depression discussion dose: ~400 mcg intranasal once daily in the morning as the most-quoted “clinic lore” figure for mood. forum
- IN high-end / lethargy talk (same ecosystem): ~800 mcg associated with lethargy in some people; “great success at 400 mcg for cognition without lethargy” if staying under ~600 mcg — anecdote from practitioner discussion, not a trial. anecdote
- IN split-nostril talk: Two sprays / one per nostril; some recommendations discuss ~400 mcg per nostril (higher total) when chasing stronger IN coverage — dose math and spray calibration vary wildly. forum
- IN standard protocol blogs (aggressive end): Tables listing 500 mcg–1 mg per nostril (1–2 mg total) 1–2× daily for 4–8 weeks appear on some sites — much higher than conservative subQ charts and than the 400 mcg morning figure; treat as marketing-heavy, not consensus. forum
- IN clinic-compound range (moderate): ~100–500 mcg per administration in 0.1–0.2 mL per nostril volumes is a commonly quoted compounded-nasal band. forum
- Frequency: Once daily dominates many write-ups; 1–2× daily appears when people worry about afternoon fade or copy nasal spray schedules. The cited day-scale mouse response is for modified analogs and does not validate either human schedule. forum
- Timing: Morning preferred — daytime mood/motivation observation and lower risk of sleep disruption; late dosing linked to stimulation/insomnia in some logs. forum
- Route debate — IN vs subQ: Practitioner lore (Yurth-class) claims intranasal works better than injection for this peptide and may need higher mcg when injected; educational charts still default to subQ for unit accuracy. Poor oral bioavailability is widely assumed for human products despite parent-line multi-route animal claims (IV, IP, ICV, SC, per os language in reviews). forum
- Microgram vs milligram confusion: PE-22-28 is discussed at micrograms, not the multi-mg doses common for BPC/TB500-class injectables; misreading mg for mcg is a real unit hazard. forum
- Vial sizes in commerce: Common research vials 5 mg and 10 mg lyophilized; spray pre-mixes skip vial math but hide true mcg/spray. forum
- Titration culture: Start low for several days–1–2 weeks, step only if tolerated; do not mega-escalate solely because “depression needs more.” forum
- Purity / identity risk: Without third-party HPLC/identity, labeled mcg is soft; short heptapeptides are easy to underfill or substitute. forum
- Framing: Discussed research/community/clinic ranges only — not medical advice, not prescriptions, not validated human protocols. Gray-market labeled mcg may not equal delivered peptide. forum
- Animal efficacy anchors (not a human map): Mouse IP roughly ~3–4 µg/kg class (examples 3.0, 3.2, 4.0 µg/kg; higher exploratory arms ~32–40 µg/kg in analog papers). ~4-day daily treatment for neurogenesis/NSF endpoints. Do not linearly scale µg/kg mouse → human mcg. In Djillani 2017, 3.0 mcg/kg refers to PE-22-28, 3.2/32 to G/A-PE-22-28 and 4.0/40 to its biotinylated G/A analog; the 32–40 mcg/kg duration arms must not be pooled as unmodified PE-22-28 amounts. animal
- No established human dose: Zero human RCTs define MTD, ED50, or safe chronic exposure. Every human figure is extrapolation or self-experiment convention. trial
How it may feel
- Hours 0–24 (first dose): Usually subtle or nothing acute — not a recreational high or stim “kick.” Nasal sting/drip more noticeable than mood for many first IN doses. forum
- Days 1–3: Early window for nasal irritation, mild headache, brief restlessness, or mood flux; a minority claim subtle ease or clarity. Clinic blogs sometimes market “hours-to-days” onset — unvalidated. forum
- Days 3–7: Aligns with rodent ~4-day neurogenesis/behavior narrative; first real “is this doing anything?” checkpoint for responders. Many still flat. An inspected self-reporter described little effect at 100 mcg and irritability/restless sleep at 300 mcg, then a two-day break before returning to 200 mcg morning SubQ and noticing effects around days 3–4; another participant reported feeling worse after about 3 weeks at 500 mcg SubQ. GLPs and later CJC/Ipamorelin confounded the positive account. forumanecdote
- Weeks 1–2: Common first keep-or-stop review for mood; non-responders rethink dose, route (IN vs subQ), product authenticity, sleep, and concurrent stressors. forum
- Weeks 3–4: Either consolidates as a steadier baseline or people drop it; expectancy and stack confounds peak here. anecdote
- Weeks 4–8 (protocol length): Matches most vendor/clinic cycle charts; full “course” reassessment; some continue only if clear benefit. forum
- Weeks 8–16 (longer titration charts): Conservative educational subQ schedules sometimes extend optional step-ups (150–200 mcg) only if tolerated — still not trial-defined. forum
- Beyond 1–2 months continuous: Few clean public long logs; durability and late sides poorly documented. forum
Cycles people discuss
- First trial (community): 2–4 weeks common for mood/cognition self-experiments before keep/drop. forum
- Most-cited protocol length: 4–8 weeks once-daily then reassess — appears across clinic blogs and vendor tables. forum
- Conservative educational longer blocks: 8 weeks minimum, optional 12–16 weeks with slow subQ titration (50→100→optional 150–200 mcg) on some dosage-education sites. forum
- Once-daily default in discussion: Once-daily use predominates in many charts; BID appears with coverage worries or nasal-spray habits. The borrowed full-day animal PD claim concerns modified analogs, not a validated human interval for PE-22-28. forum
- Time off: Inconsistent. No established PCT literature. Many simply stop after the planned block; some take days–weeks off before a re-run. The inspected positive author first described 60-day use, then clarified roughly 8 weeks on/2 weeks off, explicitly acknowledging that neither continuous use nor cycling has established safety. forumanecdote
- Open daily use: Discussed anecdotally for ongoing situational stress; long-term human safety tracking is essentially absent. anecdote
- Re-runs: After seasonal dips, grief, travel/work stress, or failed first attempt with better product/route — no standardized re-challenge data. anecdote
- Why cycle (community reasons): Cost, gray-market risk, unknown chronic TREK-1 block risks, diminishing subjective return, and desire to attribute effects. forum
- Situational short course lore: Clinic podcast framing as use during a defined life stressor then stop — contrasts with multi-month SSRI courses in that narrative. anecdote
Timing
- Daily-use rationale in community talk: Once-daily use is commonly contrasted with repeated daily use of very short plasma peptides. The borrowed near-day mouse response concerns modified analogs and does not establish human PE-22-28 coverage. forum
- Onset vs clearance: Behavioral/neurogenesis timelines (days) are not the same as plasma Tmax; “I don’t feel a kick at 30 minutes” is expected for many. forum
- Timing preference: Morning dose to observe daytime mood and avoid sleep unknowns. forum
- PD duration (mice, modified analogs): Results/Figure 7 report forced-swim half-effect times of ~14 and 21 hours for G/A-PE-22-28 at 3.2 and 32 mcg/kg, and ~17 and 23 hours for biotinylated G/A-PE-22-28 at 4 and 40 mcg/kg, respectively. The paper contrasts these with shorter spadin activity (roughly 7 hours in the abstract). These are behavioral responses, not unmodified PE-22-28 or human parent half-lives. animal
- Human PK gap: No validated human half-life, bioavailability %, Cmax, or brain-exposure curves for PE-22-28. trial
- Stability design intent: Shortened sequence selected for better in-vivo stability vs full spadin while keeping TREK-1 block. animal
- Parent multi-route claim: Reviews state spadin/analogs retained activity across IV, IP, ICV, SC, and oral (per os) in animals — does not prove human oral products are reliable. animal
More on what it is
- Why people care: Sold and podcasted as a fast mood peptide — rodent antidepressant-like effects in days rather than classic SSRI multi-week onset — plus a distinct ion-channel story (not monoamine reuptake). forum
- Name traps: PE-22-28 ≠ spadin ≠ full sortilin propeptide; Mini-Spadin is a brand/nickname, not a separate molecule. Gray-market labels may underdose or mis-ID. forum
- What it is: Synthetic 7-amino-acid peptide sequence GVSWGLR (Gly-Val-Ser-Trp-Gly-Leu-Arg) — residues 22–28 of the sortilin/NTSR3 propeptide lineage that produced spadin. Marketed and searched as Mini-Spadin. Not FDA-approved; research-chem / clinic-compound discussion only. trial
- Parent lineage: Sortilin releases a ~44-AA propeptide; structure–function work identified potent TREK-1 activity in shorter fragments. Spadin is the longer optimized fragment (commonly described as PE 12–28 / Ala12–Arg28 class). PE-22-28 is the shortest high-affinity core that still blocks TREK-1 well in the Djillani et al. analog series. trial
- Mechanism talk: Selective TREK-1 (KCNK2) two-pore-domain K+ channel blocker. TREK-1 open state damps neuronal excitability; block → more excitability in serotonergic / mood-circuit neurons (raphe, limbic, hippocampal talk). Downstream marketing also mentions BDNF, PSD-95, CREB, and hippocampal cell proliferation after multi-day rodent exposure. animal
- Potency vs spadin (in vitro): Patch-clamp on hTREK-1/HEK cells — PE-22-28 IC50 ~0.12 nM vs spadin ~40–60 nM (roughly ~300–500× lower concentration for 50% TREK-1 inhibition in that system). lab
- Stability design: Shortened spadin analogs were investigated for longer behavioral action. The ~23 h headline belongs to a biotinylated G/A-PE-22-28 analog in mice, compared with the roughly 7 h spadin activity narrative; it is not unmodified PE-22-28 plasma half-life. animal
- Evidence honesty: Strong rodent + in-vitro package (Djillani 2017 Frontiers in Pharmacology core paper; stroke/PSD follow-ons; parent spadin Mazella 2010 PLoS Biology). No published human RCTs, no Phase 1 PK package, no validated human dose. Every human mcg figure is clinic/vendor/forum convention. trial
- Not: Not an SSRI/SNRI; not a benzo; not full-length spadin; not BDNF/TrkB agonist peptide (some protocol blogs mislabel it that way — mechanism is TREK-1/spadin lineage); not FDA-approved for depression or cognition. trial
Stacks
- Mood / stress stack (most discussed): PE-22-28 + Selank (or N-Acetyl Selank Amidate) — TREK-1 mood narrative + Selank anxiolytic/GABA-enkephalin narrative. Example community table: PE-22-28 ~500 mcg IN + Selank ~300 mcg IN (illustrative only). forum
- Brain wellness / focus pair: PE-22-28 + Semax (or N-Acetyl Semax Amidate) — serotonergic/mood channel + BDNF/NGF-style nootropic. Example secondary language: Semax ~600 mcg/day alongside PE-22-28. forum
- Mood + sleep: PE-22-28 + DSIP — addresses sleep–mood loop from both directions in clinic marketing. forum
- Neuroplasticity triple talk: PE-22-28 + Dihexa + BPC-157 — cognition/repair stacking on blogs; high confound, weak single-agent attribution. forum
- Cognitive energy lists: PE-22-28 + NAD+ (sometimes with Semax) for “neuronal metabolism” marketing. anecdote
- Quad nootropic lore: Occasional logs of Semax + Selank + PE-22-28 + Pinealon for focus/clarity — pure anecdote. anecdote
- Secondary cardiac/mood blog theory: PE-22-28 + SS-31 (elamipretide) appears in some educational “memory + heart + mood” speculative guides — not a standard community core stack. forum
- Methylene blue / misc nootropics: Rare co-mentions; no synergy proof. anecdote
- SSRI / Rx antidepressant caution: Theoretical serotonergic interaction and “don’t self-stack on prescription ADs without a physician” is repeated on clinic pages — no formal interaction chart exists for PE-22-28. forum
- MAOI / serotonin-syndrome scare language: Some secondary pages list concurrent MAOI avoidance and serotonin-syndrome watch signs by analogy to serotonergic drugs — mechanistic caution, not documented PE-22-28 case series. forum
- Lifestyle co-factors: Sleep, therapy, exercise, omega-3 / nutrient density often credited when mood improves. forum
- Stack rule of thumb: Introduce one agent at a time so PE-22-28 response is isolable; never mix multiple peptides in one syringe without a defined reason. forum
Storage notes
- No mix instructions here: STUDresearch does not list reconstitution, diluent volumes, or syringe unit charts. People reconstitute many different ways and vial labels differ — that content creates more confusion than clarity. forum
- Storage (general talk only): Unopened research products are usually kept cool, dry, and away from light per the seller label. Anything after first use is product-specific — follow the label, not a universal forum SOP. forum
Watch for
- Nasal irritation (most common IN): Stinging, congestion, post-nasal drip, or mucosal irritation early on; often said to ease within the first week. forum
- Injection site: Redness, itch, mild swelling or tenderness with subQ. forum
- Headache: Mild, first few days, usually self-limiting in clinic-blog lists. forum
- Fatigue / lethargy (dose-related talk): Mild fatigue early; higher IN doses (~800 mcg class) linked to lethargy in practitioner anecdotes — often cited reason to stay mid-band. anecdote
- Nausea: Occasional, sometimes dose-related and transient. forum
- Early mood flux / restlessness: Brief mood variability, irritability, or restlessness days 1–3 in minority reports; dose reduction sometimes said to reverse irritability. anecdote
- Sleep disruption: If dosed late — increased mental stimulation / difficulty sleeping in some protocol lists; also “vivid dreams” appears on some IN protocol pages. forum
- Appetite notes: Mild reduced appetite rarely mentioned and said to be short-lived. anecdote
- Drug interactions (uncharted): Combining with Rx antidepressants, anxiolytics, MAOIs, or other serotonergic agents is not charted; clinic pages urge physician screening. forum
- Pregnancy / breastfeeding: Avoid language is standard on secondary guides — no reproductive tox package for this analog in community use. forum
- Source quality: Mislabeling, under-dosing, contamination, and sterile-technique failures on gray-market injectables/sprays. forum
- Unit / route errors: Confusing mg vs mcg, per-nostril vs total daily, and aggressive 1–2 mg IN tables vs 50–200 mcg subQ charts can produce accidental large relative overdoses. forum
- Psychiatric seriousness: Not a substitute for emergency or specialist care in major depression, bipolar, suicidal ideation, or psychosis — clinic blogs themselves usually include this boundary. forum
- Stop-and-seek-care flags (secondary checklists): Severe persistent headache, cardiac symptoms, seizure activity, severe mood worsening or suicidal ideation, serotonin-syndrome-like clusters — precautionary lists, not PE-22-28 trial endpoints. forum
- Human safety gap (primary caution): No public Phase 1 program or controlled human side-effect rates; population risk is unknown. trial
- Parent TREK-1 theoretical risks: Non-selective TREK modulation historically raised concerns about pain sensitivity, ischemia vulnerability, and seizures; spadin-line papers claim those functions were not worsened at studied doses — PE-22-28-specific chronic human risk still open. animal
- Cardiac narrative (borrowed): Spadin did not block IKr/IKs or alter BP/HR in preclinical cardiac work; PE-22-28 human cardiac data absent. animal
Evidence mix
Mostly community / anecdote tags
Full: every bullet (trial + community). Use Scan for a faster bro-science read.