# PE-22-28

TREK-1-blocking spadin fragment; fast-acting antidepressant in mice.

- Page: https://peprank.xyz/peptides/pe-22-28
- Category: Mood & anxiety (Research peptide)
- Also known as: mini-spadin
- Routes: Nasal / Injection
- Sequence: GVSWGLR (spadin fragment (sortilin propeptide 22-28))
- Safety tier: Strict: Avoid · Balanced: Caution · Evidence only: Caution
- Risk axes (0 none to 3 severe): Seen harm 1, Mechanism 2, Data gap 3, Silent harm 2, Product 2
- Positive: 54% of 29 graded reports glowing or positive, shrunk toward the 49% all-report average by 8 reports' weight
- Rank: #28 of 61 research peptides
- Graded reports: 29 (Glowing 5, Positive 11, Mixed 3, Nothing 5, Negative 2, Bad reaction 3)
- Evidence: Animal only
- Access: Grey market
- Onset: Most responders notice it on day 3-4, in line with the four-day effect in mice; a few feel a same-day lift and others only after one or two weeks.
- Lasts: About a day per dose, sometimes spilling into the next day as overstimulation; users say benefits fade back to baseline over weeks after a cycle.
- Cost per month: ≈ €36–140 (researchers' estimate)
- Updated: 2026-10-30

**Why Avoid under the strict bar:** No human data, and it blocks a channel whose loss makes animals more prone to seizures and ischaemic injury.

## What users report

Some describe life-changing lift from depression, postpartum mood or anhedonia within days; others feel worse or irritable with restless sleep at higher doses. Roughly 15-25% of reporters feel nothing and a similar share feel worse: low mood, irritability or rage, overstimulation, and single reports of racing heart with nausea and of visual snow worsening for months.

**Effects:** mood lift within days; motivation (getting to the gym); fewer meltdowns/triggers

**Downsides:** irritability and restless sleep at higher dose; worse mood in some; anger when stacked with P21

**Risks:** no human data; TREK-1 knockout mice are more vulnerable to ischaemia and seizures; chronic channel blockade could in theory lower neuroprotection or seizure threshold (spadin studies in rodents reported no such effects)

**Typical use:** 100-300 mcg/day nasal or subq (community).

**Getting it:** Sold by research-peptide vendors as vials and ready-mixed nasal sprays; one user gets it pre-mixed through a physician. Often out of stock.

**Stacked with:** Selank (Common pairing, sometimes in one nasal spray; users credit Selank with the calming and PE-22-28 with the mood lift.); Antidepressants, especially MAOIs (Used to taper off or augment them; one phenelzine user described near-serotonin-syndrome symptoms at 800 mcg, settling at 600 mcg.); P21 (One user who took both became uncharacteristically angry.); CJC-1295/ipamorelin (Paired by the best-known positive reporter for sleep.)

## Risk profile

- **Seen harm 1/3:** No human study exists. First-hand reports include rage and tachycardia, and one describes pre-existing visual snow markedly worse for months; isolated and confounded.
- **Mechanism 2/3:** Built to block the TREK-1 potassium channel, the same change that in knockout mice brings the antidepressant effect and severe vulnerability to seizures and stroke (75% vs 3% mortality after kainate). Rodent studies of the parent spadin found no such effects, so the risk is credible rather than demonstrated.
- **Data gap 3/3:** No human data of any kind.
- **Silent harm 2/3:** Seizures would be obvious, but lost neuroprotection would stay silent until a stroke or seizure trigger tested it.
- **Product 2/3:** Grey-market nasal sprays and vials.
- **Never if:** Epilepsy or a history of seizures; Stroke risk or prior stroke; Pregnancy or breastfeeding (no human reproductive data)

## Top reports

- Glowing, mood, 200 mcg/day, mornings (titrated 100-300): “I'm 40, male, with a longstanding history of depression and anxiety. Pharmaceutical treatment was not effective for me... including a game changer (for me at least): PE-22-28.” — [r/BodyHackGuide](https://www.reddit.com/r/BodyHackGuide/comments/1usdvmp/my_pe2228_experience/)
- Glowing, mood, 300-600 mcg, irregular (up to 1 mg on some days): “I am postpartum, if that helps or makes any difference. I wish I knew about this peptide after my previous 2 pregnancies. It’s kept my mood SO much more stable.” — [r/anhedonia](https://www.reddit.com/r/anhedonia/comments/1s3urrf/pe2228_experiences/oswceq7/)
- Glowing, mood: “Im at week 5 and it has been incredible for me. Im Audhd & hv cPTSD, my triggers and meltdowns have reduced immensely. I have been able to function like a human bean and socialize.” — [r/BodyHackGuide](https://www.reddit.com/r/BodyHackGuide/comments/1usdvmp/my_pe2228_experience/p5su4k7/)
- Glowing, mood, 300-400 mcg/day: “i have been on for 3 months now, and it’s been honestly incredible. i have always been a moody person but also had anhedonia from Reta, and this has helped all of it. I have a consistently good and motivated mood!” — [r/anhedonia](https://www.reddit.com/r/anhedonia/comments/1s3urrf/pe2228_experiences/p5ind5a/)
- Glowing, mood, 20 units of a 10 mg vial, 5 times a week: “I've been on it for a week and a half and feel great!!! Mood is balanced and I feel happier. Its been amazing.” — [r/NooTopics](https://www.reddit.com/r/NooTopics/comments/1mpxh69/any_review_on_pe2228/opjc5ul/)

## Cheapest in Europe

- [Europa-Peptide](https://europa-peptide.de/en/shop/pe-22-28-10mg/) (PL): PE 22-28 10mg, €50, €4.99/mg

## Studies

- [Mazella et al. 2010: spadin, a sortilin-derived peptide targeting TREK-1, as a new antidepressant concept](https://pubmed.ncbi.nlm.nih.gov/20405001/) (animal, 2010): The parent peptide spadin blocked TREK-1, raised serotonin-neuron firing and had antidepressant effects in mice after four days of treatment instead of the weeks SSRIs need; TREK-1 knockout mice are depression-resistant.
- [Djillani et al. 2017: shortened spadin analogs display better TREK-1 inhibition, in vivo stability and antidepressant activity](https://pubmed.ncbi.nlm.nih.gov/28955242/) (animal, 2017): The paper that designed PE 22-28; it blocked TREK-1 far more potently than spadin (IC50 0.12 nM vs 40-60 nM), lasted longer in vivo and reduced depression-like behaviour and raised neurogenesis in mice after four days.
- [Pietri et al. 2019: protective effects of sortilin-derived peptides on stroke recovery and post-stroke depression](https://pubmed.ncbi.nlm.nih.gov/31325429/) (animal, 2019): Mini-spadin (PE 22-28) improved motor and cognitive recovery and prevented post-stroke depression in mice; it activated TREK-1 at low doses and blocked it at higher ones.
- [Heurteaux et al. 2004: TREK-1, a K+ channel involved in neuroprotection and general anaesthesia](https://pubmed.ncbi.nlm.nih.gov/15175651/) (animal, 2004): Mice lacking TREK-1 were more vulnerable to brain ischaemia and epileptic seizures, the basis of the theoretical risk of blocking it long term.
- [Djillani et al. 2019: fighting against depression with TREK-1 blockers, a focus on spadin](https://pubmed.ncbi.nlm.nih.gov/30291907/) (review, 2019): Review by the originating group of spadin and its analogues; all efficacy data are from rodents and no human trial has been published.

## Sources

- [Heurteaux et al. 2004: TREK-1, a K+ channel involved in neuroprotection (knockout vulnerability)](https://pubmed.ncbi.nlm.nih.gov/15175651/)
- [Moha ou Maati et al. 2011: spadin, absence of TREK-1-related side effects (rodents)](https://pubmed.ncbi.nlm.nih.gov/21807005/)