A peptide for treatment resistant depression — a safer alternative to SSRI’s?

Neuropeptides, which are peptides active within the central nervous system, are increasingly recognized as key players in the development and manifestation of depression. Studies have indicated that peptides such as vasopressin, galanin, and neuropeptide Y play a crucial role in the regulation of monoamine receptor activity. This suggests that the issue with depression may not be as simple as a ‘chemical imbalance but rather a complex issue of improper chemical regulation and signaling mechanisms.

These peptide systems are not only implicated in depression but also in a variety of other neuropsychiatric disorders. For instance, schizophrenia has been linked to disruptions in several neuropeptide systems, including arginine-vasopressin, cholecystokinin, corticotropin-releasing factor, and neuropeptide Y, indicating that there may be a tangible physiological basis for the symptoms associated with these conditions.

The connection between neuropeptides and depression is further supported by the effects of electroconvulsive therapy ECT, which is known to be effective in treating severe mood disorders, has been observed to alter the levels of certain neuropeptides like neuropeptide Y, galanin, and somatostatin. This change in peptide levels suggests that the therapeutic benefits of ECT may derive from its ability to modulate neuropeptide regulation in the brain. Although research into the therapeutic potential of peptides for depression is still in the preliminary stages, several studies (and a plethora of anecdotal reports in humans) have shown tremendous promise. Today we’ll talk about one of my favorites with a long history of clinical use

PE-22-28

PE-22-28 is a synthetic derivative of the naturally occurring peptide spadin that is gaining attention for its potential benefits in treating depression. Spadin acts as an antagonist to the TREK-1 receptor, which is linked to depressive behavior and neurogenesis. Studies suggest that inhibiting TREK-1 can have antidepressant effects without the harmful side effects associated with traditional antidepressant medications.

PE-22-28 binds to and inhibits the TREK-1 receptor, modulating potassium ion flow in neural cells. This modulation influences neuronal excitability and neurotransmitter release, ultimately promoting neurogenesis and the growth of new neurons. PE-22-28 has been shown to exert antidepressant effects within four days, compared to traditional antidepressants that may take several weeks to become effective. It is effective regardless of how it is administered, making it a promising option for rapid relief from depressive symptoms.

Naturally occurring peptides like PE-22-28 generally have higher levels of safety compared to most antidepressants. They are less likely to provoke withdrawal behavior when discontinued and may have almost no harmful side effects while being equally or more effective than current antidepressants. While PE-22-28 i a relatively new peptide and human studies are limited, experiential data suggests that it holds promise as a safe and effective treatment for depression. In clinical practice, many integrative physicians are having tremendous success using PE-22-28 to get patients off antidepressant.

The dosage for PE-22-28 is typically somewhere around 400 mcg administered intranasally once a day, ideally in the morning. Injections might work better.