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Orginally posted by Pereise1 at Longecity. 

 

For those with fatigue or anhedonia, orexin is a holy grail of possibilities, as it's intimately connected to feeling pleasure from enjoyable activities and feeling awake. As a person with Narcolepsy and pathologically low orexin, I'm highly interested in increasing orexin in order to feel more normal. So for the last few weeks, I've been scouring pubmed in search of things to increase orexin, as well as things to avoid. I'll be updating this post over at the narcolepsysupport site. So without further ado:

 

How To Increase:
 
Drugs and Herbs:
3. Galantamine (Nicotine activates orexin through the a4b2 nachr, which Galantamine upregulates)
6. Olanzapine (Antipsychotic, not really recommended)
7. Candesartan (Prevents a decline from Angiotensin II)
11. Other Antipsychotics (But seriously, don’t take them)
15. Noni
17. Linalool Odor (Not sure if ingesting has the same effect)
21. Rikkunshito (Via increased Ghrelin)
22. Mazindol (Supposedly has been discovered to be an Ox2 receptor agonist)
23. Scopolamine (Probably in low, subpsychosis doses)
24. GLP-1 Agonists (The -gliptan class of diabetic meds are GLP agonists, as well as things like olive leaf extract, glutamine, alpha casein, beta casein, and chlorogenic acid)
25. Forskolin (Induced long term potentiation in Orexin neurons)
26. GHRP-6 (Yes, the bodybuilding peptide)
27. Probably CBD (“Activates wakefulness promoting neurons in the lateral hypothalamus”)
28. N-Acetylglucosamine (I say NAG because regular glucosamine doesn’t pass the BBB well)
 
Diet:
32. Saturated Fat (Coconut oil seems like a good option, as it has medium chain triglycerides as well)
36. Zinc Sulfate (Probably other types of Zinc too)
37. Short Term Fasting (Maybe Intermittent Fasting)
39. Amino Acids/Proteins (glycine > aspartate > cysteine > alanine > serine > asparagine > proline > glutamine)
40. Phytoestrogens (From soy)
43. High Salt (Via aldosterone)
 
Hormones:
47. Oxytocin (Intranasal probably works best)
50. Corticosterone (In the morning)
 
Pathways:
52. Neuropeptide S (Good luck trying to increase this)
54. Ghrelin
56. GabaB Sensitivity (Through decreased sensitivity of the GABAA receptors)
58. Pregnancy (Beginning of gestation)
59. CCR3 (Chemokine Receptor that protects Orexin from inflammation)
60. Acetylcholine (The Muscarinic M3 Receptor alone activates almost 20%)
61. Oxytocin (Fenugreek should help, as well as oleoylethanolamide, and by 0.5mg Melatonin but not 5mg Melatonin)
62. Neuropeptide Y in the hypothalamus (According to this study, Adaptogens and specifically Salidroside from Rhodiola increase Neuropeptide Y in the right places)
– Ginseng
– Gastrodin is also a good option for directly increasing Neuropeptide Y in the Hypothalamus
– Also Escitalopram and Venlafaxine, although I can’t personally recommend those.
63. Sigma 1 Receptors (By disinhibiting Orexin from Corticotropin and Histamine H3 receptors)
64. Sirt1
65. Nicotinic a4b2 receptors (Nefiracetam is an agonist at this receptor and Galantamine is a positive allosteric modulator)
 
Activities:
68. Exercise (It seems that physical activity that one enjoys is far more effective than simple exercise)
69. Cold Exposure (Possibly via the actions of Neurotensin, which increases Orexin and is activated by cold)
 
 
Things That Lower Orexin
 
Drugs:
4. THC (Attenuated by MDMA somehow)
 
Activities:
7. Heat Stress (In vitro)
 
Diet:
9. Obesity (A number of studies suggest this)
12. Glucose
 
Hormones:
 
Pathways:
14. 5-HT1B
15. Melanin Concentrating Hormone (Study notes that Orexin and MCH KO mice don’t have EDS)
19. 5-HT1A (This is exclusively the postsynaptic receptor in the hypothalamus. Orexin itself activates the presynaptic receptor in the Dorsal Raphe Nucleus)
21. Melatonin, through the MT1 receptor
22. DEC2 Circadian Gene (R-Lipoic Acid Downregulates This)

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