Aspirin Treats Depression By Lowering Cortisol And Inflammation


Mar 18, 2013
USA / Europe
This was an animal study but it follows a long thread of other studies and some of them with humans. Unfortunately, so far all of the human studies used aspirin only as an adjuvant but hopefully as new studies like the one below continue to appear the opinion on aspirin will change.
Ray has written many times about the damaging effects of cortisol on the hypocammpus and the brain as a whole. There is solid evidence that inflammation plays a role in depression and some countries have already trialed NSAIDs for depression in small pilot studies that dis not use placebo. What is good about the study below was that the dose of aspirin used was quite low, treatment was for only 14 days and aspirin had a profound lowering effect on plasma cortisol. I think this is the primary mechanism behind its anti-depressive effects at least in this study. The HED of aspirin was just 1.5mg/kg, which means that most people can get by on less than half a tablet (325mg) daily replicate this study.
What is also interesting and potentially worrying is that one of the treatment groups used dexamethasone since the model of depression was induced through inflammation. So, the dexamethasone group was expected to experience anti-depressant effects. Well, not only did that not happen but the dexamethasone group had its cortisol levels shoot up and reach levels not much different from the placebo depressed group. The reason this is worrying is that dexamethasone is a potent synthetic glucocorticoid and is used instead of cortisol for acute management of pretty much all "autoimmune" conditions, as well as cases of real adrenal failure like Addison disease. But according to the mainstream medical sources, dexamethasone is supposed to suppress plasma cortisol levels since it is itself a cortisol-type sterois. In fact, the tests for depression and Cushing syndrome are called exactly that - "dexamethasone suppression test" - since it is supposed to suppress endogenous cortisol release. If chronic treatment with dexamethasone actually increases cortisol levels, then dexamethasone "treatment" itself is likely to cause depression, Cushing syndrome, and variety of other conditions related to excess cortisol. The official version is that cannot happen since dexamethasone actually suppressed cortisol and once the "treatment" stops the cortisol levels return to normal. Well, not according to this study.

Beneficial effect of aspirin against interferon-α-2b - induced depressive behavior in Sprague Dawley rats. - PubMed - NCBI

"...The serum cortisol levels increased significantly in interferon, dexamethasone and interferon plus dexamethasone when compared with the normal control group. However, it reduced significantly in all the other treatment groups."

"...Concomitant treatment of dexamethasone in interferon treated group decreased sucrose preference but did not affect the raised cortisol levels and immobility caused by Interferon treatment. Raised corticosteroids in the body cause various actions leading to depressive behavior.53-54 It can also attribute to the changes in the hippocampus of the brain.55-56 Further, reduction in the brain serotonin levels may be a result of induction of tryptophan 2, 3 dioxygenase57 leading to decrease in brain serotonin levels as observed in the current study. The use of novel antidepressants like Antalarmin, a CRHR-1 (Corticotropinreleasing hormone receptor-1) blocker in the treatment of depression58 is strengthened by the study."

"...Aspirin treatment in interferon- α-2b model of depression for about 21 days, showed significant ntidepressant effect through the parameters such as sucrose preference test, serum cortisol levels and brain monoamines using forced swim test. There was increase in sucrose preference and reduction in serum cortisol in the interferon group pretreated with aspirin. Also, there was noteworthy decrease in immobility in the group treated with interferon- α-2b with aspirin."

"...Further, aspirin failed to show any beneficial effects in anxiety based tests such as actophotometer and elevated plus maze. However, increase in number of transitions with the use of aspirin in the light dark box suggesting anti-anxiety effects which could be attributed towards its ability to reduce cortisol levels under the study. Parallel to this, use of chronic corticosterone has been associated with anxiogenic effects in mice."

"...Thus, our findings suggest that targeting anti-inflammatory drugs (like NSAIDS) in the treatment of depression is beneficial. Our findings strengthen the possibility of aspirin intervention in the pathogenesis of depression. Aspirin may serve as a potential adjunctive therapy for individuals suffering from depression, particularly arising from use of interferon in Hepatitis B or other forms of depression. Regardless of the mechanism(s) involved, aspirin treatment appears to have a beneficial effect on depressive psychopathology."


May 3, 2015
My friend has been off his SSRI escitalopram for a month and has seemed less stressed.

After hearing about this he will try 200mg aspirin with his daily cappuccino. (I also mentioned the 112 year old who took aspirin with caffeine and that the combo can reduce digestive pain.)

Of course any effects could be placebo, but it is a relatively inexpensive placebo.
Nov 21, 2015
Good catch. This study although confounded somewhat may have reached a similar conclusion

An elevated cortisol response in the DEX/CRH test was correlated with a four- to six-fold higher risk for relapse than in individuals with a normal cortisol response. The two proposed rules for predicting relapse within the first 6 months after discharge could be optimized by including age and gender. Hence, an exaggerated cortisol response in the combined DEX/CRH test predicts the recurrence of depressive psychopathology. The test performance can be further optimized if gender and age are taken into account.


Thread starter
Mar 18, 2013
USA / Europe
Good catch. This study although confounded somewhat may have reached a similar conclusion

An elevated cortisol response in the DEX/CRH test was correlated with a four- to six-fold higher risk for relapse than in individuals with a normal cortisol response. The two proposed rules for predicting relapse within the first 6 months after discharge could be optimized by including age and gender. Hence, an exaggerated cortisol response in the combined DEX/CRH test predicts the recurrence of depressive psychopathology. The test performance can be further optimized if gender and age are taken into account.

Thanks, good find too. I have seen the cortisol response as a biomarker of depression relapse. In other words, using the dexamethasone suppression test, people with depression or at risk for relapse fail to suppress. But the study I posted shows something worse - dexamethasone actually increased baseline cortisol, which is worse than just failing to suppress it. So, what I am saying is that people who get treated with synthetic glucocorticoids may actually be given depression iatrogenically - i.e. as part of their glucocorticoid "treatment". Certainly not something anyone expects when they go to get their cortisol shot for RA, Lupus, psoriasis, etc.


Jul 23, 2015
Spokane, Washington
I was just reading this study while writing my book; thanks for posting it.


Nov 20, 2014
My appetite went to crap about 8 months ago (common sign of depression among others I am struggling with) and seems to be getting worse even though I have been taking 325mg of aspirin a day.

But my cortisol levels are normal even though I have several symptoms of adrenaline, including high stress, cold feet and frequent urination.

Should I be concerned that the Aspirin will cause my cortisol levels to drop to low since they are already normal?


Jan 11, 2019
Hi haidut, a friend of mine takes dexamethasone for adrenal insufficiency of something-hydroxy-progesterone. What would u do to help her? Should we taper her off the drug? Should she take aspirin with it? Do u know what u would do in my shoes? Shes extremely moody and mean and constantly thinks everyone's against her, I really want to help. Thanks.
Similar threads
Thread starter Title Forum Replies Date
haidut Aspirin (but Not Other NSAID) Treats Barrett’s Esophagus And Possibly GERD Scientific Studies 38
H Aspirin Both Triggers And Treats An Often-Missed Disease Articles 3
F Good aspirin source in the UK? Ask For Help or Advice 1
VendettaRed911 What, if any, effect does aspirin have on ketosis? Supplements, Pharmaceutical Drugs 0
haidut Aspirin may prevent and treat COVID-19 Scientific Studies 1
haidut DHT / Progesterone / aspirin treat, cortisol ineffective, PUFA promotes prostate cancer Scientific Studies 1
Jam Association Between Aspirin Use and Biliary Tract Cancer Survival Scientific Studies 18
F Any long term Aspirin users experience? Aspirin 27
S Aspirin & herbs interaction Ask For Help or Advice 0
Blaze There are more drug related deaths from aspirin than any other drug on the planet. Ask For Help or Advice 38
ecstatichamster Aspirin increases cancer and mortality — or does it? Scientific Studies 9
Hans Is aspirin harmful to the mitochondria? (a discussion of the research) Articles & Scientific Studies 12
D Is Willow Bark More Effective Than Aspirin > For Pain/Inflamation? Aspirin 0
Hans Is aspirin really harmful to the gut (bleeding risk)? Articles & Scientific Studies 32
Lizb Dose of aspirin for mild cognitive impairment/dementia please? K2 also? Mental Issues 6
T Aspirin and Testosterone Ask For Help or Advice 14
S Aspirin reduces testosterone and sperm count Ask For Help or Advice 89
S Low dose aspirin to treat inflamation induced insulin resisitance? Blood Sugar 1
S Aspirin for treating male pattern baldness Hair & Nails 29
K aspirin Ask For Help or Advice 3
ecstatichamster How would you take aspirin topically Aspirin 8
L Root canal , aspirin , root canal removal Oral Health 0
J The Spanish Flu's true culprit - it was aspirin all along! Miscellaneous Health Discussions 8
mayku-T-meelo Aspirin/Acetylsallicylic acid - source in Europe? Supplements, Pharmaceutical Drugs 9
K aspirin/ k2 Supplements, Pharmaceutical Drugs 0
haidut Aspirin can cure liver cancer in just 24 hours (in rabbits) Scientific Studies 2
L Aspirin/Salicylates are calorie restriction mimetics Aspirin 6
S Aspirin, niacinamide and eye bags Supplements, Pharmaceutical Drugs 7
M aspirin and increased hair loss Hair & Nails 4
J Would It Be Effective To Mix Aspirin Tablet With Charcoal For A Intestinal Disinfectant? Supplements, Pharmaceutical Drugs 3
L Aspirin As A Suppressor Of Cancer-related Epigenetic Aging Scientific Studies 2
P Aspirin Use Reduces Risk Of Death In Hospitalized COVID-19 Patients Scientific Studies 0
haidut Aspirin Has Dramatically Lower Bleeding Risk Than Pharma Anticoagulants Scientific Studies 10
lvysaur Why Does Aspirin Lower My Bilirubin? Blood Work, Labs 2
Mauritio Aspirin Reduces Deaths In COVID-19 Patients By 47% Aspirin 14
B Crickets Fed Low Dose Aspirin Live 143% Longer, Have Longer Childhoods And Higher Metabolic Rates Scientific Studies 7
ddjd Aspirin Significantly Lowers Risk Of Complications, Death In COVID Ask For Help or Advice 4
TopGun1911 Massive Brain Fog After Taking Aspirin (500 Mg) Supplements, Pharmaceutical Drugs 14
D Coffee,Milk Plus Aspirin And MB Male Issues 2
A Aspirin Gave Me Permanent Tinnitus, Help Ask For Help or Advice 59
ScurveDream For Those Who Cannot "stomach" Aspirin Or Etc Aspirin 3
_lppaiva Stopped Aspirin Cold Turkey. Any Permanent Risks? Ask For Help or Advice 9
C Is Aspirin Estrogenic? Aspirin 18
A Does Aspirin Inhibit Mitochondrial Respiration? Aspirin 54
explosionlord Aspirin + K2 + Glycine Poor Reaction; Anybody Else? Supplements 8
A. squamosa Good Aspirin Brands? Aspirin 11
jamies33 I Realized I'm Basically Always In Pain, And I've Just Gotten Used To It. Aspirin And Yoga Fixes It Metabolism 25
Energizer #33: NAD+/NADH, Stress, And Fatty Acids | How To Use T3, T4, And Aspirin | Histamine | Milk And Acne Danny Roddy 0
Amazigh Where Did All The Aspirin Powder Go? Supplements, Pharmaceutical Drugs 22
L Does Lithium Orotate Dissolve In Water Like Aspirin? Supplements, Pharmaceutical Drugs 3

Similar threads