Methotrexate an Old Drug with New Tricks 2019


Senior Member

This review can be a good point to discuss Methotrexate positive and negative effects on ME/CFS and Fibro, two syndromes that can be comorbid with rheumatic diseases.

In this review, we describe the emerging mechanisms of action of MTX as an anti-inflammatory drug and complementing its well-established immunomodulatory activity. The mechanisms involve adenosine signaling modulation, alteration of cytokine networks, generation of reactive oxygen species and HMGB1 alarmin suppression. We also provide a comprehensive understanding of the mechanisms of MTX toxic effects. Lastly, we discussed the efficacy, as well as the safety, of MTX used in the management of viral-related rheumatic syndromes.


methotrexate effect on metabolism can alter brain function by

Upregulation of:

AICAR (This happens 10 hours after MTX intake) promotes awakeness AMPK activator
ADENOSINE (This happens a bit later/48h00 after MTX intake) promotes sleepiness

Downregulation of:

IMP (fatigue cramping exercice intolerance)
INOSINE (fatigue)

What to do to reduce these brain side effects?

-Folinic Acid supplementation 10 to 12 hours after MTX intake
-Caffeine or Theophylline
-Inosine supplementation
(and thymidine?)