Thanks to Emily Deans for bringing Ketamine, magnesium and major depression – From pharmacology to pathophysiology and back to my attention some time ago, in a Tweet.
"The link to the pathophysiology of depression is not clear. An overlooked connection is the role of magnesium, which acts as physiological NMDA-receptor antagonist:
1. There is overlap between the actions of ketamine with that of high doses of magnesium in animal models, finally leading to synaptic sprouting.
2. Magnesium and ketamine lead to synaptic strengthening, as measured by an increase in slow wave sleep in humans.
3. Pathophysiological mechanisms, which have been identified as risk factors for depression, lead to a reduction of (intracellular) magnesium. These are neuroendocrine changes (increased cortisol and aldosterone) and diabetes mellitus as well as Mg2+ deficiency.
4. Patients with therapy refractory depression appear to have lower CNS Mg2+ levels in comparison to health controls.
5. Experimental Mg2+ depletion leads to depression and anxiety-like behavior in animal models.
6. Ketamine, directly or indirectly via non-NMDA glutamate receptor activation, acts to increase brain Mg2+ levels. Similar effects have been observed with other classes of antidepressants.
7. Depressed patients with low Mg2+ levels tend to be therapy refractory. Accordingly, administration of Mg2+ either alone or in combination with standard antidepressants acts synergistically on depression like behavior in animal models.
I'm wondering whether the amnesia for vivid dreams (if you wake up in the middle of one) is mediated by magnesium, as amnesia is a ketamine-like effect.
Therefore, a deficiency in magnesium may cause bad memories to linger, increasing the risk factor for situational depression.
4g/day of Epsom Salts provides 400mg/day of Magnesium. Dissolve the Epsom Salts in warm water and add the solution to your drinks over a 24 hour period, to maximise absorption & minimise laxation.
See also Ketamine, and Mechanisms underlying differential effectiveness of memantine and ketamine in rapid antidepressant responses.