Dr Paul Clayton’s Health Newsletter October 2014
Curcumin, the polyphenol derived from turmeric, is already known to have anti-inflammatory effects and to be cardio-, neuro- and chemo-protective; in the last 8 years, over 7000 studies have been completed. Now turmeric appears to be an anti-depressant too.
Various teams of scientists have shown that curcumin exerts anti-depressant activity in animal models of depression (ie Zhang et al ’14, Jiang et al ’14, Zhao et al ’14). And within the last year, three reasonably powerful clinical trials found that curcumin was more effective than placebo (Lopresti et al ’14), as effective as Prozac (Sanmukhani et al ’14) and it increased the effect of anti-depressant drugs (Panahi et al ’14). Notably, when examining the effects of curcumin in people with atypical depression, which is generally more difficult to treat, curcumin had even greater antidepressant and anti-anxiety efficacy (Lopresti et al ’14). Moreover, curcumin treatment was free of adverse side-effects.
Current antidepressant drugs have limited efficacy in controlling the symptoms of major depressive disorder, and are associated with multiple and occasionally serious adverse events particularly when used long-term. Finding a natural dietary substance that is as effective as Prozac, but does not cause side effects (such as ‘going postal’) is a real breakthrough, especially as depressive illness has increased so dramatically over the last few decades.
How does curcumin alleviate depression?
This is a moot question, particularly when nobody is even really sure how the anti-depressant drugs work, but a consensus is beginning to form. And it is a complex one …
There is evidence that three distinct but inter-related metabolic / physiological issues underlie depressive illness. These are chronic inflammation (Han & Yu ’14, Abelaira et al ’14, Popo-Wagner et al ’14), disturbed communication between the thalamus, hypothalamus and pituitary (Zajkowska et al ’14), and disruption of endocannabinoid chemistry (Crowe et al ’14).
Curcumin and many other polyphenols have potent anti-inflammatory effects (too many references to cite here!) and anti-stress effects (ie Fisher et al ’14, Poirier et al ’14) which would reduce or prevent the in-brain communication problems. The polyphenols also exert anti-oxidant effects which may well impact on endocannabinoid chemistry (ie Nunn et al ’10), and so they appear to protect against all three of the problems thought to drive depressive illness.
Which brings us to a grand, unifying theory.
Changes in our diet (thanks again to the multinational food companies) have reduced our intake of omega 3 fatty acids and increased our intake of omega 6. This has dramatically increased the 6:3 ratio in what we eat — and therefore inside our skulls — from about 2:1 in 1900 to 20:1 or even higher today.
Our intake of polyphenols has also fallen considerably, and this unfortunate dietary combination of reduced omega 3s and reduced polyphenols has left most of us in a semi-permanent state of chronic inflammation. Our endocannabinoid chemistry has greatly changed, as these compounds are derived from the type of fats in our diet. And our exposure to stress is arguably as high today as it has ever been. To make matters worse, the prevalence of Type B malnutrition (micronutrient depletion) may well have altered our brain’s ability to make neurotransmitters.
From this perspective, it is not so surprising that depressive illness has become so prevalent. It may also explain the increase in marijuana use, now so widespread as to be forcing de-criminalisation. If endocannabinoid chemistry is in a bad way, self-medication with phyto-cannabinoids could actually make sense (as well as being, I’m told, occasionally amusing).
For those who do not wish to experiment with marijuana there is PEA. PEA – or to give it its full name palmitoyl ethanolamide – is an endocannabinoid which is available as a supplement and used as an anti-inflammatory analgesic. PEA has also been found to have anti-depressant activity (Yu et al ’11), but it does not get you high. Better take PEA and flavonoids, a combination which shows significant anti-depressant effects even at very low doses (Cupri et al ’14).
Better yet to eat nutrient-dense foods and get a good omega 6:3 ratio in your diet. In a well-nourished population, I believe that both depressive illness and cannabis usage would be greatly reduced.
Abelaira HM et al. Neuroimmunomodulation in Depression:Review of Inflammatory Cytokines… Neurochem Res.2014 Jul 5. [Epub before print]
Crowe MS et al. The endocannabinoid system modulates stress… Brain Behav Immun. 2014 Jun 19. pii: S0889-1591(14)00172-X.
Crupi R et al. Effects of palmitoylethanolamide and luteolin in an animal model of anxiety/depression. CNS Neurol Disord Drug Targets. 2013 Nov;12(7):989-1001.
Fisher DR et al. Serum metabolites from walnut-fed aged rats attenuate stress-induced neurotoxicity… Nutr Neurosci. 2014 Aug 25. [Epub ahead of print]
Han QQ, Yu J. Inflammation: a mechanism of depression? Neurosci Bull. 2014 Jun;30(3):515-23.
Jiang H et al. Antidepressant-like effects of curcumin in chronic mild stress of rats… Prog Neuropsychopharmacol Biol Psychiatry. 2013 Dec 2;47:33-9.
Lopresti AL et al. Curcumin for the treatment of major depression: A randomised … study. J Affect Disord. 2014 Oct;167:368-75.
Nunn AV, Guy GW, Bell JD. Endocannabinoids, FOXO and the metabolic syndrome… Immunobiology. 2010 Aug;215(8):617-28. doi: 10.1016/j.imbio.2009.03.005. Epub 2009 May 19. Review.
Panahi Y et al. Investigation of … Curcuminoids in Major Depressive Disorder. Phytother Res. 2014 Aug 4. doi: 10.1002/ptr.5211. [Epub before print]
Popa-Wagner A et al. Perfusion deficits, inflammation & aging precipitate depressive behaviour. Biogerontology. 2014 Oct;15(5):439-48.
Poirier GL et al. Social deficits induced by peripubertal stress in rats are reversed by resveratrol. J Psychiatr Res. 2014 Oct;57:157-64.
Sanmukhani J et al. Efficacy and safety of curcumin in major depressive disorder: a … trial. Phytother Res. 2014 Apr;28(4):579-85.
Yu HL et al. N-palmitoylethanolamide, an endocannabinoid, exhibits antidepressant effects in … mice. Pharmacol Rep. 2011;63(3):834-9.
Zajkowska ZE et al. Towards a personalized treatment in depression: endocannabinoids … Pharmacogenomics. 2014 Apr;15(5):687-98.
Zhao X et al. Chronic curcumin treatment normalizes depression-like behaviors in mice … Psychopharmacology (Berl). 2014 May;231(10):2171-87
Zhang L et al. Effects of curcumin on … depressive-like behaviour and structural plasticity in … rats. Int J Neuropsychopharmacol. 2014 May;17(5):793-806