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Curcumin For Depression: An Effective Treatment?

Curcumin is considered a diarylheptanoid, or secondary metabolite derived from the plant turmeric (a member of the ginger family).  As a diarylheptanoid, curcumin is chemically composed of two aryl groups (aromatic rings) interlinked with a chain of 7 carbon atoms.  It was initially discovered by scientists Vogel and Pelletier in 1842 when they extracted and isolated the “yellow coloring” (curcumin) from the rhizomes of turmeric (Curcuma longa).

Though turmeric has been utilized as a medicinal agent for centuries, the specific mechanisms behind its therapeutic effects weren’t well-understood.  Now it is elucidated that within turmeric, it is the curcuminoids, namely “curcumin,” that elicit a host of favorable, yet complex neurophysiologic effects.  When ingested by humans, curcumin functions by modulating signals of:  pro-inflammatory cytokines, apoptotic proteins, NF–κB, cyclooxygenase-2, 5-LOX, STAT3, C-reactive protein, prostaglandin E2, prostate-specific antigen, adhesion molecules, phosphorylase kinase, transforming growth factor-β, triglyceride, ET-1, creatinine, HO-1, AST, and ALT.

For this reason, there is evidence to suggest that curcumin may exert anti-inflammatory, antioxidant, anti-cancer, anti-parasitic, chemotherapeutic, and wound healing effects.  Additionally, there is mounting research to imply that curcumin supplementation may ameliorate symptoms of severe psychiatric conditions such as major depressive disorder.  If you’re dealing with major depression, and haven’t considered testing curcumin, it may be worth investigating.

Curcumin For Depression: Mechanisms of Action

Administration of curcumin is believed to treat depression via host of mechanisms.  It is unclear as to whether one particular mechanism is responsible for the bulk of its antidepressant properties, or as to whether a blend of its neurophysiologic effects facilitate the antidepressant response.  It could be hypothesized that mechanisms responsible for the greatest antidepressant effects may vary based on the principal neurophysiologic cause of an individual’s depressive symptoms.  Included below is a list of possible ways by which curcumin supplementation may improve one’s mood.

BDNF increase: Studies have shown that curcumin can increase BDNF levels in animal models.  Low brain-derived neurotrophic factor is believed to cause a host of neurological disorders, including major depression.  Individuals (and animals with depression) tend to exhibit abnormally low BDNF.  An increase in BDNF is believed to improve mental health, wellbeing, and mood.

Another notable effect of increased BDNF is that it stimulates growth of new neurons in the hippocampus (via neurogenesis).  Neurogenesis may be one of the mechanisms by which curcumin ameliorates depressive symptoms.

  • Source: http://www.ncbi.nlm.nih.gov/pubmed/17022948

Epigenetic effects: It is understood that curcumin is capable of modulating genetic function via epigenetics. Specifically, curcumin appears to modulate histone deacetylases, histone acetyltransferases, DNA methyltransferase I, and miRNAs – all of which facilitate alterations in genetic expression.  It is the culmination of these epigenetic effects that are speculated to elicit anti-cancer and chemoprotective effects.

However, it should also be considered that these epigenetic effects may also indirectly affect genes that affect one’s mood.  Genes are complicated in that the function of one is usually interlinked to the function of others.  Changing the expression of several genes from curcumin administration may improve mood by altering the function of other genes (that affect mood) or perhaps may directly improve mood for some individuals via the elucidated epigenetic mechanisms.

  • Source: http://www.ncbi.nlm.nih.gov/pubmed/22118895
  • Source: http://www.ncbi.nlm.nih.gov/pubmed/26457241
  • Source: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3092901/

HPA axis modulation: In cases of depression, it is often observed that patients exhibit an increase of HPA (hypothalamic-pituitary-adrenal) axis activity, often to the extent of hyperactivation. This hyperactivity of the HPA axis may stem from a combination of genetic factors, exposure to aversive stimuli, exposure to neurotoxins, etc.  Most individuals with depression will exhibit abnormal HPA axis activity – whether this is a major cause or simply another neurological manifestation is unknown.

However, it is understood that administration of curcumin can modulate the HPA axis, thereby normalizing its function.  A reduction in HPA hyperactivity may in turn, elicit a cascade of secondary therapeutic effects throughout the cortex, leading to an improvement in depressive symptoms.  It is this HPA modulation that may also protect against stress, cognitive decline, and neurodegeneration.

  • Source: http://www.ncbi.nlm.nih.gov/pubmed/17022948

Neurotransmitter levels: Research supports the idea that curcumin administration reverses abnormal neurotransmission in animal models of depression.  In one study, animals with depressive symptoms exhibited abnormally low serotonin (to the extent of depletion), low norepinephrine, and low dopamine (in the prefrontal cortex).  They also exhibited abnormally high concentrations of 5-HIAA (5-hydroxyindoleacetic acid) and DOPAC (4-dihydroxyphenylacetic acid).

Chronic administration of curcumin to these animal models reversed deficits in serotonin, norepinephrine, and dopamine.  It also decreased the elevated concentrations of 5-HIAA and DOPAC.  This indicates that within animals, curcumin appears to modulate neurotransmission to a significant extent. Monoaminergic modulation may be an important mechanism by which it reverses depressive symptoms.

  • Source: http://www.ncbi.nlm.nih.gov/pubmed/23035031

Neuroinflammation reduction: Brain scans of individuals with major depression reveal that most exhibit significant neuroinflammation compared to those without depressive disorders.  Whether the inflammation is a manifestation of the depression or vice-versa is unknown.  That said, many suspect that by reducing this neuroinflammation (even slightly), depressive symptoms are likely to improve.

Since curcumin is known to reduce general inflammation via modulation of pro-inflammatory cytokines, perhaps one pivotal mechanism by which it treats depression is via reducing neuroinflammation.  Curcumin also appears to inhibit Jun N-terminal kinase (JNK), a mitogen-activated protein kinase which, when activated, inhibits glucocorticoid receptor (GR) function.  A subset of individuals with depression exhibit glucocorticoid resistance, a manifestation that appears to be reversed with curcumin via JNK-inhibition.

  • Source: http://www.ncbi.nlm.nih.gov/pubmed/23035031
  • Source: http://www.ncbi.nlm.nih.gov/pubmed/18662800
  • Source: http://www.ncbi.nlm.nih.gov/pubmed/15536494

Mitochondrial repair: Your mitochondria are like “power plants” within your cells responsible for generating energy.  If your mitochondria aren’t functioning properly, it is very likely that you could become depressed, exhibit depressive behaviors, or feel chronically fatigued.  Humans and animal models with depression often exhibit dysfunction of intracellular mitochondrial metabolism in specific brain regions linked to depression.

Chronic mitochondrial dysfunction within certain tissues is also associated with depressive symptoms.   Preliminary evidence suggests that ingestion of curcumin is able to repair mitochondrial damage, thereby correcting dysfunction and perhaps bolstering functionality of all mitochondria.  A repair of mitochondrial dysfunction should be considered as a contributing mechanism by which curcumin alleviates depression.

  • Source: http://www.ncbi.nlm.nih.gov/pubmed/23035031
  • Source: http://www.ncbi.nlm.nih.gov/pubmed/23782307

Neuroprogression: Neuroprogression is considered pathological brain rewiring that occurs in disordered states.  As the neuropsychiatric disorders like major depression increase in severity, they literally rewire the brain.  The longer and/or more severe the depressive symptoms, the greater the neuroprogression of the depressive disorder.

There is some evidence that neuroprogression is facilitated by neuroinflammation (as a result of pro-inflammatory cytokines), oxidative stress, mitochondrial dysfunction, and altered levels of neurotrophins.  When taken at high doses and/or chronically, curcumin may halt neuroprogression of neuropsychiatric disorders such as depression, likely via reducing inflammation, oxidative stress, mitochondrial dysfunction, and restoring depleted levels of BDNF.

  • Source: http://www.ncbi.nlm.nih.gov/pubmed/25046624
  • Source: http://www.ncbi.nlm.nih.gov/pubmed/23035031

Neurorestorative properties: Curcumin appears to elicit neurorestorative effects when taken chronically at high doses.  In other words, neurotransmitters, regional activation, and metabolism within the brain appear to normalize to a healthy, homeostasis following administration of curcumin.  The neurorestorative effects of curcumin are perhaps best evidenced in studies of those suffering from neurodegenerative disorders.

When administered to individuals with neurodegenerative disorders, curcumin appears to ameliorate cognitive deficits.  One mechanism by which it is believed to restore neurocognitive function is by altering signaling of tumor necrosis factor α receptor 2 (TNFR2).  It also appears to correct deficits and/or abnormal elevations of neurotransmitters in regions associated with depression.

  • Source: http://www.ncbi.nlm.nih.gov/pubmed/18662800

Oxidative & nitrosative stress reduction: Major depressive disorder is associated with abnormally low levels of important vitamins and antioxidants.  Many speculate that one cause of depressive symptoms is a lack of antioxidative activity.  A specific biomarker associated with depression is a reduction in activity of glutathione peroxidase (GPX), an enzyme responsible for major antioxidant effects throughout the body.

Researchers speculate that reduced antioxidant capacity may decrease protection from free radicals, which inevitably may damage fatty acids, proteins, and DNA.  Administration of curcumin appears to act as an antioxidant by lowering both oxidative and nitrosative stress.  Furthermore, it may modulate functionality of oxidative and nitrosative genes, thereby reducing free radical damage and improving mood.

  • Source: http://www.ncbi.nlm.nih.gov/pubmed/23035031
  • Source: http://www.ncbi.nlm.nih.gov/pubmed/26027171

Repairs intestinal hyperpermeability: In cases of intestinal hyperpermeability, the gut lining becomes hyperpermeable allowing too many toxins, microbes, undigested food, etc. to leak through; hence it is sometimes referred to as “leaky gut.”  There is some evidence to suggest that leaky gut syndrome could be a direct cause of depression, at least in certain cases.  Leaky gut syndrome has been associated with a host of problems including: ATP-depletion, pro-inflammatory cytokine production, and disturbances of the gut flora (microbiome).

Curcumin appears to repair various aspects of intestinal hyperpermeability, possibly a mechanism by which it improves depressive symptoms.  If toxins are no longer circulating throughout your system and “leaky gut” is corrected, this is likely to have beneficial implications for neurological function.  As a result, a reversal of leaky gut may directly improve a person’s mood and/or neuropsychiatric symptoms.

  • Source: http://www.ncbi.nlm.nih.gov/pubmed/23035031

Curcumin For Depression (Review of Scientific Research)

Included below is a synopsis of research investigating the therapeutic efficacy of curcumin for the treatment of major depressive disorder.  Most research highlights the fact that curcumin is an effective antidepressant regardless as to whether it’s administered as an adjunct or standalone option.  Its effects appear to be consistent across animal models with depressive symptoms, as well as in humans diagnosed with clinical depression.

2015: A meta-analysis conducted in 2015 by Al-Karawi, Al Mamoori, and Tayyar reviewed evidence of curcumin for the treatment of major depressive disorders.  They examined all literature up to August 2015 investigating the efficacy of curcumin for the treatment of depression.  Of all the studies reviewed, a total of 6 clinical trials fit inclusion criteria for this meta-analysis.

Results from the included clinical trials indicated that curcumin administration significantly reduced depressive symptoms among those with major depressive disorders.  Upon further analysis, it appeared as though middle-aged individuals derived the most benefit from curcumin supplementation for their depressive symptoms compared to other age-groups.  Additionally, longer duration of administration and high doses yielded greater benefit than short-term administration and low doses.

Furthermore, in regards to curcumin formulations, a formula known as “BCM-95” exhibited greater antidepressant properties than standardized curcumin-piperine formulas.  Researchers noted that there is evidence to support curcumin administration among individuals with major depressive disorders.  That said, further research is warranted to validate the degree to which curcumin provides antidepressant benefit.

  • Source: http://www.ncbi.nlm.nih.gov/pubmed/26610378

2015: A double-blind, randomized, placebo-controlled trial conducted by Lopresti et al. noted that curcumin supplementation at 500 mg b.i.d. (twice per day) ameliorated depressive symptoms among 50 individuals diagnosed with major depressive disorder (MDD).  Prior to administration of curcumin (or a placebo), researchers collected various blood, saliva, and urine samples from these individuals.  Thereafter (post-curcumin supplementation), they collected another round of blood, saliva, and urinary samples.

Their aim was to document any substantial changes in blood, salivary, and urinary biomarkers induced by supplementation of curcumin.  Changes in certain biomarkers, they speculated, may elucidate and/or pinpoint antidepressant mechanisms derived from curcumin.  In a 2015 report, they discussed the effects of curcumin on various biomarkers among those with depression.

It was discovered that (compared to a placebo) 8 weeks of curcumin supplementation increased urinary excretion of thromboxane B2 and substance P.  Individuals receiving curcumin also exhibited increased concentrations of plasma endothelin-1 and leptin. Comparatively, the placebo group exhibited reductions in aldosterone and cortisol.  This research highlights various biomarker changes associated with curcumin, some of which may directly facilitate an antidepressant response.

  • Source: http://www.ncbi.nlm.nih.gov/pubmed/25523883

2015: A study conducted by Yu et al. (2015) reported the fact that major depression is lifelong for approximately 16% of all individuals.  It further noted that most pharmacological options are slow-acting and are associated with numerous adverse effects.  For this reason, they decided to investigate the efficacy of curcumin, a supplement that has been shown to ameliorate depressive symptoms in both humans and animal models that appears to be void of adverse effects.

Since curcumin has been deemed effective as an antidepressant, researchers aimed to elucidate its underlying mechanism of action in humans with depression.  As a result, they conducted a study with a total of 108 adults, all of whom were middle-aged men (between 31 and 59 years).  The men were then administered either: 2 capsules of curcumin (1000 mg each) or a 2 capsules of a placebo (soybean powder).

The curcumin and placebo were administered daily for a period of 6 weeks.  Prior to the study, researchers administered the Hamilton Depression Rating Scale (HAM-D) and Montgomery-Asberg Depression Rating Scale (MADRS) to note the severity of each participant’s depressive symptoms.  Additionally, in effort to understand the impact of curcumin on biomarkers, plasma levels of interleukin 1β, tumor necrosis factor α, brain-derived neurotrophic factor, and salivary cortisol were recorded before and after the 6 weeks.

Daily supplementation with curcumin (1000 mg, b.i.d.) significantly improved depressive behaviors as evidenced by post-6-week improvements on the HAM-D and MADRS.  In regards to biomarkers, 6-weeks of curcumin supplementation: reduced inflammatory cytokines (interleukin 1β and tumor necrosis factor α), increased brain-derived neurotrophic factor, and decreased salivary cortisol concentrations (compared to the placebo group).  Results not only highlight the therapeutic antidepressant properties of curcumin, but also note corresponding biomarker alterations.

  • Source: http://www.ncbi.nlm.nih.gov/pubmed/26066335

2015: A study published in 2015 by Esmaily et al. investigated the efficacy of curcumin supplementation in targeting neuropsychiatric symptoms of anxiety and depression among individuals considered clinically obese.  A double-blind, crossover trial was designed to incorporate 30 obese individuals, each of whom were assigned at random to receive either: curcumin (1 gram per day) or a placebo.  The curcumin (1 gram) and placebo were administered for a duration of 30 consecutive days.

Following the initial 30 days, participants underwent a “washout phase” for 2 weeks.  Thereafter, each of the participants were crossed-over to receive the opposite of what they had received during the initial 30 days. Those who had initially taken the placebo were now taking the curcumin, and vice versa.

Measures of depression and anxiety were taken at pre-trial baseline, as well as at intervals of 4 weeks, 6 weeks, and 10 weeks.  Depression was recorded based on scores from the BDI (Beck Depression Inventory) and anxiety with the BAI (Beck Anxiety Inventory).  Results indicated that although anxiety was reduced among those taking curcumin, depression was unchanged.  Though this study was small-scale, it provides evidence to suggest that curcumin may not improve obesity-related depressive symptoms.

  • Source: http://www.ncbi.nlm.nih.gov/pubmed/25776839

2014: Zhang et al. attempted to elucidate various mechanisms responsible for facilitating curcumin’s antidepressant effects.  In this study, researchers investigated the effects of curcumin on a rat model exposed to chronic, unpredictable, mild stress (CUMS)-induced depression.  When rats are exposed to CUMS (chronic unpredictable mild stress), they exhibit neuro-structural alterations within the lateral amygdala (LA), as well as a downregulation in BDNF, PSD-95, and synaptophysin.

To test whether curcumin may protect against CUMS-induced depression, researchers administered curcumin at a dosage of 40 mg/kg daily for a period of 6 weeks.  The curcumin was administered prior to the exposure of a stressor.  Results indicated that curcumin administration inhibited maladaptive neurobiological alterations that normally occur as a result of CUMS.

Researchers concluded that curcumin supplementation facilitates antidepressant and neuroprotective effects among animal models with CUMS-induced depression.  Therefore, it could be speculated that curcumin supplementation among humans may protect against chronic stress-induced forms of depression.

  • Source: http://www.ncbi.nlm.nih.gov/pubmed/24405689

2014: In effort to determine the antidepressant efficacy of curcumin, Sanmukhani et al. set up a head-to-head faceoff, comparing curcumin to arguably the most popular antidepressant of all-time, Prozac (fluoxetine).  Furthermore, researchers endeavored to determine whether curcumin plus Prozac may be more effective than either option as a standalone antidepressant.  The study assigned 60 individuals diagnosed with major depression to receive either:  20 mg Prozac (fluoxetine), 1000 mg curcumin, or a combination of the two (20 mg Prozac plus 1000 mg curcumin).

Prior to receiving the Prozac and/or curcumin, participants were administered the Hamilton Depression Rating Scale (HAM-D17) to assess the severity of their depressive symptoms.  After 6-weeks of receiving 20 mg Prozac, 1000 mg curcumin, or a combination – individuals were reassessed with the HAM-D17 scale.  Results indicated that statistically significant improvement on the HAM-D17 occurred in all three groups to a similar extent.

The percentages of clinically significant responders were reported as: 77.8% for the Prozac plus curcumin group, 64.7% in the Prozac-only group, and 62.5% in the curcumin-only group.  Though none of the improvement was considered clinically significant, it is important to note that Prozac is an approved antidepressant drug and is regarded as a highly effective treatment for depression.  Since curcumin improved symptoms to the same extent as Prozac, and appeared to synergistically improve symptoms when concomitantly ingested with Prozac, it may be an effective supplement for depression.

Researchers document that unlike Prozac, curcumin isn’t associated with increased depression and suicidality.  The likelihood of experiencing unwanted side effects from curcumin is considerably lower than experiencing adverse reactions stemming from Prozac.  Researchers imply that curcumin may be a safe, first-line option for depression due to its efficacy and favorable side effect profile.

  • Source: http://www.ncbi.nlm.nih.gov/pubmed/23832433

2014: It is known that depression may result from a cumulative, complex interplay among various biological pathways.  A study published by Lopresti (2014) investigated whether curcumin could provide benefit to individuals with major depressive disorder.  Researchers hypothesized that it may attenuate depressive symptoms via modulation of: monoamines, inflammation, oxidative and nitrosative stress pathways, HPA (hypothalamic-pituitary-adrenal) axis activity, and neuroactivation.

They set up a randomized, double-blind, placebo-controlled study involving 56 participants diagnosed with major depressive disorder.  These participants were assigned to receive either: curcumin (500 mg, b.i.d.) or a placebo – each for a total of 8 weeks.  Prior to administration of curcumin and/or the placebo, researchers collected baseline measures to determine severity of depression with the self-rated IDS-SR30 (Inventory of Depressive Symptomatology).

Regardless of whether individuals had received the curcumin (500 mg, b.i.d.) or the placebo, all experienced marked improvements in depressive symptoms (as evidenced by the IDS-SR30) from baseline to Week 4.  However, thereafter from Week 4 to Week 8, only the individuals receiving curcumin (500 mg, b.i.d.) exhibited improvement in various mood-related symptoms on the IDS-SR30 scale.  Interestingly, curcumin appeared to provide greatest therapeutic antidepressant benefit to a subset of individuals diagnosed specifically with atypical subtypes of depression.

Researchers noted that there was some evidence to validate the hypothesized antidepressant efficacy of curcumin among those with major depressive disorder, particularly when taken for at least 8 weeks.  That said, authors noted limitations associated with their study including: small sample size, treatment duration, and dosage of curcumin administered.

  • Source: http://www.ncbi.nlm.nih.gov/pubmed/25046624

2014: A report published in 2014 by Andrade noted that curcumin as a nutritional supplement may provide therapeutic benefit to those diagnosed with an array of health conditions.  Curcumin supplementation is regarded as conducive to general health and appears to decrease depressive symptoms in animal models of depression.  For this reason, it was hypothesized that humans with major depressive disorders may also derive benefit from curcumin supplementation.

This report highlighted the fact that upon analysis of controlled clinical trials, there is a lack of evidence to suggest the efficacy of curcumin for depression.  Andrade noted that individuals with major depression receiving curcumin (doses of 500 mg to 1000 mg per day) didn’t experience greater symptom reduction compared to a placebo (or no treatment) after 5 to 8 weeks of either monotherapy (standalone curcumin) or augmentation (an antidepressant plus curcumin).

At this time, there wasn’t any robust evidence to suggest that curcumin is an effective antidepressant.  That said, it is important to consider that newer findings may support curcumin’s efficacy for depression.  For example, a meta-analysis published in 2015 indicated that curcumin is in fact an effective supplement for depressive symptoms.

  • Source: http://www.ncbi.nlm.nih.gov/pubmed/25373119

2014: It is well understood that individuals suffering from neuropathic pain also exhibit depressive symptoms and/or have been diagnosed with comorbid depressive disorders.  In fact, various pharmaceutical antidepressants (e.g. Cymbalta, Nortriptyline, etc.) are often prescribed for the treatment of both neuropathic pain and depression.  When administered as a dietary supplement, curcumin is known to ameliorate symptoms of neuropathic pain.

In animal models, curcumin facilitates antinociceptive and antidepressant effects simultaneously, and therefore may be useful among individuals experiencing neuropathy and comorbid depression.  A study published by Zhao et al. (2014) endeavored to examine the effects of curcumin in mice models of neuropathy.  Researchers specifically sought to determine whether the curcumin would improve neuropathy-induced depressive symptoms.

For this particular experiment, mice were given CCIs (chronic constriction injury) via manipulation of sciatic nerves.  Thereafter, nociception (pain sensation) was measured with the Hargreaves test and depressive behaviors were measured with Forced Swim Tests (FSTs) and Tail Suspension Tests (TSTs).  Measures from the Hargreaves test, particularly thermal hyperalgesia, suggested an increase in nociception among the mice following CCIs.

Nociception-induced depressive behaviors were evidenced by prolonged immobility on the Forced Swim Tests and Tail Suspension Tests.  For a 3-week period, the mice were administered 45 mg/kg curcumin (orally) twice per day.  Results indicated that administration of 45 mg/kg curcumin (b.i.d.) normalized nociceptive and depressive features among these mice.

This suggests that curcumin may provide an antidepressant effect among mice with neuropathy, possibly via modulation of serotonergic transmission and GABAergic receptivity.  It is unclear as to whether curcumin is likely to elicit similar neurophysiologic effects in humans with similar conditions.  That said, this is more evidence to suggest that curcumin is capable of reversing depressive symptoms in animal models.

  • Source: http://www.ncbi.nlm.nih.gov/pubmed/24297305

2014: Researchers Tizabi et al. (2014) published a review summarizing the potential of curcumin supplementation as an antidepressant and neuroprotective agent.  They note that curcumin appears to have minimal or nonexistent side effects and is capable of combatting neurological comorbidities including neurodegeneration and psychiatric disorders.  Researchers speculate that curcumin may exert therapeutic effects via its anti-inflammatory properties and ability to alter signal transduction proteins.

This review provides more evidence to speculate that curcumin may, at the very least, prove to be a viable adjunct for targeting inflammation-induced symptoms of neuropsychiatric conditions such as major depression, as well as neurodegenerative diseases such as Parkinson’s.  Since curcumin currently has poor bioavailability, researchers propose that a chemical analogue with superior bioavailability may prove efficacious in ameliorating a multitude of neuropsychiatric and neurological disorders.

  • Source: http://www.ncbi.nlm.nih.gov/pubmed/25514226

2013: A double-blind, placebo-controlled, randomized study published in 2013 by Bergman et al. investigated the efficacy of curcumin supplementation as an adjunct for major depressive disorder.  Prior to the study, researchers noted that curcumin exerts antidepressant effects in animal models of depression and that when administered as an “add-on” to a standard antidepressant drug, it potentiates their therapeutic effects.

  • 40 patients (First episode of depression)
  • 5-week trial
  • Double-blind, randomized, placebo-controlled

A total of 40 patients experiencing their first episode of depression were assigned to receive either 500 mg curcumin or placebo along with popular antidepressants Lexapro (Escitalopram) or Effexor (Venlafaxine).  Prior to the study, patients were rated with the Hamilton Depression Rating Scale (HDRS), Montgomery-Asberg Depression Rating Scale (MADRS), and the Clinical Global Impression Severity Scale (CGI-SS).

The findings revealed that individuals receiving both the placebo and the curcumin experienced noticeable mood improvements from baseline to the end of the study.  Changes in mood were apparent within the first week of treatment, but there was no significant difference in mood between those receiving the curcumin and placebo.  Authors documented that among those receiving the curcumin were more likely to have experienced quicker antidepressant relief compared to those receiving the placebo.

Though the study failed to prove clinical significance of curcumin as an adjunct, it should be highlighted that both groups significantly improved.  When interpreting the results of this study, it is impossible to rule out the potential clinical efficacy of curcumin as an adjunct because there may have been a significant placebo effect among the control group, simultaneously yielding a therapeutic “adjunct” effect.  Since efficacy didn’t differ between the two groups, but improvement was significant among both groups, follow-up research is warranted.

  • Source: http://www.ncbi.nlm.nih.gov/pubmed/23673908

2013: A study conducted in 2013 by Hurley et al. sought to determine the antidepressant efficacy of curcumin in a non-induced animal model of depression.  For the study, researchers utilized adult male Wistar Kyoto (WKY) rats all of which exhibited depressive symptoms.  Researchers speculated that administration of curcumin may alleviate their depressive symptoms, likely via its ability to increase BDNF (brain-derived neurotropic factor) within the hippocampal region of the cortex.

The WKY rats were then injected acutely or chronically for a 10-day term with either: 50 mg/kg, 100 mg/kg, or 200 mg/kg of curcumin.  Efficacy of curcumin in alleviating depressive symptoms was determined based on the Open Field Locomotor Activity (OFLA) and Forced Swim Test (FST).  Results demonstrated that rats exhibited significant improvements on the Forced Swim Test (a measure of helplessness) regardless of whether curcumin was administered acutely or chronically.

No significant changes were recorded on the Open Field Locomotor Activity test.  Researchers noted that the improvements stemming from chronic curcumin supplementation on the Forced Swim Test were maintained for up to 1 week after discontinuation.  This suggests that higher curcumin doses may provide longer lasting antidepressant efficacy than short-term and/or acute dosing.

It was also reported that chronic supplementation facilitated a dose-dependent BDNF increase within the hippocampal region.  Results from this study indicate that curcumin supplementation improves depressive behaviors among rats with non-induced depression.  Increases in BDNF in the hippocampus may be the chief mechanism (or one of many mechanisms) that facilitates curcumin-induced mood improvement.

  • Source: http://www.ncbi.nlm.nih.gov/pubmed/23142609

2005: An early study from 2005 published by Xu et al. notes that turmeric has long been used in traditional Chinese medicine to treat depression, stress, and other mental disorders in China.  The pharmacologically active component within turmeric responsible for its therapeutic effects is that of curcumin.  Researchers hypothesized that chronic administration of curcumin may ameliorate depressive symptoms in animal (rat) models of depression.

To test this, they administered curcumin at dosages of 1.25, 2.5, 5, and 10 mg/kg (orally) to rat models of depression.  They divided their research into two distinct studies, the first of which assessed the rat’s performance on a Forced Swim Test (FST) and the second analyzed behavior of rats that received a bilateral olfactory bulbectomy (OB).  In the first study, curcumin administration for 2 weeks decreased immobility time on the Forced Swim Test (FST).

Results from the second study noted that curcumin reversed behavioral abnormalities (e.g. hyperactivity, deficits in step-down passive avoidance, etc.) resulting from the bilateral olfactory bulbectomy (OB).  Pharmacologically, curcumin corrected abnormalities in neurotransmission induced by the bilateral olfactory bulbectomy (OB).  Specifically, curcumin administration increased serotonin and norepinephrine concentrations (both were low from the OB) and reduced hippocampal 5-HIAA and DOPAC (both of which were elevated as a result of the OB).

Evidence from this report suggests that curcumin either directly or indirectly is capable of reversing abnormalities of neurotransmission that may trigger depressive behaviors among animals.  It should therefore be hypothesized that similar modulation of monoamines may occur as a result of curcumin supplementation among humans with depression.

  • Source: http://www.ncbi.nlm.nih.gov/pubmed/16171853

Verdict: Curcumin may facilitate an antidepressant response

A bulk of the aforestated scientific literature indicates that curcumin is likely effective for the treatment of depression in humans.  Furthermore, it is well-documented that curcumin is efficacious for the treatment of depression in animal models.  However, the degree to which a human diagnosed with depression is likely to benefit from curcumin compared to mainstream antidepressants is unknown.

That said, one trial noted that the efficacy of curcumin as an antidepressant was indistinguishable from Prozac (Fluoxetine).  One should be cautious in interpreting this result and avoid automatically concluding that curcumin is therefore equally as therapeutic as Prozac.  This study was small-scale and there’s considerably more robust evidence to underscore the antidepressant efficacy of Prozac, whereas there are limitations associated with research of curcumin as an antidepressant.

Conversely, simply because there are limitations associated with the research of curcumin as an antidepressant does not automatically indicate it lacks efficacy.  In fact, it may prove to be equally as effective as standardized antidepressant treatments like Prozac.  To validate preliminary therapeutic efficacy of curcumin as an antidepressant, it is necessary to conduct and compile additional research.

Future human trials should be placebo-controlled, double-blinded, randomized, and incorporate larger sample sizes.  That said, curcumin appears to have minimal side effects (up to doses of 12 grams per day), low potential of contraindications, and minimal toxicity concerns.  In fact, most researchers believe that even if curcumin fails to ameliorate depressive symptoms, it may be conducive to other aspects of neurophysiologic health.

Potential benefits of Curcumin as an antidepressant

There are numerous benefits of taking curcumin as an antidepressant.  It appears to modulate neuroactivity in regards to regional activation, neurotransmission, and neurotrophic factors.  Furthermore, it is thought to reduce inflammation, act as an antioxidant, and enhance mitochondrial function.  Curcumin may serve as a viable standalone and/or adjunct antidepressant in certain cases.

  • Adjuvant option: Due to the fact that contraindications associated with curcumin are minimal, it may be an effective antidepressant augmentation strategy.  In other words, taking curcumin along with a prescribed antidepressant may bolster the attained antidepressant response.  Furthermore, it is possible to consider that curcumin may work synergistically with a pharmaceutical agent to improve mood better than each option as a monotherapy.  If you’re taking an antidepressant, and want to try curcumin, discuss its usage as an adjunct with a medical professional to rule out interactions.
  • Cognitive enhancer: It is understood that many individuals suffering from major depressive disorders experience cognitive impairment (usually mild) and noticeable “brain fog.”  They may report struggling in academic and/or occupational performance of cognitively demanding tasks.  This may hamper productivity and may lead to further stress, frustration, and neuroprogression of depression.  There is minor evidence to suggest that curcumin can improve aspects cognitive function, which in turn may yield a low-grade “nootropic-esque” effect.
  • Efficacy: There is solid evidence to suggest that curcumin is an effective antidepressant in animals and humans.  The degree to which it is effective, whether it is effective in all users, the optimal dosage, most effective formulation, route of administration, etc. – are up for debate.   That said, one study found it to be equal in efficacy to fluoxetine (generic Prozac), an SSRI drug considered highly-effective in treating depression.
  • Minimal contraindications: Though one should be cautious when administering curcumin along with other medications, most research suggests that it is unlikely to interact with the pharmacokinetic properties of concomitantly administered agents.  Obviously you’ll want to discuss contraindication possibilities with a medical practitioner prior to ingestion of curcumin.  However, minimal contraindications, especially with popular prescription antidepressants should be considered beneficial; many other supplements interact and may cause “serotonin syndrome.”
  • Minimal side effects: The side effects associated with curcumin supplementation pale in comparison to most other supplements and pharmaceuticals aimed at treating depression (Read: Curcumin side effects).  Unlike other antidepressants, curcumin isn’t associated with compromised libido, sexual dysfunction, fatigue, hyperactivity, and weight gain.  In fact, some speculate that curcumin may actually facilitate weight loss and combat adverse physiologic effects associated with obesity.
  • Neuroprotective properties: Maintaining optimal brain function for as long as possible is a goal for many.  After all, if your brain isn’t working properly, it impairs your ability to socialize, learn new information, and enjoy life.  There’s some evidence to suggest that curcumin acts as a neuroprotective agent by reducing pro-inflammatory cytokine markers.  Most neurodegenerative conditions are associated with high level inflammation.

Potential drawbacks of Curcumin as an antidepressant

Though curcumin appears to have minimal safety concerns, its safety isn’t well-established as a dietary supplement.  Though it is thought to be safe, a publication entitled “The Dark Side of Curcumin” highlights the potential drawbacks associated with its usage for the treatment of medical conditions such as depression.  That said, when the risks of curcumin are compared to those of already-approved pharmacological agents, they seem to be minimal.

Bioavailability (Low): One major drawback associated with curcumin supplementation is its low bioavailability.  Though researchers are attempting to devise new curcumin formulas in which the bioavailability is high (using nanocarriers), highly bioavailable curcumin is not yet available.  This has lead some to question whether the curcumin is really eliciting an antidepressant effect in humans.

Some believe that BCM-95 curcumin or additives such as bioperine appear to increase its bioavailability to a significant extent, thereby facilitating a therapeutic response in humans.  That said, despite major increases in bioavailability from BCM-95 and bioperine, the overall bioavailability is still extremely low.  This indicates that to attain an antidepressant effect, large doses may be required, or worse, that they may be relatively useless.

Interactions: It should be noted that curcumin may interact with various pharmaceutical agents when concomitantly ingested.  Curcumin is known to inhibit activity of drug-metabolizing enzymes including: CYP450 isoenzymes, glutathione-S-transferase, and UDP-glucuronosyltransferase.  Inhibiting functionality of these enzymes may lead to abnormally high plasma concentrations of certain drugs, leading to adverse effects.  More research is necessary to understand whether curcumin interacts with other drugs (and/or supplements).

Questionable efficacy: The efficacy of curcumin for the treatment of depressive disorders is not fully known.  Though most research highlights its efficacy in ameliorating depressive symptoms within animal models, curcumin’s efficacy in humans is regarded as questionable.  There is a need for large-scale, placebo-controlled, randomized, double-blinded trials in humans to know whether curcumin is likely a clinically effective antidepressant.

Side effects: The side effects of curcumin supplementation, especially at high doses, may be underreported and/or underestimated by researchers.  Most research involving curcumin aims to elucidate its beneficial effects and may downplay potential adverse reactions and long-term effects.  Some researchers are concerned that the full extent of curcumin-induced side effects aren’t known.

Several reports suggest that curcumin may lower iron levels, decrease blood glucose, and possibly compromise the male reproductive system (reducing testosterone and sperm motility).  Curcumin can trigger side effects such as diarrhea, nausea, an increase in serum alkaline phosphatase, and lactate dehydrogenase.  For this reason, it may be necessary to investigate the extent to which these effects occur among humans, as well as the specific dosages at which they are likely to occur.

Toxicity: Some studies have noted that curcumin may actually upregulate ROS (reactive oxygen species) via modification of thioredoxin reductase, an antioxidative enzyme.  It may also induce DNA damage via mediation of topoisomerase II and deactivate tumor suppressor protein.  Toxic effects of curcumin are speculated to be triggered by the presence of 2 a,b-unsaturated ketones in its chemical structure.

A reaction known as “Michael addition” may occur as a result of the aforementioned chemical groups reacting covalently with thiol groups of protein cysteine residues. These toxic effects that have been reported in various studies are often overlooked, but may warrant reevaluation.

Unknown long-term safety: Many people mistakenly assume that because a substance like curcumin is a dietary supplement, it is devoid of safety concerns.  It is possible that long-term, regular administration of curcumin (especially at high doses) may be toxic to neurophysiologic processes and/or yield unwanted long-term effects.  Though evidence from studies indicates that curcumin appears to be safe over the short-term, long-term changes aren’t well-documented.

Some evidence indicates that curcumin’s iron-chelation properties may be of concern, especially for individuals prone to anemia.  Curcumin may also affect iron metabolism, leading to a diagnosis of anemia.  Furthermore, should there be long-term toxicity concerns, we are unaware of the threshold dosage and duration over which curcumin must be administered to yield toxic effects.  Until more research is conducted regarding long-term effects, some may wish to err on the side of caution and avoid curcumin altogether.

  • Source: http://www.ncbi.nlm.nih.gov/pubmed/19830693

Taking Curcumin for Depression: A Personal Anecdote

Curcumin is a supplement that I highly recommend not only because it has the potential to improve mood, but evidence suggests that it is likely to improve many aspects of health.  I began taking curcumin not to correct my depression, but as a neuroprotective agent.  After taking it for over a month consistently, I believe that it has helped slightly with my mood.

I don’t believe the antidepressant benefit attained from curcumin (at least in my case) is anything significant, but I do believe that it is marginal and noticeable.  Then again, this could be nothing more than a placebo effect (which I’m also satisfied with).  If I had to rate the efficacy of curcumin for depression on a scale of 1 to 10, I’d give it around a 3.  Still, even slight mood improvement with virtually no side effects should be considered a “win.”

I have experienced some side effects from my supplementation including: stomach aches and an increased frequency of bowel movements.  However, these side effects were easily reduced by lowering my curcumin dosage to 1000 mg per day and taking it with food.  I’m unaware of the long-term effects of regular curcumin supplementation, so I’m likely going to take it for several months, cycle off of it for awhile, then cycle back on.

Nonetheless, it doesn’t seem like a supplement that is likely going to promote a neurophysiologic tolerance of sorts.  I should note that I personally take the Viva Labs brand Curcumin (with Bioperine) and believe that the Bioperine enhances bioavailability to a significant extent.  That said, there are other BCM-95 formulations that are supposedly better (and this is supported by some research); whether BCM-95 is actually superior warrants further investigation.

If you’re thinking about curcumin supplementation, I suggest trying both formats and determining which gives you the most benefit.  Some users swear by the Bioperine-formatting, while others truly believe that the BCM-95 formats provide greater benefit.  Both have a relatively low bioavailability, but can be effective for certain conditions like inflammation, and perhaps depression to a modest extent.

How much Curcumin should you take for depression? (Dosage)

There is no “universally effective” dosage of curcumin that is likely to treat depression.  Assuming certain formulations of curcumin supplements may exhibit greater bioavailability than others, the greater the bioavailability, the lower the dose necessary for a therapeutic effect.  Most research suggests that taking high doses of curcumin, over a long-term, provides the most significant effect in the reversal of depressive symptoms.

If you’re simply eating more turmeric in effort to ingest more curcumin, know that curcumin only accounts for approximately 2-5% of turmeric by weight.  Therefore, a tablespoon of turmeric spice (6.8 grams) would contain between 136 and 340 milligrams of curcumin.  Individuals with depression and other health conditions typically take between 1 and 12 grams of curcumin daily for symptomatic relief.

When starting curcumin, be sure to talk to a medical professional for guidance in terms of dosing and rule out possible contraindications with your current medications.  Next, you may want to start at a low dose, give your body time to adjust, and titrate the dosage upwards – this should help reduce likelihood of adverse effects (e.g. diarrhea).  Some curcumin users report having success in treating depression with doses from 1 to 6 grams per day, but as was mentioned earlier, a therapeutically effective dosage may be contingent upon the bioavailability of the specific curcumin formula.

As a result of individual variation, and due to the fact that bioavailability may vary (based on the specific curcumin formulation), it is necessary to realize that you’ll likely need to determine an ideal curcumin dosage on your own.  If you do plan on taking curcumin, be cognizant of the potential drawbacks and unknown toxicities associated with long-term, high-dose administration.  To minimize likelihood of adverse effects, especially over a long-term, it may be wise to supplement with the minimal effective dose.

Have you tried Curcumin for depression?

If you’ve taken curcumin (or are still taking it) for your depression, share your experience in the comments section below.  Mention the specific brand of curcumin you take, your daily dosage, as well as how long you’ve been taking it.  Discuss whether you’ve notice any subjective improvement in mood since you began supplementing.

To help others get an idea of your situation, note whether you are taking curcumin as a standalone supplement, with other supplements, and/or with other pharmaceutical medications.  Also report any unwanted side effects that you experienced from your curcumin supplementation.  Realize that although curcumin may not facilitate an antidepressant response in all users, there is evidence to suggest that it’s a supplement at least worthy of testing among those with depression.

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{ 3 comments… add one }
  • Maddie March 31, 2016, 1:18 pm

    Very interesting. I have ordered 1400mg Curcumin to take. I suffer with long standing depression and anxiety. Will report back in a months time. Thank you for bringing it to my attention.

    • Kika June 18, 2016, 4:52 pm

      How are you, Maddie? Has curcumin helped you? Did you buy BCM-95 formula?

  • CZgator August 14, 2016, 5:03 pm

    Great article! I just started taking it myself after a trial of DLPA for chronic osteoarthritic pain and related depression. I have been using bromelain and 5-HTP for awhile, which I like very much but was looking for something to improve symptoms even more. The DLPA worked but after learning about curcumin’s many other benefits, I thought I’d give it a try.

    Reading up on the literature about bioavailability, I noticed that studies showed that administration with fats can boost its solubility. I chose a brand with Bioperine but people might want to experiment by taking a little olive, canola or coconut oil in their meals when they take the curcumin.

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