Obsessive compulsive disorder (OCD) is exactly what the name says it is.

It’s basically a mental condition where an individual experiences bothersome, intrusive, and worrisome thoughts that elicit a feeling of discomfort and/or fear that often leads to obsessive-compulsive behaviors.

It can manifest in a wide variety of ways, for example (R):

• Body dysmorphic disorder (BDD), where the person can’t stop thinking about one or more perceived defects or flaws in their appearance. For example, “if I just had a smaller forehead, or if I were 3 inches taller, I would be perfect and everyone would love me.”
• Hoarding disorder.
• Trichotillomania, which is urges involved in pulling out hair from the scalp, eyebrows, and other areas of the body.
• Excoriation (skin-picking) disorder.
• Obsessive/repeated checking, e.g. if you locked the door, etc.
• Washing of hand and being a germophobe.
• Intrusive thoughts and rumination.
• Ritualized eating behavior, as found in eating disorders.
• Preoccupation with substances or gambling, as seen in substance-related and addictive disorders.
• Preoccupation with having an illness, as found in illness anxiety disorder.
• Sexual urges or fantasies, as found in paraphilic disorders.
• Impulses, as seen in disruptive, impulse-control, and conduct disorders.
• Guilty ruminations, as occurring in a major depressive disorder.
• Thought insertion or delusional preoccupations, as found in schizophrenia spectrum and other psychotic disorders.
• Repetitive behavior patterns, as found in autism spectrum disorder.
• Fears, such as fears of contamination, fears of aggression/harm, sexual fears, religious fears, and need to make things “just right.”  The compensatory compulsions for these obsessions include washing and cleaning, checking, reassurance-seeking, repeating, and ordering, arranging, etc.

As you can see from the symptoms above, OCD is mostly found alongside other disorders, such as anxiety, depression, autism, fear, etc., so there can be overlapping “treatments”, because something that can reduce anxiety, for example, can improve OCD.

Let’s get into a few mechanisms in the body that potentially contribute to OCD.

HPA axis, glutamate and GABA

HPA (hypothalamus-pituitary-adrenal) axis

The whole stress cascade is elevated in OCD. From the hypothalamus, which secretes the inflammatory corticotrophin-releasing hormone (CRH), all the way to the adrenals, which secrete cortisol.

The lack of cortisol suppression on the dexamethasone suppression test (DST) is an indication of HPA axis abnormality in OCD patients, which may be explained by a possible insensitivity of the pituitary gland due to high CRH levels (R). Interestingly, acetylcholine can reduce CRH sensitivity, and lead to elevated levels of CRH, ACTH and cortisol.

Atropine, an anticholinergic, upregulates CRH receptors in the cerebral cortex and shows that excess acetylcholine can contribute to CRH insensitivity and lead to high CRH levels (R).

The high acetylcholine syndrome

By “taming” the HPA axis, we can dramatically reduce OCD symptoms. And that’s been found with many adaptogens, such as Ashwagandha, valerian, magnesium, etc.

> Read more here on how to lower cortisol

DHEA-S and GABA

OCD patients also have higher plasma levels of dehydroepiandrosterone-sulfate (DHEAS), a neuroactive steroid having opposite effects to that of allopregnanolone (R). In this study, the anti-OCD effects of allopregnanolone were comparable to that of fluoxetine and the benefits were blocked by finasteride (R).

DHEA-S opposes GABA, whereas allopregnanolone is pro-GABA. Too much DHEA-S can leave you in a state of overactivation, such as in ADHD, ADD, anxiety, rumination, depression, etc. GABA is needed to put a brake on glutamate, which is chronically elevated in OCD.

A note on acetylcholine again:

Lowering acetylcholine, by either blocking its receptors or presynaptically activating M2/M4 mAChRs (which act as inhibitory autoreceptors), reduces glutamate release. Excess glutamate is implicated in depression.

…

glutamatergic hyperactivity is associated with OCD, which may be because nicotinic receptor activation releases glutamate (R).

The high acetylcholine syndrome

Glutamate

Some studies have shown that the concentration of glutamate is significantly higher in the cerebrospinal fluid of patients with OCD compared to healthy controls. The higher glutamate concentration is related to excitotoxicity and oxidative stress (glutamate is excitotoxic and neurotoxic) among patients with OCD, and this seems to be correlated with symptom severity (R).

Glutamate acts on a variety of receptors, with NMDA being one of them. Quinolinic acid is also an agonist of that receptor and can cause neurotoxicity in high amounts. Quinolinic acid is created in the kynurenine pathway, which is upregulated by inflammation. Reducing inflammation, by reducing polyunsaturated fat intake, reducing excess iron (and other heavy metals) in the body, lowering parathyroid hormone and aldosterone, calming gut inflammation, etc., can help to lower excess inflammation.

Turmeric, taurine, glycine, carnosine, niacinamide, magnesium, zinc, selenium, cocoa, vitamin C, E, aspirin, vitamin D and a variety of other herbs and supplements can help to reduce inflammation.

GABA keeps glutamate (as of other neurotransmitters) in check, so when GABA is inhibited, neurotransmitters, such as glutamate, CRH, serotonin, acetylcholine, etc., can go too high.

GABAergic supplements are of great help against OCD. Supplements such as:

• Progesterone and its 5-alpha reduced metabolite, 5alpha dihydroprogesterone (5a-DHP)
• Niacinamide (lots of people say that niacin and/or niacinamide worked great against their OCD anxiety)
• Taurine
• Valerian root
• Zinc (for anxiety and intrusive thoughts (R).
• Skullcap
• Magnolia
• etc.

Another method that has been used for OCD, is deep brain stimulation (DBS). The procedure involves them drilling holes in your skull and putting rods in your brain that alters the function of various nuclei. It’s been shown to inhibit the HPA axis and increase thyroid hormones which correlate with improved symptoms (R).

So this is most likely only something that 0.01% of people with OCD would do, but it’s interesting to notice that the DBS lowered cortisol and boosted thyroid. So thyroid function is most likely also suboptimal in people with OCD.

This study found that OCD patients have blunted TSH responses to TRH, which means that they will most likely have insufficient T4 and T3 with elevated prolactin (TRH increases prolactin) (R).

Melatonin

In OCD patients, the 24-hour secretion of melatonin was reduced as compared with that in healthy control subjects, whereas its circadian rhythm was preserved (R).

Agomelatine, a melatonin receptor agonist, but also serotonin receptor 5-HT2C antagonist is useful against OCD (R, R).

Serotonin

Serotonin seems to be involved/dysregulated in almost all mental disorders.

Serotonin is created by tryptophan hydroxylase 2 (TPH2) in the brain from the amino acid tryptophan. Serotonin binds to its receptors, 5-HT1 to 5-HT7.

Stress, social defeat, early life trauma, submission, etc., increase TPH2 and lead to elevated serotonin in the brain, which contributes to OCD, depression, anxiety, learned helplessness, etc (R, R).

Activating the serotonin receptors, 5-HT1A, 1B and 1D have anti-OCD effects by lowering the production of serotonin (R, R). Ketamine, a 5-HT1B agonist, has fast anti-OCD properties in animal models in small doses (R).

mCPP, a strong serotonergic drug, when given to untreated OCD patients increases their anxiety, depression, and dysphoria, and worsens their OC symptoms (R).

Clomipramine, the gold standard drug for OCD, inhibits the re-uptake of serotonin and noradrenaline, but it’s a potent antagonist to the of the α₁-adrenergic receptor, the histamine H₁ receptor, the serotonin 5-HT_2A, 5-HT_2C, 5-HT₃, 5-HT₆, and 5-HT₇ receptors, the dopamine D₁, D₂, and D₃ receptors, and the muscarinic acetylcholine receptors (M₁–M₅).

Clearly, “beneficial” serotonergic drugs don’t just work by increasing serotonin, as shown above, as the gold standard serotonergic drug blocks most of the serotonin receptors.

Metergoline on the other hand, which is an anti-serotonergic, doesn’t improve OCD symptoms, because it happens to be a 5-HT1B/D antagonist, which means that it might increase serotonin in certain areas in the brain and can worsen mood disorders for some people.

Antagonism of the 5-HT2A and 5-HT2C receptors have anti-OCD effects, as both of these receptors have increased sensitivity in OCD (R). Fluoxetine, another serotonergic drug, can be beneficial for OCD by desensitizing 5-HT2C sensitivity (R).

Agomelatine disinhibits/increases noradrenaline and dopamine release specifically in the frontal cortex, by inhibiting the 5-HT2C receptor, which makes it very useful against OCD (R, R).

Desensitization of serotonin receptors and a decrease in prolactin (associated with less 5-HT2C activation) is associated with improved symptoms (R). A similar alteration in the response to endogenous serotonin may mediate clomipramine’s anti-obsessional effects (R).

Furthermore, 5-HT3 antagonism by ondansetron can be helpful against OCD (R).

Vitamins & Minerals

Vitamin D

The level of vitamin D is negatively correlated with symptom severity in patients with OCD (R). People with OCD tend to have low vitamin D and are more prone to ADHD (R). Vitamin D reduced OCD hair pulling (trichotillomania) (R). Vitamin D:

• Increases tyrosine and tryptophan hydroxylase which can lead to higher dopamine and serotonin levels.
• Has antioxidant effects and inhibits inducible nitric oxide synthase, which has neuroprotective properties, similar to agmatine.

Zinc, selenium, iron and magnesium

Zinc, selenium, iron and magnesium have been found to be low in some people with OCD. In a randomised placebo-controlled clinical trial, one group received fluoxetine plus zinc while the other group received fluoxetine plus placebo for 8 weeks. This study showed that the zinc group had a greater improvement compared with the placebo group (R).

Magnesium and OCD:

Magnesium administration decreases anxiety, panic and phobia and ameliorates the attention deficit and sleep disorders. We consider that magnesium acts mainly by: a) the reduction of presynaptic glutamate release; b) the reduction of NMDA receptor activity by competing with calcium at NMDA receptor coupled calcium channels; c) the positive allosteric modulator effect at the level of some metabotropic presynaptic glutamate receptors, thereby decreasing presynaptic glutamate release and stimulating GABA release; and d) the decrease of catecholamine release by a direct presynaptic effect under the action of some factors including calcium. The stimulation of catecholamine release under stressful conditions leads to increased magnesium waste that is an essential event in the appearance of the functional cerebral changes characteristic of neurosis symptomatology.

Reference

Folate and B12

According to this study, OCD patients tend to have a higher probability of having low folate and B12 with elevated homocysteine, which significantly correlates with symptom severity (R).

Nitric oxide

Nitric oxide modulates the neurotransmitters implicated in OCD and patients with OCD exhibit higher plasma nitrate levels, and drugs useful in OCD lower nitric oxide (R). Agmatine is effective in ameliorating the compulsive-like behavior in mice which appears to be related to nitric oxide in the brain (R).

> Read more here on nitric oxide and how to lower it

Useful supplements

• Amantadine (100mg) (R).
• Memantine (5-20mg) (R).
• NAC (500mg-2g daily) (R).
• Caffeine (300mg) (R)
• Pro-opioid substances (which can help to lower anxiety) (R), such as tianeptine (R), selank (R), agmatine (enhances the effect of other opioids), gluten, dairy, etc.
• Saffron. “Our findings suggest that (30mg) saffron is as effective as fluvoxamine in the treatment of patients with mild to moderate OCD” (R).
• Minocycline. Minocycline is a fat-soluble anti-biotic that can pass through the blood-brain barrier. In the brain, it has neuroprotective and neurogenic properties in amyotrophic lateral sclerosis and Parkinson’s disease. Minocycline lowers pro‐inflammatory agents, including nitric oxide, tumor necrosis factor‐α, and interleukin‐1β and decreases glutamate‐induced neurotoxicity. Minocycline has therapeutic effects on neurodegenerative diseases and this might be achieved through the blockage of glutamate‐mediated excitotoxicity (R).
  And I don’t just think it’s only beneficial because it lowers inflammation, but also because it’s an anti-biotic. Earlier onset of sudden OCD that is preceded by a Streptococcus infection has been known as PANDAS (pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections) (R).
• Myo-inositol. 18g/day appears to be useful against OCD (R).
• Glycine (60g, but this dose caused high drop out rates due to nausea and vomiting (R)).
• Milk thistle. “Results of the only randomised controlled trial (n=35) of milk thistle for OCD treatment revealed no significant difference in treatment effects between milk thistle (600 mg/d) and fluoxetine. It is indicated that milk thistle has similar effects with fluoxetine in OCD symptoms and its positive effect starts in the fifth week without severe side effects” (R).
• Valerian extract at a dose of 765 mg/day is useful against OCD, by activating the GABA system (R).
• Ashwagandha 120mg/day (crude extract) (R).
• Curcumin. “After the oral curcumin administration for 35 days, compulsive checking and ritualistic behaviours were significantly reduced, and quinpirole-induced deteriorations were reversed. These effects of curcumin were comparable with paroxetine” (R).
• Borage extract (500mg) (R).
• Vitamin B1. It helps against the anxiety part of OCD. Doses of 250 mg/day (thiamine HCL) are usually used (R). You can always try sulbutiamine, benfotiamine or allithiamine which might be superior to normal thiamine.
• Psilocybin (R).
• Uridine. I don’t have a scientific reference for this one but there are lots of anecdotal evidence that it helps with OCD. It’s most likely because it increases dopamine and increases the dopamine receptors which are reduced in OCD (R, R).
• Kundalini Yoga (R). Not a supplement, but it can be dosed like a supplement if you want to think of it like that. And it’s not just Kundalini yoga, but other styles of yoga or mediation as well, because it’s about quieting the mind, deep breathing and lowering overall stress.

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Have I helped people with OCD before?

Yes, I have had clients before with OCD, and I was able to help them improve their health and reduce their symptoms quite a lot, just by tweaking/making changes to their daily lifestyle, improving their diet, etc. But I would have to say that the biggest limiting factor about helping someone with OCD is when/if they are too OCD about taking supplements and changing their diet too much. This is a big limiting factor if the person wants to improve his health to a greater extent but doesn’t want to make the necessary changes in order to do so.

To read further discussion on this article, click here.

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