OCD, or Obsessive Compulsive Disorder, is a debilitating condition that involves intrusive thoughts and time-consuming, repetitive behaviors. It impacts 80 million worldwide, 2-4% of the US population or 1 in 100 people here in the US.
It can be difficult to overstate the suffering caused by OCD, not only for those with this condition but also for their family members. In addition to the distress caused by the obsessional thoughts and compulsions, there can be shame and loss - loss of more meaningful, purposeful, or pleasant thoughts and behaviors. and loss of time connecting with others or engaging in purposeful or enjoyable activities.
Other conditions associated with obsessive-compulsive disorder include:
Body dysmorphic disorder
Skin picking
Trichotillomania (hair pulling)
Hoarding
Hypochondria
Olfactory reference syndrome (an irrational feeling or belief that one emits a foul smell and often attempts to remove the odor).
It´s not unusual for someone with OCD to have other conditions, such as:
Other forms of anxiety
Depression
ADHD
Autism spectrum disorder
Eating disorders
Tourettes
Research suggests that having OCD raises one´s vulnerability to developing dementia. Many other brain conditions, however, also appear to increase this vulnerability similarly.
Treatment Challenges
OCD is particularly challenging to treat. Of those with OCD, 60% do not respond to typical therapies (often medication in combination with psychotherapy involving gradual exposure to that which is being avoided). Typical medications include:
SSRI´s (Selective Serotonin Reuptake Inhibitors) -e.g., sertraline, fluoxetine, fluvoxamine, citalopram, paroxetine
Tricyclic antidepressant - clomipramine
SNRI - (Serotonin and Norepinephrine Reuptake Inhibitor) - venlafaxine
Atypical antipsychotic medications are sometimes added
Medication is combined with CBT (Cognitive Behavioral Therapy), which involves exposure and response prevention, or CBT is used alone.
As you can see, most medication approaches aim to increase serotonin activity. Serotonin, however, is just one of the neurotransmitters involved. What has become increasingly clear from the research is that OCD involves abnormal activity at the NMDA receptor - a glutamate receptor.
NMDA & Glutamate
The NMDA receptor is found throughout the brain. Glutamate, the primary excitatory neurotransmitter in the central nervous system, binds to the NMDA receptor. NMDA and glutamate are involved in synaptic plasticity (creating neuronal connections), learning, memory, and motor function.
The synapse is the space between communicating neurons.
Presynaptic neurons release glutamate, which binds to the NMDA receptor on postsynaptic neurons. This results in a cascade of signaling events that lead to “neuronal excitation.” The problem arises when this receptor has too much (or too little) activity. In the case of OCD, there is too much activity.
Implications
Dysregulation at the NMDA receptor appears to play a role in OCD, depression, PTSD, schizophrenia, bipolar disorder, and substance use disorders.
Weak memory extinction can result from high activity at the NMDA receptor. While memory is a good thing, we can have problems with too much memory - or rather, problems putting our memories aside. This can look like thoughts getting stuck, for example:
Intrusive thoughts in OCD
Flashbacks in PTSD
Delusions in psychotic disorders
Cravings in addiction.
Neurodegenerative disorders, such as Alzheimer’s, Parkinson’s, and ALS, have also been linked to NMDA receptor malfunction.
Methylation & NMDA
Those who are undermethylated, especially those with OCD or addictions, have high activity at the NMDA receptor. To remind you, undermethylation is a biochemical process with many functions, including the breakdown of histamine, support of detoxification, and support of serotonin activity. When someone is undermethylated, they can tend to have allergies (from high histamine), be perfectionistic, competitive, strong-willed, have obsessive-compulsive tendencies, be ritualistic, have dietary inflexibility, and have high accomplishment or have family members with high accomplishment.
Undermethylation can contribute to the low serotonin activity seen in OCD. Simply addressing undermethylation, like merely addressing serotonin, will only bring partial benefit. To address undermethylation, those of us trained by the Walsh Research Institute, use SAMe and/or methionine, B12, B6, magnesium, and antioxidants. We address this before starting methylation treatment for those with high homocysteine.
But how can we also decrease activity at the NMDA receptor?
Blocking NMDA & Normalizing Glutamate Activity
Esketamine or Ketamine, which has been getting much attention in recent years, can impact the brain in various ways; however, its primary mechanism is as an NMDA blocker or antagonist. For some, it can serve as a rapid-acting and highly effective antidepressant. It can also decrease OCD symptoms. Other NMDA-blocking drugs include memantine and dextromethorphan (combined with bupropion). Lamotrigine can decrease glutamate release and has been used as an adjunct medication for OCD.
Nutrients, however, play an important role in the NMDA receptor.
NAC or N-acetyl cysteine is a precursor to glutathione and, thus, an antioxidant. It is also anti-inflammatory and a binder for a particular toxin made by candida and mold. But, it is also a potent NMDA antagonist (decreases activity at NMDA) and has been shown to reduce obsessions and compulsions of OCD. It has also been studied in alcoholism, opiate addiction, cocaine abuse, gambling disorder, shopping disorder, cigarette addiction, and trichotillomania. It has been used by itself and as an adjunct to medication therapy. NAC has become part of the Walsh undermethylation nutrient protocols for those with OCD and/or addiction.
Zinc also plays an important role in regulating functioning at the NMDA receptor. The Walsh Research Institute found that 90% of those with brain symptoms had relatively low zinc. Dosing of zinc is determined after testing plasma zinc levels using a narrow range (the Walsh/Pheiffer range differs from typical lab ranges). Zinc is checked in conjunction with copper. Zinc has been found to improve treatment response in those with OCD treated with SSRIs.
Zinc can be depleted because of very high oxidative stress and/or high pyrroles, which also cause low B6. Because B6 is needed to make serotonin, pyrroles are also important to address if elevated.
Inositol is a nutrient involved in the serotonin and glutamate signaling systems. It, too, is beneficial for OCD symptoms; however, it can require very high doses.
The challenge of research, as you can see, is that these approaches are all looked at in isolation, as opposed to, for example, addressing undermethylation, optimizing zinc, decreasing activity at the NMDA and addressing sources of oxidative stress.
Candida & Mold
Aside from undermethylation, low serotonin activity, and high activity at the NMDA receptor, those with OCD appear to have high oxidative stress, as is the case with most brain-related conditions. One of the more common sources of oxidative stress I see in my practice is candida overgrowth in the GI tract, which often follows antibiotic exposure and /or mold toxicity due to water damage causing seen or unseen toxic mold. Because mold and candida (yeast) thrive on sugar and a high-carb diet, symptoms can fluctuate with sugar or carb intake.
How might candida and mold intersect with the NMDA receptor? Mold and yeast can contribute to high histamine states. Histamine can increase activity at the NMDA receptor.
Estrogen
For women and teen girls that I see with OCD, there is often a fluctuation in their OCD symptoms with their cycle. Typically, their symptoms worsen during the times of the month when estrogen is the highest. This may be because estrogen can increase activity at the NMDA receptor.
PANDAS & PANS
When a child has an abrupt onset of OCD symptoms, PANDAS and PANS should be considered.
PANDAS = Pediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcal Infections
PANS = Pediatric Acute-Onset Neuropsychiatric Syndrome
PANDAS and PANS are autoimmune conditions, meaning the immune system is acting on the body, in this case, a part of the brain called the basal ganglia, that involves an acute onset of OCD symptoms. Other symptoms can include restricted eating, mood symptoms, regression in academic or social skills, and motor tics.
While triggers are often viral, bacterial (strep in the case of PANDAS), candida,or other microbial source, what is underlying the dysregulated immune response to such microbes, in my experience, is mold toxicity.
Summary
Because OCD can be difficult to treat, my hope in sharing this information is to raise awareness that effective OCD treatments can require a multifaceted approach that includes:
addressing methylation (and high pyrroles if present) to improve serotonin activity
decreasing activity at the NMDA receptor
by optimizing zinc
using supplements or medication
addressing sources of inflammation and high histamine
address sources of oxidative stress - trauma, stress, toxins, inflammation
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As always, I welcome your comments, questions, and experience.
Until next time,
P.S. To learn more about non-patient consultations, treatment, and monthly mentorship groups, please visit my website at:
Medical Disclaimer:
This newsletter and podcast episode is for educational purposes and not intended or implied to be a substitute for professional medical advice, diagnosis, or treatment for yourself or others, including but not limited to patients you are treating (if you are a practitioner). Consult your physician for any medical issues that you may be having.
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