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Cbd oil for pyrroluria

Effectiveness of Cannabidiol Oil for Pediatric Anxiety and Insomnia as Part of Posttraumatic Stress Disorder: A Case Report

Assistant Clinical Professor of Psychiatry at the University of Colorado School of Medicine in Fort Collins. E-mail: [email protected]

Naturopathic Physician at the Wholeness Center in Fort Collins, CO. E-mail: [email protected]

Abstract

Introduction

Anxiety and sleep disorders are often the result of posttraumatic stress disorder and can contribute to an impaired ability to focus and to demonstration of oppositional behaviors.

Case Presentation

These symptoms were present in our patient, a ten-year-old girl who was sexually abused and had minimal parental supervision as a young child under the age of five. Pharmaceutical medications provided partial relief, but results were not long-lasting, and there were major side effects. A trial of cannabidiol oil resulted in a maintained decrease in anxiety and a steady improvement in the quality and quantity of the patient’s sleep.

Discussion

Cannabidiol oil, an increasingly popular treatment of anxiety and sleep issues, has been documented as being an effective alternative to pharmaceutical medications. This case study provides clinical data that support the use of cannabidiol oil as a safe treatment for reducing anxiety and improving sleep in a young girl with posttraumatic stress disorder.

INTRODUCTION

Cannabidiol (CBD) oil is a naturally occurring constituent of industrial hemp and marijuana, which are collectively called cannabis. CBD oil is 1 of at least 85 cannabinoid compounds found in cannabis and is popular for its medicinal benefits. After tetrahydrocannabinol (THC), CBD oil is the second-most-abundant component of cannabis. Other names for CBD oil include CBD-rich hemp oil, hemp-derived CBD oil, or CBD-rich cannabis oil. Considered to be generally safe, CBD has been used medicinally for decades. However, CBD is not medical marijuana and should be distinguished from high-CBD strains of medical marijuana, which do contain THC, such as “Charlotte’s Web.”

The most abundant compound in cannabis, THC is also a cannabinoid. The THC component induces the psychoactive effect, “high.” A cannabis plant has different amounts of CBD and THC depending on the strain and thus provides different recreational or medicinal effects. The cannabinoid profile of industrial hemp or medical marijuana is ideal for people looking for the medical benefits of CBD without the “high” of the THC.

The mechanism of action of CBD is multifold.1–3 Two cannabinoid receptors are known to exist in the human body: CB1 and CB2 receptors. The CB1 receptors are located mainly in the brain and modulate neurotransmitter release in a manner that prevents excessive neuronal activity (thus calming and decreasing anxiety), as well as reduces pain, reduces inflammation, regulates movement and posture control, and regulates sensory perception, memory, and cognitive function. a 2 An endogenous ligand, anandamide, which occurs naturally in our bodies, binds to the CB1 receptors through the G-protein coupling system. CBD has an indirect effect on the CB1 receptors by stopping the enzymatic breakdown of anandamide, allowing it to stay in the system longer and provide medical benefits.4 CBD has a mild effect on the CB2 receptors, which are located in the periphery in lymphoid tissue. CBD helps to mediate the release of cytokines from the immune cells in a manner that helps to reduce inflammation and pain.2

Other mechanisms of action of CBD include stimulation of vanilloid pain receptors (TRPV-1 receptor), which are known to mediate pain perception, inflammation, and body temperature.5 In addition, CBD may exert its anti-anxiety effect by activating adenosine receptors which play a significant role in cardiovascular function and cause a broad anti-inflammatory effect throughout the body.5 At high concentrations, CBD directly activates the 5-HT1A serotonin receptor, thereby conferring an antidepressant effect.6 Cannabidiol has been found to be an antagonist at the potentially new third cannabinoid receptor, GPR55, in the caudate nucleus and putamen, which if stimulated may contribute to osteoporosis.7

Since the 1940s, a considerable number of published articles have dealt with the chemistry, biochemistry, pharmacology, and clinical effects of CBD.8 The last decade has shown a notable increase in the scientific literature on CBD, owing to its identification for reducing nausea and vomiting, combating psychotic disorders, reducing inflammation, decreasing anxiety and depression, improving sleep, and increasing a sense of well-being.9–12 Findings presented at the 2015 International Cannabinoid Research Society at its 25th Annual Symposium reported the use of CBD as beneficial for kidney fibrosis and inflammation, metabolic syndrome, overweight and obesity, anorexia-cachexia syndrome, and modification of osteoarthritic and other musculoskeletal conditions.13–16

Although studies have demonstrated the calming, anti-inflammatory, and relaxing effects of CBD, clinical data from actual cases is minimal. This case study offers evidence that CBD is effective as a safe alternative treatment to traditional psychiatric medications for reducing anxiety and insomnia.17

CASE PRESENTATION

A ten-year-old girl presented in January 2015 for a reevaluation of behaviors related to her diagnosis of posttraumatic stress disorder (PTSD) secondary to sexual abuse. Her chief issues included anxiety, insomnia, outbursts at school, suicidal ideation, and self-destructive behaviors. Her grandmother, who has permanent custody of the patient and her younger brother, accompanied her.

Our patient had been seen for an initial evaluation in January 2012 and received a diagnosis of PTSD secondary to sexual abuse on the basis of her history, clinical observations, and behaviors ( Table 1 ). Her father had died 6 months earlier in a motor vehicle accident, and our patient’s maternal grandparents became her permanent guardians. Before her father’s death, our patient had no supervision from her father and very little supervision from her mother. An 11-year-old boy had molested her when she was 3 years old. Her medical history included her mother having methadone addiction, alcoholism, bipolar disorder, and depression. Her mother used marijuana her entire pregnancy with the girl. The patient presented in January 2012 as displaying aggressive, disobedient, impulsive, and sexually inappropriate behaviors. She also demonstrated low self-esteem and anxiety and had poor sleep (restless, interrupted, and unable to sleep alone).

Table 1

Date Presentation Medications Supplements Other
January 31, 2012 New evaluation: 7.5-year-old girl. History of sexual abuse and neglect. Issues: Insomnia, sexual behaviors. Diagnosis: PTSD secondary to sexual abuse. None Melatonin, 1 mg/night February 14, 2012, laboratory values: TSH, 2.46 mIU/L (reference range, 0.47–4.68 mIU/L); ferritin: 21 ng/mL (reference range, 10–150 ng/mL).
February 16, 2012, laboratory values: Vitamin D3: 39 ng/mL (reference range, 20–50 ng/mL)
February 20, 2012 Sleeping 2–3 hours/night. Started counseling; Cooperative and good behavior at counseling session. Anxious, traumatized. Clonidine, 0.05 mg (half tablet) at bedtime Inositol, 3 g 3 times/d; EPA fish oil, 500 mg/d Eye movement desensitization and reprocessing therapy recommended
February 22, 2012 Did not do well with clonidine because of hallucinations, so she discontinued that treatment. Behavior still very rough; sleep poor. Started imipramine therapy, 25 mg at bedtime March 7, 2012: ECG was normal
August 8, 2012 a Good summer. In play therapy. Overall better sleep and energy with imipramine therapy. Patient’s 6-year-old brother also now in therapy. Imipramine, 25 mg at bedtime
January 21, 2015 Returned for evaluation and treatment after 3 years. Suicidal ideation; cut self on leg; defiant and stubborn. Had psychotherapy 3 years straight twice a month. Sleeps with brother; can’t sleep alone. Off all medications for past 18 months Melatonin, 5 mg; St John’s wort, 450 mg twice/d; magnesium, 300 mg/d; diphenhydramine, 25 mg/night
February 16, 2015 Hard to manage. Has outbursts at school. Magnesium and St John’s wort: stopped treatment; EPA fish oil, 750 mg/d; diphenhydramine, 25 mg/night February 11, 2015: Normal cortisol and DHEA levels
March 16, 2015 Better overall. Started animal-assisted therapy. EPA fish oil, 750 mg/d; diphenhydramine, 25 mg/night Started a regimen of CBD oil, 25 mg (1 capsule)/d at 6 pm
April 14, 2015 Sleeping better with CBD treatment. Getting biofeedback. Has stomachaches. Mood is more at ease. EPA fish oil, 750 mg/d; diphenhydramine, 25 mg/night CBD oil, 25 mg (1 capsule)/d at 6 pm
May 26, 2015 “Ghosts” waking patient up at night. EPA fish oil, 750 mg/d CBD oil, 25 mg (1 capsule)/d at 6 pm
July 22, 2015 Sleeping better; able to sleep in own room 3–4 nights/wk. EPA fish oil, 750 mg/d CBD liquid, 12 mg (in 4 sublingual sprays)/night; 12 mg more (in 4 sublingual sprays) during the day as needed for anxiety, typically 3 or 4 times/wk
August 24, 2015 Sleeping well. Handling school well. EPA fish oil, 750 mg/d CBD oil, 25 mg (1 capsule)/night; CBD liquid, 6–12 mg (in 2–4 sublingual sprays) as needed for anxiety, typically 2 or 3 times/wk
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CBD = cannabidiol; DHEA = dehydroepiandrosterone; ECG = electrocardiogram; EPA = eicosapentaenoic acid; PTSD = posttraumatic stress disorder; TSH = thyroid stimulating hormone.

Workup during 2012 included laboratory studies, which ruled out a thyroid dysfunction and an iron or vitamin D deficiency. The patient was started on a regimen of 1 mg/night of melatonin, which helped her sleep duration. Three grams of inositol 3 times a day and 500 mg/d of eicosapentaenoic fish oil were also helpful in reducing her anxiety. A trial of clonidine was implemented, which resulted in hallucinations and thus was discontinued. The patient was switched to a regimen of 25 mg of imipramine at bedtime to decrease her anxiety, which appeared to be helpful. Counseling sessions were started. The patient continued psychotherapy for 3 years, but she was not seen again in our clinic until the return visit in January 2015, when she was not receiving any of her medications and supplements.

At the patient’s return in January 2015, she demonstrated the same prominent symptoms as at her initial presentation. At that time, the initial treatment included the following supplements and medications to assist with her sleep and anxiety: melatonin, 5 mg/night; magnesium, 300 mg/d; and diphenhydramine (Benadryl), 25 mg/night. Our patient demonstrated slight gains but was still having outbursts at school and was reportedly difficult to manage at home. In addition, her underlying anxiety continued.

Cannabidiol oil was explored as a potential additional treatment to help her insomnia and anxiety, but we deferred for two months while we waited for a response from other interventions. The grandmother preferred reducing the pharmacologic load given her granddaughter’s failure to respond long term to psychiatric medications.

In March 2015, CBD oil was recommended as a potential additional treatment to help her insomnia and anxiety, and her grandmother provided full informed consent. Our patient was administered the Sleep Disturbance Scale for Children18 and the Screen for Anxiety Related Disorders (SCARED)19 before taking the CBD oil and each month afterward for the next 5 months. Test scores on the Sleep Disturbance Scale for Children and Screen for Anxiety Related Disorders demonstrated an improvement ( Table 2 ).

Table 2

Patient’s clinical progress in sleep and anxiety

Date of visit Sleep scale score a SCARED score b
March 16, 2015 59 34
May 25, 2015 42 24
July 22, 2015 41 19
August 24, 2015 37 16
September 22, 2015 38 18

a A score of more than 50 is considered indicative of a sleep disorder on the Sleep Disturbance Scale for Children.

SCARED = Screen for Anxiety Related Disorders.

A trial of CBD supplements (25 mg) was then initiated at bedtime, and 6 mg to 12 mg of CBD sublingual spray was administered during the day as needed for anxiety. A gradual increase in sleep quality and quantity and a decrease in her anxiety were noted. After 5 months, the patient was sleeping in her own room most nights and handling the new school year with no difficulties. No side effects were observed from taking the CBD oil.

DISCUSSION

Studies repeatedly recognize the prevalence of an anxiety-provoked sleep disorder after a traumatic experience.20 Our patient was definitely experiencing this phenomenon, which was aggravated by daily stressful activities.

The main finding from this case study is that CBD oil can be an effective compound to reduce anxiety and insomnia secondary to PTSD. A review of the literature suggests some benefits from the use of CBD because of its anxiolytic and sleep-inducing effects.9 Animal studies support use of this treatment and report that “CBD may block anxiety-induced [rapid eye movement] sleep alteration via its anxiolytic effect on the brain.”21

The strength of this particular case is that our patient was receiving no pharmaceutical medications (other than nonprescription diphenhydramine) but only nutritional supplements and the CBD oil to control her symptoms. Her scores on the sleep scale and the anxiety scale consistently and steadily decreased during a period of 5 months (see Table 2 ). She was ultimately able to sleep through the night most nights in her own room, was less anxious at school and home, and displayed appropriate behaviors. The patient’s grandmother (her caregiver) reported: “My granddaughter’s behaviors are definitely better being on the CBD. Her anxiety is not gone, but it is not as intense and she is much easier to be around. She now sleeps in her own room most of the time, which has never happened before.”

Further study will need to be conducted to determine the permanency of our patient’s positive behaviors and how long she will need to continue taking the CBD oil. We do not have a reasonable foundation to recommend dosing from the scientific literature. However, in our experience, this supplement given 12 mg to 25 mg once daily appears to provide relief of key symptoms with minimal side effects. Our patient did not voice any complaints or discomfort from the use of CBD. We routinely asked about headache, fatigue, and change in appetite or agitation in addition to conducting a routine psychiatric evaluation. Although CBD is considered generally safe,17 the long-term effects are yet to be studied.

The ultimate goal is to gradually taper her off the use of CBD oil and transition our patient into lifelong coping strategies such as yoga, meditation, and various other therapeutic activities.

Marijuana and Medicine

Scientific data indicate the potential therapeutic value of cannabinoid drugs, primarily [tetrahydrocannabinol], for pain relief, control of nausea and vomiting, and appetite stimulation; smoked marijuana, however, is a crude [tetrahydrocannabinol] delivery system that also delivers harmful substances.

— Joy JE, Watson SJ Jr, Benson JA Jr. Marijuana and medicine: Assessing the science base. Washington, DC: National Academies Press; 1999.

Acknowledgments

CannaVest Corp, San Diego, CA, which had no involvement in the case study or distribution of the product, provided the CBD oil that was administered to the patient. No financial support was provided.

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Kathleen Louden, ELS, of Louden Health Communications provided editorial assistance.

Footnotes

a GW Pharmaceuticals is the founder of the Cannabinoid Research Institute, directed by Philip Robson, MD. Further research articles listed.

Disclosure Statement

The author(s) have no conflicts of interest to disclose.

References

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Pyroluria: The Most Common Unknown Disorder

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Pyroluria: The Unknown Disorder

Pyroluria, also called Malvaria, is a unique metabolic condition that is very rarely recognized in both the medical and natural health world. Some researchers in the orthomolecular medicine and orthomolecular psychiatry believe that up to 10% of the population has this metabolic condition (1). It is considered by many in the functional medicine world the most common unknown disorder. Pyrolurics need a specific diet, lifestyle and supplementation program to get well.

Pyroluria is a genetic condition that is typically related to familial alcoholism and/or environmental toxicity. If an individual has a family history of alcoholism they may very well have this genetic mutation. It can be induced with childhood trauma or a chronic infection early in life. The onset usually begins in the late teens and is often triggered by a traumatic life event.

The Symptoms Associated with Pyroluria:

It is estimated that as many as 50% of those with autism, 40% of alcoholics, 70% of schizophrenics, 70% of depressed individuals and 30% of people with ADHD have pyroluria (2, 3). When this goes undiagnosed and untreated it becomes very challenging for these individuals to ever get well despite the use of holistic therapies. Most will struggle with their health throughout their life and never find any long-term answers.

The symptoms of pyroluria include chronic anxiety, poor stress tolerance, digestive issues, poor immunity, joint pain, acne or eczema, mood swings and poor short term memory. These individuals often have difficulty digesting and absorbing protein and they are easily wrecked by increasing stress (4, 5, 6).

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Diagnosing Pyroluria:

Pyroluria can be diagnosed through a specific Kryptopyrroles urine test. Normal amounts of kryptophyrroles in the urine should be less than 20 ug/dl. Numbers greater than 20 ug/dl would be a positive test for the diagnosis of pyroluria (7). Many clinicians have found that this number should be less than 15 ug/dl.

The lab that I use for this test measures kryptopyrroles in mcg/dl and the number should be less than 9 mcg/dl. Anything between 10-15 is considered mild pyroluria, 15-19 is moderate and anything above 20 mcg/dl, we consider a severe case.

Other warning signs you may have this disorder include an inability to remember dreams, hair loss, light, thin pale skin that is prone to stretch marks, white spots on the fingernails and poor tooth enamel (8).

What is Pyroluria:

There are several waste products that are produced when the body makes hemoglobin for the red blood cells. These waste products are called kryptopyrroles which are technically called hydroxyhemoppyrrolin-2-one (HPL) which are typically excreted by our body. Individuals with pyroluria are unable to clear the HPL effectively and they build up in the system (9, 10).

The HPL binds strongly to zinc, biotin and vitamin B6 which are critical nutrients for cellular metabolism. Over a period of time, the body becomes very deficient in these critical nutrients and symptoms arise. These people will often go years suffering the effects of this disorder despite a clean diet, supplementation and holistic therapies.

Nutrition & Supplementation:

Pyrolurics have a greater need for omega-6 fatty acids than most in our society (11, 12). They need both arachidonic acid (AA) and Gamma linolenic acid (GLA). A diet rich in pastured eggs, pasture-fed butter, grass-fed beef and wild game and organ meats supplies the body with significant amounts of essential fats. These foods are also rich in zinc.

GLA is found in borage oil, evening primrose oil, black current seed oil and hemp oil. This is typically supplemented with one of these sources as it is hard to get enough in our diet.

These individuals need to supplement with zinc and co-enzymated form of vitamin B6 called P-5-P (13, 14). A general methyl donating supplement with P-5-P and other methyl donors such as trimethylglycine, methyl-folate, methyl-B12 and riboflavin 5’phosphate sodium is quite effect with this process.

Vitamin B6 is found in seafood, meat and green leafy veggies among other things. However, the number one way we get B6 into our system is through fiber that our gut microbes break down and produce B6 as a byproduct of their metabolism of the fibers. Probiotics and fermented foods are also necessary for these individuals to reduce inflammatory gut related stress and heal appropriately.

Lifestyle & Supplements Get Results:

With the right diet, supplementation and stress reduction most pyrolurics see results very quickly. More severe cases usually experience slow progressive results. Very stubborn cases are typically having issues with heavy metals or mold toxins.

They will need to remain on this lifestyle with moderate supplementation for the rest of their life or risk symptoms coming back. Typically, large doses of supplementation is used in the beginning and the individual tapers down to smaller doses as they feel better and have a return to nutrient sufficient status.

Clinically, I use high doses of zinc, methylation support, mitochondrial support (CoQ10, Lipoic Acid, N-Acetyl Cysteine), Probiotics and GLA.

Testing for Zinc and B6 Status:

The easiest way to test for zinc sufficiency is through a zinc tally test. This is a test done by tasting a liquid zinc supplement. With zinc sufficiency the liquid tastes awful but those who are deficient in zinc will not taste the liquid supplement. This is a positive flag for a zinc deficiency. Blood work could also be done to verify but most experts like the zinc tally test as it is easy and inexpensive.

The subjective test for B6 sufficiency is the return of regular dreaming that the individual can remember. They don’t have to remember the entire dream but bits and pieces is a sign of sufficiency. When they are deficient they will typically be unable to remember anything about their dreams (15).

Additional Tips to Know:

Pyrolurics also need to be sure to eat very clean and avoid phytate containing foods such as grains, nuts, legumes and soy. Phytic acids in these foods bind to major minerals like zinc and render them useless in our body (16). Soaking and sprouting legumes and nuts reduces the phytate count.

Due to zinc deficient states they are more susceptible to heavy metal toxicity from mercury, cadmium and copper. When the individual is unable to develop a zinc sufficient state despite very large supplemental usage it is most likely related to heavy metal toxicity. Special testing can be done for heavy metal levels.

Chronic stress, alcohol consumption, sugar consumption, smoking and pharmaceutical drugs will all further aggravate the symptoms and severity of pyroluria.

Pyroluria Questionnaire:

The following includes the most common symptoms associated with the condition Pyroluria. If you answer “yes” to 15 or more of these then further testing may be worthwhile:

1. Little or no dream recall

2. White spots on finger nails

3. Poor morning appetite +/- tendency to skip breakfast

4. Morning nausea

5. Pale skin +/- poor tanning +/- burn easy in sun

6. Sensitivity to bright light

7. Hypersensitive to loud noises

8. Reading difficulties (e.g. dyslexia)

9. Poor ability to cope with stress

10. Mood swings or temper outbursts

11. Histrionic (dramatic) tendency

12. Argumentative/enjoy argument

13. New situations or changes in routine (i.e., traveling) particularly stressful

14. Much higher capability and alertness in the evening, compared to mornings

15. Poor short term memory

16. Abnormal body fat distribution

17. Belong to an all-girl family with look-alike sisters

20. Reaching puberty later than normal

21. Difficulty digesting, a dislike of protein or a history of vegetarianism

22. Tendency toward being a loner and/or avoiding larger groups of people

23. Stretch marks on skin

24. Poor sense of smell or taste

25. Feel very uncomfortable with strangers

26. Frequently experience fatigue

27. A tendency to overreact to tranquilizers, barbiturates, alcohol or other drugs (in other words, a little produces a powerful response)

28. A tendency toward anemia

29. History of mental illness or alcoholism in family

30. Easily upset by criticism

31. Sweet smell (fruity odor) to breath or sweat when ill or stressed

32. Prone to acne, eczema or psoriasis

33. A tendency toward feeling anxious, fearful and carrying lifelong inner tension

34. Difficulty recalling past events or people

35. Bouts of depression or nervous exhaustion

36. Prone to frequent colds or infections

I have a specific blood test that lets me know if someone is positive for the Pyroluric condition and I have a specialized nutrition and supplement protocol to help these individuals regain their health.