1. Low Dose Naltrexone
Presented By: Craig Batagowski, PharmD, IACP (Presenter)
Created By: Kiley Shelley, PharmD Candidate (Creator)
Edited By: Paraj Patel, PharmD Candidate (Editor)

2. What is Naltrexone? Opiate antagonist on mu receptors
FDA approved for treatment of alcohol and opiate addiction
Oral dose generally 50 mg daily
Blocks opioid receptor 24 hours per day
Behavioral Modification
FDA approved - by blocking opiate receptor you prevent addicted patients from being able to obtain euphoria achieved by taking drugs or alcohol

3. Low Dose Naltrexone (LDN)
Use in Irritable Bowel Disease
Use in Chronic Fatigue Syndrome and Fibromyalgia
Use in Thyroid Disorders
Use in Digestive Relief
Quicker onset and relief for digestive issues

4. What is Low Dose Naltrexone? (LDN)
Same active drug as Naltrexone(Vivitrol) available on the market
Doses ranging from 0.5 to 4.5 mg daily
(10-40x lower doses than traditional dosing)
Seems to be effective in autoimmune diseases
Currently there is a lack of sufficient clinical studies
Doses 10-40x lower than traditional dosing of naltrexone in addiction
Endorphins and opioid receptors are involved in almost every biological system that regulates the immune response
Lack of studies could be why the drug is used less

5. Very Low dose Naltrexone (VLDN)
Adjunct therapy to opioid treatment
Reduces titration of opioids
Reduces tolerance of opioids

6. Naltrexone Doses Alcohol & opioid addiction 50 mg (standard dosing)
Low Dose Naltrexone
0.5 – 10 mg
Very Low Dose Naltrexone
1- 5 mcg

7. How does LDN work in the body?
Many disease states are caused by malfunctioning of immune system
Immune system is regulated by endorphins
Endorphins act primarily on opiate receptors
Blocking opiate receptor with LDN for about 6 hours = increased endorphin production
Increased endorphins can correct the immune system malfunction
Blocked for 6 hours, vs. 24 hours with traditional dosing

8. What side effects occur with LDN?
Agitation
Headache
Insomnia
Constipation
Diarrhea
Nightmares
Stomach cramping
Flu-like symptoms
Vivid
Dreams
Reduced renal function
Elevated liver enzymes
May gradually increase the dose to target dose to avoid side effects
Insomina, nightmares, vivid dreams most common

9. LDN in irritable bowel disease (IBD)
Crohn’s Disease (CD) and Ulcerative Colitis (UC)

10. How can LDN be beneficial in IBD?
Standard approach to IBD treatment:
1. Decrease inflammation in intestinal lining
2. Suppress immune system
3. Administer antibodies against pathogenic antigens
Steroids, antibiotics, biologics, pain relievers
About 50% of patients do not achieve remission on biologics
Patients may also develop resistance over time due to antibodies
Biologics are expensive and more potential side effects
Resistance due to antibodies to biologic protein in meds

11. LDN in Crohn’s Disease Dr. Jill Smith and colleagues
More than 50%of patients had already failed or had side effects to biological agents
Patients on LDN had more symptomatic, endoscopic, and histologic improvement compared to group that was not taking LDN
Several patients demonstrated clinical response & closure of fistulas

12. LDN in Crohn’s Disease
Study Presented at the 2015 American Gastroenterology Association meeting
37 of 56 patients experienced complete or partial remission on LDN therapy
Results support potential use of LDN for active Crohn’s Disease in those not responding or achieving remission with standard regimens

13. LDN in Ulcerative Colitis
Unlike Crohn’s Disease, large controlled trials have not been completed
Typically LDN is offered in those failing standard therapy, including biologics
In combination with biologics, may lead to remission

14. Benefits and limitations of LDN for IBD
1. Mucosal healing
2. Decreased inflammation
3. Does not suppress immune system
4. Does not increase risk of infection
5. Low toxicity
Further studies are needed to make any firm conclusions regarding the likelihood of responding to LDN therapy

15. LDN in chronic fatigue syndrome (CFS) and Fibromyalgia (FM)

16. How can LDN be beneficial in cFS and FM?
No clear etiology or treatment
Associated with physiological abnormalities – immune dysfunction
Definitions of these diseases do not address underlying cause for disease
Unlikely that there is a single causative agent or process occurring, so simple RX is not likely to be totally effective
Not addressing underlying cause = physician has no incentive to determine the underlying abnormalities that are occurring

17. Standard treatment for cfs and fm
Muscle relaxants, antidepressants, NSAIDs, stretching, exercise
FDA approved for FM: pregabalin (Lyrica), duloxetine (Cymbalta), milnacipran (Savella)
2% of patients experience complete recovery
64% of patients experience some improvement
50% of physicians not confident in knowledge of CFS or FM
40% of patients remain unable to work
- Tx approved for FM is simple, symptomatic tx

18. Ldn in cfs and/or fm Over 4,000 patients in study
85% on LDN improved by 4th visit
56% of patients reported significant improvement

19. Benefits & limitations of LDN for CFS & FM
1. Proven effective
2. Physicians can prescribe it and help patients without investing extensive time and multiple visits
3. Low toxicity
Further studies are needed to make any firm conclusions regarding the likelihood of responding to LDN therapy

20. LDN in thyroid disorders
Graves’ Disease and Hashimoto’s Disease

21. How can LDN be beneficial in thyroid disorders?
Unbalanced immune system attacks the thyroid
LDN can modulate immune system to reduce abnormal production of antibodies
LDN can also benefit in depression, insulin resistance, diabetes, obesity, anxiety, and other related chronic illnesses
Graves’: antibody stimulates thyroid receptor = hyperthyroid
Hashimoto: antibody and inflammation destroy thyroid gland tissue = hypothyroid
LDN improved transport of TSH into cells, increases T4 to T3, and reduces T4 to reverse T3

22. Benefits & limitations of LDN for thyroid disorders
1. Can reduce abnormal inflammation and normalize immune abnormalities
2. Improves transport of thyroid hormone into cells
3. Low toxicity
Further studies are needed to make any firm conclusions regarding the likelihood of responding to LDN therapy

23. In summary… LDN Effective and low toxicity
Clinically beneficial for Crohn’s Disease and Ulcerative Colitis
May be effective at improving symptoms of Chronic Fatigue Syndrome and Fibromyalgia
Should be considered in patients with symptoms suggestive of thyroid disorders such as Hasimotos Disease
LDN
- IBD: promotes mucosal healing, decreases inflammation, and improved QOL

24. resource
Elsegood L ed. The LDN Book. White River Junction, VT: Chelsea Green Publishing; 2016.

25. What questions do you have?