Low Dose Naltrexone and Parkinson's Disease III: Dosage-Timing Updates

LDN Updates and Finding a Compounding Pharmacist

We wrote about Low Dose Naltrexone on May 31, 2009 as a possible PD treatment adjunct. On June 8, 2009 we posted an update on the possible side effects.

Naltrexone (Reviva) is an opioid blocker, it blocks all of the opioid receptors in the brain. It was approved by the FDA to treat recovering addicts. Since it is generic, we won't see additional presentation to the FDA for other conditions.

The low dose version triples the body's production of endorphins which supposedly kicks the immune system into full operation. The drug doesn't fight the diseases directly, the body fights the diseases after the immune system is back to normal. The LDN (about 4.5 mg daily after titrating up from 1.5 mg) effectiveness lies in its intermittent blockage of the opioid receptors allowing for endorphin levels to increase for 1-3 days.

A special Thank You to the reader, Solutions for Stressed Caregivers, who took the time to post a comment which provided a link to the recent and first Low Dose Naltrexone Conference held in April, 2009 in Glasgow, Scotland.

SSC also noted that the dosing time recommendations had changed. According to what we read daytime is now a favored time. However, at the conference it was observed that in chronic fatigue syndrome, a morning dose is recommended due to sleep issues. MS patients who have found significant help through LDN, the times should vary according to need and sleep requirements.

I thought that we had mentioned that liquid LDN was available but what we didn't realize was that it could actually be compounded with care at home. Although that is not something we would try or recommend, we did find a link to advice for doing just that. Mr Delaney has also provided practical suggestions for finding a compounding pharmacist. If you reside in the United States you will want to make sure that the pharmacy or pharmacist belongs to the Professional Compounding Centers of America. In the US you can also contact the PCCA. For those in the UK, the contact information is in the article. Many thanks to Mr Delaney.

Remember, before adding supplements, adding a medication, changing dosage and times, or stopping a medication, always consult your physician.  And please let your doctor know about any seemingly benign supplements you are taking because there can be interactions to certain medications.

Although the Parkinson's LDN database at LDN World Database is small, it will provide some helpful information.  If you are using LDN for PD or know someone who is, it would be a great idea to make your addition to the database.

Addemdum 4/04/11
Just a cautionary:  Some medications may do not work well with LDN for some people although they might work just fine for you - we'll be adding to this list:
Clonazapam (klonopin), a benzodiazepine
Prednisone
We'll be expanding this list

Addendum 6/27/11
I just read a very inportant tip for PwPs taking LDN. We be pass it along because of the Parkinson's risk of falls and breaks and the very real possibility that you could be given a narcotic painkiller in such an emergency.
If you are taking Low Dose Naltrexone, it would be a good idea wear a medical alert bracelet/pendant/dogtag stating just that: Low Dose Naltrexone (4.5mg) rather than LDN which people might not recognize.
It is important that the information be directly available before treatment is initiated using a painkiller which will cause you incredible pain if you are on LDN which blocks certain receptors.
And of course carry a wallet card which lists allergies and other pertinent information.

Addendum 9/27/11
Dr Weintraub reports that clinical trial NCT01052831 is still enrolling for Parkinson's disease patients in the Philadelphia, PA area.  This trial is being funded by the MIchael J Fox Foundation.

Is Spinal Cord Stimulation a Future Treatment for Parkinson's Disease

What Is Spinal Cord Stimulation?

Spinal cord stimulation (SCS) for pain reduction has been around since 1967. How it works is actually a little more complicated that in might seem now that there are almost 50,000 of these surgical procedures performed around the world every year. The purpose of SCS is activation of neurons, making them positive electrically or depolarized so that they can generate action potential.

Theoretically pain messages are sent when the "gate" in the spinal cord dorsal horn is opened and there are more small rather than large diameter fibers active. In SCS it was found that electrical stimulation of peripheral nerves can reduce pain by activating the large diameter gated fibers in the dorsal horn of the spine. It is the opening of the large fiber gates and closing of the small gate which is supposed to prevent the pain signals from reaching the brain.

There are more mechanisms at work such as stimulation at higher frequencies causing the nerve fibers to fail to conduct the action potentials, the inhibition of impulse transmission in the spinothalamic tract and an increase of serontonin, adenosine, GABA and Substance P with a decrase in glutamate and aspartate in the dorsal horn of the spinal cord.

The procedure is to insert the epidural leads and test for 3 to 21 days. If the treatment works a pacemaker-sized generator is implanted and the external remote is provided. The procedure is not a cure of the problems at the root of the pain, the treatment is to reduce the level of pain as it threatens quality of life. Nor does the procedure work for all types of pain.

The use of SCS technology is expanding. One of the most recent areas of focus is Parkinson's disease. At Duke University in North Carolina Dr Miguel Nicolelis, Professor of Neuroscience is investigating using the spinal cord rather than the brain to treat PD symptoms because the spinal cord is the primary pathway by which the body signals the brain and the brain sends signals to the body.

In the lab rodents with induced PD, the scientists found that within 3.5 seconds of getting electrical stimulation the stiff, slow movements became essentially normal. The team experimented with higher and lower levels of electrical stimulation and with a combination of L-Dopa. What they found was that even without levadopa the animals were 26 times more active. When they received two doses of levadopa their ability to move was similar to receiving five doses without stimulation.

Since it is known that eventually L-Dopa will not only cease to work but may exaccerbate symptoms, the modified SCS should enable a serious reduction of meds if successful for the patient.

Dr Nicolelis realized that the brain activity of mice with induced PD was similar to the low frequency oscillations of rodents with seizures and epilepsy which he had previously studied. Furthermore it is felt that these low frequency corticalstriatal oscillations impair motor function so that with electrical stimulation, the activity of the neurons could be normalized and motor function could be restored.

The Duke group is working with a team from Brazil to perform pretrial testing of their device.

references and reading:
"Spinal Cord Stimulation Restores Locomotion in Animal Models of Parkinson's Disease."Romulo Fuentes, Per Petersson, William B. Siesser, Marc G. Caron, and Miguel A. L. Nicolelis.Science 20 March 2009 323: 1578-1582.DOI: 10.1126/science.1164901
http://www.sciencemag.org/cgi/content/abstract/sci;323/5921/1578

Dr Nicolelis has also worked on brain-machine interfaces:
http://www.guardian.co.uk/science/2009/mar/19/parkinsons-disease-spinal-implant-electrical-stimulation