|Low Dose Naltrexone and Multiple Sclerosis (MS) - Posted in the Fall of 2000
8/30/00 update from Dr. Bernard Bihari's Web Site: http://www.lowdosenaltrexone.org/index.htm
There are 31 patients with MS who are being followed in Dr. Bihari's practice. Of these, 26 have begun LDN since January 2000. Of the 31, 22 have the relapsing-remitting form of the disease and 9 suffer from the chronic progressive form. Those who began LDN prior to 2000 have been followed for a mean of 5 years, including one patient who has been taking it for 14 years. In the approximately 30 "patient years" of treatment represented by all of the patients combined, there has not been a single disease episode while taking LDN. None of the patients with chronic progressive MS has shown progression on annual neurological examinations.
It appears that some one-third of patients starting LDN have some reduction in chronic symptomatology. For the most part, this involves a diminution in muscle spasm and tightness. In two patients, chronic visual impairment due to old episodes of optic neuritis has shown fluctuating improvement. Patients who are in the midst of an acute exacerbation when they start LDN have generally shown rapid resolution of the attack.
A growing number of studies have shown a specific functional defect in CD4 cells in people with MS. This leads to an impaired ability of macrophages and cytotoxic CD8 cells to distinguish between "self" and "non-self" molecular structures in the body. This in turn allows macrophages in particular to attack the myelin sheath surrounding nerve fibers because of their inability to recognize myelin as "self". The underlying mechanism of much of LDN's action in MS appears to be a correction of the impaired regulation of immunological cells through the raising of endorphin levels to normal.
In May 2000, Bernard Bihari, MD reported four occurrences of surprisingly rapid clinical improvement in people with multiple sclerosis, presumably related to LDN use. Three were female patients for whom Dr. Bihari had prescribed nightly LDN:
The 31-year-old patient has a history of relapsing-remitting MS, and recently had developed not only slurred speech and trouble finding the right word (dysphasia) but also had noted weakness in one hand and one leg. She started LDN and reported that within one week her problems with speech had substantially cleared and there was a marked improvement in her gait.
The patient who is 44 years old has chronic progressive MS (as do the other two women to be discussed below). She had reached the point some time ago where she needed to use a walker in the home in order to get around. On the third night after starting LDN, she got up and went to the bathroom without using the walker -- for the first time in two years. She reports having experienced a prompt 20%-30% improvement in her balance.
The third patient, a woman in her early 50's, reported prompt improvement in walking after starting LDN.
The fourth case came to Dr. Bihari's attention in late April 2000 when a woman telephoned his office to leave a message of thanks for him. She has the diagnosis of MS and for the past ten years has had variable visual impairment in one eye, to the extent that she has had to wear eyeglasses to mask that eye. She said her neurologist had begun to prescribe LDN three months ago. Within two days after starting LDN she regained unimpaired binocular vision. She said that she had recently forgotten to take her LDN at bedtime for two nights in a row, and the eye problem returned --only to subside within a day or two after restarting the medication.
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AN INTERESTING INTERVIEW
DR DAVE'S INTERVIEW WITH DR BAHARI MARCH 2000
DR DAVE: MULTIPLE SCLEROSIS IS CERTAINLY ONE OF THE DEVASTATING AUTOIMMUNE DISEASES. I'M TALKING ON THE LINE WITH DR BERNARD BIHARI, AND HE IS ONE OF THE PEOPLE TO BRING TO THE SURFACE OR BRING TO THE FORE LOW DOSE NALTREXONE. AND THERE'S BEEN SOME PRETTY REMARKABLE DEVELOPMENTS AND WE'RE LOOKING MOST HOPEFULLY AT THIS. DOCTOR, I THANK YOU FOR JOINING ME.
DR BIHARI: YES. THANK YOU
DR DAVE: HOW DOES LOW DOSE NALTREXONE WORK?
DR BIHARI: WELL IT'S A 3MG DOSE TAKEN LATE AT NIGHT, PREFERABLY AT BEDTIME, AND NOT BEFORE 9PM. AND THE ENDORPHIN SUPPLY FOR THE NEXT DAY IS PRODUCED BY THE PITUITARY GLAND AND THE ADRENAL GLAND IN THE MIDDLE OF THE NIGHT FROM 2 TO 4AM. AND THE NALTEXRONE WORKS BY GIVING IN A SENSE THE BRAIN A FALSE MESSAGE THAT THE BODY DOESN'T HAVE ENOUGH ENDORPHINS. THE BRAIN SENDS OUT MESSAGES TO THE GLANDS TO MAKE MORE. THE NALTREXONE IS GONE, BECAUSE IT'S A SMALL DOSE, WITHIN 3 HOURS, BUT THE ENDORPHIN LEVELS ARE MORE THAN DOUBLED.
DR DAVE: AND THE NET EFFECT OF THE ENDORPHINS IS?
DR BIHARI: WELL, THE ENDORPHINS HAVE A LOT OF FUNCTIONS. BUT ONE OF THE MOST IMPORTANT IS REGULATING THE IMMUNE SYSTEM. THAT WAS THE BASIS FOR MY COLLEAGUES AND I ORIGINAL WORK ON IT.
DR DAVE: I SEE. NOW I'VE SEEN PEOPLE POST ON THIS MESSAGE BOARD THAT HAVE SAID THINGS LIKE "I UNDERSTAND THAT AS LONG AS I CONTINUE TO TAKE THIS I WON'T REGRESS."
DR BIHARI: WELL WHAT HAPPENED WAS, THE FIRST STUDY I DID WITH NALTREXONE WAS FOR PEOPLE WITH HIV AND AIDS IN 1985 AND 86. AND IN THE MIDDLE OF THE TRIAL, WHICH WAS A CLASSICAL TRIAL WITH HALF THE PEOPLE GETTING A PLACEBO - IN THE MIDDLE OF THE TRIAL MY DAUGHTER'S BEST FRIEND, WHO WAS THEN 24 YEARS OLD, HAD A SERIES OF ATTACKS OF TRANSVERSE MYELITIS, WHICH IS ONE OF THE MOST FRIGHTENING WAYS THAT MS CAN START. AND IN 8 MONTHS SHE HAD 3 EPISODES. EACH ONE CREATED.ABOUT 95% AND BY HER THIRD EPISODE I WENT TO SEE HER IN THE HOSPITAL BECAUSE I FELT THAT NALTREXONE, BY REGULARLISING THE IMMMUNE SYSTEM, MIGHT HELP TO CONTAIN HER AUTOIMMUNE DISEASE. SHE STARTED ON THE DRUG IN 1986.
DR DAVE: AND YOU WERE USING A 3MG DOSE?
DR BIHARI: 3MGS ONCE A DAY AT THAT TIME. AND THE NEXT TIME SHE HAD ANY MS ACTIVITY WAS 5 YEARS LATER WHEN SHE RAN OUT OF THE DRUG. SHE HAD MOVED TO UPSTATE NEW YORK TO GO TO GRADUATE SCHOOL, AND MY DAUGHTER WHO LIVED IN NEW YORK CITY KEPT HER FRIEND SUPPLIED WITH THE DRUG FROM A LOCAL PHARMACY AND SHIPPED IT UP TO HER. AND IN 1991 SHE RAN OUT AND FORGOT TO LET MY DAUGHTER KNOW ABOUT IT. AND I THINK MYSELF AT THAT POINT THAT SHE MAYBE THOUGHT SHE DIDN'T HAVE THE DISEASE, THERE WAS SOME DENIAL. AND THREE AND A HALF WEEKS LATER HAD THE ONLY ATTACK SHE'D HAD IN THE LAST 14 YEARS. HER LEFT ARM BECAME WEAK, SPASTIC, NUMB AND INCO-ORDINATED VERY RAPIDLY OVER A
48 HOUR PERIOD.
DR DAVE: THERE ARE A NUMBER OF SYMPTOMS THAT ARE PRETTY STANDARD SYMPTOMS THAT MS PEOPLE SUFFER. HAVE YOU NOTICED ANY PARTICULAR ONES MOST AMENABLE TO THIS THERAPY?
DR BIHARI: WELL WHAT I HAVE NOTICED, AND I'VE TREATED AT THIS POINT ABOUT 30 PEOPLE - ABOUT HALF OF THEM ONLY THE STARTED TREATMENT RELATIVELY RECENTLY. WHAT I'VE NOTICED IS THAT WHATEVER THE STATE, WHETHER THE PERSON HAS EXASCERBATING REMITTING MS OR CHRONIC PROGRESSIVE, THE MOST CLEAR CUT THING THE NALTREXONE DOES IS TO STOP DISEASE PROGRESSION. PEOPLE STOP HAVING ATTACKS.
DR DAVE: THAT'S WONDERFUL. THAT'S VERY EXCITING
DR BIHARI: AND THE DRUG HAS NO SIDE EFFECTS.
DR DAVE: THAT'S EVEN BETTER!
DR BIHARI: YES. I DIDN'T DO ANYTHING ABOUT IT FOR A LONG TIME BECAUSE I WAS WORKING ON AIDS. BUT IT WAS VERY CLEAR CUT, AND MY DAUGHTER;S FRIEND, IN 14 YEARS, HER ONLY ATTACK, EVEN THOUGH THE DISEASE STARTED WITH A VERY MALIGNANT LOOKING BEGINNING, THE ONLY ATTACK SHE HAD WAS A MONTH AFTER SHE RAN OUT OF THE DRUG AND FORGOT TO RENEW IT. NEEDLESS TO SAY, SHE'S BEEN TAKING IT REGULARLY SINCE.
DR DAVE: HAVE YOU EXPERIENCED PATIENTS WHO ARE ALSO USING PROCARIN?
DR BIHARI: I HAD 2 PATIENTS RECENTLY WHO WERE ALREADY ON PROCARIN.
DR DAVE: NO PROBLEM? NO INTERACTION?
DR BIHARI: NO. THERE IS POSSIBLY - IT'S HARD TO TELL WITH JUST 2 PATIENTS, BUT THERE'S POSSIBLY SOME SYNERGY, BECAUSE THOSE PATIENTS HAVE BOTH SHOWN A LITTLE IMPROVEMENT IN MOBILITY, WHICH I HADN'T SEEN BEFORE. WHAT I'D SEEN BEFORE WAS THAT THE DISEASE SIMPLY STOPPED PROGRESSING. AND THE PATIENTS ON PROCARIN PLUS NALTREOXONE (BUT IT'S JUST TWO)HAVE BOTH CALLED ME AND SAID WITHIN 3 OR 4 DAYS THEIR MOBILITY INCREASED BY 30 OR 40%. AND BOTH OF THEM REPORTED THAT THEY HADN'T GOTTEN MUCH RESPONSE FROM THE PROCARIN ALONE. BUT THEY STAYED ON IT. AND WHEN THEY ADDED THE NALTREXONE HAD SOME IMPROVED MOBILITY.
DR DAVE: WELL I'D SAY THAT'S A VERY ENCOURAGING EFFECT, A VERY ENCOURAGING SIGN. AND OF COURSE THIS WILL HAVE TO BE STUDIED AT SOME LENGTH AND SURVEYED SCIENTIFICALLY -
DR. BIHARI: OH, THE DIFFICULT THING WILL BE THAT IT COSTS ABOUT 30 TO 40 MILLION DOLLARS TO DO -
DR DAVE: ISN'T THAT INCREDIBLE.
DR BIHARI: - AN MS TRIAL.
DR DAVE: AND IT TAKES SO LONG.
DR BIHARI: AND IT TAKES ABOUT 2 YEARS.
DR DAVE: I UNDERSTAND OF COURSE THAT NALTREXONE HAS ALREADY BEE FDA APPROVED
DR BIHARI: THERE'S A 50MG TABLET FOR TREATING HEROIN ADDICTS AND ALCOHOLICS AND ALL THE PHARMACY HAS TO DO IS TO EITHER GRIND UP THE 50MG TABLET AND MAKE 3MG CAPSULES. OR MORE RECENTLY IT'S BECOME AVAILABLE IN A POWDERED FORM FOR PHARMACIES, AND THEY WOULD POUR IT INTO AUTOMTIC CAPSULE-MAKING MACHINES AND SET THE MACHINE AND JUST PRODUCE 3MG CAPSULES.
DR DAVE: WHAT WOULD BE THE STOPPERS OR RED FLAGS THAT WOULD KEEP YOU FROM USING IT WITH A PARTICLAR MS PATIENT? I KNOW THAT NOT EVERY MS PATIENT SHOULD JUST AUTOMATICLY GO ON THAT, AND A CONSULTATION WITH YOU IS REALLY RECOMMENDED.
DR BIHARI: I THINK THERE NEEDS TO BE A CONSULTATION, NUMBER ONE, SO THAT THERE'S A BASE LINE TO EVALUATE HOW THE PATIENT'S DOING, SO THAT BEFORE THEY START THE DRUG I CAN DOCUMENT THEIR BASELINE POSITION. AND I TRAINED IN NEUROLOGY SO THAT'S NOT DIFFICULT. THEN WE CAN TELL OVER TIME WHETHER THE DRUG IS WORKING IN THAT PATIENT OR NOT BY ADDONG SOME CONTACT EVERY THREE MONTHS OR SO. AND THAT'S REALLY THE IMPORTANT THING AT THIS POINT, SINCE THAT 40 MILLION DOLLAR TRIAL ISN'T GOING TO BE DONE FOR A LONG TIME.
DR DAVE: YOU SHOULDN'T HOLD YOUR BREATH WAITING. DR BAHARI, WOULD YOU GIVE YOUR PHONE NUMBER SO PEOPLE CAN REACH YOU?
DR BIHARI: YES, IT'S 212 929 4196
DR DAVE: GREAT. AND YOU HAVE A VERY IMPRESSIVE WEBSITE. www.lowdosenaltrexone.org
DR BIHARI: OH, THANK YOU. THE WEBSITE DOESN'T SAY MUCH ABOUT MS. IT GIVES A HISTORY OF THE DRUG AND DESCRIBES SOME OF THE MECHANISMS OF ACTION AND USES OF IT.