Dr. Goldstein's "Resurrection Cocktail"

Dr. Goldstein's "Resurrection Cocktail"

Dr. Goldstein believed ME/CFS was a disorder of disturbed central nervous system processing and developed a unique protocol for treating it.

He also wrote three books in the 1990's and in 2004: "Betrayal of the Brain: The Neurologic Basis of Chronic Fatigue Syndrome, Fibromyalgia Syndrome, and Related Disorders" and "The Limbic Hypothesis" and Tuning the Brain".

Erica Verillo describes how he worked
"Typically, when Dr. Goldstein saw new patients, he would test them sequentially with minute quantities of many psychoactive drugs in order to 1) identify the source of the problem, and 2) establish which drugs would be most effective.

This method allowed Dr. Goldstein to assess the patient rapidly, and at minimal cost. Dr. Goldstein halted sequential trials when the patient was “virtually asymptomatic.” Dr. Goldstein claimed that using this protocol most patients were dramatically improved in one or two office visits."
He retired from practice in 2003.

Dr. Goldstein gave his "Resurrection Cocktail" to patients who had been bedridden for more than a year and for whom he would only see once. It apparently was a mix of the most potent drugs he had for ME/CFS.
  • Ketamine
  • IV ascorbate
  • IV lidocaine
  • IV thyrotropin- releasing hormone (which raises all biogenic amines plus acetylcholine)
  • Nimotop
  • Neurontin (still the most effective oral agent but is being pushed by Tasmar)
Ketamine, by the way, was his most effective drug:
"The best single agent for CFS/FMS and all other neurosomatic disorders. Known best as an NMDA receptor antagonist (the NMDA receptor is one of the several receptors for the excitatory amino acid glutamate), it increases dopamine in the limbic system, a very important objective in CFS."

I administer it by slow intravenous infusion or in PLO gel for transdermal (through the skin) absorption. The intravenous route is more effective, but transdermal application can be done daily, and if effective, can obviate peaks and valleys and need for IVs.

I have seen no cases of Ketamine abuse among my patients."
The Resurrection Cocktail - A Deeper Look by ZZZ

(Thanks to ZZZ for allowing Health Rising to publish it)

Usually, in cases like this, I perform what I term a "resurrection". Mrs. Jones arrives by ambulance in a hospital bed where she has been confined for months or years (take your pick). That day will be, I'm sure, my only crack at her. I can usually get Mrs. Jones ambulatory, often with intravenous medications, by the end of the day, so that she can walk into my office on her next visit.
From "Tuning the Brain" by Dr. Goldstein​
To those of us who aren't even as sick as the patients he describes, such a "resurrection" sounds pretty miraculous. For the many people who experienced it, it felt like nothing short of a miracle, and the word "miracle" was frequently heard around Dr. Goldstein's office.

But what exactly did Dr. Goldstein use to perform his "resurrections"? Unfortunately, in typical Goldstein style, he doesn't go into any further details at this point. Nor is the word "resurrection" even mentioned in the rest of the book, or in any of his other books. At first glance, then, it would now appear that we are at a dead end.

However, Dr. Goldstein did write a description of these resurrections in an article he posted on his Web site, entitled “Tiptoe Through The Treatments: A Brief Guide To Some of What's New Since Betrayal by The Brain."

As the article's title implies, it was written between the publication of Betrayal by the Brain and Tuning the Brain. And although much of what is in the article is superseded by what was published in Tuning the Brain, there are various bits and pieces of information that appear in this article and nowhere else.

Dr. Goldstein's Web site disappeared shortly after his retirement in 2003. However, thanks to his dedicated followers, "Tiptoe Through The Treatments" can still be found in various places. Among the more reliable sources is Erica Verrillo's Web site. Erica Verrillo is probably best known at the author of Chronic Fatigue Syndrome: A Treatment Guide (2nd Edition), which is considered by many to be the best treatment guide currently available for ME/CFS.

"Tiptoe Through The Treatments" lists a number of drugs in alphabetical order that Dr. Goldstein started using after the publication of Betrayal by the Brain. Among them is ketamine. In the second half of the description of ketamine, there appears the complete list of ingredients for Dr. Goldstein's resurrection cocktail:
Ketamine is one component of my "resurrection cocktail," for patients who have been bedridden for more than a year and whom I may only see once. The others are IV ascorbate, IV lidocaine, IV thyrotropin- releasing hormone (which raises all biogenic amines plus acetylcholine), Nimotop, and Neurontin...
As is made clear in the text immediately preceding the quote above in Tuning the Brain, Dr. Goldstein always tried the naphazoline eyedrops first, as sometimes they made the resurrection cocktail unnecessary.

So at this point we have all the ingredients. It is also worth noting, in Dr. Goldstein's words, the power of some of the ingredients. For ketamine:
The best single agent for CFS/FMS and all other neurosomatic disorders. Known best as an NMDA receptor antagonist (the NMDA receptor is one of the several receptors for the excitatory amino acid glutamate), it increases dopamine in the limbic system, a very important objective in CFS. I administer it by slow intravenous infusion or in PLO gel for transdermal (through the skin) absorption. The intravenous route is more effective, but transdermal application can be done daily, and if effective, can obviate peaks and valleys and need for IVs. I have seen no cases of Ketamine abuse among my patients.
For IV lidocaine:
In addition to its actions mentioned in Betrayal by the Brain, it also acts as an NMDA antagonist. It is the second best treatment. I have given it about a thousand times without a serious adverse drug reaction. Patients have come with great difficulty from other states or countries with the common lament of "If you can't help me I'm going to kill myself' (I hear this about twice a week). At least two patients, achieving complete symptomatic relief with IV lidocaine, returned home and could not find a physician or nursing service to administer it. Since they could not move to southern California, they were again bedridden and had to crawl to the bathroom. Not able to live this way any longer, they committed suicide, a worse outcome than the lidocaine toxicity, which never happens. Many physicians will not prescribe any of the medications I use, even if they help their patients a lot. Some medium-sized cities have not one physician who will care for CFS patients. I must treat them from afar, a hazardous practice medicolegally.
Now we have a list of all the ingredients in the resurrection cocktail. But what were the amounts of each, and how were they prepared? "Tiptoe Through The Treatments" is silent on these issues.

Back to Tuning the Brain. On page 369, in the section entitled "Lamotrigine" (which actually has only five sentences about lamotrigine), there is the following sentence:
Ketamine may be combined in the same IV bag with lidocaine, ascorbate, MgSO(4), and Ca gluconate.
And:
Lidocaine is almost tied with ketamine for effectiveness in neurosomatic disorders and can be used daily, if necessary, by the IV route.
Now for the doses of the individual drugs. First, ketamine. On page 60 of Tuning the Brain:
I give ketamine by slow intravenous infusion in normal saline at a dose of 0.5 mg/kg (Schmid RL et al, 1999).
On page 347:
My experience coincides with the literature: Ketamine, when properly administered, does not cause hallucinations or impairment of cognitive functioning (Schmidt RL et al., 1999). The intravenous dosage I use, less than 2.5 micrograms/kg per minute, does not produce plasma levels greater than 50 mcg/ml...I administer 25 to 100 mg of ketamine in 500 ml normal saline over three hours or so, adjusting the rate to the patient's side effects, which should be minimal. If Intravenous ketamine (or lidocaine) is infused too rapidly (even with midazolam), the results will often be poor, and sometimes the patient will no longer respond to the drug (Sorenson J et al, 1997). In the typical patient, an infusion of ketamine has a beneficial effect lasting up to a week.​
Lidocaine dosing is describe on page 46 of Betrayal by the Brain:
I find IV lidocaine 200 to 300 mg in 500 ml of normal saline to be a rapidly effective analgesic in FMS patients.The effects sometimes last for days or weeks, perhaps by inducing long-term potentiation (see p. 65), and often global symptoms are improved. About half of my patients respond to this treatment after being refractory to all oral agents. IV lidocaine... has the unusual property of greater symptom relief and duration of action with each successive use, plateauing after four infusions, and lasting three to seven days.
Although Dr. Goldstein refers specifically to fibromyalgia here, he considers that all CFS patients with considerable muscle pain have fibromyalgia.

Dosing for ascorbic acid is described on page 132 of Betrayal by the Brain:
Administration of ascorbic acid is done in doses of 25 to 50 grams diluted in half-normal saline or Ringer's lactate over a period of about 90 minutes. It is beneficial to add 500 mg of calcium gluconate since ascorbic acid is a calcium chelator and could possibly lower serum calcium.
From the beginning of that paragraph:
Adding magnesium sulfate is recommended because ascorbic acid can cause magnesium shifts from extracellular to intracellular compartments.
In other words, the magnesium is actually optional, but the presence of ascorbic acid can cause it to be absorbed more effectively. In this environment, no more than one gram of magnesium should be used, and that much only in people who are known to tolerate magnesium well.

Now we have all the ingredients, but what about the fluid? According to Dr. Goldstein, all of these ingredients can be combined in one 500 ml bag. However, normal saline is recommended for ketamine and lidocaine, while half normal saline or Ringer's lactate is recommended for ascorbate, due to its high osmolality. In this case, the osmolality of the ascorbate is the controlling factor, and Dr. Goldstein would use half normal saline or Ringer's lactate for the combination. The infusion time should be three hours in order to avoid unwanted side effects.

For thyrotropin-releasing hormone, Dr. Goldstein used an intravenous injection of 500 mcg, as described on page 62 of Tuning the Brain. The dose of nimodipine (Nimotop) used is one 30 mg tablet, while the dose of gabapentin (Neurontin) used is 100 to 300 mg, typically in capsule form.

So now we have all the ingredients of the resurrection cocktail. Here they are, along with their doses, as used sequentially:
  • Naphazoline eyedrops, 0.1% solution, one drop in each eye
  • 500 ml of half normal saline or Ringer's lactate, administered over three hours, and containing the following:
    • Ketamine in a dose of 25 to 100 mg
    • Lidocaine in a dose of 200 to 300 mg
    • Ascorbic acid in a dose of 25 to 50 grams
    • Calcium gluconate in a dose of 500 mg
    • (Optional) Magnesium in a dose of up to one gram
  • Thyrotropin-releasing hormone (TRH) administered as an IV injection of 500 mcg
  • Nimodipine in the form of one 30 mg tablet
  • Gabapentin in a dose of 100 to 300 mg, typically in capsule form
I believe that this is the first time that the complete formula and dosage of Dr. Goldstein's resurrection cocktail has been published outside of his office, as it involves a number of references from two of his books plus one unpublished article.

Once again, I would like to emphasize that this cocktail helped most of the very sickest bed bound ME/CFS patients get on their feet and walking in a matter of hours. And although there were a substantial minority who did not attain that level of recovery, it can be reasonably inferred that many of them had substantial improvements nonetheless.

This cocktail is not a cure, of course. It was used simply to get people to a high functioning level very quickly. To maintain that level, it was usually necessary to administer some of the regular treatments described in Betrayal by the Brain and Tuning the Brain.

The publication of this resurrection cocktail is intended to give people hope. For those people with this illness who are in dire straights (of whom there are far too many), this list can be taken to their doctors, along with the primary sources as well, if possible. Unfortunately, as Dr. Goldstein indicates, very few doctors would consider even the lidocaine portion of this cocktail, much less the whole thing. Great persistence would be needed in finding a doctor who would be willing to administer this cocktail. In any case, it is extremely important for reasons that Dr. Goldstein noted that the IV infusion be done over a period of a full three hours.

If ketamine is the only deal breaker in this cocktail, the formula should work almost as well without it.

Many (if not most) doctors would take one look at this formula and say, "This is crazy!" Such a verdict would not surprise Dr. Goldstein. Going back to the April 18, 1989 issue of The Los Angeles Times, entitled
Chronic Fatigue: A Mystery Unravels:
Dr. Jay Goldstein of Anaheim Hills has spent the last five years researching and treating patients with chronic fatigue syndrome, a debilitating disease characterized by incapacitating exhaustion and a range of other perplexing symptoms. Explaining his theory... Goldstein pauses. "You know," the family practitioner says, "some very respected physicians will tell you I am crazy."​
And as my dear late grandmother would say, "So there you are."
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