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Opioids Vitamin C: Opioid Addiction Cure?

Tchort

Bluelight Crew
Joined
Mar 25, 2008
Messages
2,392
There are a number of articles and studies about the analgesic effect of Ascorbite/Ascorbic Acid/Vitamin C. I came across this article the other day, while reading up on the Temple of the True Inner Light (who believe ethneogens to be the eucharist; flesh of God). Anyway, this article is from the journal Orthomolecualr Psychiatry, Volume 6, Number 4, 1977, Pp.300-308.

Very interesting concept, with some thought provoking explanations. I don't believe a word of it :) but thought it might be interesting to other BL members. I should note the bias of the authors leads them to exaggerate or flat out lie about Methadone and the original Morphine/Heroin clinics set up in the teens-twenties. The NYC clinic was a failure, because it was horribly run. The other Morphine/Heroin maintenance clinics, like the Shreveport & New Orleans clinics, were successful beyond anyones expectations. Anyway, keep that in mind. Enjoy.

The Hypoascorbemia-Kwashiorkor
Approach to Drug Addiction Therapy:
A Pilot Study

by Alfred Libby and Irwin Stone

(Part 1)

Drug addictions, like cancer, are terrifying conditions to the
victims because of the feelings of hopelessness and abandonment generated
by the rigors of and general failure of the orthodox "treatments."
Although crude opium addiction has a very long history, the
large-scale addictive use of morphine salts, in this country, is
generally dated from their use on wounded Civil War soldiers. Following
1864, morphine addiction was realized to be an emerging socially
significant problem in this country; therefore searches were instituted
to find less addicting drugs. The year 1890 saw the introduction of heroin.
For about five more decades, to the year 1912, nothing was done to stop
the rising tide of morphine and heroin users in this country. The
realization of that fact promped in that year the organizing of legal
opiate clinics, not however, to treat the addict, only to support the
user's habit in an attempt to stem the rising crime rate and sales of
black market drugs. These legal opiate clinics remained open until 1924
when they were closed down as dismal failures. It took until the
mid-1950's, another fallow period of about 30 years, before another major
attempt started, the Methadone Program, which has continued up to the
present. This program embraces the concept of orally giving a legally
addicting drug (methadone) in place of an illegal addicting drug
(heroin).
The lack of success in handling drug addictiion, until now, is due
to placing the emphasis on the legal aspects of the problem, mainly that
of the crime and punishment concept, and ignoring the mental and physical
condition of the addicts and neglecting to treat the health and metabolic
problems of the victims. Drug addicts suffer from severe metabolic
dysfunctions and are very sick people. Any attempted solution to the
drug addiction problem which fails to bring total health back to the
addict is doomed to failure.

Drug Addiction and the Genetic Disease, Hypoascorbemia

Drug addicts, like other humans, are born carrying a defective gene
for the synthesis of the liver-enzyme protein, l-gulonolactone oxidase
(GLO). This birth defect (Stone, 1966), causes a potentially fatal, but
now easily correctable (Stone, 1967), genetic liver-enzyme disease,
Hypoascorbemia (Stone, 1966a). This "inborn error of carbohydrate
metabolism" has destroyed the capability of the human liver to synthesize
ascorbate from blood glucose, and thus deprives mankind of this important
mammalian mechanism for combatting stresses. The normal mammalian
response to stress is to increase liver-synthesis of ascorbate as an
antistressor and detoxicant to maintain biochemical homeostasis within
the body (Stone, 1972).
Most mammals carry the intact gene for GLO and normally produce,
under conditions of little stress, about 10 to 20 g. of ascorbate per day
per 70 kg body weight to take care of their daily physiological needs. A
biochemical feedback mechanism evolved in the early mammals (Stone,
1972a) which increased daily ascorbate production possibly three to
five fold under a variety of chemical and physical stresses. Humans,
among the very few mammals deprived of this homeostatic protective mechanism,
suffer more physiological damage from equivalent stresses unless
exogenous ascorbate is supplied. Thus a daily intake of 10 to 20 g of
ascorbate by a relatively unstressed adult human is not "excessively
high," but well within the normal mammalian range. Under stress humans
require about 30 to 100 g or more a day to maintain health. The
therapeutic use of mega levels of ascorbate has met with great success in
the treatment of the viral diseases (Klenner, 1974; Cathcart, 1976),
cancer (Stone, 1976), and many other pathologies. The sub-subsistence,
"homeopathic" daily intakes of ascorbate, recommended for the past 40
years by the nutritionists as "vitamin C" for humans, would barely
suffice to keep the other mammals alive and certainly not in good health.
The wide acceptance of this erroneous nutritional hypothesis by modern
medicine has only led to the continued persistence of chronic subclinical
scurvy (CSS Syndrome) (Stone, 1972; Stone, 1977) as our most wide-spread
and insidious human disease at present.

Physiological Effects of Drug Addiction

The usual history of addiction follows this sort of pattern: The
future addicts are born with the genetic defect for GLO, and already at
birth are suffering from the CSS Syndrome. The CSS Syndrome usually
continues throughout childhood, adolescence, and adulthood without much
of an attempt at any significant correction. It has been our experience
that all of the addicts we have dealt with began their introduction into
the drug culture at an early age. They usually begin as a weekend
'high," escalating into a daily habit from which they can't escape. Each
of these stresses further depletes the already dangerously low body
stores of ascorbate leading to the severe exacerbation of the CSS
Syndrome already present. Adequate repletion of the body stores of
ascorbate is nonexistent.
On drugs, the addicts lose their appetite for food. Food
deprivation or restriction leads to severe protein and vitamin
malnutrition. All the chronic addicts tested suffer from
hypoaminoaciduria. This has led us to regard a confirmed addict as
suffering from a Hypoascorbemia-Kwashiorkor type of syndrome, and our
treatment procedure was designed as an intensive holistic approach for
the full correction of these genetic and multimalnutritional
dysfunctions. The procedure is completely orthomolecular, and no foreign
substance or toxic narcotic or drug is used.
Briefly, by fully correcting this Hypascorbemia-Kwashiorkor
Syndrome, we are able to take the addicts off heroin or methadone,
without the appearance of withdrawal symptoms. If during the period of
full correction they take a "fix," it is immediately detoxified or
otherwise handled by the body so that no "high" occurs. It is like
injecting pure water provided the dosage of ascorbate is high enough.
After a few days on the regimen, appetite returns and they start eating
voraciously. They also have restful sleep. Restless sleep or no sleep
at all are characteristic of heroin and methadone withdrawl.
"Full correction" in the addicts treated comprised giving them 25 to
85g sodium ascorbate a day in spaced doses along with high intakes of
the other vitamins, essential minerals, and high levels of predigested
proteins. This is continued for four to six days, and then the dosages
are gradually reduced to lower holding dose levels that varied from about
10 to 30 g per day. Both the therapeutic and the holding dose levels may
vary widely according to the clinical response of the particular addict
being treated. The therapeutic dosage is usually slightly beyond the
bowel tolerance level, held for 12 to 24 hours. Selection of proper
dosage is based on clinical experience and observation and responses of
the patient. Bowel tolerance is a concept introduced by Robert Cathcart
M.D. (1976) for judging the toxicity of the pathology and the required dosage
of ascorbate needed for treatment. Cathcart found the bowel tolerance
increases with increased stresses on the organism. The general
improvement in the well-being of the addicts within 12 to 24 hours after
beginning sodium ascorbate detoxification is striking. It is
demonstrated by improved mental alertness and visual acuity; appetite is
returning, and the addict is amazed that treatment is succeeding without
the use of another narcotic.

Some Recent Studies on Ascorbate

We do not claim to be the first to suggest or use ascorbate in the
addiction problem, but we do claim to be the first to use sodium
ascorbate properly to get these desired results. Ascorbate injected into
rats at the rate of 100 mg per kg body weight attenuated and abolished
the narcotic effects of morphine (Ghione, 1958). Ascorbate's
detoxification of a wide variety of inorganic and organic poisons was
reviewed (Stone, 1972) and included Klenner's study on the successful
megascorbic treatment of barbiturate poisoning, snakebite, and Black
Widow spider bites. It was also suggested in this review that
megasdoses of ascorbate be used in drug addiction (Stone, pp. 157-158,
l972). Two interesting papers appeared in 1976, one from Thailand which
showed that the sleeping time induced in rabbits by 15 mg of
pentobarbital could be progressively reduced by increasing amounts of
ascorbate injected five minutes prior to the pentobarbital. The sleeping
times in minutes for ascorbate dosages of 0, 250 mg, 500 mg, 750 mg were
50, 29 27, 23, and at 1,000 mg ascorbate the rabbits did not fall asleep
at all (Bejrablaya and Laumjansook, 1976). The other paper (Scher et
al., 1976) was originally presented in 1974 to the North American
Congress on Alcohol and Drug Problems, by these authors from the National
Council on Drug Abuse and the Methadone Maintenance Institute, and was
entitled, "Massive Vitamin C as an Adjunct in Methadone Maintenance and
Detoxification." These authors realized that scurvy played a large part
in the drug abuse problem, but they only saw ascorbate as a means to
reduce some of the side effects of methadone administration like
constipation, loss of libido, and restless sleep. For this they used
about 5 g of ascorbic acid a day. It apparently never occurred to them
that by switching to sodium ascorbate and increasing their dosage by a
factor of 10, they could completely eliminate the ill-conceived Methadone
Program with all its problems and at the same time have a simple,
nontoxic, and elegant solution to the drug abuse problem.

The Orthomolecular Procedure for Correcting the H-K Syndrome

Originally in our early testing, when the addict came in we took a
sample of urine for the simple C-STIX test for urinary spillover of
ascorbate and a 24-hour specimen for a compelte quantitative individual
amino acid and related constituent column fractionation and assay. The
results were so consistently low on the amino acids, and with no
spillover of ascorbate, that we no longer go to the expense or bother of
these tests. The narcotic intake is stopped, and the addict is given the
first dose of sodium ascorbate, high levels of multivitamins and
minerals, and nine tablespooons per day of PHH-Pro, in divided doses, a
predigested protein preparation. Since the addicts have a rather
abnormal digestive system, it is an aid to direct absorption of the amino
acids into the vascular system if the liquid amino acid dosage is held in
the mouth as long as comfortable before swallowing. The total amount of
ascorbate given a day will vary with the extent of the drug addiction.
It is never less than 25 g a day in spaced doses and can go to 85 g or
more per day. As a rough rule-of-thumb means of judging dosage:
a $50/day habit needs 25 to 40 g sodium ascorbate, $150 to $200/day about
60 to 75 grams. Judging dosage comes with experience, and any errors
should be on the high-dosage side because of ascorbate's extremely low
toxicity and lack of side effects. The megadoses are continued for four
to six days. During this time no withdrawl symptoms should be encountered
(if any appear, increase the soldium ascorbate intake.) Generally, in two or
three days appetite returns and most patients begin to eat well and have
restful sleep for the first time since the chronic addiction began. One
of the first observations to be made of the patient on this
orthomolecular therapy is the rapid change in well-being: they feel
good. The mega doses are then gradually reduced to holding dose levels
of about 10 g per day of sodium ascorbate and lower levels of the
vitamins and mienrals. The predigested protein is discontinued if the
patients are eating well.

Typical Case Histories

Case 1. T.M., male, age 23. Using drugs for 10 years. At 15, used
heroin for a "weekend high." At the time our treatment was started, he
was supporting a $100-a-day habit. He had tried, on several occasions,
the hospital detoxification programs of methadone and liquid Darvon.
Each time this program of substituting another narcotic for the heroin
failed to give him satisfactory relief. The first thing he did when he
came out of the hospital was to inject heroin becasue of the insatiable
craving and being sick form the methadone or liquid Darvon. On coming
in, his urine was tested for urinary spillover of ascorbate and amino
acids. There was no urinary spillover, confirming the presence of
hypoascorbemia and hypaminoaciduria. He was given 25 g of sodium
ascorbate in 4 g doses along with the vitamins, minerals, and the protein
supplements. After three days on the regimen, he began eating and
feeling so much better and thinking more clearly, stating that "I don't
want to go stealing no more," and he began to have restful sleep. The
ascorbate was reduced to 10 g per day on the sixth day. He has now been
on this holding dose for about three months and is completely drug-free
and has lost his "desire" for the drug. He has graduated from the
Manpower program and in now gainfully employed for the first time in his
adult life.

Case 2. A.C. male, age 24. Began using heroin at age 15 and now
had a habit costing between $150 and $200 a day. Had tried at least
seven different hospitals for detoxification and was on methadone
maintenance for three years. He stil "fixed" with heroin, or order to
take the methadone, as it upset his stomach and made him ill. "Methadone
kills your insides," to quote the patient. He was such a skeptic of the
value of our orthomolecular program that on a Sunday he first took 45 g
of sodium ascorbate and then in the space of five hours he "shot-up"
$300-$400 worth of heroin, and he felt no effect from this large amount
of heroin. He continued on the ascorbate, 45 g per day for 10 days,
along with the vitamins, minerals, and protein supplement. Then the
dosage was reduced to 10 g sodium ascorbate and continued for another 30
days. The patient has moved out of the area, but when last seen, he was
drug-free and had an extreme sense of well-being and a good attitude.

Case 3. F.F., male, age 35. He had been on drugs for 23 years, the
last seven on the methadone maintenance program. He suffered the typical
symptoms of methadone; severe constipation, loss of sleep, loss of
libido. He would take laxatives and enemas, and still was unable to
move his bowels. When he did have a bowel movement, the stool was so
hard and impacted that he would "faint or blackout from the pain." He
was given the sodium ascorbate at the rate of 25 g per day for four days;
then increased to 45 g, then after one day reduced to 10 g of the 50-50
mixture of NaA and AA. He is still on this dosage level one month later
and was seen at this time. He was doing so well that his mental attitude
was excellent, appetite had returned, he has normal bowel movements
without laxxatives, and his sex drive is slowly returning. He was
advised to remain on the holding doses and return in one month for
another checkup. Methadone maintenance is much more difficult to deal
with than heroin addiction due to the adverse metabolic effect methadone
has on the body.
At the time this paper was written, 30 out of 30 patients were
successfully treated in this pilot study under the supervision of AFL.
This reported 100 percent rate of success is the same as that noted
by Dr. Cathcart in his megascorbic therapy of the viral disease, "it
works every time," provided enough ascorbate is used.

Orthomolecular Treatment of Drug Overdosage

Drug overdosage is a common occurrence because of the wide
variability in the potency of the illicit "street" drugs and the tendency
among addicts to mix different drugs. This causes many deaths among
addicts. A nonspecific orthomolecular treatment of OD's which acts as an
antidote and rapidly relieves the stricken addict, is as follows: If the
victim is unconscious, immmediately but slowly inject 30 or more grams of
sodium ascorbate intravenously; if conscious and can swallow and retain
liquids, give about 50 grams of sodium ascorbate dissolved in a glass of
milk.

Case History

A mother brought in her 16-year-old son who was totally "spaced out"
on "Angel Dust" (PCP). This boy was incoherent and totally out of tune
with reality. He was given 30 grams of sodium ascorbate mixed in a glass
of milk, and within 45 minutes he could hold a normal conversation. If
he had been given 50 grams, it is likely he would have become rational
sooner. With intravenous ascorbate, this recovery time could be cut down
to minutes.

Discussion

This joint pilot study was started in January, 1977, after a series
of coincidences between the authors. Both authors had been studying
independently on the drug abuse problem for many years. Libby conducting
occasional clinical tests on addicts since 1974 and getting exceedingly
promising results, and Stone studying the theoretical, genetic, and
biochemical background. We heard of each other's studies in December,
1976, and pooled our knowledge and experience. Stone had been trying
unsuccessfully to get some clinical research started for over a decade.
His latest and most discouraging attempt came in November, 1976, when a
megascorbic clinical research protocol was turned down by one of the "top
men" in the field with, "there is no evidence for usefulness of massive
doses of vitamin C in any disorder (except scurvy)--least of all in
conditions associated with heroin addiction." "Massive doses of vitamin
C are potentially toxic." "There is no known scientific basis for
thinking that vitamin C would be beneficial in methadone maintenance or
detoxification."
If we had not regarded this authoritarian certitude as utter
nonsense, this promising new therapy of drug addiction could have been
again delayed for years. This prevailing attitude toward megascorbics,
however, convinced us that the orthodox drug abuse agencies were not the
proper means for starting or conducting exploratory clinical tests on
megascorbics in drug abuse. We also realized that getting any support
for clinical studies involving megascorbics, the black sheep of orthodox
funding agencies, would be next to impossible to obtain, and certainly
impossible to obtain quickly. Libby's preliminary tests were so
impressive and this study had been delayed for so long, that in view of
the poor record of achievement by orthodox medicine, we felt immediate
action was demanded. We eliminated all the time-consuming funding red
tape by simply operating on our own personal funds and time.
The clinical results have been so successful in 100 percent of the
30 drug addicts treated to date of this writing, that we regarded the
prmpt presentation and publication of our data to be an absolute
necessity.
As a consequence of the lack of funds, we have not been able to dot
all the "i's" and cross all the "t's.", and chase down all our
speculations. We have, however, gone to a point where we can offer a
reliable, nontoxic, simple, and practical procedure that has many
advantages over the present orthodox means of handling drug addicts.
Even though this therapy utilizes sodium ascorbate, vitamins,
minerals, and predigested protein, we believe that the main antinarcotic
effect is due to the sodium ascorbate, and the other materials are
necessary adjuncts. High levels of sodium ascorbate have analgesic
properties as shown by the observations of Cameron and Baird (1973) and
Saccoman (1976) in terminal cancer and by Klenner (1974) in the relief of
pain of severe burns and snakebite.
In terminal cancer, the ascorbate analgesia was so good that the
patients' heavy toxic morphine schedules were discontinued. Thus high
levels of sodium ascorbate mimic morphine and probably fit into the
opiate receptor sites. The fact that these terminal cancer patients
abruptly removed from their morphine showed no withdrawl symptoms was one
piece of evidence that indicated our megascorbic treatment of drug
addiction would be successful.
As previously noted, ascorbate is a general detoxicant for many
different poisons, but its mode of action is mostly unknown. Klenner
(1974) points out, "Ascorbic acid can be lifesaving in shock. Twelve
grams of the sodium salt given with a 50 cc syringe will reverse shock in
minutes. In barbiturate poisoning and monoxide poisoning, the results
are so dramatic that it borders on malpractice to deny this therapy."
The detoxicating effect of sodium ascorbate on narcotics appears to be so
rapid that this very rapidity seems to preclude a mechanism involving
direct chemical attack on the narcotic molecule to convert it into some
inactive derivative. Also it succeeds on so many different types of
narcotic molecules. A more compatible hypothesis would be to view the
action as a competition for opiate receptor sites of the brain, wherein
high levels of sodium ascorbate in the brain prevent the attachment and
displace narcotic molecules already attached to these sites.

Brain Receptor Sites

The research of S.H. Snyder et al on the binding of morphine-like
substances to brain opiate receptor sites was recently reviewed (Snyder,
1977). They have shown that the largest amount of binding occurs in
cells from the very primitive limbic system deep within the brain. They
also showed that the very primitive hagfishes and sharks have as much
opiate receptor binding sites as the most advanced of the mammals,
monkeys, and man. They found that the properties of these receptor sites
in these early and most recent vertebrates were similar, indicating that
few changes have been made during the course of about 400 million years
of evolution. It is states that, "This suggested that the opiate
receptor is normally concerned with receiving some molecule that has
remained the same throughout evolution....possibly a neurotransmitter
which acts at these sites." Also the presence of high levels of sodium
helps dislodge the narcotic from the receptor sites.
We speculate that these binding sites were evolved in the early
vertebrates to concentrate and localize, from the very low concentrations
existing in these animals, the electronically labile ascorbate molecules,
which aid in neurotransmission. The fact that these sites bind narcotics
is purely happenstance, because of a possible similarity in molecular
shape. There does not seem to be any obvious physiological evolutionary
reason for concentrating narcotics in the nerve endings of this newly
developing control system, whereas there may have been a great need to
concentrate and obtain high levels of ascorbate at synpases to aid is
efficient nerve impulse transmission. Ascorbate is a molecule that
appears to have changed little in the last 400 million years and was
present on the evolutionary scene long before the fishes appeared (Sone,
1977a). If this hypothesis is valid, then the receptor sites should be
renamed "ascorbate receptors" instead of "opiate receptors." It should
not be difficult to experimentally test the validity of these theoretical
considerations.
The rapid quenching of the narcotic effect by mega levels of
ascorbate led us to speculate on the possibility of utilizing this
phenomenon for other purposes than drug addiction namely:

Implications

In surgery it might be possible to eliminate the patient
spending hours in the recovery room "coming out" of the anesthetic which
also requires nursing attendance. If the patient at the termination of
the operative procedure was given a massive intravenous injection of
sodium ascorbate, possibly in the neighborhood of 30 to 50 grams, it
might be possible for the patient to be awake before leaving the
operating room. Giving the patient large doses of ascorbate immediately
before an operation should be generally avoided, because it would
increase the amount of anesthetic required to give an equivalent
anesthetic effect. Giving the patient this post-operative dose of
ascorbate would also have other salutary healing and anti-shock effects.

Materials and Sources

All the materials used in this study are orthomolecular and are
commonly available. No toxic chemicals or narcotics are employed.
The ascorbate may be obtained in several different types and forms,
and it is best to have a sufficient supply of all to meet individual
requirements. One should become familiar with the properties of
ascorbate in its different forms. Sodium ascorbate can be obtained both
as the pure crystalline power and as 1 gram tablets. The crystalline
poweder is very soluble in water, milk, and foods, is essentially
tasteless, and a level teaspoon weighs about 3 grams. A solution has a
pH of slightly over 7. Ascorbic acid, while also quite soluble in water,
has a very sour taste and is limited in the number of foods to which it
may be added because of this sour taste. It has a pH of about 3 and will
curdle milk if added thereto. Sodium ascorbate is the preferred
substance for the megadosages.
The high-potency vitamin and mineral preparations were commercial
multi-vitamin and mineral preparations in tablet form. Six tablets
supplied the dosages listed in Table 1.

Table 1

Vitamins Minerals

Vitamin A 10,000i.u. Calcium 500mg
Vitamin D 400i.u. Phosphorous 200mg
Vitamin E 400i.u. Iron 20mg
Vitamin B1 50mg Iodine 0.15mg
Vitamin B2 50mg Magnesium 500mg
Vitamin B6 100mg Potassium 90mg
Niacin 100mg Manganese 5mg
Ca Pantothenate 200mg Zinc 50mg
Vitamin B12 10mcg Copper 1mg
Folic Acid 0.1mg

Sterile injectable sodium ascorbate is supplied in 30 or 50 ml vials
containing a 25 percent solution. Use only the "preservative-free"
product. The intravenous route of administration of sodium ascorbate is
more rapid and efficient than the oral route, since it bypasses the
digestive tract. In drug overdoses and in occasional other cases it may
have to be used.
In an effort to reduce the number of separate products used in this
procedure we have been experimenting with a single combined product
comprising sodium ascorbate with the vitamins and minerals to be
available soon both as a crystalline powder and tablets.
For the protein supplementation, we used a product called "P.H
H-PRO"comprising a liquid predigested collagen solution containing mostly
easily assimilatable amino acids. This is available in plastic bottles
up to 1 gallon size.

Summary

Chronic drug addiction produces in the victims severe subclinical
scurvy along with multivitamin and mineral dysfunction and protein
deficiencies. The widely used Methadone Program for "treating" these sick
people merely substitutes a legal narcotic for an illicit one, which only
continues the severe biochemical stresses contributing to their illness.
This pilot study regarded the addicts as suffering from a serious
Hypoascorbemia-Kwashiorkor type of syndrome. Our procedure was designed
to fully correct both the genetic defect causing the Hypoascorbemia and
also the multimalnutritional disturbances and protein deficiencies
involved in the Kwashiorkor. The treatment is entirely orthomolecular
and inexpensive, is non-toxic, and uses no drugs or narcotics. It is
rapidly effective in bringing good health to the addicts. In the initial
phases of the procedure, sodium ascorbate is administered at 25 to 85
grams perday or more, along with high doses of multivitamins, essential
minerals, and protein hydrolysate. Under this treatment, the heroin or
methadone is stopped and no withdrawl symptoms are encountered. Should a
"fix" be taken, it is immediately detoxified and no "high" is produced.
It is like injecting plain water. There is a great improvement in
well-being and mental alertness. In a few days appetite returns and the
"methadone-constipation" is relieved. After about four to six days the
dosages are reduced to holding dose levels. In the 30 addicts tested in
this pilot study, the results were excellent in all cases, and it would
appear that this simple nontoxic procedure should serve as the basis for
large-scale testing to develop a new program for freeing drug addicts of
their addiction. In drug overdosage, sodium ascorbate can be a
life-saving measure. Unconscious overdosed addicts are given the sodium
ascorbate intravenously, 30 to 50 grams, while those able to swallow can
be given the same quantity dissolved in a glass of milk. This antidote
is nonspecific and succeeds on all drugs, so no time need be wasted in
identifying the drug. We speculate on ascorbate's action as due to the
high levels of sodium ascorbate in the brain as competing for and
displacing the narcotic from the opiate receptor sites. If this be the
case, then it might be possible to use this phenomenon postoperatively on
surgical patients to quickly bring them out of anesthesia.

References

Bejrablaya, d., and Laumjansook, K.,: Effect of Various Doses of
Ascorbic Acid Upon Pentobarbital: J. Med. Assoc. Thailand 59: (4)
188-189,1976

Cameron, E. and Baird, G.: Ascorbic Acid and Dependence on Opiates in
Patients with Advanced Disseminated Cancer, J. Internat. Res. Communc. 1:
(6) 33, 1973

Cathcart. R.: Vitamin C and Viral Disease. Talk presented at the Annual
Meeting of the California Orthomolecular Medical Socieity, Feb. 19, 1976,
San. Fran.

Ghione, R.: Morphine Spasm and C-Hypervitaminosis. Vitaminologia (Turin)
16:131-136, 1958

Klenner R. Significance of High Daily Intake of Ascorbic Acid in
Preventive Medicine: J. Internat. Acad. Prev. Med. 1: 45-69, 1974

Saccoman W.: Personal Communication 1976.

Scher, J. Rice, H. Suck-Oo, Kim, DiCamelli: Massive Vitamin C as an
Adjunct in Methadone Maintenance and Detoxification, J. Orthomolecular
Psychiatry 5: (3) 191-198, 1976

Snyder, S. : Opiate Receptors and Intercranial Opiates. Scientific American,
236: (3) 44-56, March, 1977

Stone, I. On the Genetic Etiology of Scurvy. Acta Genet. Med. Gemellol:
15: 356-360, 1966.

Stone, I. Hypoascorbemia, the Genetic Disease Causing the Human
Requirement for Exogenous Ascorbic Acid. Perspect. Biol. Med. 10:
133-134, 1966a.

Stone, I: Hypoascorbemia: A Fresh Approach to an Ancient Disease and
Some of its Medical Implications. Acta Genet. Med. Gemellol. 16: 52-62,
1967.

Stone, I.: The Healing Factor: "Vitamin C", Against Disease. Grosset
and Dunlap Inc., New York, 1972.

Stone, I: The Natural History of Ascorbic Acid in the Evolution of the
Mammals and Primates and Its Significance for Present Day Man. J.
Orthomolecualr Psychiatry, 1, (2-3): 92-90. 1977a

Stone, I: Hypoascorbemia, Our Most Widespread Disease, Bull. Nat. Health
Fed. 18: (10) 5-9 1972b.

Stone I: The Genetics of Scurvy and the Cancer Problem. J.
Orthomolecualr Psychiatry :5, (3): 183-190, 1976.

Stone, I: The CSS Syndrome: A Medical Paradox. Northwest Acad. Prev.
Med. 1: (1) 24-28, 1977.

http://members.tripod.com/~psychede/opiates
 
LOL,
next time I'm really dopesick, I'll try eating an apple...but my guess is that I'll either shit it out or puke it up long before it has any effect.
 
Make fun of the article all you want but it does have some truth to it. I have a 4 month long opiate habit and the only way I keep my tolerance down and maintain a steady dosage is with lots of Vitamin C during the day. It keeps me productive and keeps my mind off the cravings. However, come night time, I have to allow myself some "free time" and that has been my method for these months. I can't say how much it would cure withdraw, but it does provide a little energy boost and makes you feel better...for some time.
 
Make fun of the article all you want but it does have some truth to it. I have a 4 month long opiate habit and the only way I keep my tolerance down and maintain a steady dosage is with lots of Vitamin C during the day. It keeps me productive and keeps my mind off the cravings. However, come night time, I have to allow myself some "free time" and that has been my method for these months. I can't say how much it would cure withdraw, but it does provide a little energy boost and makes you feel better...for some time.

Sure, but that energy boost isn't a cure for addiction. You say "It does have some truth", well what truth is that? The article is dealing with its effects on addiction, not its energy restoring properties.

As to what you said on cravings, placebo, placebo, placebo. I met people who claimed their cravings for opiates were absolutely cured after being given a placebo 'cure'. Its all about mind.

...For instance, I am on methadone daily. I wake up every day craving opiates. I know mentally that methadone will cure my craving if I get out of bed and dose, and I usually do this. Within minutes my cravings are gone, though methadone generally takes an hour or more to have any effect in the brain. Its all about comforting the mind, giving the person a resolution. If the person thinks vitamin C is the answer, they will most likely have very noticeable effects. But that doesn't make it a good replacement for a real medically sound detox.
 
^ I agree. I took a gram of Vitamin C when I was in rehab if I had a cold and it didn't help the cravings at all. After getting out of rehab, I took Vitamin C for a month or so every single day to prevent me from catching a cold and that's the only thing it seemed to help with. Of course I had no idea about this info at the time, but obviously it didn't work for me.
 
Sure, but that energy boost isn't a cure for addiction. You say "It does have some truth", well what truth is that? The article is dealing with its effects on addiction, not its energy restoring properties.

As to what you said on cravings, placebo, placebo, placebo. I met people who claimed their cravings for opiates were absolutely cured after being given a placebo 'cure'. Its all about mind.

...For instance, I am on methadone daily. I wake up every day craving opiates. I know mentally that methadone will cure my craving if I get out of bed and dose, and I usually do this. Within minutes my cravings are gone, though methadone generally takes an hour or more to have any effect in the brain. Its all about comforting the mind, giving the person a resolution. If the person thinks vitamin C is the answer, they will most likely have very noticeable effects. But that doesn't make it a good replacement for a real medically sound detox.

Well then I have a powerful brain, because I don't crave until night time. Not to mean I disagree with what you're saying, you make a good point. I don't think it could cure addiction and I retract my statement...but during the day my mind is off opiates and on my work. I guess my mind has made a connection with night and opiates...(not to say I don't love a good Saturday with OCs, haha)
 
Ascorbic acid (vitamin C) effects on withdrawal syndrome of heroin abusers

Background: Ascorbic acid (vitamin C), administered orally in high doses has been observed to relieve pain and reduce opioid use in cancer patients. In vitro studies have also shown that antioxidants, such as vitamin C, may, at high concentrations, inhibit the endogenous opioid degrading metallo-enzyme and increase endorphin levels. In the present study the effects of oral administration of high doses of vitamin C on withdrawal syndrome of heroin abusers were investigated. Materials and patients: Ascorbic acid at doses of 300 mg/kg b.w/day, supplemented with vitamin E (5 mg/kg b.w/day), was orally administered in two groups of heroin addict subjects consisting of in-patients (Group A, 30 males) and one of out-patients(Group B,10 males), for a minimum of 4 weeks. The group A in-patients were also administered the conventional (diazepam + analgesic) medication. The results on the intensity of withdrawal syndrome (WS), estimated according to DMS-III criteria, were compared to a third group of heroin addict in-patients (group C, 30 males-control group), treated only by conventional medication. Results: The patients of the vitamin C-treated groups (in-patients and out-patients) experienced mild WS (in 46.6% to 50% of the subjects) in contrast to the control group patients, who experienced mild WS in 6.6% of the cases. The vitamin C-treated subjects expressed major WS ranging from 10% to 16.6%, in contrast to the untreated subjects (control group), who expressed a major WS in 56.6% of the cases. Conclusions: The results indicate that high doses of ascorbic acid administered orally, may ameliorate the withdrawal syndrome of heroin addicts. Further studies are needed in order to estimate the dose- and time-dependent effects of ascorbic acid treatment, and to clarify its mechanisms of action in the withdrawal syndrome.


Evangelou, A., Kalfakakou, V., Georgakas, P., Koutras, V., Vezyraki, P., Iliopoulou, L., Vadalouka, A. 2000 In Vivo 14 (2), pp. 363-366
 
this article is total BS, vitamin C doesn't cross BB barrier and can't bind to mu receptors + 50 grams of pure vitamin C would probably lead to severe allergic reaction, I remember when I was a kid and one summer I was working on tomato farm picking them up and of course eating and after a week I had very bad allergic reaction (swollen tung,rash...) so doctor told me that's because of vitamin C in tomatoes and 2 days after I stopped eating them I was fine.
I'm sure massive doses of Vitamin C are not gonna help with addiction but this can be dangerous on couple levels:
1)if one uses pure Vitamin C it's an acid and in massive doses leads to allergic reactions and problems with stomach
2)if one uses massive doses of sodium ascorbate it has sodium in it and high levels of sodium are not good for your hard and cardiovascular system+ some people use calcium ascorbate which is even worse for simular reson
3)in one study high doses of VC in mice led to canser and kidny stones...
I know what I'm talking about back when I was in college my graduation work was about Vitamin C and I studied Biotechnology and Organic chemistry and I did a lot of research about this subject and never heard about 80+grams use for humans of ascorbic acid it's like with every substance difference between medicine and poison is in concentration.
I think this patients in this study had placebo effect. But Vitamin C in small doses(500mg-1.5gram) is good for your body.It takes part in a lot of biochemical reactions in the body including formation of some neurotransmiters but claim that it can revers overdoses is BS.Ask any doctor at ER to use vitamin C to revers heroine overdose and see what he or she has to say.
You will probably hear a lot of F words.
 
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Ascorbic acid (vitamin C) effects on withdrawal syndrome of heroin abusers




Evangelou, A., Kalfakakou, V., Georgakas, P., Koutras, V., Vezyraki, P., Iliopoulou, L., Vadalouka, A. 2000 In Vivo 14 (2), pp. 363-366

Keep in mind this isn't just one or two studies, there has been an ongoing Ascorbate debate in parts of the medical community for years. Especially its efficacy as an analgesic.

Plus, they are not talking about one or two multivitamins worth of Vitamin C, or the amount you would get from eating an orange- they're using very high doses. Doses up to and beyond 75-85 grams of sodium ascorbate a day; this is over 10 times the amounts considered 'very high'.
 
this article is total BS, vitamin C doesn't cross BB barrier and can't bind to mu receptors + 50 grams of pure vitamin C would probably lead to severe allergic reaction, I remember when I was a kid and one summer I was working on tomato farm picking them up and of course eating and after a week I had very bad allergic reaction (swollen tung,rash...) so doctor told me that's because of vitamin C in tomatoes and 2 days after I stopped eating them I was fine.
I'm sure massive doses of Vitamin C are not gonna help with addiction but this can be dangerous on couple levels:
1)if one uses pure Vitamin C it's an acid and in massive doses leads to allergic reactions and problems with stomach
2)if one uses massive doses of sodium ascorbate it has sodium in it and high levels of sodium are not good for your hard and cardiovascular system+ some people use calcium ascorbate which is even worse for simular reson
I know what I'm talking about back when I was in college my graduation work was about Vitamin C and I studied Biotechnology and Organic chemistry and I did a lot of research about this subject and never heard about 80+grams use for humans of ascorbic acid it' like with every substance difference between medicine and poison is in concentration.
I think this patients in this study had placebo effect. But Vitamin C in small doses(500mg-1.5gram) is good for your body.

I'm skeptical about it as well, but I dont make any definite claims unless I've got something to back it up with.

Can you show me some studies that support what you say?

I'm interested in the pharmacology of all of this
 
This is the first time I've ever heard anything about this... its really strange!


Megadoses of vitamin C prevent the development of tolerance and physical dependency on morphine in mice

In mice ascorbate, when co-administered with morphine, suppresses the development of tolerance and physical dependence on the drug, without significantly affecting its analgesic properties as inferred from unaltered ED50 values. The duration of morphine-induced analgesia, however, is progressively reduced with an increase in the amounts of ascorbate. Ascorbate at 1g/kg body weight does not alter the pH of blood, and has no effect on the levels of lipid-neroxides in blood and brain. Studies presented in this paper suggest the potential use of ascorbate in the prevention of development of tolerance in therapeutic applications of narcotics as analgesics.

Khanna, N.C., Sharma, S.K. 1983 Life Sciences 33 (SUPPL. 1), pp. 401-404
 
I find Vitamin C to be very helpful against many drug related "problems".

Large doses does help make me feel a bit better while wding. also a mega dose will eliminate 80% of a ritalin crash if taken half an hour b4.
also I found it to help potentiate tramadol a bit. placebo or not I love my VC. It's suppose to help your body heal faster.
 
I recken that artical could be about anything and people would come forward and say "yep that works for me"
 
I'm skeptical about it as well, but I dont make any definite claims unless I've got something to back it up with.

Can you show me some studies that support what you say?

I'm interested in the pharmacology of all of this
coworker of one of the doctors(Stone) that did the study actully found that in mice massive doses of vitamin c lead to canser and was fired and 2 more studies after that found that everything after 1gram of vitamin c in human body can't be digested, we just piss it out.
and no benefits were found of triting anything
I can spend some time on the web and give you links and names of this. will do it tomorrow
 
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coworker of one of the doctors(Stone) that did the study actully found that in mice massive doses of vitamin c lead to canser and was fired and 2 more studies after that found that everything after 1gram of vitamin c in human body can't be digested, we just piss it out.
and no benefits were found of triting anything
I can spend some time on the web and give you links and names of this. will do it tomorrow

Those links would be great.

The other paper (Scher et
al., 1976) was originally presented in 1974 to the North American
Congress on Alcohol and Drug Problems, by these authors from the National
Council on Drug Abuse and the Methadone Maintenance Institute, and was
entitled, "Massive Vitamin C as an Adjunct in Methadone Maintenance and
Detoxification." These authors realized that scurvy played a large part
in the drug abuse problem, but they only saw ascorbate as a means to
reduce some of the side effects of methadone administration like
constipation, loss of libido, and restless sleep. For this they used
about 5 g of ascorbic acid a day. It apparently never occurred to them
that by switching to sodium ascorbate and increasing their dosage by a
factor of 10, they could completely eliminate the ill-conceived Methadone
Program with all its problems and at the same time have a simple,
nontoxic, and elegant solution to the drug abuse problem.

Very interesting. I do know that some clinics recommend Vitamin C to treat side effects of MMT (specifically sweating). William Burroughs used to take it daily for this purpose while on MMT until his death.
 
Actually, this all makes sense. I looked at the ingredients of RELACORE, and low and behold, the primary ingredient was none other than vitamin C (555% of the daily dose per 2 capsules).

The Binge Artist withdrawal regimine consists of the following:
1. Imodium for the "you-know-whats"
2. Benzos and weed for the Jimmy legs and restless nights
3. Nyquil for the general aches and pains (Dayquil during the day)
4. RELACORE for just about everything else (sweating, feeling like you can't hardly move, loss of motivation, etc etc).

I swear, six RELACORE in the morning and my eyes hardly even water. The overall feeling is very close to that "can do" attitude that one gets with a small dose of oxy.

RELACORE, people, RELACORE.
 
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I'm sure Linus Pauling would give this thread two stiff thumbs up. =D

The article looks interesting, I'm going to have to come back when I have time and read the whole thing, even though I always play the skeptic.
 
this article is total BS, vitamin C doesn't cross BB barrier and can't bind to mu receptors + 50 grams of pure vitamin C would probably lead to severe allergic reaction, I remember when I was a kid and one summer I was working on tomato farm picking them up and of course eating and after a week I had very bad allergic reaction (swollen tung,rash...) so doctor told me that's because of vitamin C in tomatoes and 2 days after I stopped eating them I was fine.
I'm sure massive doses of Vitamin C are not gonna help with addiction but this can be dangerous on couple levels:
1)if one uses pure Vitamin C it's an acid and in massive doses leads to allergic reactions and problems with stomach
2)if one uses massive doses of sodium ascorbate it has sodium in it and high levels of sodium are not good for your hard and cardiovascular system+ some people use calcium ascorbate which is even worse for simular reson
3)in one study high doses of VC in mice led to canser and kidny stones...
I know what I'm talking about back when I was in college my graduation work was about Vitamin C and I studied Biotechnology and Organic chemistry and I did a lot of research about this subject and never heard about 80+grams use for humans of ascorbic acid it's like with every substance difference between medicine and poison is in concentration.
I think this patients in this study had placebo effect. But Vitamin C in small doses(500mg-1.5gram) is good for your body.It takes part in a lot of biochemical reactions in the body including formation of some neurotransmiters but claim that it can revers overdoses is BS.Ask any doctor at ER to use vitamin C to revers heroine overdose and see what he or she has to say.
You will probably hear a lot of F words.




Title:Ascorbic acid inhibits development of tolerance and dependence to opiates in mice: Possible glutamatergic or dopaminergic modulation.

In a recent study, it has been demonstrated that ascorbic acid possessed antidopaminergic activity and modulate the glutamatergic neurotransmission in mice. With this background, the present study was undertaken to study the effect of ascorbic acid on the development of tolerance and dependence to opiate and its mechanism of action. Male Swiss mice weighing 20-25 g were used in the present study. Mice were made physically dependent on opioid by the chronic administration of morphine (10 mg/kg, twice a day, for 9 days) intraperitoneally. Ascorbic acid, haloperidol (dopamine antagonist) or MK 801 (NMDA receptor antagonist) was administered daily for 9 d before challenging the animals with morphine. The development of tolerance was assessed by noting the tail-flick latency on day 1, 3, 9 and 10. On the 10 th day after the measurement of tail-flick latency, animals were challenged with naloxone (2 mg/kg., i.p.) and incidence of escape jumps were recorded by placing the animals in 45 cm high plexiglass container. Ascorbic acid (400-1600 mg/kg) dose dependently inhibited development of tolerance and dependence to morphine as noted from tail-flick latency. When given along with MK 801 (0.01 mg/kg., i.p) or haloperidol (0.1 mg/kg i.p.), ascorbic acid (800 mg/kg., i.p.) potentiated the response of MK 801 or haloperidol. In conclusion, it is hypothesized that inhibition of development of tolerance and dependence to morphine by ascorbic acid appears to have two components, namely dopaminergic and glutamatergic.

Various reports have confirmed the involvement of excitatory amino acids (EAA) in morphine tolerance and dependence [1] . Non-competitive NMDA receptor antagonist (like MK 801) and competitive NMDA receptor antagonist (like LY 274614) blocked morphine tolerance and dependence in rats [2],[3] . Besides, in morphine tolerant and abstinent rats, binding of [ 3 H] MK 801 in the presence of glutamate and glycine is decreased in some brain regions [4],[5] , however, in the absence of glutamate and glycine, binding of [ 3 H] MK 801 decreased modestly only in the cortex [6] . These data suggest that activities of endogenous glutamate and glycine are perhaps altered following activation of NMDA receptors in chronic morphine- treated animals. Ascorbic acid (AA) is shown to regulate NMDA receptor activity. Through the redox phenomena, AA has inhibitory role on NMDA receptor functioning [7] . Also, a growing body of research indicates that ascorbic acid is capable of modulating the effects of dopamine in the mammalian forebrain. Ascorbic acid enhanced the effect of catalepsy produced by dopaminergic antagonists as well as various nitric oxide synthase inhibitors [8],[9] . Also ascorbic acid blocked the amphetamine-induced turning behaviours in rats with unilateral nigrostriatal lesion produced by 6-hydroxydopamine [10] . These findings coupled with inhibition of dopamineric agonists and antagonists in radioligand binding studies suggested antidopaminergic-like action of ascorbic acid. Recently, we have shown that ascorbic acid potentates the antipsychotic activity of both typical and atypical antipsychotics thus possessing antidopaminergic effect [9] . Thus, it was hypothesized that ascorbic acid has protective effect in the development of tolerance and dependence by modifying the dopaminergic or glutamatergic neurotransmission. With this background, ascorbic acid was tested for its ability to prevent the development of tolerance and dependence to opioids in mice and also to understand the possible mechanism of its action.

Materials and Methods

The following drugs were used: Ascorbic acid (S. D. Fine Chemicals, Mumbai, India), MK 801 [(+)-5-methyl-10,11-dihydroxy-5H-dibenzo(a,d)cyclo-hepten-5,10-imine], (Merck, Sharp and Dohme, England), haloperidol (Searle, Skokie, IL, USA), and morphine (Government Analytical Laboratory, Chandigarh). Haloperidol was dissolved in few drops of glacial acetic acid while morphine was dissolved in a few drops of dilute hydrochloric acid and volume made with distilled water. All the drugs were freshly prepared and administered intraperitoneally in a constant volume of 1 ml/100 g of body weight.

Male Swiss mice weighing between 20-25 g were obtained from the disease free small animal house, Hissar. The animals were housed under standard laboratory conditions and maintained on natural light and dark cycle and had free access to food and water. Animals were acclimatized to laboratory conditions before the experiment. Each animal was used only once. All the experiments were carried out between 0900 and 1500 h. The experimental protocols were approved by Institutional Animal Ethics Committee (IAEC) and conducted according to the Indian National Science Academy (INSA) Guidelines for the use and care of experimental animals.

Experimental procedure: The development of tolerance was assessed by tail-flick latency [11] and as modified by Kulkarni [12] , while dependence was quantified by naloxone-precipitated withdrawal syndrome. The experimental protocol was the same as described by Kulkarni and Verma [13] . The animals were randomly divided into following groups: (i) saline: saline, (ii) saline: morphine (iii) ascorbic acid alone or in combination with other drugs (MK 801 or haloperidol): morphine (iv) ascorbic acid alone or in combination with other drugs (MK 801 or haloperidol). Ascorbic acid alone or with MK 801 or haloperidol was administered 30 min prior to morphine from days 1 to 9. Tail-flick latency was calculated on day 1, 3, 9 and 10. On day10, treatments were reversed such that, the animals that received, ascorbic acid alone or with MK 801 or haloperidol followed by morphine from day 1 to 9 were challenged with morphine alone and animals that received ascorbic acid alone or with MK 801 or haloperidol from day 1 to 9 were challenged with ascorbic acid alone or in combination with MK 801 or haloperidol followed by morphine. Immediately after the measurement of tail-flick latency, animals were challenged with naloxone (2 mg/kg., i.p.) and incidence of escape jumps were recorded in 45 cm high plexiglass container.

Statistical analysis: Data expressed as mean [+ or -] SEM was analyzed by one-way analysis of variance (ANOVA) followed by Dunnett's t-test. p < 0.05 was considered as statistically significant.

Results and Discussion

Mice receiving chronic treatment with morphine (10 mg/kg, twice daily) showed maximal antinociceptive effect on days 1 and 3 of treatment. However, the animals showed rapid development of tolerance as the tail-flick latency time reached near the baseline latency by day 10. Mice treated with ascorbic acid (800 or 1600 mg/kg) followed by morphine (10 mg/kg) for 9 d showed considerable antinociception on day 1, 3 and 9 of testing. Challenging each group with saline followed by morphine on day 10 evoked considerable antinociceptive response. The effect was, however, not significant with low dose of AA (400 mg/kg) [Figure 1].

Mice receiving MK 801 (0.01 mg/kg) followed by morphine (10 mg/kg) on days 1-9 displayed maximal antinociceptive effect on day 1 and 3 of treatment. However, the reaction time reached the baseline latency by day 9 of testing showing development of tolerance. On day 10, the tail-flick latency was no greater than that of control group receiving saline followed by morphine from day 1 to 10. However, mice pretreated with MK 801 (0.01 mg/kg) in combination with ascorbic acid (800 mg/kg) followed by morphine (10 mg/kg) on days 1-9 displayed significant antinociception throughout the testing period [Figure 2].

Mice receiving haloperidol (0.1 mg/kg) followed by morphine (10 mg/kg) on day 1-9 exhibited maximum antinociception on days 1 and 3. However, animals showed development of tolerance as the reaction time reached the basal latency by day 9 of testing. On day 10, when the mice were challenged with saline followed by morphine (10 mg/kg), exhibited tail-flick latency almost similar to that of control group receiving saline followed by morphine from day 1 to 10. However, animals receiving a combination of haloperidol (0.1 mg/kg) and ascorbic acid (800 mg/kg) on days 1-9 showed significant antinociception throughout testing period. Challenging the same group with saline followed by morphine on day 10 also evoked significant antinociceptive response [Figure 3].

Animals treated with ascorbic acid (800 mg/kg), haloperidol (0.1 mg/kg) or MK 801 (0.01 mg/kg) alone or in combination followed by saline failed to exhibit any significant antinociceptive response on days 1, 3 and 9. Challenging these groups with their respective treatments followed by morphine (10 mg/kg) on day 10 produced significant antinociception; a response similar to morphine effect on day 1 [Figure 4].

Mice receiving repeated treatment with saline followed by morphine (10 mg/kg) displayed numerous escape jumps in response to injection of naloxone (2 mg/kg) on day 10. Mice treated with ascorbic acid (400-1600 mg/kg) followed by morphine on day 1 to 9 dose-dependently inhibited the incidence of escape jumps. The effect, however, was not significant with ascorbic acid 400 mg/kg. Mice receiving MK 801 (0.01 mg/kg) followed by morphine (10 mg/kg) on day 1-9 failed to reduce naloxone-precipitated jumps significantly. However chronic treatment with haloperidol (0.1 mg/kg) alone and in combination with ascorbic acid (800 mg/kg) followed by morphine (10 mg/kg) from day 1-9 significantly decreased the naloxone-precipitated jumps. Similarly, mice receiving MK-801 (0.01 mg/kg) in combination with ascorbic acid (800 mg/kg) followed by morphine on day 1-9 significantly decreased the number of naloxone-precipitated jumps [Figure 5].

The development of physical dependence and tolerance with repeated use is a characteristic feature of all the opioid drugs and offer major limitation in their clinical use. Tolerance and dependence are thought to result from neuronal adaptations produced by repeated drug exposure [14],[15] .

A series of reports have shown that non-competitive NMDA receptor antagonist, MK 801, blocks development of tolerance or dependence to several psychoactive substance including opiates [16],[17] . The prevention of development of tolerance and dependence to opiates in our study appears to be due to different components of action of AA. The inability of low dose of ascorbic acid (400 mg/kg) given chronically to alter tolerance or dependence is consistent with observation that, ascorbic acid at low doses, has potentiating action on dopaminergic and glutamatergic system [9],[18] . Ascorbic acid at high doses (800-1600 mg/kg), however, has profound inhibitory role over NMDA receptor function and a haloperidol-like antidopaminergic activity [7],[19] . These activities might be acting simultaneously with the resultant inhibition of development of tolerance and dependence to morphine.

Dopamine antagonists like haloperidol and butaclamol inhibit wet-dog shakes and aggressive behavior observed during withdrawal [20],[21],[22] . Our findings showing inability of haloperidol to block development of tolerance may in part be due to low dose of haloperidol. However, ascorbic acid potentiated its antidopamineric action, as it does in stereotypy or catatonia [19] . Ascorbic acid inhibited the binding of both dopamine agonists and antagonists in dose dependent manner [23],[24],[25] . Furthermore, ascorbic acid also potentiated antidopaminergic activity of haloperidol [9],[19] . Similarly, ascorbic acid significantly potentiated the activity of MK 801 that has no effect either on development of tolerance or dependence to opioids at low dose (0.01 mg/kg). Thus summing up the results, it appears that inhibition of development of tolerance and dependence by ascorbic acid has bi-directional component (or differential regulation). Since, even very high doses of ascorbic acid are known to be virtually non-toxic, it may be used therapeutically to treat morphine abstinence syndrome.

It is hypothesized that inhibition of development of tolerance and dependence to morphine by ascorbic acid appears to have two components, namely dopaminergic and glutamategic, and ascorbic acid prevents the development of tolerance and dependence to morphine in mice.




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