What we know about ascorbate for withdrawal and cravings
Part 2 in my three-part series on vitamin C, pain, and opioid use disorder.
I first heard that vitamin C could help with opioid use disorder when I was asked to write an article on vitamin C, mood, and addiction for Nutrition in Focus. The idea that an affordable, widely available vitamin could help with addiction seemed far-fetched, but as I researched the topic, I realized there was more to it than I had originally thought. A few months later, I was fortunate to meet a woman with opioid use disorder (opioid addiction) who was using sodium ascorbate, a form of buffered vitamin C, to taper down her opioid usage. I spoke with her M.D., who confirmed that the patient was, indeed, reducing her opioid dosage faster than the other patients in the program, and more quickly than is typically seen at the center – with almost no symptoms of withdrawal.
Since then, I have taken a deep-dive into the subject,1 and found that vitamin C may, indeed, help those with opioid* use disorder reduce their drug use or stop it entirely, primarily by easing the symptoms of opiate withdrawal and alleviating drug cravings.2
High doses of oral vitamin C have also been observed to ease the symptoms of opiate withdrawal in at least a couple of human studies:
In a trial conducted at the Haight-Ashbury Free Clinic in San Francisco by Newmeyer et al.,3 1 to 3 grams of buffered vitamin C taken by mouth daily was found to significantly ameliorate withdrawal symptoms in people detoxifying from stimulants and opiates. One-third of the 60 patients reported that 70% or more of their acute withdrawal symptoms improved when taking buffered vitamin C during the active detox phase of the program, and half of the patients reported at least 60% relief. Aftercare clients (those already finished with active detox phase at the start of the study) seemed to benefit the most from vitamin C supplementation, with a median relief of 90% of their withdrawal symptoms.
High doses of oral vitamin C have been observed to ease the symptoms of opiate withdrawal.
In a 2000 study of humans with heroin addiction in rehab, oral supplementation with vitamin C and vitamin E ameliorated withdrawal symptoms in both inpatients (30 males) and outpatients (10 males).4 Those in the experimental group were administered oral vitamin C (300 mg of vitamin C per kilogram of the patient’s body weight) and vitamin E (5 mg/kg) daily for a minimum of four weeks; those in the control group received the benzodiazepine drug diazepam and an analgesic daily during the same time period. 57% of the patients in the vitamin C- and E- group experienced significant reductions in withdrawal symptoms, whereas only 7% of the control group could say the same.
57% of the patients in the vitamin C- and E- group experienced significant reductions in withdrawal symptoms, whereas only 7% of the control group could say the same.
Animal studies have consistently found that vitamin C supplementation makes opioid-addicted animals take fewer “hits” of morphine and clearly reduces opioid tolerance and dependency.5–8 In guinea pigs (fellow mammals that, like humans, cannot synthesize their own vitamin C), ascorbate has likewise been shown to ease morphine withdrawal,9 as well as to reduce the number of opioid binding sites in the brain.10
There are also some case reports in the medical literature of humans who have benefitted from using high dose vitamin C while tapering down their opioid use gradually or upon quitting abruptly (quitting “cold turkey.”)
One of these reports comes from Alexander G. Schauss, PhD.11 After reading a paper that hypothesized that vitamin C could occupy specific opioid receptor sites thus block their neuromodulatory effect,12 Schauss tested the concept first in guinea pigs and then in a human study. His trial was performed at a heroin treatment facility in Harlem, New York. The 20 study participants – all of whom were heroin-dependent and had attempted cold turkey withdrawals in the past – drank a glass of diluted fruit juice containing buffered vitamin C (sodium ascorbate) every two waking hours for several days. The dose of vitamin C varied day by day, ranging anywhere from 1 to 7.5 grams of sodium ascorbate every two hours. Schauss reports that the cocktail aborted the signs and symptoms of opioid withdrawal in 100% of the participants, all of whom quit “cold turkey” as part of the study protocol.40
Schauss’ work caught the attention of other scientists and practitioners, including two-time Nobel Laureate Linus Pauling, PhD and Vic Pawlack, MD, who added niacin to the vitamin C regimen.13 The addiction psychiatrist Jordan Scher, MD paired high doses of vitamin C with methadone,14 and Janis Keller-Phelps, MD administered vitamin C to patients at an addiction treatment facility in King County, Washington.15
Drs. Alfred F. Libby and Irwin Stone also published some case reports in 1977,2 claiming their heroin-addicted patients underwent “full correction” after taking repeated mega doses of sodium ascorbate. To put the high dosage of Libby and Stone’s protocol into perspective: The average over-the-counter vitamin C supplement contains anywhere from 300mg to 1,000mg (1 gram) per serving. Libby and Stone’s patients, in contrast, took 25 to 85 grams daily in divided doses.
Like Schauss, Libby and Stone instructed their patients to quit using heroin cold turkey. They report that within two or three days of starting the high dose vitamin C protocol and that patients reported sleeping restfully and overall feeling well while on vitamin C. After four to six days, the dose of sodium ascorbate was gradually reduced to a maintenance dose of 10 to 30 g per day. Libby and Stone report that 30 out of 30 patients (100%) in their pilot study were successfully treated with this protocol.
Is it safe to mega-dose vitamin C?
High doses of “regular” vitamin C (ascorbic acid) taken by mouth can cause the inconvenient side effects of diarrhea and gastrointestinal upset. Sodium ascorbate, a form of buffered vitamin C, however, is gentler on the bowels and generally well tolerated even at high doses.16,17 The alkalinizing substances used in buffered vitamin C supplements – such as the ionized calcium, sodium, or magnesium – might further support the detoxification process,18 strengthening the case for using buffered preparations of vitamin C.
It is typically safe to take high doses of ascorbic acid and sodium ascorbate by mouth.
Whether regular or buffered, vitamin C comes with very few risks – but risks worth mentioning. Large doses of vitamin C are typically not recommended to people with renal (kidney) insufficiency, to those undergoing hemodialysis, to individuals with iron overload conditions, and to those who form oxalate kidney stones.19
Studies assessing the connection between vitamin C supplementation and lithogenesis (kidney stone formation) have yielded mixed findings.20 One prospective cohort analysis, however, found that vitamin C intake was associated with a higher risk of uroliths (kidney stones) in men, but not in women.21
It is well established that vitamin C significantly enhances the gut’s absorption of iron.22 That’s why patients with iron deficiency anemia are often advised to take their iron supplements together with vitamin C.23,24 People with iron overload conditions like hemochromatosis may therefore run the risk of exacerbating their high-iron state if they take high doses of vitamin C.25
Although oral supplementation with high doses of ascorbic acid and sodium ascorbate are typically safe, it’s worth noting that high dose intravenous (IV) vitamin C is controversial in patients with a genetic deficiency of the enzyme glucose-6-phosphate dehydrogenase (G6PD).26 Those of African or Mediterranean ancestry are thus advised to get tested for G6PD deficiency before receiving high dose vitamin C via IV.
As with any therapy, the risks and benefits of high dose vitamin C supplementation must be weighed in consideration of each unique patient. The potential risks of vitamin C must also be weighed against those of methadone, buprenorphine, and naltrexone — the prescription medications commonly used in the management of opioid use disorder.27
Like all opioids, methadone and buprenorphine can lead to sedation, lightheadedness, reduced breathing, low blood pressure, sleep apnea, and sexual dysfunction – in addition to withdrawal, if discontinued too quickly.28,29 These medications can also disrupt the endocrine (hormone) system: methadone disrupts the hypothalamic pituitary gonadal axis,30,31 and buprenorphine might do the same.32 Methadone also commonly causes abdominal pain (typically worse than that seen with ascorbic acid) and can trigger cardiac arrhythmias (irregular heart beat).
Naltrexone’s common side effects include dizziness, headache, anxiety, insomnia, fatigue and sleepiness, constipation, nausea, vomiting, loss of appetite, abdominal pain, and myalgias (body pains). More serious reactions can include depression, suicidal ideation, and hepatotoxicity (liver toxicity).33 By comparison, vitamin C seems to be a rather safe therapy that can be used in addition to opioid replacement therapies.
Frequent mega-doses of vitamin C may help individuals with opioid use disorder (opioid addiction) comfortably reduce their narcotic usage by mitigating the symptoms of withdrawal and reducing drug cravings. Vitamin C may also support people who are ready to stop using opioids entirely – whether they choose to wean off gradually, or quit “cold turkey.”
In most cases, vitamin C may be used in conjunction with opioid and opioid-replacement prescriptions, and it typically very safe and well tolerated in patients of all ages.
More in this series
This article is Part Two in my three-part series on vitamin C, pain, and opioid addiction.
…And check out Part Three, in which I answer the question, “How does it work?” and explore vitamin C’s mechanisms of action in potentially preventing and treating opioid addiction.
- Zelfand E. Vitamin C, Pain and Opioid Use Disorder – PubMed. Integr Med . 2020;19(3):18-29. https://pubmed.ncbi.nlm.nih.gov/33132774/. Accessed May 23, 2021.
- Libby AF SI. The hypoascorbemia – kwashiorkor approach to drug addiction therapy: a pilot study. Australas Nurses J. 1978;7(6):4-13. https://pubmed.ncbi.nlm.nih.gov/418764/. Accessed June 8, 2020.
- Newmeyer J, et al. Efficacy of buffered ascorbate compound (BAC) in the detoxification and aftercare of clients involved in opiate and stimulant abuse.; 1983.
- Evangelou A, et al. Ascorbic acid (vitamin C) effects on withdrawal syndrome of heroin abusers. In Vivo (Brooklyn). 2000;14(2):363-366.
- Alaei H, et al. The effect of vitamin C on morphine self-administration in rats. Adv Biomed Res. 2014;3(1):178.
- Khanna NC, Sharma SK. Megadoses of vitamin C prevent the development of tolerance and physical dependence on morphine in mice. Life Sci. 1983;33(SUPPL. 1):401-4.
- Alaei H, et al. Ascorbic acid decreases morphine self-administration and withdrawal symptoms in rats. Pathophysiology. 2005;12(2):103-7.
- Kulkarni S, et al. Ascorbic acid inhibits development of tolerance and dependence to opiates in mice: Possible glutamatergic or dopaminergic modulation. Indian J Pharm Sci. 2008;70(1):56-60.
- Johnston PA, Chahl LA. Chronic treatment with ascorbic acid inhibits the morphine withdrawal response in guinea-pigs. Neurosci Lett. 1992;135(1):23-7.
- Dunlap C 3rd, et al. Ascorbate destruction of opiate stereospecific binding in guinea pig brain homogenate. Mol Pharmacol. 1979;16(1):105-19.
- Schauss AG. Attenuation of heroin withdrawal syndrome by the administration of high-dose vitamin C. J Orthomol Med. 2012;27(4):189-97. https://www.isom.ca/wp-content/uploads/2013/01/Attenuation-of-Heroin-Withdrawl-Syndrome-by-the-Administration-of-High-Dose-Vitamin-C-27.4.pdf.
- Beckett AH, Casy AF. Synthetic analgesics: stereochmical considerations. J Pharm Pharmacol. 1954;6(1):986-1001.
- Pawlack V. Megavitamin Therapy and the Drug Wipeout Syndrome: An Introduction to the Orthomolecular Approach as a Treatment for after-Effects of Drug Use/Abuse. San Francisco: Bolerium Books; 1975.
- Scher J, et al. Massive vitamin C as an adjunct in methadone maintenance and detoxification. J Orthomol Psych. 1976;5:191-8.
- Keller-Phelps J, Nourse A. The Hidden Addiction and How to Get Free. New York, NY: Little, Brown, and Company; 1986.
- Heuser G, Vojdani A. Enhancement of natural killer cell activity and T and B cell function by buffered vitamin C in patients exposed to toxic chemicals: The role of protein kinase – C. Immunopharmacol Immunotoxicol. 1997;19(3):291-312.
- Padayatty SJ, Levine M. Vitamin C: the known and the unknown and Goldilocks. Oral Dis. 2016;22(6):463-93.
- Minich DM, Bland JS. Acid-alkaline Balance: Role in Chronic Disease and Detoxification – PubMed. Altern Ther Heal Med. 2007;13(4):62-5.
- Rivers J. Safety of high-level vitamin C ingestion . Int J Vitam Nutr Res Suppl. 1989;30:95-102.
- Traxer O, et al. Vitamin C and Stone Risk. Review of the Literature. Prog Urol. 2003;13(6):1290-4.
- Ferraro PM, et al. Total, dietary, and supplemental Vitamin C intake and risk of incident kidney stones. Am J Kidney Dis. 2016;67(3):400-7.
- Hallberg L, Hulthén L. Prediction of dietary iron absorption: an algorithm for calculating absorption and bioavailability of dietary iron. Am J Clin Nutr. 2000;71(5):1147-60.
- Lynch SR, Cook JD. Interaction of Vitamin C and Iron. Ann N Y Acad Sci. 1980;355(1):32-44.
- Simonson W. Should vitamin C routinely be given with oral iron supplements? Geriatr Nurs (Minneap). 2019;40(3):327-8.
- Gerster H. High-dose vitamin C: A risk for persons with high iron stores? Int J Vitam Nutr Res. 1999;69(2):67-82.
- Marik PE. Is intravenous vitamin C contraindicated in patients with G6PD deficiency? Crit Care. 2019;23(1).
- Approach to treating opioid use disorder – UpToDate. https://www-uptodate-com.nunm.idm.oclc.org/contents/approach-to-treating-opioid-use-disorder. Accessed June 21, 2020.
- Methadone Adult Dosing – Epocrates Online. https://online.epocrates.com/drugs/52/methadone. Accessed June 21, 2020.
- Buprenorphine Adult Dosing – Epocrates Online. https://online.epocrates.com/drugs/1671/buprenorphine. Accessed June 21, 2020.
- Schoofs N, et al. Methadon und Levomethadon – Dosierung und Nebenwirkungen. Psychiatr Prax. 2014;41(2):82-7.
- Ortman HA, Siegel JA. The effect of methadone on the hypothalamic pituitary gonadal axis and sexual function: A systematic review. Drug Alcohol Depend. 2020;207.
- Varma A, et al. Impact of opioid therapy on gonadal hormones: focus on buprenorphine. Horm Mol Biol Clin Investig. 2018;36(2).
- Naltrexone Adult Dosing – Epocrates Online. https://online.epocrates.com/drugs/53/naltrexone. Accessed June 21, 2020.
* A note on “opiates” vs. “opioids:” These terms are sometimes used interchangeably, as they both refer to analgesics – but they do not mean the same thing!
The term “opiate” refers to a natural opioid derived from poppy, such as opium, morphine, and codeine.
The term “opioid” is a broader description. “Opioid” can refer to any drug that binds to opioid receptors in the brain, producing opioid-like effects. Opioids can be natural (in which case they are called “opiates”), semi-synthetic (such as heroin, hydromorphone, hydrocodone, and oxycodone), or entirely synthetic (such as fentanyl and methadone).
All opiates are opioids, but not all opioids are opiates.
[This article by Dr. Erica Zelfand was first published at Allergy Research Group and is reposted here with permission.]