Cognitive Health Health Recovery

9 Supplements To Counteract The Negative Effects of Alcohol

Despite clinical proof that alcohol has detrimental effects on the human body, even more so than certain illegal substances, it still remains one of the world’s most readily available and favorite intoxicants. Alcohol has been a mainstay in nearly every society for thousands of years, and its commonality leads some people to not even recognize it as a drug. From sporting events to celebrations with family, it’s likely you will toss back a few drinks on occasion.

However, even moderate alcohol use can carry negative side effects. Consequently, many people seek supplements that will help mitigate some of the deleterious effects on the human body caused by consumption. Whether it’s for an occasional night on the town or more frequent use, or even for recovering from years of alcoholism, there are natural herbs, supplements, and nootropics that have been proven effective for harm reduction with alcohol use.

  • Before consuming any substance along with alcohol, be careful to check for any known interactions. Some nootropics have not been extensively studied and may possess undocumented interactions.
  • GABAergic nootropics like phenibut should be avoided because they can boost the effect of alcohol by producing similar effects of intoxication. It is generally not a good idea to mix alcohol with other depressants.
  • Many ADHD medications that contain amphetamine salts or methylphenidate can delay the onset of alcohol effects leading to increased consumption and potential heart problems.

Dihydromyricetin (DHM)

dihydromyricetinDihydromyricetin, a flavonoid, increases metabolism of both alcohol and its primary metabolite, acetaldehyde, by increasing key enzymatic action. In addition to ridding your body of these toxins, it has demonstrated effectiveness at blocking alcohol at the neurological level by binding to GABA receptors in place of alcohol. [1] While this compound theoretically shows promise for hangover prevention, many clinical studies need to take place before it’s classified as a safe supplement for human use.

Milk Thistle

Milk_thistle_flowerMilk Thistle, used as a natural medicine for over 2000 years, can accelerate the regeneration of liver cells and reduce fatty liver deposits that build up with alcohol use. It has been hypothesized that milk thistle increases the rate of protein synthesis in the liver, allowing it to more readily repair itself from alcohol-induced damage. [2] Milk thistle contains silibinin, which is thought to be the main active constituent of the plant.[3] Many users take milk thistle as a daily supplement, but it can also be consumed after a night of drinking to aid the liver in detoxification.

N-Acetylcysteine (NAC)

NAC is a nutritional supplement that is able to increase levels of the endogenous peptide glutathione [4], an important antioxidant. If you take NAC before a session of drinking, it can potentially reduce the oxidant side effects of alcohol. [5] It can also decrease the acetaminophen toxicity induced by alcohol. [6]
NAC also has anti-addictive properties.


emoxypineEmoxypine (also known as Mexidol) is an antioxidant drug that is molecularly similar to pyroxidine, a form of vitamin B6. Emoxypine was first synthesized in Russia, where it is used in the medical field for its anxiolytic, nootropic, neuroprotective, and anti-inflammatory effects, among others. [7] Emoxypine possesses general antioxidant properties, but also can specifically counteract the negative effects of alcohol. It displays therapeutic effects against health issues caused by chronic alcohol use and acute intoxication. In experiments, emoxypine administration reversed the learning deficits caused by chronic alcohol use in rats. [8] Emoxypine also lowers lipofuscin amounts in the cerebrum, much like piracetam. In terms of acute alcohol use (one night of heavy drinking), emoxypine significantly reduces the physical and mental feelings of intoxication that alcohol produces, specifically improving muscle coordination and mental clarity.[9]

Tauroursodeoxycholic Acid (TUDCA)

TUDCATUDCA is a bile acid that is found in trace amounts within humans. However, additional supplementation may be beneficial for those who are attempting to recover from alcoholism. TUDCA is used in some countries to treat gallstones and cirrhosis of the liver, but it is not FDA approved for this purpose in the United States.[10] TUDCA has been demonstrated to increase healing rates in unhealthy livers, specifically ones that have been damaged by alcohol. [11] TUDCA should not be consumed before drinking, as it carries the possibility of potentiating liver damage. Rather, TUDCA should be supplemented after drinking, or could be used on a regular basis by former alcoholics who wish to promote healing in their liver. [12]


HER-ASH01-2Ashwagandha is an herbal supplement that contains various chemicals known collectively as withanolides. These chemicals have been found to be effective at decreasing social anxiety when paired with alcohol, and ineffective threshold doses of either appear to be highly effective when combined. [13] However, the social disinhibition produced by alcohol alone may make this combination unnecessary for some users. Another use of this popular supplement is to aid in quitting alcohol consumption altogether. Indeed, alcohol cessation cold turkey can lead to an increase in anxiety. Ashwagandha has been clinically proven to reduce spikes in anxiety from abstinence. [14]


Agmatine is an amino acid and neurotransmitter derived from the amino acid, L-Arginine. It has been noted for its positive effects on neuropathic pain and drug addiction. Agmatine appears to reduce symptoms of alcohol withdrawal and dependence, such as anxiety and tremors. [15] [16] One note of caution: Agmatine is known to be a gastro-protective agent but when co-ingested with alcohol it can enhance ulcer formation. [17]


piracetam_structure_500pxWhile moderate alcohol use does not typically cause damage to the brain, cognitive functions are significantly impaired following the consumption of alcohol, and can continue to be impaired the next day or so after it is consumed. Nootropics that possess cholinergic mechanisms are potentially effective in improving cognition against alcohol-induced impairment. [18] Alcohol consumption increases neuronal lipofuscin, which contributes to age-related neurodegenerative disorders. [19] Piracetam and other racetams, in general, inhibit the accumulation of neuronal lipofuscin, counteracting neurodegeneration. [20]


Matcha is a Japanese green tea with a very high content of L-Theanine

The amino acid theanine, which is naturally found in green tea, is another important supplement that may provide liver protection from alcohol consumption. In one study, mice treated with L-theanine prior to alcohol consumption had lower ethanol concentrations in their blood after one hour compared to mice that were administered only alcohol. [21] This implies that L-Theanine could help the body recover faster from the negative effects of alcohol. (Consequently, this also implies Theanine could also decrease the duration of alcohol’s “positive” recreational effects.) Alcohol use typically impairs the antioxidant capabilities of hepatocytes (liver cells), and L-theanine has been found to restore the antioxidant capabilities of these cells. [22]


Alcohol has maintained its status as society’s drug of choice throughout history. As a result, it will continue to be used extensively and excessively by many despite its potential health risks. Those who are well armed with the knowledge of the aforementioned substances can use them to counteract and overcome the neurological and physical difficulties caused by alcohol consumption.

At the end of the day, supplements and nootropics can only do so much to prevent the negative effects of alcohol. A cautious and responsible approach to alcohol consumption is ultimately the most important component of using alcohol safely.

References   [ + ]

1. Dihydromyricetin As A Novel Anti-Alcohol Intoxication Medication (2012)
2. Biochemical effects of the flavonolignane silibinin on RNA, protein and DNA synthesis in rat livers. (1986)
3. Silibinin protects OTA-mediated TNF-alpha release from perfused rat livers and isolated rat Kupffer cells. (2009)
4. Alcohol and thermally oxidized pufa induced oxidative stress: role of N-acetyl cysteine (2004)
5. Antioxidant therapy attenuates deficient bone fracture repair associated with binge alcohol exposure (2011)
6. Clinical course of repeated supratherapeutic ingestion of acetaminophen.
7. Comparative Analysis of the Anxiolytic Effects of 3-Hydroxypyridine and Succinic Acid Derivatives (2015)
8, 9. Antioxidant Mexidol. The main neuropsychotropic effects and the mechanism of action. mechanism of action. (2009)
10. The clinical profiles of primary biliary cirrhosis with a suboptimal biochemical response to ursodeoxycholic acid. (2011)
11. Endoplasmic reticulum stress inhibition protects steatotic and non-steatotic livers in partial hepatectomy under ischemia-reperfusion. (2010)
12. Toxicity of ethanol and acetaldehyde in hepatocytes treated with ursodeoxycholic or tauroursodeoxycholic acid. (2004)
13. Effect of Withania somnifera Dunal in ethanol-induced anxiolysis and withdrawal anxiety in rats. (2008)
14. Evaluation of Ashwagandha in alcohol withdrawal syndrome (2012)
15. Effects of agmatine on ethanol withdrawal syndrome in rats. (2000)
16. Agmatine, an endogenous imidazoline receptor ligand modulates ethanol anxiolysis and withdrawal anxiety in rats. (2010)
17. Investigation on the mechanism involved in the effects of agmatine on ethanol-induced gastric mucosal injury in rats. (2000)
18. Can nootropic drugs be effective against the impact of ethanol teratogenicity on cognitive performance? (2001)
19. Chronic alcohol consumption induces lipofuscin deposition in the rat hippocampus. (1986)
20. The effects of piracetam on lipofuscin of the rat cerebellar and hippocampal neurons after long-term alcohol treatment and withdrawal: a quantitative study. (1991)
21. Effects of theanine on alcohol metabolism and hepatic toxicity. (2005)
22. L-Theanine prevents alcoholic liver injury through enhancing the antioxidant capability of hepatocytes. (2012)
Cognitive Health Memantine Nootropics Recovery

Can Nootropics Help With Drug Abuse and Addiction?

In recent years, evidence has compiled suggesting a common pathologic mechanism underlying addictive behaviours of several substances. Dysregulation of glutamatergic neurotransmission within the prefrontal cortex (PFC) and nucleus accumbens (NA) appears to predispose to a higher tendency towards drug-seeking behaviour.

Thus far, this mechanism has been associated with the addiction potential of cocaine, heroin, nicotine, cannabis, & alcohol, with possible implications for other substances and even non-drug-related compulsive habits such as pathological gambling. Discovery of this shared pathology has led to the investigation of the potential application of existing agents, such as Memantine and n-acetylcysteine.

Could nootropics targeting elements in this key glutamatergic circuit reduce symptoms and complications of substance use disorders?

Glutamate Spillover

«Glutamate spillover» refers to the pathologic cascade in brain chemistry that occurs with chronic abuse of certain substances that results in reinforcement of the behaviour[1].

McClure EA, Gipson CD, Malcolm RJ, Kalivas PW, Gray KM. Potential role of N-acetylcysteine in the management of substance use disorders. CNS Drugs. 2014 02;28(2):95-106.

Prolonged exposure to substances of abuse leads to several maladaptive changes in the glutamatergic PFC-NA pathway, specifically:

  • Downregulation of glial glutamate transporter-1 (GLT1) expression in the nucleus accumbens. By removing glutamate from the extrasynaptic space, GLT1 prevents inappropriate excitatory stimulation due to an accumulation of the excitatory neurotransmitter.
  • Decreased ability of presynaptic metabotropic glutamate receptor 2 (mGluR2) to inhibit glutamate release. In normal physiology, mGluR2 autoreceptors manage a feedback loop where increased extracellular glutamate levels trigger a reduction in the presynaptic release of glutamate. This auto-regulatory mechanism also serves to prevent an extracellular accumulation of glutamate.

When glutamate spillover within the non-synaptic extracellular space does occur as a result of the combination of these processes, the following sequelae are may manifest:

  • Stimulation of postsynaptic mGluR5, AMPA and NMDA receptors.
  • Upregulation of AMPA and NMDA receptors (increased synaptic plasticity).
  • Stimulation of extrasynaptic glutamate receptors may also occur.

Increased excitatory tone due to these two processes culminates in impaired inhibition with regard to drug-seeking behaviour as well as increased risk of relapse. Furthermore, persistently elevated glutamatergic tone may lead to neurotoxicity secondary to excessive Ca2+ ion influx. This pathology has also been associated in neurodegenerative disorders such as Alzheimer’s, Parkinson’s, and Huntington’s disease.


n-acetylcysteine (NAC) is a cysteine precursor that has a long history of use for indications ranging from bronchopulmonary disorders to paracetamol overdose. It produces many beneficial effects through a variety of mechanisms ranging from supporting antioxidant processes to suppressing over-reactive immune responses to inhibiting apoptosis. NAC’s glutamatergic modulation, however, is of key interest in managing substance use disorders[2].

Brown RM, Kupchik YM, Kalivas PW. The story of glutamate in drug addiction & of n-acetylcysteine as a potential pharmacotherapy. JAMA Psychiatry. 2013 09;70(9):895-7.

NAC is converted to L-cysteine in vivo, which enhances the activity of the cysteine/glutamate exchange transporter positioned near the pre-synaptic terminal. This increases the concentration of extracellular glutamate, resulting in increased tonic activation of pre-synaptic mGluR2 autoreceptors. This causes a subsequent decrease in glutamate release. NAC also increases expression of GLT1 and the cysteine/glutamate exchange transporter, promoting the removal of glutamate from the extrasynaptic space and ‹putting it back› in the pre-synaptic area. These effects in concert have been shown to mitigate the complications from glutamate spillover, & have been tested in several small trials with promising results.

  • When administered in patients with a history of cocaine addiction, NAC was shown to decrease self-reported cocaine use within the 28 days of treatment (mean 8.1 days out of 28 days before treatment & 1.1 days during treatment, p = 0.001)[3], desire to use cocaine (F = 5.07; df = 1,13; p = 0.05), & response to cocaine cues (F = 4.79, df = 1,13, p = 0.05)[4]. A magnetic resonance spectroscopy study confirmed elevated glutamate levels in the dorsal anterior cingulate cortex of cocaine users when compared against non-users (t(7) = 3.08, p = 0.02), and also showed a reduction 1 hour after a single 2.4 g dose of NAC[5].
  • With regard to cannabis, 2.4 g/day NAC decreased craving in one 4-week open label study of 24 patients[6]; in a double-blind placebo-controlled trial, subjects given 2.4 g/day NAC in addition to counselling were 2.4 times more likely to test negative on urinalysis (95%CI 1.1 to 5.2) but there was no difference in number of reported days of cannabis use[7].

The dosage for managing consequences of substance use disorders in trials ranged from 1.2 to 2.4 g by mouth daily. Benefits on neurochemistry may occur with single doses although significant alterations in behaviour may take days to weeks. The pharmacodynamic effect also depends upon the history of substance use and individual predisposition to addictive behaviour.

NAC is significantly protein-bound (80%). It is metabolised in the liver via non-CYP450 pathways. NAC and its metabolites are primarily eliminated in the urine, with a half-life of 5.6 hours in adults[8].

NAC is generally well-tolerated. Nausea, vomiting, rash, and fever have been reported.


Memantine (Namenda®) is an uncompetitive NMDA receptor antagonist most commonly used in the management of moderate-to-severe Alzheimer’s disease. In addition to its glutamatergic modulation, memantine also acts as an agonist at the D2 and nicotinic acetylcholinergic receptors (nAChR). Memantine binds and inhibits NMDA receptors with low-to-moderate affinity, most effectively in states of excess glutamatergic activity (such as in substance use disorder). By blocking NMDA receptors, memantine decreases glutamatergic tone[9].

Clapp P, Bhave SV, Hoffman PL. How adaptation of the brain to alcohol leads to dependence: a pharmacological perspective. Alcohol Res Health. 2008;31(4):310-39.
Neurochemical effects of alcohol intoxication in various contexts.

Upregulation of NMDA receptors has been observed with chronic alcohol consumption. Abrupt discontinuation of alcohol removes GABAergic suppression, resulting in the characteristic acute sequelae of alcohol withdrawal (symptoms of excitotoxicity): seizures, hallucinations, tachycardia, and shock. By inhibiting these receptors, memantine may theoretically attenuate symptoms of alcohol withdrawal.

  • In one RCT of 18 moderate alcohol drinkers (10-30 drinks/week), 30 mg/day memantine significantly decreased alcohol craving before alcohol consumption in comparison to 15 mg/day and placebo[10]. Another placebo-controlled RCT with 10-40 mg/day showed no difference[11].
  • A subsequent study of 38 patients utilising 20-40 mg/day memantine showed dose-dependent reductions in cue-induced craving[12].
  • In another RCT of 127 male patients undergoing alcohol withdrawal, administration of 10 mg memantine three times a day decreased apparent withdrawal symptom severity, dysphoria, and need for diazepam[13].
  • Administration of 60 mg significantly alleviated subjectively-rated symptoms of naloxone-induced opioid withdrawal in 8 heroin-dependent patients[14].
  • In a study of 67 heroin-dependent subjects, 10-30 mg/day memantine significantly reduced heroin craving, depression, and state & trait anxiety compared to placebo after 3 weeks of use. A separate treatment arm using amitriptyline 75 mg/day achieved similar results but with a higher incidence of side effects and a higher dropout rate[15].
  • Clinical data on application in cocaine[16],[17] and nicotine abuse[18] is less promising.

The dosage for mitigating substance use disorders in trials ranged from 5 to 60 mg, with 30 mg by mouth once daily showing the best effects for alcohol abuse and 30 to 60 mg by mouth once daily shown to be most effective in limited trials for opioid dependence. Safety is best characterised at doses up to 30 mg, as this dosage is used in Alzheimer’s disease. Memantine is typically initiated at 5 mg daily then titrated by 5 mg per week up to the goal dose (30 to 60 mg depending upon the indication).

Memantine undergoes favourable non-hepatic metabolism; its metabolites are minimally active. Individuals with a history of kidney disease should consult a doctor or pharmacist before use, as memantine undergoes significant renal elimination (74% is excreted in the urine). The half-life of memantine ranges from 60-80 hours.

The most common side effects noted at therapeutic doses higher than 7 mg/day are dizziness, headache, confusion, anxiety; increased blood pressure; cough; & constipation[19].


  • Disrupted regulation of glutamatergic pathways in the prefrontal cortex-nucleus accumbent pathway has been implicated as an underlying pathology among several substance use disorders, including cocaine, alcohol, and opioid dependence.
  • Therapies such as n-acetylcysteine (NAC) and memantine have demonstrated efficacy in attenuating the symptoms of some of these disorders in small trials.

References   [ + ]

1. McClure EA, Gipson CD, Malcolm RJ, Kalivas PW, Gray KM. Potential role of n-acetylcysteine in the management of substance use disorders. CNS Drugs. 2014 02;28(2):95-106.
2. Brown RM, Kupchik YM, Kalivas PW. The story of glutamate in drug addiction & of n-acetylcysteine as a potential pharmacotherapy. JAMA Psychiatry. 2013 09;70(9):895-7.
3. Mardikian PN, LaRowe SD, Hedden S, Kalivas PW, Malcolm RJ. An open-label trial of n-acetylcysteine for the treatment of cocaine dependence: a pilot study. Prog Neuropsychopharmacol Biol Psychiatry. 2007;31:389-94.
4. LaRowe SD, Myrick H, Hedden S, Mardikian P, Saladin M, McRae A, et al. Is cocaine desire reduced by n-acetylcysteine? Am J Psychiatry. 2007;164:1115-7.
5. Schmaal L, Veltman DJ, Nederveen A,van den Brink W, Goudriaan AE. n-acetylcysteine normalizes glutamate levels in cocaine- dependent patients: a randomized crossover magnetic resonance spectroscopy study. Neuropsychopharmacology. 2012;37:2143-52.
6. Gray KM, Watson NL, Carpenter MJ, LaRowe SD. n-acetylcysteine (NAC) in young marijuana users: an open-label pilot study. Am J Addict. 2010;19:187-9.
7. Gray KM, Carpenter MJ, Baker NL, DeSantis SM, Kryway E, Hartwell KJ, et al. A double-blind randomized controlled trial of n-acetylcysteine in cannabis-dependent adolescents. Am J Psychiatry. 2012;169:805-12.
8. Medscape® 5.1.2, (electronic version). Reuters Health Information, New York, New York.
9. Zdanys K, Tampi RR. A systematic review of off-label uses of memantine for psychiatric disorders. Prog Neuro-Psychopharmacol Biol Psychiatry. 2008 8/1;32(6):1362-74.
10. Bisaga A, Evans SM. Acute effects of memantine in combination with alcohol in moderate drinkers. Psychopharmacology 2004;172:16–24.
11. Evans SM, Levin FR, Brooks DJ, Garawi F. A pilot double-blind treatment trial of memantine for alcohol dependence. Alcoholism: Clin Exp Res 2007;31(5):775–82.
12. Krupitsky EM, Neznanova O, Masalov D, Burakov AM, Didenko T, Romanova T, et al. Effect of memantine on cue-induced alcohol craving in recovering alcohol-dependent patients. Am J Psychiatry 2007a;164(3):519–23.
13. Krupitsky EM, Rudenko AA, Burakov AM, Slavina TY, Grinenko AA, Pittman B, et al. Antiglutamatergic strategies for ethanol detoxification: comparison with placebo & diazepam. Alcoholism: Clin Exp Res 2007b;31(4):604–11.
14. Bisaga A, Comer SD, Ward AS, Popik P, Kleber HD, Fischman MW. The NMDA antagonist memantine attenuates the expression of opioid physical dependence in humans. Psychopharmacology 2001(157):1–10.
15. Krupitsky EM, Masalov DV, Burakov AM, Didenko TY, Romanova TN, Bespalov AY, et al. A pilot study of memantine effects on protracted withdrawal (syndrome of anhedonia) in heroin addicts. Addict Disord Treat 2002;1(4):143–6.
16. Collins ED, Vosburg SK, Ward AS, Haney M, Foltin RW. Memantine increases cardiovascular but not behavioral effects of cocaine in methadone-maintained humans. Pharmacol Biochem Behav 2006;83(1):47–55.
17. Collins ED, Ward AS, McDowell DM, Foltin RW, Fischman MW. The effects of memantine on the subjective, reinforcing, & cardiovascular effects of cocaine in humans. Behav Pharmacol 1998;9(7):587–98.
18. Thuerauf N, Lunkenheimer J, Lunkenheimer B, Sperling W, Bleich S, Schlabeck M, et al. Memantine fails to facilitate partial cigarette deprivation in smokers—no role of memantine in the treatment of nicotine dependency? J Neural Transm 2007;114:351–7.
19. Micromedex® 1.0 (Healthcare Series), (electronic version). Truven Health Analytics, Greenwood Village, Colorado, U.S.A. Available at: