Alcohol Hangover is Classified as a Disease: What Does That Mean For Treating Hangovers Therapeutically?

New research may offer pharmacists a better means of helping customers manage the symptoms of an alcohol hangover.

As pharmacists, we see all sorts of ailments, diseases, and health problems in search of some form of a remedy. Traditionally, the ailment referred to as an alcohol hangover has been treated with folk lore or supplements, but mostly in real or perceived terms what the average consumer would call, “snake oil.”

However, new research and potentially promising approaches may offer pharmacists a better means of helping their customers thrive. Let me unpack this a little more.

Alcohol hangover treatment: Past and future

Since the discovery of alcohol thousands of years ago, drinkers have enjoyed consuming alcoholic beverages but also suffer from the next-day negative effects of alcohol intake. This so-called alcohol hangover is defined as the combination of negative mental and physical symptoms, which can be experienced after a single episode of alcohol consumption, starting when blood alcohol concentration approaches zero.

Indeed, the hangover experienced the day after an evening of alcohol consumption can have a significant impact on planned activities. For example, research has shown that hangovers have a negative impact on work performance (both presenteeism and absenteeism), reduced performance in students, and significantly impaired driving performance.

Social activities such as meeting up with friends and family may be cancelled, and mood changes during the hangover state can interfere with social interactions. However, in the current 24/7 society, many people are living in the fast lane and wish to fully enjoy all aspects of life.

After a busy day at work or being a student, a pleasant evening of alcohol consumption should not be followed by a hangover, as these drinkers also wish to perform optimally the next day. Given this, it is understandable that most drinkers are in favor of the development of an effective and safe hangover treatment, and willing to buy and use it once available. In fact, this interest was validated by a recent study in the Netherlands.

Pathology

Although some individual ingredients showed promising results, a search of the scientific literature shows that there is currently no marketed effective and safe hangover treatment. A few treatments containing high-dose aspirin are available in the United States; however, their safety and efficacy have never been proven nor substantiated by the FDA.

Given its great socioeconomic consequences, it is surprising that so little research has been devoted to the development of hangover treatments. The absence of effective hangover treatments is caused by the lack of understanding of the alcohol hangover.

For decades, it was believed that the hangover was caused by dehydration. More recent research disproved this assumption. Current research on alcohol metabolism revealed that alcohol consumption elicits an inflammatory response that is probably responsible for the development of the alcohol hangover.

It is thought that by counteracting this inflammatory response, hangovers can be reduced or prevented. As none of the marketed hangover treatments (claim to) have a mechanism of action that reduces this inflammatory response, it is understandable that these products are not effective in reducing or preventing hangovers.

Recently, the International Classification of Diseases 11th Revision (ICD-11) listed the alcohol hangover as a separate entity. This is in line with the FDA, which considers the alcohol hangover as a disease and requires treatments to be registered as drugs.

The listing of alcohol hangover in the ICD-11 has significant consequences because disease claims are prohibited for dietary supplements and foods, which comprise all of the currently marketed hangover treatments. As a consequence, the FDA is regularly sending warning letters to companies that disobey their regulations.

Current hangover treatments: Supplemental snake oil?

A recent review of hangover treatments that are marketed in the United States was published by Verster et al. in the scientific journal Addictive Behaviors. A total of 82 hangover products were identified, registered as dietary supplements.

The most frequently reported ingredients of these products were vitamin B, vitamin C, milk thistle extract (silymarin), dihydromyricetin (DHM), and N-acetyl L-cysteine (NAC). Usually, the products were a combination of one or more of these ingredients. Of concern, there is no peer-reviewed human data demonstrating either safety or efficacy of any of the 82 evaluated hangover products.

Most products were never investigated, whereas for others, including the currently popular DHM, research showed that it is ineffective in reducing or preventing hangover. Also, approximately half (45.1%) of the products contain NAC as an ingredient.

However, NAC is registered as a drug by the FDA, and its inclusion in dietary supplements or food is therefore prohibited. For dietary supplements, it is not allowed to make explicit disease modification claims on the package, insert or product website, however, this was done by the majority (64.6%).

Notwithstanding this, it is obviously not in the interest of consumers that the safety and efficacy of marketed hangover treatments are unproven, irrespective of whether these are registered as medicinal drugs or dietary supplements.

Sen-Jam Pharmaceutical is currently developing a new hangover treatment, SJP-001, comprised of a combination of naproxen (a nonsteroid anti-inflammatory drug, painkiller) and fexofenadine (a H1-antagonist, antihistamine drug).

Sen-Jam has an open FDA Investigational New Drug Application to begin a phase 1 and 2 clinical trial. If approved, the drug should be available both OTC and via prescription. The mechanism of action of SJP-001 aims to reduce the inflammatory response after alcohol consumption, which should then reduce or prevent a next-day hangover.

As naproxen and fexofenadine have been used successfully for decades to combat pain and allergy, respectively, there is evidence to believe that SJP-001 is safe. In addition, the results from a recent pilot study suggest that SJP-001 was significantly more effective in reducing hangover severity than placebo; however, the sample size of this study was small and further research is warranted.

Therefore, in the near future, an extensive clinical trial will be conducted to further evaluate the efficacy of SJP-001. For this study, the effects of SJP-001 on hangover severity will be investigated in a large group of drinkers, including the assessments of biomarkers of immune fitness to demonstrate the mechanism of action of SJP-001.

For everyone who enjoys alcohol consumption but suffers from hangovers, it is hoped that these promising developments turn out to be successful. Until then, the best way to prevent hangovers is to moderate alcohol consumption or abstain altogether.

About the Author

Jackie Iversen, RPh, MS, Author, Founder and Head of Clinical Development at Sen-Jam Pharmaceutical

Further reading

Van de Loo AJEA, Mackus M, Kwon O, Krishnakumar IM, Garssen J, Kraneveld AD, Scholey A, Verster JC. The inflammatory response to alcohol consumption and its role in the pathology of alcohol hangover. Journal of Clinical Medicine 2020, 9, 2081. https:// doi.org/10.3390/jcm9072081

Mackus M, van de Loo AJEA, Garssen J, Kraneveld AD, Scholey A, Verster JC. The role of alcohol metabolism in the pathology of alcohol hangover. Journal of Clinical Medicine 2020, 9, 3421. https://doi.org/10.3390/jcm9113421

Mackus M, van Schrojenstein Lantman M, van de Loo AJAE, Nutt DJ, Verster JC. An effective hangover treatment: friend or foe? Drug Science, Policy and Law 2017, https:// doi: 10.1177/2050324517741038

Verster JC, van Rossum CJI, Lim YN, Kwon O, Scholey A. P.0309. The effect of dihydromyricetin (dhm) from hovenia dulcis extract on alcohol hangover severity. European Neuropsychopharmacology 2021, 53 (Suppl. 1), S224-S225. https://doi.org/ 10.1016/j.euroneuro.2021.10.292