How Synthehol Works

By: Stephanie Watson

Can we enjoy alcohol without the negative side effects?
Can we enjoy alcohol without the negative side effects?

Alcohol is a big part of our culture. But for all of its enjoyable aspects, drinking can take a toll on the body. What if we could enjoy all of the pleasurable effects of alcohol without having to worry about the harmful side effects? On the TV show "Star Trek: The Next Generation," the characters enjoy all the buzz of drinking alcohol without the nasty hangovers and other negative effects, thanks to a fictional creation called "synthehol." A similar alcohol alternative could soon become a reality.

To understand how synthehol could work, let's look briefly at how intoxication works. The ethanol (ethyl alcohol) in alcoholic drinks causes the "buzz" as well as the hangovers and other health problems. Ethanol is a form of alcohol produced by the fermentation process, in which yeast breaks down sugars in the absence of oxygen. Ethanol interferes with the transmission of nerve cells in the brain. In part, it enhances the effect of a neurotransmitter called GABA (gamma amino butyric acid). GABA acts as an inhibitory neurotransmitter on the central nervous system. It has a sedative effect and causes sleepiness.


Ethanol is a GABA-A agonist. This means that when ethanol attaches to signaling molecules known as GABA-A receptors, it causes the release of GABA-A. There are several different subtypes of GABA-A receptors, each of which triggers a different reaction to alcohol, from the sedative effect to memory loss to nausea.

Ethanol also acts as an antagonist at the NMDA receptor. NMDA is a receptor for glutamaine, a neurotransmitter responsible for passing messages from one nerve cell to another. Ethanol blocks its action. When the NMDA receptor is activated, it enhances stimulation of the nervous system. But when the receptor is blocked by an antagonist, it suppresses the nervous system response and enhances the sedative effect of alcohol.

Many of the positive effects that people feel when drinking alcohol are related to how it affects the cerebral cortex -- the highest portion of your brain. There alcohol depresses the behavioral inhibitory centers. In other words, when we drink, we often become more social and confident. Alcohol also raises the level of the chemical dopamine in the brain's reward center, which creates that "buzzed" feeling. These effects get more pronounced as the blood alcohol level (BAC) increases. To learn more about how alcohol affects the brain, check out How Alcohol Works.On the next page, learn about several methods that may remove alcohol's harmful effects.­

Alcohol Alternatives

Many bars serve non-alcoholic and lower-alcohol beverages, but some people complain about the taste.
Many bars serve non-alcoholic and lower-alcohol beverages, but some people complain about the taste.
Image courtesy Daniel Scherber/Stock.xchng

Researchers have proposed several different methods for removing some or all of alcohol's harmful health effects, while maintaining its pleasurable ones. These methods range from lowering the amount of alcohol in beverages to creating a substance that would change the effects of alcohol on the brain.

­Lower-alcohol, non-alcoholic beers and other types of low-alcohol beverages are already available, but they haven't really caught on because many people don't like the taste. And aside from pregnant women and others who can't drink alcohol for health reason­s, many people pass on low-alcohol beverages because they are seeking the "buzz" that only alcohol can give them. Reducing the alcohol content is the easiest way to make alcohol less toxic to the body. Creating a safer alternative that still produces the same "buzz" reaction is more difficult, but researchers say it's not impossible.


Scientists have already created drugs that act like alcohol on the brain. Alcoholics who are trying to quit can take a class of drugs called benzodiazepines. These drugs are also prescribed for anxiety, panic disorders, insomnia, muscle spasms and some forms of epilepsy (the commonly-prescribed drugs Xanax, Valium and Klonopin are all benzodiazepines). Like alcohol, these drugs are full GABA receptor agonists, meaning that they enhance the effects of the brain chemical GABA. But taking benzodiazepines can cause significant side effects, including dizziness, weakness and upset stomachs, and people who use these drugs can become dependent on them.

David Nutt from the University of Bristol proposes making an alcohol alternative that contains a GABA-A partial agonist. It would bind to a GABA-A receptor, but only partially activate it, triggering a weaker response. Because a partial agonist takes the place of a true agonist, it blocks the agonist from latching on to the receptor and causing the full effect.

In theory, an alcohol alternative could contain a chemical agent that would bind only to the receptors that affect the positive effects of drinking (relaxation, pleasure), but not to the receptors that affect the negative effects (nausea, memory loss). In other words, if you drink it, you'd still get a "buzz" without having some or all of the harmful effects of alcohol on your body. And when the body breaks down this alcohol alternative, it would not produce acetaldehyde, the toxic substance that leads to hangovers and other ill effects of drinking. And, if people drink too much of this alcohol alternative, they could take the benzodiazepine antidote flumazenil (brand name Annexate), which would instantly help them sober up so they could drive home. Flumazenil is sometimes used in hospital emergency rooms to awaken patients who are unconscious for no apparent reason.

Get a better understanding of GABA receptors and alcohol alternative research on the next page. 

Understanding GABA Receptors

Ethanol in alcoholic drinks binds to GABA receptors
Ethanol in alcoholic drinks binds to GABA receptors
2006 HowStuffWorks

­ Recent re­search has inc­reased scientists' understanding of the GABA receptors. But although there have been some studies done on partial GABA-A receptor agonists, there hasn't been enough evidence to show that they are free of the side effects of full agonists such as the benzodiazepine Diazepam, or Valium.

David Nutt and some other researchers believe an alcohol alternative is possible. Nutt says those tested so far have been relatively safe. They have shown little sedation, and few signs of dependence or withdrawal symptoms. Also, they don't tend to interact with the real thing, so even if someone drinks a few beers after having one of these alternatives, there is little risk of a dangerous interaction.


Finding an alcohol alternative and putting it on the market won't be easy, though. Researchers will probably need to use different compounds that work on all of GABA-A receptors to remove all of the negative effects of alcohol. Some researchers wonder if drug companies will invest money to research and develop a product not designed to treat a disease. They may not be interested in helping an alcohol alternative pass the Food & Drug Administration's safety testing requirements.

Researchers will also have to find the best way to deliver the alcohol alternative. Part of the enjoyment of drinking alcoholic drinks is in the taste and feel of sipping on them. An alternative might have to be a liquid to satisfy drinkers - a pill version probably won't gain acceptance. Also, it may need to come in different strengths, just like alcoholic drinks, to compare with, say drinking a glass of wine versus drinking a vodka martini. And, it would probably need to be absorbed and enter the brain in a similar way to alcohol, to help steady drinkers easily make the switch.

To find out more about synthehol and other alcohol alternatives, check out our links page.

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  • Brumback, Kate. "Now a drug that gives you that alcohol buzz, but without a hangover."Columbia News Service, May 2, 2006.
  • Christensen, Bill. "Hangover-free Buzz: Star Trek's Synthehol Now Possible."LiveScience, April 12, 2006.
  • Cox, W. Miles. "Alcohol alternatives - a goal for psychopharmacology?" Journal of Psychopharmacology, 20(3)2006:327-328.
  • Hall, Wayne. "The regulatory challenges in engineering a safer tipple." Journal of Psychopharmacology, 20(3)2006:321-322.
  • Longo, Lance and Brian Johnson. " Benzodiazepines--Side Effects, Abuse Risk and Alternatives." American Family Physician, April 1, 2000.
  • Nutt, David J. "Alcohol alternatives - a goal for psychopharmacology?" Journal of Psychopharmacology 20(3) 2006:318-320.
  • Nutt, David J. "What Is Pharmacology's Place In Finding Alternatives To Alcohol?" Medical News Today.
  • Ragan, Ian. "Alcohol alternatives - a goal for psychopharmacology?" Journal of Psychopharmacology, 20(3)2006:325-326.
  • Room, Robin. "For alcohol alternatives, the science is not the hardest part." Journal of Psychopharmacology, 20(3)2006:323-324.