Archive for the ‘alcohol’ Category

by Tori Rodriguez, MA, LPC

Individuals with major depressive disorder (MDD) have double the risk of alcohol use disorders (AUDs) and vice versa, and it has previously been proposed that some people with MDD may use alcohol to self-medicate. Though alcohol can become depressant if used chronically, alcohol initially has an antidepressant effect, though the underlying mechanisms have not been identified. Findings reported in September 2016 in Nature Communications begin to elucidate the basis of this action.

Behavioral and molecular evidence of the rapid antidepressant activity of NMDA receptor (NMDAR) antagonists, which have been found to be effective within 2 hours of administration and remain so for 2 weeks, represents a significant advance in depression treatment. Antidepressant efficacy involves the induction phase and the sustained phase.

The sustained phase of rapid antidepressants requires “both new protein synthesis and an increase in protein stability… for the GABABR shift in function necessary to increase” the activity of mTORC1, a mechanistic target of rapamycin complex 1, the authors explained in their paper. Rapamycin (mTOR) is a “serine/threonine kinase essential for messenger RNA translation” and is required for the sustained impact of rapid antidepressants.

Citing previous findings that ethanol (EtOH) also blocks NMDARs in the hippocampus, scientists at the University of Texas at Austin and Wake Forest University School of Medicine in Winston-Salem, North Carolina, aimed to determine whether EtOH and NMDAR antagonists exert rapid antidepressant effects via the same synaptic pathways in rodents. They hypothesized that EtOH “has lasting antidepressant efficacy, shares the same downstream molecular signaling events as rapid antidepressants, and requires de novo protein synthesis.”

First, they found that acute exposure to EtOH led to antidepressant and anxiolytic behaviors in rodents for up to 24 hours. They then discovered that, like NMDAR antagonists, EtOH alters the expression and signaling of GABABR, increases dendritic calcium, and leads to the synthesis of new GABABRs. This synthesis requires fragile-X mental retardation protein (FMRP), an RNA-binding protein of which precise levels are needed for normal neuronal functioning.

The antidepressant effects and the changes in GABABR expression and dendritic calcium were not observed in in Fmr1-knockout (KO) mice, supporting the concept that FMRP has in important role in regulating protein synthesis after EtOH exposure, and thereby facilitating its antidepressant efficacy.

These results point to a shared molecular pathway for the antidepressant activity of EtOH and rapid antidepressants, and highlight a mechanism involved in the initial antidepressant action of alcohol. “A shift in GABABR signaling is observed with both rapid antidepressants and acute EtOH treatment, which may provide insight into the molecular basis for the high comorbidity between major depressive disorder and AUD,” the authors concluded.

http://www.psychiatryadvisor.com/addiction/rapid-antidepressant-effect-of-alcohol/article/567335/?DCMP=EMC-PA_Update_RD&cpn=psych_md%2cpsych_all&hmSubId=&NID=1710903786&dl=0&spMailingID=15723696&spUserID=MTQ4MTYyNjcyNzk2S0&spJobID=881842067&spReportId=ODgxODQyMDY3S0

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Professor David Nutt. Neuropsychopharmacology.

Professor David Nutt. Neuropsychopharmacology.

by Katie Forster

A new type of synthetic alcohol has been discovered which could allow people to enjoy the sociable effects of a few pints, but skip the hangover that usually follows.

The new drink, known as ‘alcosynth’, is designed to mimic the positive effects of alcohol but doesn’t cause a dry mouth, nausea and a throbbing head, according to its creator Professor David Nutt.

The Imperial College Professor and former government drugs advisor told The Independent he has patented around 90 different alcosynth compounds.

Two of them are now being rigorously tested for widespread use, he said – and by 2050, he hopes alcosynth could completely replace normal alcohol.

“It will be there alongside the scotch and the gin, they’ll dispense the alcosynth into your cocktail and then you’ll have the pleasure without damaging your liver and your heart,” he said.

“They go very nicely into mojitos. They even go into something as clear as a Tom Collins. One is pretty tasteless, the other has a bitter taste.”

By researching substances that work on the brain in a similar way to alcohol, Professor Nutt and his team have been able to design a drug which they say is non-toxic and replicates the positive effects of alcohol.

“We know a lot about the brain science of alcohol; it’s become very well understood in the last 30 years,” said Professor Nutt.

“So we know where the good effects of alcohol are mediated in the brain, and can mimic them. And by not touching the bad areas, we don’t have the bad effects.”

Advocates of alcosynth believe it could revolutionise public health by relieving the burden of alcohol on the health service.

According to Alcohol Concern, drinking is the third biggest risk factor for disease and death in the UK, after smoking and obesity.

“People want healthier drinks,” said Professor Nutt. “The drinks industry knows that by 2050 alcohol will be gone.”

“They know that and have been planning for this for at least 10 years. But they don’t want to rush into it, because they’re making so much money from conventional alcohol.”

Early experiments into alcosynth, such as those reported on by BBC’s Horizon in 2011, used a derivative of benzodiazepine – the same class of drugs as Valium.

Mr Nutt said his new drinks did not contain benzodiazepine, and their formulas would remain a closely guarded, patented secret.

However, the huge cost of funding research into the drug and regulatory concerns mean it could be a long time before people can order an alcosynth cocktail at their local pub.

Professor Nutt, who was sacked from his position as the government drugs tsar in 2009 after he claimed taking ecstasy was less dangerous than riding a horse, said he was unsure if the use of synthetic alcohol would be restricted by the new Psychoactive Substances Act, which came into force in May.

“It’s an interesting idea, but too much in its infancy at the moment for us to comment on,” a Department of Health spokesperson told The Independent.

“I don’t think we’d give money to it until it was a little further along,” said the spokesperson. “If [Professor Nutt] were to apply for funding, it would go through the process of everything else and would be judged on its merits.”

“It would be great for producing better workforce efficiency if no one was hungover,” they added.

According to Professor Nutt, the effects of alcosynth last around a couple of hours – the same as traditional alcohol.

He said he and his team have also managed to limit the effects of drinking a lot of alcosynth, so in theory it would be impossible to ever feel too ‘drunk’.

“We think the effects round out at about four or five ‘drinks’, then the effect would max out,” he said.

“We haven’t tested it to destruction yet, but it’s safer than drinking too much alcohol. With clever pharmacology, you can limit and put a ceiling on the effects, so you can’t ever get as ill or kill yourself, unlike with drinking a lot of vodka.”

Researcher Guy Bentley worked with Professor Nutt on a new report by the liberal think tank the Adam Smith Institute into alcosynth regulation.

Mr Bentley told The Independent he hoped to persuade the government to accept the drug as a way of reducing the harm caused by alcohol.

“[The report] is trying to spark what happened with e-cigarettes and tobacco, but with alcohol,” he said. “Professor Nutt has been experimenting on this for a long time, but I thought to myself – ‘where is it?’ I wanted my hangover-free booze.”

However, not everyone was as keen on the new discovery.

Neil Williams, from the British Beer and Pub Association, said alcosynth was not necessary, as “there are other ways of avoiding a hangover”.

“There are plenty of low-strength drinks, particularly beers,” he told The Independent. “We should all drink in moderation so we shouldn’t need to have a hangover anyway.”

“I’d want to know more about it before I tried it myself,” he said.

http://www.independent.co.uk/life-style/health-and-families/health-news/hangover-free-alcohol-david-nutt-alcosynth-nhs-postive-effects-benzodiazepine-guy-bentley-a7324076.html?cmpid=facebook-post

By Christopher Ingraham

As acceptance of and usage of marijuana have become more widespread, a whole lot of interesting questions for public health researchers have been raised: How will legal marijuana affect our children? Our jobs? Our relationships?

Or how about our sex lives?

That latter question inspired a research project by Joseph Palamar and his colleagues at New York University. “Since the landscape is changing, and marijuana continues to increase in popularity, research is needed to continue to examine if and how marijuana use may influence risk for unsafe sexual behavior,” they write in the July issue of the journal Archives of Sexual Behavior.

To that end, Mr. Palamar and his colleagues recruited 24 heterosexual adults to take part in a series of in-depth interviews about prior sexual experiences that happened under the influence of either alcohol or marijuana. This was not meant to be a national sample. Rather, the purpose was to obtain a rigorous qualitative assessment of the different effects of alcohol and marijuana on people’s sexual behaviors and to use this as a jumping-off point for future quantitative research.

Here are a few of the observations the researchers drew from the interviews.

1. Beer goggles are real.

Respondents “overwhelmingly reported that alcohol use was more likely to [negatively] affect the partners they chose,” the study found. Both men and women were fairly likely to say that alcohol had the effect of lowering their standards for whom they slept with, in terms of character and appearance. With marijuana, this seemed to be much less of an issue.

“With weed I know who I’m waking up with. With drinking, you don’t know. Once you start drinking, everybody looks good,” a 34-year-old female said.

Marijuana use also was more associated with sex with people the respondents already knew — girlfriends and boyfriends, for instance. But alcohol “was commonly discussed in terms of having sex with strangers [or someone new],” the study found.

2. Drunk sex often leads to regret. Stoned sex typically doesn’t.

“The most commonly reported feeling after sex on alcohol was regret,” the study found. “Both males and females commonly reported that regret, shame, and embarrassment were associated with alcohol use, but this was rarely reported for marijuana.”

“I want to cook the person something to eat [after sex] when I’m high,” one male respondent said. “When I’m drunk, it’s like, ‘I’m out of here.’ Or get away from me.”

These negative emotions are seen as at least partly due to drunk sex being associated more with strangers.

3. Drunk sex can make you sick. Stoned sex can make you distracted.

“Nausea, dizziness, feeling sick [and vomiting], and blacking out were commonly reported to be associated with alcohol use,” the study found. One male said he accidentally fell asleep during sex while drunk. Another told of multiple instances where sex had to be interrupted because “I’ve had to stop and go hurl.”

There were fewer adverse effects reported with marijuana, and these tended to be more mental. One respondent said that marijuana use lessened his motivation to have sex. Another reported that being high distracted her from the experience.

“You’re so high [on marijuana] … you start thinking sex is weird. ‘What is sex?’ ” a female respondent reported.

4. The pleasure is usually better on marijuana.

The study found that “alcohol tended to numb sensations and marijuana tended to enhance sensations.”

“Alcohol tends to be a lot more numb,” a male respondent said. “Everything is sort of blunted and muted, whereas with marijuana it’s intensified.”

This “numbness” was associated with a longer duration of sex while drunk. But that wasn’t necessarily a good thing.

It “sometimes lasts too long,” one female respondent said. “Compared to when you’re high — it feels so great and it might be a little shorter.”

The study found that both men and women reported longer and more intense orgasms on marijuana, with one woman reporting hers were “magnified at least by five times.”

Also, marijuana led to “more tender, slow, and compassionate sexual acts, and to involve more sensation and sensuality than alcohol,” the report found.

5. Drunk sex is riskier overall.

“With regard to sexual risk behavior, the majority of participants felt that alcohol was riskier, sexually, than marijuana,” Mr. Palamar and his colleagues found. People typically said they exercised poorer judgment when drunk than when stoned, and were more likely to black out and forget whom they were with, what they were doing or whether they used protection.

Participants generally didn’t note this type of behavior with marijuana and said that while under its effects, they felt more in control overall. “One participant interestingly pointed out that marijuana use decreased his likelihood of engaging in risk behavior because while high he was too paranoid to give in,” the study found.

There were some take-homes viewed as useful from a public health perspective. First, the findings confirm one thing that numerous other studies have shown: Alcohol use seems to be closely associated with high-risk sexual behavior.

Aside from the link with unprotected sex and the corresponding risk of unexpected pregnancy or sexually transmitted diseases, studies have also drawn disturbing parallels between alcohol use and sexual assault. That link appeared even in the very small sample in Mr. Palamar’s study: One out of the 12 women interviewed reported an instance of sexual assault while under the effects of alcohol.

These negative consequences appear to be less pronounced with marijuana. Research found significantly lower incidences of domestic violence among couples who smoke marijuana, for instance.

http://www.post-gazette.com/news/health/2016/08/08/Serious-researchers-studied-how-sex-is-different-when-you-re-high-vs-when-you-re-drunk/stories/201608080044

Thanks to Michael Moore for bringing this to the It’s Interesting community.

drugs

dr nutt
Nutt says politicians often have a “primitive, childish” way of thinking about drugs.

David Nutt is trying to develop a new recreational drug that he hopes will be taken up by millions of people around the world. No, the 62-year-old scientist isn’t “breaking bad.” In fact, he hopes to do good. His drug would be a substitute for alcohol, to create drinks that are just as intoxicating as beer or whiskey but less toxic. And it would come with an antidote to reverse its effects, allowing people to sober up instantly and drive home safely.

Nutt, a neuropsychopharmacologist at Imperial College London and a former top adviser to the British government on drug policy, says he has already identified a couple of candidates, which he is eager to develop further. “We know people like alcohol, they like the relaxation, they like the sense of inebriation,” Nutt says. “Why don’t we just allow them to do it with a drug that isn’t going to rot their liver or their heart?”

But when he presented the idea on a BBC radio program late last year and made an appeal for funding, many were appalled. A charity working on alcohol issues criticized him for “swapping potentially one addictive substance for another”; a commentator called the broadcast “outrageous.” News-papers likened his synthetic drug to soma, the intoxicating compound in Aldous Huxley’s dystopian novel Brave New World. Some of his colleagues dismissed the idea as scientifically unfeasible.

Nutt wasn’t surprised. As a fierce advocate of what he says are more enlightened, rational drug policies, he has been a lightning rod for a long time. Politicians, in Nutt’s view, make irrational decisions about drugs that help them win votes but cost society dearly. Drug policy is often based on the moral judgment that people should not use drugs, he says. Instead, it should reflect what science knows about the harms of different drugs—notably that many are far less harmful than legal substances such as alcohol, he says. The plan for a synthetic alcohol alternative is his own attempt to reduce the damage that drug use can wreak; he believes it could save millions of lives and billions of dollars.

Such views—and the combative way in which he espouses them—frequently land Nutt in fierce disputes. Newspaper commentators have called him “Professor Nutty” or “the dangerous professor.” In 2009, he was sacked from his position as chair of the United Kingdom’s Advisory Council on the Misuse of Drugs, tasked with giving scientific advice to the home secretary, after he criticized a government decision on cannabis.

But in November 2013, he received the John Maddox Prize for standing up for science. “In circumstances that would have humiliated and silenced most people,” wrote neurobiologist Colin Blakemore, one of the judges, “David Nutt continued to affirm the importance of evidence in understanding the harms of drugs and in developing drug policy.”

Controversial comparisons
David Nutt does not look like a dangerous professor. Short and heavyset, he has a jovial, round face and an old-fashioned mustache; one could mistake him for a London taxi driver. He limps slightly, has a down-to-earth way of speaking, and laughs a lot when he talks. “He is a real personality,” says psychopharmacologist Rainer Spanagel of Heidelberg University in Germany. “You can be in a meeting and almost have a result, then he will come in an hour late, stir everything up, and in the end convince everyone of his position.”

Nutt says he realized at an early age that “understanding how the brain works is the most interesting and challenging question in the universe.” When he was a teenager, his father told him a story of how Albert Hofmann, the discoverer of LSD, took a dose of that drug and felt that the bike ride home took hours instead of minutes. “Isn’t that incredible, that a drug can change time?” he asks. On his first night as an undergraduate in Cambridge, he witnessed the powers of drugs again when he went drinking with fellow students. Two of them couldn’t stop. “I just watched them transform themselves. One of them started wailing and crying and the other became incredibly hostile.”

During his clinical training, Nutt says he treated many alcoholics but failed “to get anyone interested in how to reduce their addiction to the drug that was harming them.” He set out to answer that question, first in the United Kingdom, later as the chief of the Section of Clinical Science at the U.S. National Institute on Alcohol Abuse and Alcoholism, a job he held for 2 years. Today, he runs the department of neuropsychopharmacology at Imperial College, using modern imaging techniques to see what happens in the brain when people take drugs or develop an addiction.

But his biggest contribution to science, he says, was a discovery he made quite early in his career: that some molecules don’t just block receptors in the brain, but actually have the opposite effect of the molecules that normally stimulate them—and in doing so shut down a brain pathway. Nutt called these molecules contragonists, and he has made a second career out of being a bit of a contragonist himself, trying to calm society’s overexcited responses to the steady stream of alarming news about drugs.

Fictional affliction
In 2009, Nutt published an article in the Journal of Psychopharmacology comparing the harms from ecstasy with those caused by horse riding. Every 10,000th ecstasy pill is likely to hurt someone, he calculated, while an average horse enthusiast can expect a serious accident every 350 hours of riding. The sport, he concluded, was more dangerous than the notorious party drug. That “raises the critical question of why society tolerates—indeed encourages—certain forms of potentially harmful behaviour but not others such as drug use,” he added.

Politicians were not amused, and Nutt’s whimsical reference to a fictional affliction he called equine addiction syndrome, or “equasy,” did not help. In his book Drugs – Without the Hot Air, Nutt provided his account of a phone conversation he had with U.K. Home Secretary Jacqui Smith after the paper was published. (Smith calls it an “embroidered version” of their talk.)

Smith: “You can’t compare harms from a legal activity with an illegal one.”

Nutt: “Why not?”

“Because one’s illegal.”

“Why is it illegal?”

“Because it’s harmful.”

“Don’t we need to compare harms to determine if it should be illegal?”

“You can’t compare harms from a legal activity with an illegal one.”

Nutt says this kind of circular logic crops up again and again when he discusses recreational drugs with politicians. “It’s what we would call ‘splitting’ in psychiatric terms: this primitive, childish way of thinking things are either good or bad,” he says.

He’s often that outspoken. He likens the way drug laws are hampering legitimate scientific research, for instance into medical applications for psychedelic compounds, to the church’s actions against Galileo and Copernicus. When the United Kingdom recently banned khat, a plant containing a stimulant that’s popular among people from the Horn of Africa and the Arabian Peninsula, he compared the decision with banning cats. And he accuses the Russian government of deliberately using alcohol to weaken the opposition. “However miserable they are, however much they hate their government and their country, they will just drink until they kill themselves, so they won’t protest,” he says.

But it’s his stance on cannabis that got him sacked. In early 2009, ignoring advice from Nutt’s advisory council, Smith upgraded cannabis from class C to class B, increasing the maximum penalty for possession from 2 to 5 years in prison. A few months later, Nutt criticized the decision in a public lecture, arguing that “overall, cannabis use does not lead to major health problems” and that tobacco and alcohol were more harmful. When media reported the remarks, Alan Johnson, who succeeded Smith as home secretary in mid-2009, asked him to resign. “He was asked to go because he cannot be both a government adviser and a campaigner against government policy,” Johnson wrote in a letter in The Guardian.

Nutt did not go quietly. With financial help from a young hedge fund manager, Toby Jackson, he set up a rival body, the Independent Scientific Committee on Drugs, “to ensure that the public can access clear, evidence based information on drugs without interference from political or commercial interest.” Politics have skewed not just drug laws but research itself, he argues. “If you want to get money from the U.S. government to work on a drug, you have to prove it damages the brain,” he says.

One of his favorite examples is a paper that Science published in September 2002. The study, led by George Ricaurte at Johns Hopkins University, seemed to show that monkeys given just two or three doses of ecstasy, chemically known as MDMA, developed severe brain damage. The finding suggested that “even individuals who use MDMA on one occasion may be at risk for substantial brain injury,” the authors wrote. The paper received massive media attention, but it was retracted a year later after the authors discovered that they had accidentally injected the animals not with MDMA but with methamphetamine, also known as crystal meth, which was already known to have the effects seen in the monkeys. Nutt says the mistake should have been obvious from the start because the data were “clearly wrong” and “scientifically implausible.” “If that result was true, then kids would have been dropping dead from Parkinson’s,” he says.

Some resent this combative style. “He is a polarizing figure and the drug policy area is polarized enough,” says Jonathan Caulkins, a professor of public policy at Carnegie Mellon University in Pittsburgh, Pennsylvania. But Jürgen Rehm, an epidemiologist at the Centre for Addiction and Mental Health in Toronto, Canada, says Nutt has helped stimulate debates that were long overdue. “You don’t get to be on the front page of The Lancet and The New York Times unless you sharpen your arguments a little bit,” Rehm says. “I can live with that.”

Ranking the drugs
In 2010, Nutt sparked a new firestorm when he published another comparison: a Lancet paper ranking drugs according to the harm they cause. Nutt and other experts scored a long list of drugs on 16 criteria, nine related to the user, such as death from an overdose or wrecked relationships, and seven related to society, such as drug-fueled violence and economic costs. In the end, every drug was given a score between 0 and 100 to indicate its overall harm. Alcohol came out on top, ahead of heroin; mushrooms and ecstasy were at the low end.

Critics said the study’s methodology was flawed because it didn’t address drug interactions and the social context of drug use. “For instance, the number of fatalities caused by excessive alcohol use is going to depend in part on gun control laws,” says Caulkins, who calls the whole idea of expressing drug harm as a single number “embarrassing.”

Caulkins adds that even if a perfect ranking of drug harms were possible, it wouldn’t mean that politicians should put the tightest control measures on the most harmful drugs. Suppose drug A is more harmful to the individual and society than drug B, he says, but impurities in drug A, when illegally produced, can lead to potentially fatal organ failure while they just taste bad in drug B. If you were going to prohibit only one of the two drugs, it should be drug B, he says, even though it causes less harm per se, because criminalizing drug A would lead to a more dangerous product and more deaths. Nutt’s ranking of drugs, he says, is “a pseudoscientific exercise which is trying to take control of the policy process from a technocratic perspective in a way that isn’t even sound.”

Other scientists defended the paper. Using Nutt’s harm scales, “flawed and limited as they may be, would constitute a quantum leap of progress towards evidence-based and more rational drug policy in Canada and elsewhere,” two Canadian drug scientists wrote in Addiction. Regardless of its quality, the paper has been hugely influential, Rehm says. “Everyone in the E.U. knows that paper, whether they like it or not. There is a time before that paper and a time after it appeared.”

Nutt says his comparisons are an essential first step on the way to more evidence-based drug policies that seek to reduce harm rather than to moralize. The best option would be a regulated market for alcohol and all substances less harmful to the user than alcohol, he argues.

That scenario, under which only heroin, crack cocaine, and methamphetamine would remain illegal, seems unlikely to become a reality. But Nutt says he can already see more rational policies taking hold. Recently, Uruguay and the U.S. states of Colorado and Washington legalized the sale of recreational cannabis, going a step further than the Netherlands, which stopped enforcing laws on the sale and possession of small amounts of soft drugs decades ago. Nutt was also happy to read President Barack Obama’s recent comment that cannabis is less harmful than alcohol. “At last, a politician telling the truth,” he says. “I’ll warn him though—I was sacked for saying that.”

New Zealand, meanwhile, passed a law in 2013 that paves the way for newly invented recreational drugs to be sold legally if they have a “low risk” of harming the user. Nutt, who has advised the New Zealand government, is delighted by what he calls a “rational revolution in dealing with recreational drugs.” The main problem now, he says, is establishing new drugs’ risks—which is difficult because New Zealand does not allow them to be tested on animals—and deciding what “low risk” actually means. “I told them the threshold should be if it is safer than alcohol,” he says. “They said: ‘Oh my god, that is going to be far too dangerous.'”

Safer substitute
Nutt agrees that alcohol is now one of the most dangerous drugs on the market—which is why he’s trying to invent a safer substitute. The World Health Organization estimates that alcohol—whose harms range from liver cirrhosis, cancer, and fetal alcohol syndrome to drunk driving and domestic violence—kills about 2.5 million people annually. “When I scan the brains of people with chronic alcohol dependence, many have brains which are more damaged than those of people with Alzheimer’s,” Nutt says.

In a paper published this month in the Journal of Psychopharmacology, Nutt and Rehm summarize the top six interventions that governments should consider to reduce the harms of alcohol, such as minimum prices and restrictions on the places that can sell hard liquor. They also argue that governments should support the development of alternatives. Nutt points to e-cigarettes—devices that heat and vaporize a nicotine solution—as a model. “In theory, electronic cigarettes could save 5 million lives a year. That is more than [the death toll from] AIDS, malaria, tuberculosis, and meningitis put together,” he says. “I would argue that the e-cigarette is going to be the greatest health invention since vaccination.”

Can an alcohol alternative do the same? “I think that idea is utopian,” says Spanagel, the German psychopharmacologist. One reason is that researchers have recently developed a much more complex picture of what ethanol, as chemists call it, actually does. Twenty years ago, they thought that once it reached the brain, alcohol elicited its many effects by infiltrating the membranes of neurons there and changing their properties. “Now we know that’s nonsense. You would have to drink 5 liters of schnapps for that to happen,” Spanagel says.

In fact, scientists have learned that alcohol, like other drugs, interacts with the receptors for certain neurotransmitters. But unlike other drugs, it acts on a wide range of them, including receptors for GABA, NMDA, serotonin, and acetylcholine. That will make it hard to find a substance to emulate most of alcohol’s wanted effects while avoiding the unwanted ones, Spanagel predicts.

Nutt is concentrating on the GABA system—the most important inhibitory system in mammalian brains. Alcohol activates GABA receptors, effectively quieting the brain and leading to the state of relaxation many people seek. Nutt has sampled some compounds that target GABA receptors and was pleasantly surprised. “After exploring one possible compound I was quite relaxed and sleepily inebriated for an hour or so, then within minutes of taking the antidote I was up giving a lecture with no impairment whatsoever,” he wrote in a recent article.

But he wants to go one step further. “We know that different subtypes of GABA mimic different effects of alcohol,” he says. Nutt combed the scientific literature and patents for compounds targeting specific GABA receptors, and, in an as-yet unpublished report that he shared with Science, he identifies several molecules that he says fit the bill. Compounds targeting subtypes of the GABAA receptor called alpha2 and alpha3 are particularly promising, he says. Some of these molecules were dropped as therapeutic drug candidates precisely because they had side effects similar to alcohol intoxication.

Gregg Homanics, an alcohol researcher at the University of Pittsburgh, is skeptical that another substance could mimic all the positive effects of alcohol. “You could come up with a drug that might make you feel good. But is it going to be the same good feeling as alcohol? I doubt that.” Such a drug might have downsides of its own, warns Andreas Heinz, an addiction researcher at Charité University Medicine Berlin. It could still turn out to be addictive or to harm a small proportion of the population. “There is an advantage when you have known drugs for hundreds of years and you know exactly what they do,” he says.

Still, Nutt’s appearance on the BBC radio program attracted new investors, ranging “from Ukrainian brewers to American hedge funds,” he says, and Imperial Innovations, a company that provides technology transfer services, is working with him “to consider a range of options for taking the research forward,” a spokesperson says. “We think we have enough funding now to take a substance all the way to the market,” Nutt says—in fact, he hopes to be able to offer the first cocktails for sale in as little as a year from now.

Even a very good alcohol substitute would face obstacles. Many people won’t forsake drinks they have long known and loved—such as beer, wine, and whiskey—for a new chemical, Spanagel says. The idea will also trigger all kinds of political and regulatory debates, Rehm says. “How will such a new drug be seen? Will you be able to buy it in the supermarket? In the pharmacy? Will society accept it?”

Whatever the outcome, Nutt’s quest for a safer drink has already made people think about alcohol in a new way, Rehm adds. “It’s provocative in the best sense of the word.” Much the same could be said of the scientist who thought it up.

http://www.sciencemag.org/content/343/6170/478.full

Artisanal Beer Brewers Find Growing Niche In Berlin

According to a new study, alcohol can boost your immune system. Researchers vaccinated animals and then gave them access to alcohol. Researchers found that the animals that had consumed alcohol also had faster responses to the vaccines. The researchers hope this study leads to a better understanding of how the immune system works, and how to improve its ability to respond to vaccines and infections. Moderate alcohol consumption has long been associated with a lower mortality rate.

Moderate alcohol consumption boosts your immune system while chronic alcohol consumption leads to a suppressed vaccine response. The difference between moderate and chronic is defined by the National Institute on Alcohol Abuse and Alcoholism. They define moderate as no more than four drinks on a single day and no more than 14 in a week for men. For women, it is defined as no more than three drinks on a single day and no more than seven in a week.

The study was published in the journal Vaccine.

http://www.sciencedirect.com/science/article/pii/S0264410X13014734

sprite_620x350

Chinese researchers have found that Sprite may actually be one of the best options for getting over a hangover.

Rather than focusing on a cure, researchers at Sun Yat-Sen University in Guangzhou looked at how a hangover could be prevented before it even started. To do this, they looked at the metabolic processes that the body goes through when drinking alcohol. First, the ethanol in alcoholic drinks gets metabolized by an enzyme known as alcohol dehydrogenase (ADH) into acetaldehyde. Acetaldehyde is believed to be the real cause of alcohol-related effects, including hangovers. It’s then metabolized into acetate by the enzyme aldehyde dehydrogenase (ALDH). Contrary to acetaldehyde’s effects, acetate could be responsible for some of alcohol’s health benefits, the researchers said.

Knowing these processes, the researchers tested 57 different drinks, including herbal infusions, teas, and carbonated beverages, and gauged their effects on ADH and ALDH. They found that every drink had a different effect. For example, an herbal infusion with huo ma ren seeds, also known as hemp seeds, increased the ADH process and inhibited the ALDH process, meaning that the adverse effects of drinking would linger for a longer time. Conversely, Sprite, known as Xue bi, was among the drinks that increased the ALDH process, causing acetaldehyde to break down at a faster pace, and reducing the duration of alcohol-related effects on the body.

“These results are a reminder that herbal and other supplements can have pharmacological activities that both harm and benefit our health,” Edzard Ernst, an expert in medicinal science at the University of Exeter in the U.K., told Chemistry World about the study. But he also noted that the tests should be done over, in living organisms, before the tests are regarded as conclusive. The researchers plan to do this next.

Sprite is also a more reasonable “cure” for the hangover. One recent fad had people drinking Pedialyte, the baby formula, in hopes of replacing lost vitamins and minerals from drinking. Still, going even further, some Vietnamese millionaires felt that the keratin in rhinoceros horns, which costs as much as gold per ounce, was the answer to their morning-after woes.

Source: Li S, Gan L, Li S, et al. Effects of Herbal Infusion, Tea and Carbonated Beverage on Alcohol Dehydrogenase and Aldehyde Dehydrogenase Activities. Food & Function. 2013.

http://www.medicaldaily.com/sprite-could-cure-your-hangover-beverage-shortens-duration-alcohols-damaging-metabolic-process

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When a 61-year-old Texas man came into an emergency room claiming he was dizzy and was found to have a blood alcohol concentration of 0.37 percent, doctors assumed he was drunk. Despite the fact the man claimed he hadn’t consumed alcohol that day, most doctors still thought he was a “closet drinker,” NPR reported.

It turned out that those medical professionals were wrong: the man had “auto-brewery syndrome.” His stomach contained so much yeast that he was making his own in-house brew, literally. Before he was diagnosed with the syndrome, the patient’s wife — who was a nurse — was so concerned with her husband’s constantly drunk condition that she had him regularly tested with a Breathalyzer. He would record numbers as high as 0.33 to 0.4 percent, considerably higher than the U.S. legal driving limit of 0.08 percent.

Barbara Cordell, the dean of nursing at Panola College in Carthage, Texas, and Dr. Justin McCarthy, a gastroenterologist in Lubbock, Texas, decided to figure out what was really going on.

“He would get drunk out of the blue — on a Sunday morning after being at church, or really, just anytime,” Cordell told NPR.

After isolating the patient for 24 hours and making sure there was no alcohol or sugar available, the team continued to check his blood alcohol level. The levels were as high as 0.12 percent without any alcohol consumption. The doctors then realized that he must have been infected with high levels Saccharomyces cerevisiae, a kind of yeast that is used in alcohol fermentation and baking. They suspected that because the patient had been put on antibiotics following surgery for a broken foot in 2004, the medications might have killed all his gut bacteria. This allowed the yeast to thrive in his body.

The Environmental Protection Agency said the organism is not considered to be a pathogen, and some people take large quantities of the yeast daily as part of a “health food” diet.”No one takes potential danger from Saccharomyces cerevesiae seriously,” Dr. Michael D. Gershon, a professor in the department of pathology and cell biology at Columbia University in New York, told CBSNews.com.

Gershon added that the yeast is so non-threatening that it is often used by researchers in studies without any additional precautions.

Interviews revealed the man ate a lot of carbohydrates. That meant each time the patient ate something with starch, the high amounts of yeast in his body turned the sugars into ethanol or ethyl alcohol, which made him drunk from the inside. To cure his illness, the patient was placed on a low-carbohydrate diet and prescribed antifungal medication to get rid of the excess yeast.

His case study was published in the International Journal of Clinical Medicine earlier this summer.

The researchers acknowledge that this condition is extremely rare. Only a handful of cases have been reported in the last three decades, including a 13-year-old girl with short gut syndrome who would get drunk if she ate carbohydrates. Another 3-year-old with the same condition became drunk when she had a fruit drink high in carbohydrates.

“This is a rare syndrome but should be recognized because of the social implications such as loss of job, relationship difficulties, stigma, and even possible arrest and incarceration,” the authors noted. “It would behoove health care providers to listen more carefully to the intoxicated patient who denies ingesting alcohol.”

Thanks to Mike Moore for bringing this to the attention of the It’s Interesting community.