Dr. David Nutt on Alcohol

Rebutting industry myths.

A couple of years ago, the European Alcohol Policy Alliance, known as EuroCare, put together a brochure addressing the common messages the liquor industry attempts to drive home through its heavy spending on advertising. The messages are not just designed to sell product, but also to influence alcohol policy at the political level. According to EuroCare, the “industry”—the alcohol and tobacco companies—“has traditionally worked closely together, sharing information and concerns about regulation. They have used similar arguments to defend their products in order to prevent or delay restrictions being placed on them.”

I wrote a blog post on EuroCare’s list of alcohol untruths called “7 Myths the Alcohol Industry Wants You to Believe." Here they are:

Message 1: Consuming alcohol is normal, common, healthy, and very responsible.

Message 2: The damage done by alcohol is caused by a small group of deviants who cannot handle alcohol.

Message 3: Normal adult non-drinkers do not, in fact, exist

Message 4: Ignore the fact that alcohol is a harmful and addictive chemical substance (ethanol) for the body.

Message 5: Alcohol problems can only be solved when all parties work together.

Message 6: Alcohol marketing is not harmful. It is simply intended to assist the consumer in selecting a certain product or brand.

Message 7: Education about responsible use is the best method to protect society from alcohol problems.

Recently, I ran across a great response to these same 7 myths by Dr. David Nutt, the British psychiatrist perhaps best known in the states as the scientist who got fired a few years ago from his post on the government’s Advisory Council on the Misuse of Drugs. Nutt’s primary sin was to suggest that, on a straightforward calculation of risks and harms, horseback riding was probably a more dangerous activity than taking the drug Ecstasy. The Home Secretary at the time insisted that you couldn’t compare a legal activity to an illegal one, or something like that, and Nutt compounded his sins by suggesting that marijuana was a safer drug than alcohol. British politicians took a serious dislike to him, the more so since most of the published medical science was on his side. After the dust settled, Nutt was one of the primary founders of the Independent Scientific Committee on Drugs (ISCD), formed to offer alternative views on drugs and addiction grounded in science.

Anyway, in his book, Drugs Without the Hot Air, Nutt has his own responses to the 7 Myths, which I excerpt here:

1. Consuming Alcohol is Normal: It’s normal, so long as you have the “normal” high-activity variant of the ALDH2 enzyme. If you don’t have that form of the enzyme, Nutt reminds his readers, as many Asians and Aleuts do not, then alcohol will affect you quite non-normally through the so-called alcohol flush reaction. Moreover, many cultures and societies unfamiliar with its effects “suffer hugely when new types of alcohol appear, particularly if they are aggressively marketed.”

2. Alcohol damage is caused by a small group of deviants: According to Dr. Nutt, statistics show that “millions of people, NOT a tiny minority, suffer harm from their own alcohol consumption, or cause harm to others…. It is the everyday drinking of people who have come to see alcohol as an essential part of life rather than the luxury it used to be, that has created a spike in cancers and stomach problems, and will see liver disease match heart disease as the leading cause of death in the UK by 2020.”

3. Normal adult non-drinkers do not exist: The alcohol industry is forever reminding politicians of how unpopular alcohol restrictions are to the voting populace. “The existence of non-drinkers obviously threatens this portrayal of society, so the industry tends to dismiss them as having something wrong with them. While some teetotalers are recovering alcoholics, many others have made a positive choice not to drink.” And there are others, I would add, often referred to as “sick” teetotalers, who have quit drinking for medical reasons unrelated to alcoholism.

4. Ignore alcohol’s harm to the body: Nutt reminds us that “there is no other drug which is so damaging to so many different organ systems in the body…. Most other drugs cause damage primarily in one or two areas—heart problems from cocaine, or urinary tract problems from ketamine. Alcohol is harmful almost everywhere.”

5. Alcohol problems can be solved when everybody works together: “In practice, what the industry means by ‘working together’ is bring in voluntary codes rather than statutory regulation—solving problems through rules that the industry CHOOSES to comply with, rather than laws which they MUST comply with.”

6. Alcohol marketing is intended to assist consumers in selecting products: Specifically, 800 million British pounds every year for advertising and promotion, according to Nutt. That’s just the kind of civic-minded bunch those alcohol sellers are. The reality, of course is that “marketing communications do have a marked effect on consumption…. All this further entrenches the false division between alcohol and illegal drugs, persuades people that consuming alcohol is safe, and makes realistic discussions of the harm alcohol causes very difficult.”

7. Education about responsible use is the best approach: “It is useful for the drinks industry,” Nutt explains, “to emphasize the value of education, because it takes the focus off regulation…. There is also extensive evidence gathered by the WHO from around the world, showing that merely providing information and education without bringing in other policy measures doesn’t change people’s drinking behavior.”

As I wrote in my original post: Who could be against the promotion of responsible alcohol use? Irresponsible zealots and deviants, that’s who. Why should all of us happy drinkers be made to suffer for the sins of a few rotten apples?

Indeed, all of the messages, overtly or covertly, send the same signal: You should drink more. It’s good for you.

Graphics Credit: http://www.holyrood.com/2011/04/at-what-price/

Reward and Punish: Say Hello to Dopamine’s Leetle Friend

  Dopamine recruits a helper to track drug rewards.

Ah, dopamine. Whenever it seems like researchers have finally gotten a bead on how that tricky molecule modulates pleasure and reward, and the role it plays in the process of drug and alcohol addiction, along come new findings that rearrange its role, deepening and complicating our understanding of brain function.

We know that the ultimate site of dopamine activity caused by drugs is the ventral tegmental area, or VTA, and an associated structure, the nucleus accumbens. But dopamine neurons in the VTA actually perform two distinct functions. They discriminate acutely between the expectation of reward, and the actual reward itself. Pavlov showed how these dual functions are linked, but the manner in which dopamine neurons computed and then dealt with the differences between expectation and reward—a controversial concept known as reward prediction error—was not well understood.

We all know about reward and punishment, however. Years ago, behaviorism’s emphasis on positive and negative reinforcement demonstrated the strong connection between reward, punishment, and learning. As Michael Bozarth wrote in “Pleasure Systems in the Brain,” addictive drugs “pharmacologically activate brain reward mechanisms involved in the control of normal behavior. Thus, addictive drugs may be used as tools to study brain mechanisms involved in normal motivational and reward processes.”

But how does the evolutionary pursuit of pleasure or avoidance of punishment that guarantees the survival of an organism—fighting, fleeing, feeding, and… fornicating, in the well-known “4-F” configuration—become a pathological reversal of this function? To begin with, as Bozarth writes, “the direct chemical activation of these reward pathways does not in itself represent any severe departure from the normal control reward systems exert over behavior…. Simple activation of brain reward systems does not constitute addiction!”

What does, then? Bozarth believes addiction results from “motivational toxicity,” defined as deterioration in the “ability of normal rewards to govern behavior.” In an impaired reward system, “natural” rewards don’t alter dopamine function as strongly as drug rewards. “Direct pharmacological activation of a reward system dominates the organism’s motivational hierarchy at the expense of other rewards that promote survival,” Bozarth writes. The result? Drug addicts who prefer, say, methamphetamine to food.

How does an addict’s mind become so addled that the next hit takes precedence over the next meal? A group of Harvard-based researchers, writing in Nature, thinks it may have a handle on how the brain calculates reward expectations, and how those calculations go awry in the case of heavy drug and alcohol use.

The dopamine system somehow calculates the results of both failed and fulfilled expectations of reward, and uses that data in future situations. Cellular biologists, with some exceptions, believe that dopamine neurons effectively signal some rather complicated discrepancies between expected and actual rewards. Dopaminergic neurons were, in effect, computing reward prediction error, according to the theory. They were encoding expectation, which spiked when the reward was better than expected, and fell when the reward was less than expected. As Scicurious wrote at her blog, Neurotic Physiology “If you can’t predict where and when you’re going to get food, shelter, or sex in response to specific stimuli, you’re going to be a very hungry, chilly and undersexed organism.” (See her excellent and very readable post on dopamine and reward prediction HERE. )

But nobody knew how this calculation was performed at the cellular level.

Enter research mice.

As it turns out, dopamine is not the whole story. (A single neurotransmitter rarely is.) Dopaminergic neurons account for only about 55-65% of total neurons on the VTA. The rest? Mostly neurons for GABA, the inhibitory transmitter. “Many addictive drugs inhibit VTA GABAergic neurons,” the researchers note, “which increases dopamine release (called disinhibition), a potential mechanism for reinforcing the effects of these drugs.” By inhibiting the inhibitor, so to speak, addictive drugs increase the dopamine buzz factor.

The researchers used two strains of genetically altered mice, one optimized for measuring dopamine, the other for measuring GABA. The scientists conditioned mice using odor cues, and offered four possible outcomes: big reward, small reward, nothing, or punishment (puff of air to the animal’s face). Throughout the conditioning and testing, the researchers recorded the activity of neurons in the ventral tegmental area. They found plenty of neurons with atypical firing patterns. These neurons, in response to reward-predicting odors, showed “persistent excitation” during the delay before the reward. Others showed “persistent inhibition” to reward-predicting odors.

It took a good deal of sorting out, and conclusions are still tentative, but eventually the investigators believed that VTA dopamine neurons managed to detect the discrepancy between expected and actual outcomes by recruiting GABA neurons to aid in the dendritic computation. This mechanism may play a critical role in optimal learning, the researchers argue.

Furthermore, the authors believe that “inhibition of GABAergic neurons by addictive drugs could lead to sustained reward prediction error even after the learned effects of drug intake are well established.” Because alcohol and other addictive drugs disrupt GABA levels in the brain’s reward circuitry, the mechanism for evaluating expectation and reward is compromised. GABA, dopamine’s partner in the enterprise, isn’t contributing properly. The ability to learn from experience and to accurately gauge the likelihood of reward, so famously compromised in active addiction, may be the result of this GABA disruption.

Naoshige Uchida, associate professor of molecular and cellular biology at Harvard, and one of the authors of the Nature paper, said in a press release that until now, “no one knew how these GABA neurons were involved in the reward and punishment cycle. What we believe is happening is that they are inhibiting the dopamine neurons, so the two are working together to make the reward error computation.” Apparently, the firing of dopamine neurons in the VTA signals an unexpected reward—but the firing of GABA neurons signals an expected reward. Working together, GABA neurons aid dopamine neurons in calculating reward prediction error.

In other words, if you inhibit GABA neurons through heavy drug use, you screw up a very intricate dopamine feedback loop. When faced with a reward prediction error, such as drug tolerance—a good example of reward not meeting expectations—addicts will continue taking the drug. This seems nonsensical. If the drug no longer works to produce pleasure like it used to do, then why continue to take it? It may be because dopamine-active brain circuits are no longer accurately computing reward prediction errors. Not even close. The research suggests that an addict’s brain no longer registers negative responses to drugs as reward errors. Instead, all that remains is the reinforcing signals from the dopamine neurons: Get more drugs.

[Tip of the hat to Eric Barker (@bakadesuyo) for bringing this study to my attention.]

Cohen, J., Haesler, S., Vong, L., Lowell, B., & Uchida, N. (2012). Neuron-type-specific signals for reward and punishment in the ventral tegmental area Nature DOI: 10.1038/nature10754

Photo Credit: http://www.zazzle.com 

U.S. Leads World in Prescription Drug Use

It’s complicated.

Wait, wait, it’s a good thing. Mostly.  Or maybe.

While the headline may suggest a story that is either shocking or self-evident, depending upon your point of view, the British study it refers to is based on the level of uptake of prescription drugs for 14 different diseases in 14 different countries. It is not a study of prescription drug abuse, but rather a look at legitimate medical treatment of diseases like cancer, multiple sclerosis, and Hepatitis C.

Measured by volume of use per capita, Americans consume more prescription drugs than any other country.  We’re number one! They can’t touch us! (Spain ranked second, and France was third. New Zealand, Sweden, and Germany ranked at the bottom.)

Seriously, though, we mostly knew that about America already. Another way to look at these numbers is to turn the question around: Why, for example, is the UK in 10th place for cancer drug usage, despite near-universal health coverage? Why aren’t other countries dispensing larger amounts of recognized medications for such diseases as Hepatitis C and rheumatoid arthritis? So, one question the report seems to raise is: why do other developed countries have worse access to prescription drugs than we do?

UK Health Secretary Andrew Lansley, quoted in an article for Nature News, stressed that “high usage does not necessarily equal good performance, nor does low usage indicate a failing.” At the same time, however, Lansley announced a new government fund of 50 million English pounds  “to increase access to cancer drugs.”

With those caveats in mind, we find that the report concludes… well, in the end, the report acknowledges the wide variations in international usage, but concludes that “there does not appear to be a consistent pattern between countries or for different disease areas or categories of drug.”  The study group did not find any uniform patterns that held across drug categories or disease regions. In fact, the report invites interested stakeholders to submit their best thoughts on the matter to internationaldruguse@dh.gsi.gov.uk

Despite this absence of firm conclusions or hypotheses, the report does manage to note some common themes:

-- “Differences in health spending and systems do not appear to be strong determinants of usage.” But even here, the report goes on to offer some thoughts on the dominance of the U.S. “For example, ‘supplier-induced demand’ was felt to be a greater issue in the USA because of the payment structures in that country: where suppliers can charge more for delivering a particular treatment, this may provide perverse incentives to prescribe those drugs.” And: “The majority of countries reviewed provide (almost) universal coverage, with residence in the given country being the most common basis for entitlement to healthcare. The USA is the only country not offering universal access to healthcare; entitlement to publicly funded services is dependent on certain conditions…”

--“Clinical culture and attitudes towards treatment remain important determinants in levels of uptake.” The same reasoning would apply to the U.S., as psychotherapists have struggled for a foothold in the brave new world of medications for diseases with strong mental and emotional components.

--“A country that spends more on healthcare or a country which operates few controls on prescribing could be expected to use more drugs.” But I thought the report said that differences in health spending and systems didn’t make any difference…

Here is the problem with attempts at surveys of this kind. (Departments at the United Nations do a lot of them, as do individual countries.) Mike Richards, the UK’s National Cancer Director, compiled the report--“Extent and causes of international variations in drug usage”—and further qualified the findings: “For some disease areas, high usage may be a sign of weaknesses at other points in the care pathway and low usage a sign of effective disease prevention.”

It is similar to the problem of quantifying addiction. The amount of addictive drug consumed often tells us very little about the problem, or the prospects for amelioration.  However, in a survey like this one, I think coming out on the top is, on balance, better than coming out on the bottom.

A High Old Time in Rhode Island

Feds release annual drug numbers.

[Map: Illicit drug use other than marijuana in the past month among people aged 12 or older based on 2007-2008 figures.]→

It’s time again for the government’s annual state-by-state survey of drug use in America.  Assembled by the Substance Abuse and Mental Health Services Administration (SAMHSA), the yearly numbers are argued over by states and agencies competing for federal health and medicine dollars. In this year’s sweepstakes, dark horse Rhode Island upset the reigning champion, the District of Columbia, as the state with the highest number of monthly users of illicit drugs other than marijuana. 

Usage figures were based on numbers compiled in 2007 and 2008. Overall, eight per cent of Americans aged 12 or older used an illicit drug other than pot in the prior month, essentially unchanged from last year’s report based on 2006-2007 figures. Using the percentage of monthly users as a yardstick, other states in the highest group included Arizona, Arkansas, Kentucky, Nevada, Oklahoma, Oregon, Colorado, and Tennessee. Among the states in the lowest group were Maine, Minnesota, Nebraska, Mississippi, New Jersey, the Dakotas, Wyoming—and the lowest of them all--Iowa.

According to SAMSHA, five states showed significant changes compared to a year ago. Iowa, Louisiana and Wyoming showed marked decreases, while usage of drugs other than marijuana in Hawaii and Oregon increased.

As for alcohol, SAMSHA pegs the national rate of alcohol use among people age 12 or older at 51.4 per cent. The highest rate of alcohol use was found in the 18-25 age group (big surprise there). This year the state drinking trophy goes to New Hampshire, with Utah coming in dead last, as usual. High-drinking states include Colorado, Massachusetts, New Hampshire, Rhode Island, Vermont, and Wisconsin. (What is it with New England?)

Interestingly, eight out of the ten lowest states for drinking are found in the South: Alabama, Arkansas, North Carolina, and Virginia, among others. However, the South makes up for it in tobacco usage. States with the highest prevalence of tobacco use were Arkansas, Kentucky, Ohio, West Virginia—and, okay, Wyoming. The state with the fewest smokers? Do you have to ask? Utah. The national smoking average still hovers around 24 per cent.

For a longer view, SAMSHA compared the current study figures with numbers compiled in 2002-2003. Iowa, Missouri, and Pennsylvania showed significant drops for drugs other than marijuana. Only Rhode Island and Tennessee showed marked increases.

Tennessee also showed increases in marijuana usage, while less pot was smoked in Florida, Iowa, Missouri, and Pennsylvania. Overall, usage decreased slightly compared to the 2002-2003 period.

The most meaningful change compared to the 2002-2003 period was a 2.5 per cent decrease in the use of cocaine among people 12 or older. Nationwide, the percentage of alcohol use remained almost identical (51.4 per cent).

Photo Credit: SAMSHA

Liking It Vs. Wanting It

The Joylessness of Drug Addiction.

Hedonism, the pursuit of pleasure for its own sake, is not really the answer to the riddle of drug addiction. The pursuit of pleasure does not explain why so many addicts insist that they abuse drugs in a never-ending attempt to feel normal. With compulsive use and overuse, much of the pleasure eventually leaches out of the primary dysphoria-relieving drug experience. This does not, however, put an end to the drug-seeking behavior. Far from it. This is the point at which non-addicts tend to believe that there is no longer an excuse—the pleasure has dribbled away, the thrill is gone—but even when addicts aren’t getting the full feel-good benefits of the habit, they continue to use.

And now we know why. Any sufficiently powerful receptor-active drug is, in its way, fooling Mother Nature. This deceit means, in a sense, that all such drugs are illicit. They are not natural, however organic they may be. Yet, the human drive to use them is all-pervasive. We have no real built-in immunity to drugs that directly target specific receptors in the limbic and cortical pleasure pathways. 

The act of “liking” something is controlled by the forebrain and brain stem. If you receive a pleasant reward, your reaction is to “like” it. If, however, you are anticipating a reward, and are, in fact, engaging in behaviors motivated by that anticipation, it can be said that you “want” it. The wholly different act of wanting something strongly is a mesolimbic dopamine-serotonin phenomenon. We like to receive gifts, for example, but we want food, sex, and drugs. As Nesse and Berridge  put it, “The ‘liking’ system is activated by receiving the reward, while the ‘wanting’ system anticipates reward and motivates instrumental behaviors. When these two systems are exposed to drugs, the “wanting” system motivates persistent pursuit of drugs that no longer give pleasure, thus offering an explanation for a core paradox in addiction.” 

The absence of pleasure does not mean the end of compulsive drug use. Researchers are beginning to understand how certain drugs can be so alluring as to defeat the strongest of people and the best of intentions. It certainly does not eliminate the pain of drug hunger, of craving, to know that it is physically correlated with “a pathological overactivity of mesolimbic dopamine function,” combined, perhaps, with “increased secretion of glucocorticoids.” For such a wide variety of drugs, exhibiting a wide variety of effects, the withdrawal symptoms, while varying by degree, are nonetheless quite similar. The key, as we have seen, is that the areas of the brain that control “wanting” become sensitized by reward pathway drugs.

Under the biochemical paradigm, a runaway appetite for non-stop stimulation of the reward pathway is a prescription for disaster. The harm is physical, behavioral, and psychological—as are the symptoms. Peer pressure, disciplinary difficulties, contempt for authority—none of these conditions is necessary for drug addiction to blossom. What the drug itself does to people who are biologically vulnerable is enough. No further inducements are required. 

Graphics Credit: http://rmcute.multiply.com/

Just for Fun: Simple Science Facts

Back to basics.

[Guest post adapted from 50 Simple Science Facts Everyone Should Know (But Doesn’t), from the folks at X-Ray Technician Schools.]

While obviously not everyone remains ignorant of the realities behind the myths, it is the sad truth that many of the following facts remain entirely obscured in the common consciousness – victims of myth and misconception in spite of reliable evidence to the contrary:

--Eating poppy seeds will not always result in a failed drug test. : The common myth about eating poppy seeds can lead to failing a drug test has a solid foundation in reality, as heroin, morphine, codeine, and other opiates are created from the plants. But Indiana University sheds some light on the reality of the situation, pointing out that only the seeds of opiate poppies cause false positives. For those who have eaten the offending poppyseeds, however, there are ways to determine whether or not the opiate traces come from narcotics or a harmless bagel.

--Do not mix ammonia and bleach together. : While death does not generally factor into the equation, blending ammonia and bleach together releases extremely harmful chlorine and other noxious gases that can cause serious damages to the lungs and brain – if not outright kill, of course. The State of New Jersey provides more details on using these cleansers safely.

--Acid into water, never water into acid. : The reliable mnemonic relating the procedure to A&W Root Beer helps students and chemists alike remember that the opposite effect may result in painful or disfiguring chemical burns. University of Oregon has more information on this and other lab safety tips.

--What goes up, must come down. : Anyone shooting a bullet or other dangerous projectile straight into the air ought to think towards one major aspect of Newton’s Universal Law of Gravitation, as explained by the University of Tennessee at Knoxville.

--Lightning can actually strike the same place twice. : Information on lightning striking the same location multiple times abounds online, but no research acts as the most compelling evidence to the same extent as NASA’s exhaustive testing of the myth at hand. Not only can it hit a target more than once, but the likelihood of it happening ended up being 45% higher than anticipated.

--Shaving does not cause thicker, darker hair. : Mayo Clinic weighs in on the myth that shaving directly causes hair to grow back thicker and darker, providing a much-needed dose of reality to a concerned populace. Lawrence E. Gibson, M.D. sheds light on how genetics determine hair structure and the ways in which the perception of coarser, darker strands initially came into play.

--The “5 second rule” is a fallacy. : Popular schoolyard mantras dictate that any food dropped on the floor fails to pick up microbes within the first 5 seconds. Paul Dawson, a food scientist at Clemson University, discovered that bacteria climbs onto food particles immediately upon contact and thus dispelled this eerily common myth.

--There is actually gravity in space. : Northwestern University lays to rest the general claim of zero gravity in outer space by explaining how its influence relates to distance. Every entity in the universe is actually subjected to some degree of gravitational pull, no matter its location.

Photo Credit: www.worldsciencefestival.com

The Nucleus Accumbens

Final destination for addictive drugs.

The release of dopamine and serotonin in the nucleus accumbens lies at the root of active drug addiction. The pattern of neural firing that results from this surge of neurotransmitters is the “high.” It is the chemical essence of what it means to be addicted. Part of the medial forebrain bundle (MFB), which mediates punishment and reward, the nucleus accumbens is the ultimate target for the dopamine released by the ingestion of cocaine, for example.

The release of dopamine and serotonin in the nucleus accumbens appears to be the final destination of the reward pathway—the last act in the pleasure play. If you think about a drug, take a drug, or crave a drug, you are lighting up the nucleus accumbens with a surge of electrochemical activity. These are essentially the same pathways that regulate our food and water-seeking behavior. By directly or indirectly influencing the molecules of pleasure, drugs and alcohol trigger key neurochemical events that are central to our feelings of both reward and disappointment. In this sense, the reward pathway is a route to both pleasure and pain.

Alcohol, heroin, cigarettes, and other drugs caused a surge of dopamine production, which is then released onto the nucleus accumbens. The result:  Pleasure. When scientists pipe a dopamine-mimicking substance into the nucleus accumbens, targeting dopamine D2 receptors, withdrawal symptoms are blocked in morphine-addicted rats. Similarly, when scientists block dopamine receptors in the accumbens, the morphine-dependent rats exhibit withdrawal symptoms.

When you knock out large slices of the nucleus accumbens, animals no longer want the drugs. So, one cure for addiction has been discovered already—but surgically removing chunks of the midbrain just won’t do, of course.

Dopamine is more than a primary pleasure chemical—a “happy hormone,” as it has been called. Dopamine is also the key molecule involved in the memory of pleasurable acts. Dopamine is part of the reason why we remember how much we liked getting high yesterday. The nucleus accumbens (also known as the ventral striatum) seems to be involved in modulating the emotional strength of the signals originating in the hippocampus. This implicates the hippocampus in relapse, even though this area of the brain does not light up as strongly during actual episodes of craving.

The fact that we know all this is nothing short of amazing, but it is part of a larger perspective afforded by the insights of contemporary neurobiology. We know, for example, that the emotion of fear arises, in large part, through chemical changes in a peanut-sized limbic organ called the amygdala. Does this information make fear any less, shall we say, fearful? It merely locates the substrate upon which the sensation of fear is built.

Studies of the nucleus accumbens have demonstrated abnormal firing rates in scanned addicts who were deep into an episode of craving. The craving for a reward denied causes dopamine levels in the nucleus accumbens to crash dramatically, as they do when users go off drugs. Dopamine, serotonin, and norepinephrine activity soars just as dramatically when a drug user relieves withdrawal symptoms by relapsing. Drug hunger in abstinent addicts is not all in the head, or strictly psychological. Craving has a biological basis.  

Finding a way to override serotonin- and dopamine-mediated mid-brain commands is the essential key to recovery from addiction. One of the aims of a biological understanding of addiction is to tease out the mechanisms by which the reinforcing effects of addictive drugs become transformed into long-term adaptive changes in the brain.

Graphics credit: http://thebrain.mcgill.ca/

Adapted from The Chemical Carousel: What Science Tells Us About Beating Addiction by Dirk Hanson © 2008.