The Year in Drugs

Top Posts at Addiction Inbox.

By the look of it, readers had marijuana on their minds in 2012. Of the posts at Addiction Inbox with the highest number of page views, an overwhelming majority are concerned with marijuana, and specifically, with marijuana addiction, withdrawal, and brain chemistry. Of the 9 most heavily trafficked posts of the year, only one involved alcohol. Readers were also interested in the safety of e-cigarettes, and the mysteries of neurotransmitters like serotonin and dopamine. Happily, all the top posts were patently science-oriented articles.

See you in the New Year.

•  Marijuana Withdrawal

For Some Users, Cannabis Can Be Fiercely Addictive.

For a minority of marijuana users, commonly estimated at 10 per cent, the use of pot can become uncontrollable, as with any other addictive drug. Addiction to marijuana is frequently submerged in the welter of polyaddictions common to active addicts. The withdrawal rigors of, say, alcohol or heroin tend to drown out the subtler, more psychological manifestations of cannabis withdrawal.

•  Serotonin and Dopamine: A Primer

The Molecules of Reward

Serotonin and dopamine are part of a group of compounds called biogenic amines. In addition to serotonin and dopamine, the amines include noradrenaline, acetylcholine, and histamine. This class of chemical messengers is produced, in turn, from basic amino acids like tyrosine, tryptophan, and choline.

•  Marijuana Fact and Fiction

Why cannabis research is a good idea.

There is little doubt among responsible researchers that marijuana--although it is addictive for some people--is sometimes a clinically useful drug. However, there is little incentive for commercial pharmaceutical houses to pursue research on the cannabis plant itself, since they cannot patent it.

• Anandamide: The Brain’s Own Marijuana

Anxiety and the THC receptor.

Several years ago, molecular biologists identified the elusive brain receptor where THC, the active ingredient in marijuana, did its work. Shortly after that discovery, researchers at Hebrew University in Jerusalem identified the body’s own form of THC, which sticks to the same receptors, in pulverized pig brains.

•  The Mysteries of the Blunt

Why do so many smokers combine tobacco with marijuana?

People who smoke a combination of tobacco and marijuana, a common practice overseas for years, and increasingly popular here in the form of “blunts,” may be reacting to ResearchBlogging.orgsome unidentified mechanism that links the two drugs. Researchers believe such smokers would be well advised to consider giving up both drugs at once, rather than one at a time, according to an upcoming study in the journal Addiction.

•  Are E-Cigarettes a Good Idea or a Bad Idea?

A group of nicotine researchers argue for an alternative.

Electronic cigarettes are here to stay. If you're not familiar with them, e-cigarettes are designed to look exactly like conventional cigarettes, but they use batteries to convert liquid nicotine into a fine, heated mist that is absorbed by the lungs. Last summer, even though the FDA insisted on referring to e-cigarettes as “untested drug delivery systems,” Dr. Neal Benowitz of the University of California in San Francisco--a prominent nicotine researcher for many years--called e-cigarettes “an advancement that the field has been waiting for.”

•  Cannabis Receptors and the “Runner’s High”

Maybe it isn't endorphins after all.

A perennial favorite, the runner’s high post shows what long-distance running and marijuana smoking have in common. Quite possibly, more than you’d think. A growing body of research suggests that the runner’s high and the cannabis high are more similar than previously imagined….Endocannabinoids—the body’s internal cannabis—“seem to contribute to the motivational aspects of voluntary running in rodents.” Knockout mice lacking the cannabinioid CB1 receptor, it turns out, spend less time wheel running than normal mice. 

• Topamax for Alcoholism: A Closer Look

Epilepsy drug gains ground, draws fire as newest anti-craving pill.

A drug for seizure disorders and migraines continues to show promise as an anti-craving drug for alcoholism, the third leading cause of death in America, the Journal of the American Medical Association (JAMA) reported in its current issue.

•  Is Marijuana Addictive?

The argument continues.

Marijuana may not be a life-threatening drug, but is it an addictive one?
There is little evidence in animal models for tolerance and withdrawal, the classic determinants of addiction. For at least four decades, million of Americans have used marijuana without clear evidence of a withdrawal syndrome. Most recreational marijuana users find that too much pot in one day makes them lethargic and uncomfortable. Self-proclaimed marijuana addicts, on the other hand, report that pot energizes them, calms them down when they are nervous, or otherwise allows them to function normally.


Graphics Credit:  http://1.bp.blogspot.com (Creative Commons)

A Six-Pack of Prior Posts

Don’t fear the chemistry. 

This isn’t a top 10 list, just a compilation of five previous posts here at Addiction Inbox that have continued to draw reader interest since they were first published. If there is a theme running through this set, it is neurochemistry at its most basic level. Take a look, if any of the subjects interests you. (My most popular post of all, on Marijuana Withdrawal, has turned into a self-help message board. I note it here, but leave it off the list, as it has become a blog of its own for all practical purposes.)
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1) Don’t let anyone tell you that the basic notions involved in neurotransmitter action in the brain are over everyone’s head. This post about serotonin and dopamine basics has always been popular, partly because serotonin and dopamine have gone from obscure abstractions to pop buzzwords. But I think it also shows a growing awareness of brain science and its real-world applications among interested readers.

“…. Addictive drugs have molecules that are the right shape for the amine receptors. Drugs like LSD and Ecstasy target serotonin systems. Serotonin systems control feeding and sleeping behaviors in living creatures from slugs to chimps. Serotonin, also known as 5-HT, occurs in nuts, fruit, and snake venom. It is found in the intestinal walls, large blood vessels, and the central nervous system of most vertebrates. The body normally synthesizes 5-hydroxytryptamine, as serotonin is formally known, from tryptophan in the diet….”

Serotonin and Dopamine: A primer on the molecules of reward
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2) Continuing on the chemistry theme, this post on anandamide, the brain’s own form of internal marijuana, has garnered steady attention since 2008. It may be coincidental, but the post also makes mention of serotonin and dopamine.

“…Several years ago, molecular biologists identified the elusive brain receptor where THC, the active ingredient in marijuana, did its work. Shortly after that discovery, researchers at Hebrew University in Jerusalem identified the body’s own form of THC, which sticks to the same receptors, in pulverized pig brains. They christened the internally manufactured substance “anandamide,” after the Sanskrit ananda, or bliss…”

Anandamide, the Brain’s Own Marijuana: Anxiety and the THC receptor.
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3) Interest in the anti-craving drug Topamax, an anti-seizure medication used to treat alcoholism, remains strong with blog readers, although the drug has not become the universal blockbuster many advocates had hoped.

“…Dr. Bankole Johnson, chairman of Psychiatry and Neurobehavioral Sciences at the University of Virginia, told Bloomberg News that Topamax does everything researchers want to see in a pharmaceutical treatment for alcoholism: “First, it reduces your craving for alcohol; second, it reduces the amount of withdrawal symptoms you get when you start reducing alcohol; and third, it reduces the potential for you to relapse after you go down to a low level of drinking or zero drinking…"

Topamax for Alcoholism: A Closer Look. Epilepsy drug gains ground, draws fire as newest anti-craving pill
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4) One of the most popular posts to date was this examination of neurological questions surrounding marijuana and memory loss. Inquiring minds, uh, forget the question. Oh yeah: Does the strain of dope you smoke determine how forgetful you’ll become?

“…As far as memory goes, THC content didn't seem to matter. It was the percentage of cannabidiol (CBD) that controlled the degree of memory impairment, the authors concluded. "The antagonistic effects of cannabidiol at the CB1 receptor are probably responsible for its profile in smoked cannabis, attenuating the memory-impairing effects of THC. In terms of harm reduction, users should be made aware of the higher risk of memory impairment associated with smoking low-cannabidiol strains of cannabis like 'skunk' and encouraged to use strains containing higher levels of cannabidiol..." 


Marijuana and Memory: Do certain strains make you more forgetful?
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5) Finally, a popular post focusing on the biochemistry of nicotine in e-cigarettes, the new, smokeless nicotine delivery system. Are they safe? The latest in harm reduction strategies, or starter kits for youngsters?

“…You may never have heard of it—but it’s the newest drug in town. It’s called an electronic cigarette, or “e-cigarette.” Electronic cigarettes use batteries to convert liquid nicotine into a fine, heated mist that is absorbed by the lungs. No smoke, but plenty of what makes cigarettes go, if you don’t account for taste—or ashtrays and smoke rings….”

E-Cigarettes and Health: Smokeless nicotine comes under scrutiny.

Photo Credit: http://www.livingim.com/

X-ed Out.

Another look at MDMA and serotonin.

A study by Canada’s Centre for Addiction and Mental Health (CAMH) has confirmed earlier findings that chronic users of ecstasy (MDMA) have abnormally low levels of serotonin transporter molecules in the cerebral cortex.

While a decade of research on the effects of ecstasy on brain serotonin has been controversial and largely inconclusive, the latest study used drug hair analysis to confirm levels of MDMA in 49 users and 50 controls. An additional division was made between chronic X users who also tested positive for methamphetamine, and those who did not. Regular usage of MDMA was defined as two tablets twice a month.

The Canadian study, funded by the U.S. National Institute on Drug Abuse (NIDA) and published in the journal Brain, suggests that the serotonin surge responsible for ecstasy’s effects results in a net depletion in regular X users. That is not a new finding--but the Canadian study goes further, suggesting that the serotonin depletion is localized in one area of the brain.

“We were surprised to discover that SERT was decreased only in the cerebral cortex and not throughout the brain,” said study leader Stephen Kish in a press release, “perhaps because serotonin nerves to the cortex are longer and more susceptible to changes.”

Low serotonin transporter (SERT) levels in the cerebral cortex were found in all X users, with or without amphetamine. Dr. Kish noted that the CAMH findings replicate what Kish referred to as “newer data” from Johns Hopkins University. In 1999, a controversial serotonin study of ecstasy users at Johns Hopkins laboratory was criticized for overestimating the level of danger posed by ecstasy-induced serotonin impairments.

Okay, the finding is becoming more robust. But what does it mean? According to co-author Isabelle Boileau, a low SERT level does “not necessarily” indicate structural brain damage. “There is no way to prove whether low SERT is explained by physical loss of the entire serotonin nerve cell, or by a loss of SERT protein within an intact nerve cell.”

For his part, Dr. Kish indicated that his concerns centered on the connection between lower serotonin measurements and MDMA tolerance levels. “Most of the ecstasy users of our study complained that the first dose is always the best, but then the effects begin to decline and higher doses are needed,” he said. “The need for higher doses, possibly caused by low SERT, could well increase the risk of harm caused by this stimulant drug.” The published study concluded that “behavioural problems in some ecstasy users during abstinence might be related to serotonin transporter changes limited to cortical regions.”

However, in addition to the confounding variable of methamphetamine (see my post, “How Pure is Ecstasy?”), it remains unclear whether the SERT alterations detected in the study are transient or permanent. Moreover, the nature of the link that “might” exist between lower SERT levels and cognitive impairment in the brains of regular ecstasy users remains a subject of dispute in the drug research community, as in this earlier post.  (And just to emphasize that drugs are complicated things, a spate of promising recent research has suggested that ecstasy might be an effective option for treating people with post-traumatic stress disorder).

The CAMH, affiliated with the University of Toronto, is Canada’s largest mental health and addiction teaching hospital.

Kish, S., Lerch, J., Furukawa, Y., Tong, J., McCluskey, T., Wilkins, D., Houle, S., Meyer, J., Mundo, E., Wilson, A., Rusjan, P., Saint-Cyr, J., Guttman, M., Collins, D., Shapiro, C., Warsh, J., & Boileau, I. (2010). Decreased cerebral cortical serotonin transporter binding in ecstasy users: a positron emission tomography/[11C]DASB and structural brain imaging study Brain DOI: 10.1093/brain/awq103

Graphics Credit: pubs/teaching/teaching4/Teaching3.html

Three Drug-Related Posts (Good Ones)

And a plea for your vote.

The DrugMonkey blog, written by an anonymous NIH-funded biomedical researcher,  takes on the question of why doctors dislike narcotics abusers but tolerate drinkers and smokers, and investigates whether there is something about opiates that “turns you into a jerk" in a post titled “Does one drug cause the user to be more annoying?”

Also at DrugMonkey this month, “UK Bans Mephedrone” is  a succinct summation of the dizzy panic going on in the UK over a new party drug that has similarities to the African drug khat. Did Britain institute a hasty and ill-considered ban on the substance based on political rather than scientific concerns?

Over at the Neuroskeptic blog, a British neuroscientist presents some intelligent background to the renewed interest in psychedelic research in his post, “Serotonin, Hallucinations & Psychosis.”

And lastly--although this couldn't possibly be any more off topic--my favorite tourist village--Ely, Minnesota--is currently leading the contest for "American's Coolest Small Town" at Budget Travel magazine's online site HERE.

If you are at all familiar with Ely (Gateway to the Boundary Waters Canoe Area Wilderness, Land of Sky Blue Waters, Canoe Capital of America, Summer Home to Ten Thousand Paddling Boy Scouts) vote early and vote often! Contest closes May 9.

Photo Credit: http://www.aglabs.com/

The Addiction Inbox Top Ten

A rundown of the most popular posts.

What are readers of Addiction Inbox interested in? Although scarcely scientific, a look at the most-viewed posts here over the past couple of years is indicative of general interest—or at least indicative of the general drift of Google searches on topics related to addiction and drugs.

Ranked by overall page views, from most to least, here are the ten most-visited blog posts on Addiction Inbox:

1. Marijuana Withdrawal

The most popular post on Addicton Inbox by a considerable margin. With almost 700 reader comments, this post has evolved into a message board for people having problems related to marijuana dependence and withdrawal. Very interesting first-person stuff attached to a rather straightforward post. Continues to grow like Topsy.

2. Is Marijuana Addictive?

A continuation of the discussion of marijuana withdrawal, or, as the director of the National Institute on Drug Abuse (NIDA) Nora Volkow calls it, “cannabis withdrawal syndrome.” 100 reader comments thus far.

3. Serotonin and Dopamine: A Primer

Sometimes you just gotta get back to basics.  Inquiring readers want to know.

4. E-Cigarettes and Health

A lively debate on the new, smokeless nicotine delivery system. Electronic cigarettes use batteries to convert liquid nicotine into a heated mist that is absorbed by the lungs. The latest in harm reduction strategies, or starter kits for youngsters?

5. Topamax for Alcoholism: A Closer Look

Another good response to a medical post about a drug for seizure disorders and migraines that shows promise as an anti-craving drug for alcoholism. People are getting more accustomed to hearing about medications for addiction.

6. Bill to Legalize Marijuana Offered in U.S.

Not a big surprise.

7. Marijuana Withdrawal Rivals Nicotine

Another comment-heavy post concerning a controversial study of withdrawal effects from smoking cigarettes and pot.

8. Anandamide: The Brain’s Own Marijuana

Something of a merger here between two consistently popular topics--cannabis and brain science. After the Sanskrit “ananda,” meaning bliss.

9. Food Addiction and Dopamine

Readers seem to take seriously the notion that certain forms of overeating are substance addictions.  This post focused on sugar's drug-like effect on the nucleus accumbens, a dopamine-rich brain structure in the limbic system.

10. Coffee Addiction

Increased tolerance, craving, and verifiable withdrawal symptoms--the primary determinants of addiction--are easily demonstrated in victims of caffeinism.

What’s a Neurotransmitter, Anyway?

A brief guide for the perplexed.

A neurotransmitter is a chemical substance that carries impulses from one nerve cell to another. Neurotransmitters are manufactured by the body and are released from storage sacs in the nerve cells. A tiny junction, called the synaptic gap, lies between brain cells. (Think of Michelangelo’s Sistine Chapel, with the finger of Adam and the finger of God not quite touching, yet conveying energy and information.)

Neurotransmitters squirt across the synaptic gap, and this shower of chemical messengers lands on a field of tiny bumps attached to the surface of the nerve cell on the other side of the synaptic gap. These bumps are receptors, and they have distinctive shapes. Picture these receptors, brain researcher Candace Pert has suggested, as a field of lily pads floating on the outer oily surface of the cell.

Neurotransmitter molecules bind themselves tightly to these receptors. The fact that certain drugs of abuse also lock tightly into existing receptors, and send messages to nerve cells in the brain, is the key to the mystery of addiction.

The fact that certain drugs essentially “fool” receptors into receiving them is one of the most important and far-reaching discoveries in the history of modern science. It is the reason why even minute amounts of certain drugs can have such powerful effects on the human nervous system. The lock-and-key arrangement of neurotransmitters and their receptors is the fundamental architecture of action in the brain. Glandular cells are studded with receptors, and many of the hormones have their own receptors as well. If the drug fits the receptor and elicits a response, it is called an agonist. If it simply blocks the receptor site without stimulating a response, it is an antagonist. Still other neurotransmitters have only a secondary effect, causing the target cell to release other kinds of neurotransmitters and hormones.

Two of the most important neurotransmitters are serotonin and dopamine. The unfolding story of addiction science, at bottom, is the story of what has been learned about the nature and function of such chemicals, and the many and varied ways they effect the pleasure and reward centers in our brains.

In 1948, three researchers—Maurice Rapport, Arda Green, and Irvine Page—were looking for a better blood pressure medication. Instead, they managed to isolate a naturally occurring compound in beef blood called serotonin (pronounced sarah-tóne-in), and known chemically as 5-hydroxytryptamine, or simply 5-HT. The researchers determined that serotonin was involved in vasoconstriction, or narrowing of the blood vessels, and in that respect resembled another important chemical messenger in the brain—epinephrine, better known as adrenaline.

Even though there is at most 10 milligrams of the substance in our bodies, serotonin turned out to be one of nature’s signature chemicals—a chemical of thought, movement and behavior, as well as digestion, ejaculation, and evacuation. The body’s all-purpose neurotransmitter, involved in sleep, mood, appetite, among dozens of other functions. The cortex, the limbic system, the brain stem, the gut, the genitals, the bowels: serotonin is a key chemical messenger in all of it.

Another key neurotransmitter—dopamine—is considered to be one of the brain’s primary “pleasure chemicals,” and is found in areas of the brain linked to experiences of joy and reward.

Dopamine pathways play a role in carrying signals related to attention, movement, problem solving, pleasure, and the anticipation of rewarding experiences. Dopamine is one of the reasons why, after you have a pleasurable experience with food, drink, sex, or certain drugs, you are likely to feel a desire to repeat the experience. Dopamine is implicated in not just the drug high, but in the craving that accompanies withdrawal as well.

Feelings of pleasure, or joy, are natural drug highs. The fact that they are produced by chemical alterations in brain state does not make the fear or the pleasure feel any less real.

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


Photo Credit: NIDA

addiction drugs dopamine

Bulimia: What To Look For [Guest Post]

Signs and symptoms of a dangerous disorder.

[Today’s guest post was contributed by Heidi Taylor. I include it here as part of a continuing series of guest posts having to do with the so-called “lifestyle addictions,” such as perceived addictions to gambling, sex, video games, or shopping—areas in which I can claim no special expertise, and diagnoses which remain controversial among addiction researchers. However, I do strongly believe that the case has been made for the addictive nature of certain eating disorders—bulimia and carbohydrate-craving obesity in particular—in which the ingested substance is food, not “drugs” as we commonly think of them. Eating is one of the most obvious ways in which we alter the neurochemistry of our brains every day. As for treatment, serotonin abnormalities are believed to be the culprit. Many bulimics improve on SSRI antidepressants.]
--Dirk Hanson

Detecting Bulimia in a Loved One

It’s not a disease that’s visible at first or even second sight, but even so, it is one that’s largely ignored and left untreated more because most people are not even aware of its existence. But bulimia, or to be exact, bulimia nervosa is an eating disorder that could end up having physical, psychological and sociological consequences that are hard to digest. Bulimics tend to eat more than they should – in fact, they gorge on food – and then force themselves to throw up using emetics, visit the toilet with laxatives, or go without food for the next day or so. In short, they compensate for their over-eating in ways that are neither healthy nor advisable.

While it may not seem like a dangerous disorder, bulimia can have devastating consequences if left unchecked – people affected are prone to suffer from an inflamed throat and neck glands, a torn esophagus, decaying and unhealthy teeth, acid reflux disorder, ruptured intestines, irritable bowels, dehydration and malfunctioning kidneys. Besides these physical symptoms, they’re also going to be obsessed with their weight, suffer from depression and anxiety, and face other mental and social problems. So if you suspect a loved one may be bulimic, here are a few symptoms that will help you detect the disorder and get them professional help as soon as possible:

• Eating more than the normal amount possible in a single meal or over the course of a few meals.
• Frequent visits to the toilet after a meal.
• A washed out and drained look that happens because they’re dehydrated and their body is low in minerals from all the purging and use of laxatives.
• Mood swings that seem to come on for no apparent reason.
• Sores in the mouth and/or on their fingers (because they may be sticking it in their throats to induce vomiting).
• Inflamed throats and bad teeth.
• Bouts of depression or uncalled for anxiety attacks.
• Exercising for a long time, at odd hours of the day and being obsessed with the way they look.
• It’s the women and the teenagers who are more susceptible to this disorder because of their obsession with their weight and the way they look. So if you have a daughter or a close female friend or relative who acts in a way that points suspicion to bulimia, talk to them and get them much-needed medical intervention before the situation worsens.

Even if you just suspect bulimia and are not really sure, you’d do well to talk to the person concerned and get them to see a doctor who can help. Remember, it may sound like a minor thing, but bulimia is a very serious disorder.
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This post was contributed by Heidi Taylor, who writes about the Masters in Healthcare. She welcomes your feedback at HeidiLTaylor006 at gmail.com

Graphics Credit: Graham Menzies Foundation