Talking to NIDA about addiction research- Nicotine, cocaine, treatment matching and more

It’s not everyday that I get an invite to speak with NIDA‘s director, Dr. Nora Volkow, and so, even though it required my creative use of some VOIP technology from a living room in Tel-Aviv, I logged onto a conference call led by the leading addiction researcher. When my colleagues, Dirk Hanson and Elizabeth Hartney, were introduced, I knew I was in good company.

Addiction research directions the NIDA way

The call focused on some NIDA interests, including a nicotine vaccine, which Dr. Volkow seemed confident will triumphantly exit phase 3 trials in less than two years and potentially enter the market after FDA approval in three years or less. The vaccine, which seems to significantly and effectively increase the production of nicotine antibodies in approximately 30% of research participants, has shown promise as a tool for smoking cessation in trials showing complete cessation, or significant reduction in smoking among participants that produced sufficient antibodies. Obviously, this leaves a large gap for the 70% of participants for which the vaccine was not effective, but a good treatment for some is much better than no treatment for all. For more on the vaccine, check out Mr. Hanson’s post here.

Aside from the nicotine vaccine (and on a similarly conceived cocaine vaccine), our conversation centered on issues relevant to the suggested new DSM-5 alterations in addiction-related classifications. Dr. Volkow expressed satisfaction at the removal of dependence from the title of addictive disorders, especially as physical dependence is often part of opiate administration for patients (especially pain patients) who are in no way addicted to the drugs. Dr. Volkow also noted that while physical dependence in relatively easy to treat, addiction is not, a matter that was made all the more confusing by the ill-conceived (in her opinion, and in mine) term. Additionally, the inclusion of severity ratings in the new definition, allowing for a more nuanced, spectrum-like, assessment of addiction disorders, seemed to make Dr. Volkow happy in her own, reserved, way.

Treatment matching – rehab search for the 21st century

As most of my readers know, one of my recent interests centers on the application of current technology to the problem of finding appropriate treatment for suffering addicts. I brought the problem up during this talk, and Dr. Volkow seemed to agree with my assessment that the current tools available are nowhere near adequate given our technological advancements. I talked a bit about our upcoming addiction-treatment-matching tool, and I hope that NIDA will join us in testing the utility of the tool once we’re up and running. I truly believe that this tool alone will allow more people to find appropriate treatment increasing the success rate while maximizing our system’s ability to treat addicts.

Involving the greater public in addiction research

It wasn’t until the end of the conversation that I truly understood the reason for the invitation (I’m slow when it comes to promotional issues) – NIDA is looking to move the discussion about it’s goals and directions out of the academic darkness in which they’ve lurked for years, and into the light of online discussion. I’m in no way offended by this, especially since this was exactly my point in starting All About Addiction in the first place. If anything, I’m honored to be included in the select group of people NIDA has chose to carry their message, especially since the conversation was an open, respectful, and data-centered one. I hope more of these will occur in the future.

Resolving confusion about addiction

One of the final points we got to discuss in the too-short hour we had Dr. Volkow on the “phone” had to do with the oft misunderstood concept of physical versus psychological addictions. I’ve written about this misconception in the past, and so I won’t belabor the point here, but it’s time that we gave our brain the respect it deserves by allowing it to join the rank, along with the rest of our body, and the physical realm. We’re no longer ignorant of the fact that our personalities, memories, feelings, and thoughts are driven by nothing more than truly physical, if miniature, happenings in our brains. In the same way that microbe discovery improved our well-being (thank you Pasteur), it’s time the concept of the very physical nature of our psychological-being improves our own conceptualization of our selves.

We are physical, spiritual, and awesome, but only if we recognize what it is that makes “us.”

About Addiction- marijuana, tanning, tobacco and more

We have some great new weekly links for you to enjoy and learn from this week.  And as always please give us feedback if there are topics you would like to see more/less of in our weekly links and articles so we can best help you.

CNBC: This article talks about the legalization of marijuana. It talks about a poll that found support for legalization to be as high as 56% of those polled.

Center for substance abuse research: College students celebrating their 21st birthday drink more than anticipated. They drink an average of 12 drinks though researchers had predicted about 7 .

AOL StyleList: This article describes a new study that states that tanning is as addictive as drug abuse. The research was conducted using a questionnaires given to 421 students.

And students who tan may be different than others in other ways as well, according to the new study (reported on in Business Week as well), which found that students who tan drink more alcohol and smoke more pot. 42% of tanning addicts reported to use more than one drug in the previous month.

New England Journal of Medicine: This article talks about tobacco product regulation. According to the article, tobacco use causes 400,000 deaths annually in the United States. It talks about the by Obama signed Family Smoking Prevention and Tobacco Control Act.

CNN: This article talks about a Nicotine vaccine that is promising. Researchers announced a vaccine that would help smokers stop smoking at a national meeting this week.

Psychology Today: This article states that when someone deals with mental illness and drug abuse his or her treatment is complicated and more difficult. The article states several reasons why it is more difficult to treat mental illness and drug abuse when they are co-morbid.

Nicotine vaccine? It seems addicts would love one!

Okay, so there’s no vaccine for nicotine yet, but if researchers ever find one (like they did for cocaine), this recent study by a group at the University of Pennsylvania suggests that smokers are ready and willing. In fact, more than half of them were biting at the bit!

In case you’re wondering (and don’t feel like reading), the vaccine would work by producing nicotine antibodies in the vaccinated individuals. Those antibodies would attach to any nicotine in the blood and prevent it from doing its thing (binding to nicotinic Ach receptors) thereby making smoking, well… boring. Hopefully, when smokers stop feeling the effect, they’ll stop smoking. Or that’s the thinking behind the whole idea anyway. Given other research that shows that nicotine smoking leads to some pretty strong contextual associations (read: “the environment and other associated stimuli become very rewarding”), I doubt whether the vaccine would work as well as people hope.

But, at least smokers seem willing to try it!

Drugs and Pregnancy Part II: Cigarettes and Weed

We’ve already covered the issue of drinking alcohol while pregnant. Now it’s time for smoking.

When a pregnant mother smokes cigarettes, nicotine and carbon monoxide pass across the placental barrier. This disrupts the normal transfer of oxygen and nutrients to the developing fetus, harming its development.

Smoking in pregnancy

It’s been estimated that nearly 1 in 10 American women smoke cigarettes while pregnant (1). This is an alarming statistic considering that studies have repeatedly shown maternal smoking to be associated with adverse birth outcomes such as low birth weight (LBW), miscarriage, and infant mortality.

LBW infants are the result of a preterm birth, intrauterine growth retardation, or both. Nearly twice as many infants born to smokers have a low birth weight when compared to infants of nonsmokers (1), putting them at risk for cerebral palsy, mental retardation, and learning problems. Smoking during pregnancy has also been linked to respiratory disease and sudden infant death syndrome (2).

The effect of maternal smoking on the fetus depends on when it occurs. As we’d reported with drinking, smoking does the most harm during the early stages of pregnancy and the least during the later stages of pregnancy.

What about marijuana?

Woman smoking weedStudies of marijuana use during pregnancy provide some inconsistent results. Some studies link maternal marijuana use to growth retardation, preterm birth, decreased head circumference, and learning disabilities (3). One study concluded that marijuana has no adverse effects on children up to the age of 3, but after age 3, children who are exposed to cannabis in-utero are more likely to demonstrate attention deficit, hyperactivity, delinquent behavior, and decreased reasoning ability (4). Other studies find absolutely no association between marijuana and adverse birth outcomes.

The truth is, we don’t really know what marijuana use during pregnancy does to an infant, partially because researchers face two unique problems when studying maternal marijuana use:

1) Social stigma against drug use during pregnancy is likely causing women nationwide to under report their marijuana use.

2) Marijuana users are more likely to be using alcohol, cigarettes, and other illicit drugs. It is well known that poly-drug use during pregnancy greatly increases the chance of adverse birth outcomes (5).

So, smoking cigarettes and weed apparently does not consistently cause the same harm that drinking causes. However, the harm brought about by smoking seems to depend less on the amount smoked and more on the combination of substances used and its timing.

Keep on the lookout for more posts on drug use during pregnancy!

Citations:

1. Martin, J. A., Hamilton, B. E., Sutton, P. D., et al., (2003). Births: Final data for 2005, National Vital Statistics Reports, 56(6)

2. Difranza, J. R., Aligne, C.A., & Weitzman, M., (2004). Prenatal and postnatal environmental tobacco smoke exposure and children’s health, Pediatrics, 113, pg 1007-1015

3. Hatch, E. E., & Bracken, M.B., (1986) Effect of marijuana use in pregnancy on fetal growth, American Journal of Epidemiology, 124, pg 986-993.

4. Huizink, A. C., Mulder, E. J. H., (2006). Maternal smoking, drinking, or cannabis use during pregnancy and neurobehavioral and cognitive functioning in human offspring, Neuroscience and Biobehavioral Reviews, 30, pg 24-41

5. Hall W., and Solowij, N., (1998). Adverse effects of cannabis. The Lancet, 352, pg 1611-1616

Smoking cigarettes just makes it better… The enhancement effect of nicotine

A recent study by a Kansas state researcher (find it here) reports that part of the power of nicotine may be in its enhancement of other experiences that go hand in hand with it.

While the online source I included suggests that nicotine’s effect may be only in this indirect enhancement, my reading of the article proved that in fact, at high doses, nicotine alone provided the same effects all by itself.

Nicotine as an enhancer

My dissertation is actually going to be based on a nicotine experiment, so this is a topic I know quite a bit about now. As this recent study reports, it seems that animals are rarely willing to work for nicotine alone, something I found surprising at first. I mean, given how many people are addicted to cigarettes, I thought this stuff would be an easy sell. Instead, it’s taken quite a bit of work to figure out how exactly to make nicotine rewarding enough without making its effects almost too much to bare initially. As someone who used to smoke and remembers the nausea I felt the first time I tried, I understand.

Even still, I’ve had to play around quite a bit to make my my nicotine worthy of lever presses and nose-pokes. I now firmly believe that nicotine addiction has quite a bit to do with the context, behaviors, and other factors associated with smoking.

Is nicotine different from alcohol, meth, and cocaine?

So, much like the previous post I put up regarding the finding that drinking enhances people’s enjoyment when they smoke, it seems that not-surprisingly, the same thing happens the other way around – Smoking makes drinking better.

In truth, this isn’t all that surprising, there has been a lot of research showing that many drugs make the animals in research do more of other things they like. This has been shown for crystal meth, cocaine, and a number of other stimulants, and I wouldn’t be surprised if the same is true for other drugs. The thing that makes nicotine a little different is that it is almost never rewarding all by itself. Well, at least in the lab…

Citation:

Nadia Chaudhri, Anthony R. Caggiula, Eric C. Donny, Sheri Booth, Maysa Gharib,Laure Craven, Matthew I. Palmatier, Xiu Liu & Alan F. Sved (2007) Self-administered and noncontingent nicotine enhance reinforced operant responding in rats: impact of nicotine dose and reinforcement schedule.Psychopharmacology, 190, pg. 353–362

Nicotine addiction and genetics – It’s the little things that matter in smoking addiction

We’ve known for a while that genes play a role in addiction in general and that nicotine is addictive at least in part because it activates receptors for a chemical called Acetylcholine (ACh) that are found all over the brain and body. Nevertheless, finding the specific mechanism for the genetic predisposition has been difficult.

Some recent large-scale studies undertaken at the University of Colorado and other institutions  around the country have made some very exciting discoveries in this area.  It seems that up to now, researchers were focusing on the most common type of ACh receptor, but that several other types play very important roles in determining how people will respond to nicotine the first time they use it, and how much they’ll be likely to use in that early period. It should be pretty obvious that both there factors can play a huge role in nicotine addiction, and indeed, it seems they do.

So here’s a little breakdown of the findings:

  • Initially, research examining the influence of ACh receptor proteins on nicotine addiction focused on the α4 and β2 subunits. These are the most common ACh subunit proteins in the brain. Animal and human imaging studies have shown that ACh receptors consisting of two α4 and three β2 subunits are critical for the rewarding effects of nicotine.
  • The new studies focused on genes that code for less common ACh receptor proteins. Researchers have implicated the genes for the α3, α5, and β4 proteins in early initiation of smoking, the transition to dependence, and two smoking-related diseases: lung cancer and peripheral arterial disease.
  • Investigators also found that whether or not a person becomes dizzy the first time he tries smoking, as well as his or her risk of addiction, depends in part on the genes for the α6 and β3 proteins.

Taken together, the results suggest that genes for several ACh receptor proteins drive different aspects of the multi-step process of nicotine addiction.

The importance of the first time

Interestingly, the findings regarding first smoking experience seem to suggest that the intensity of it, rather than simply how pleasurable it was, are associated with the likelihood of becoming dependent later on, according to Dr. Ehringer, one of the studies’ lead author. For example, the same people that reported feeling extremely dizzy their first time were more likely to report that they became addicted to nicotine. The genetics analysis supported this same finding.

From trying to becoming addicted

Other studies revealed that additional genetic variations, including those in the the gene for the α3 ACh subunit, the β3 subunit, and the α5 subunit seem to code for the likelihood of being able to quit smoking. The α5 protein, which is present in the brain’s reward area, seems to influence the risk of smoking a pack of cigarettes a day as compared with smoking fewer than 5 cigarettes a day.

Conclusions for smoking addiction

I’ve said it before and I’ll say it again and again – no matter how much we try to ignore it, genetics play a huge role in every aspect of our being, including the likelihood that we will become addicted to a substance. By learning more about the role of specific genes and specific types of receptors, researchers can attempt to uncover possible medications that will help us in treating addiction. Still, I think that the bigger take-home message is this: There are reasons behind the development of addiction that are beyond anyone’s control. Thinking of genetic causes and relating them to morality simply makes no sense.

 Citation:

Lori Whitten (2009). Studies Link Family of Genes to Nicotine Addiction – Genes for protein constituents of nicotinic acetylcholine receptors influence early smoking responses and the likelihood of nicotine dependence. NIDA Notes, 22.