Is marijuana addictive? You can bet your heroin on that!

marijuana“Is marijuana addictive?” seems to be the ultimate question for many people. In fact, when discussing addiction, it is rare that the addiction potential for marijuana doesn’t come up.

Some basic points about marijuana:

The active ingredient in marijuana, THC, binds to cannabinoid receptors in the brain (CB1 and CB2). Since it is a partial agonist, it activates these receptors, though not to their full capacity. The fact that cannabinoid receptors modulate mood, sleep, and appetite is why you get the munchies and feel content and why many people use it to help with sleep.

But how is marijuana addictive? What’s the link to heroin?

What most people don’t know is that there is quite a bit of interaction between the cannabinoid receptor system (especially CB1 receptors) and the opioid receptor system in the brain. In fact, research has shown that without the activation of the µ opioid receptor, THC is no longer rewarding.

If the fact that marijuana activates the same receptor system as opiates (like heroin, morphine, oxycontin, etc.) surprises you, you should read on.

The opioid system in turn activates the dopamine reward pathway I’ve discussed in numerous other posts (look here for a start). This is the mechanisms that is assumed to underlie the rewarding, and many of the addictive, properties of essentially all drugs of abuse.

But we’re not done!

Without the activation of the CB1 receptors, it seems that opiates, alcohol, nicotine, and perhaps stimulants (like methamphetamine) lose their rewarding properties. This would mean that drug reward depends much more heavily on the cannabinoid receptor system than had been previously thought. Since this is the main target for THC, it stands to reason that the same would go for marijuana.

So what?! Why is marijuana addictive?

Since there’s a close connection between the targets of THC and the addictive properties of many other drugs, it seems to me that arguing against an addictive potential for marijuana is silly.

Of course, some will read this as my saying that marijuana is always addictive and very dangerous. They would be wrong. My point is that marijuana can not be considered as having no potential for addiction.

As I’ve pointed out many times before, the proportion of drug users that become addicted, or dependent, on drugs is relatively small (10%-15%). This is true for almost all drugs – What I’m saying is that it is likely also true for marijuana (here is a discussion of physical versus psychological addiction and their bogus distinction).

Citation:

Ghozland, Matthes, Simonin, Filliol, L. Kieffer, and Maldonado (2002). Motivational Effects of Cannabinoids Are Mediated by μ-Opioid and κ-Opioid Receptors. Journal of Neuroscience, 22, 1146-1154.

Obesity, drug addiction, and dopamine

Eating junk-food can be addictive, and apparently, it causes brain changes that look eerily similar to drug addiction. That’s the message not only from the rapidly fattening waistlines of Americans everywhere, but also from the Johnson and Kenny labs at the Scripps Institute.

Food and drug addiction

The idea that obesity is caused by a compulsive pattern of eating, and that there could be a similarity between such compulsive eating and drug addiction isn’t super new. In fact, Dr. Volkow from NIDA seemed to make research into this association her goal when taking  the helm of the addiction research kingdom.

When you think about it, the notion isn’t far-fetched: Drug addicts continue to take drugs, in increasing amounts, even though they’d often like to stop (at some point) and in the face of negative consequences and the common loss of other important life functions (like family, work, etc.). Obese individuals are quite the same, eating more and more food regardless of their desire to adopt a healthier diet and in-spite of ridicule, low self-esteem, and decreased functioning that often accompanies extreme weight gain.

The research by Johnson and Kenny examined whether exposure to the kind of high-fat, super high-calorie foods that floods the junk-food market are responsible for creating food-addicts in a similar way to drugs that alter the brain in ways that make stopping more difficult.

Dopamine, reward, and junk-food

The study took three groups of rats and gave them either the regular chow diet lab animals are used to or the worse kind of birthday party food: bacon, sausage, cheesecake, pound cake, frosting and chocolate. You can imagine the party going on in the rat cages that got to eat that! Of the two groups that got to eat the crazy-fat food, one had unlimited access while the other got to binge for only one hour a day.

The bottom line: Only the rats that got unlimited access to the fat-party food developed compulsive eating habits that resulted in roughly twice the weight gain of the other two groups and the ability to continue eating even in the face of signals for punishment (a light that they were trained to associate with shocks).

When the researchers looked deeper, they found that the brains of these rats suffered a significant reduction in the density of a specific kind of dopamine receptor (D2) in a brain part known as the striatum, the same kind of reduction common in drug addicted people and obese individuals. This receptor type is often thought to be important for regulation of impulses, both physical and otherwise. It therefore makes sense that losing this type of function would cause uncontrollable eating or drug taking.

Are drug- and food-addictions the same?

While this research isn’t saying that compulsive eating, or obesity, are the same as drug addiction, it does strongly suggest that there are common mechanisms in both. More importantly, it reveals a common process that unfolds when over-exposure to the reward, in this case food, occurs. This tells us that there can likely be common pathways to these different addictive disorders, though whether any specific person ended up a food- or drug-addict because of this kind of process is still an open question. I wonder if we’ll see something like this with sex addiction soon…

Citation:

Johnson and Kenny (2010) Dopamine D2 receptors in addiction-like reward dysfunction and compulsive eating in obese rats. Nature neuroscience, 13, 635-641.

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.