THC for Huntington’s Disease? Cannabinoid receptors are important for more than drug use

Here at A3, we believe in equal opportunity. We recognize that saying we have an addiction problem is not the same as saying we have a drug use problem and that just because some people abuse substances (or belief systems) doesn’t means that these have no actual value when not abused. Enter this recent paper on CB1 receptors, THC, and Huntington’s Disease.

Those of you who haven’t been reading A3 for too long (shame on you!) may not be familiar with my comparison of the cognitive (or mental) impulsivity associated with substance use disordersand the physical “impulsivity” common to Huntington Disease(HD) patients. To make a long story short – both of these dysfunctions have to do with the striatum, a brain area responsible for inhibiting and controlling unwanted brain output (as in thoughts or actions). When this area starts malfunctioning, everything goes awry. When it comes to HD, “goes awry” doesn’t really do the disorder justice. Patients with a progressive form of the condition end up flailing their limbs in a manner that’s been coined the “Huntington Dance,” a euphemism if I ever heard one. This motor flailing is closely followed by severe cognitive impairments and a premature death. Not a pretty story. Continue reading “THC for Huntington’s Disease? Cannabinoid receptors are important for more than drug use”

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.

Proteins and cocaine: Addiction is a disease, not a question of morality.

While there are some people who still argue about whether drug addiction is a disease or a condition that results from the moral failing of an individual, most of the scientific community has long agreed that there are at least some influences on it that are far beyond a person’s control.

I’ve mentioned the genetic influences that have been shown to be associated with a risk for addiction before (look here). However, most of the research I’ve been involved in myself recently has more to do with the way that trying drugs changes your brain in ways that make it more likely that you’ll try them again.

Along these lines, a recently published study has shown that very specific molecular targets can have a huge impact on the probability that addicts will keep going after drugs. The molecules studied were common targets of cocaine that are altered after long-term use of coke.

The interesting thing is that the research found that deactivating each of these targets produced completely different effects:

Animals that had the GluR1 receptor subunit turned off were unable to stop themselves from searching for cocaine in a spot where it used to be long after normal mice gave up. I don’t know about you, but that sounds more than a little relevant for addiction given what I know, and have experienced. We’ve been studying this sort of stuff for a while, but the fact that a single molecule can make an animal pursue drugs in a way that is completely irrational is amazing!

Animals that had the NR1 receptor subunit turned off experienced a different effect. While normal mice relapse to drug use when they experience a drug after a long break, the NR1 deficient mice just wouldn’t go back to their addictive behavior when they got a little sample. Again, the implications for relapse preventions are promising to say the least.

In short, while some people may think there’s still a reason to argue whether people with addiction should simply be left to god’s mercy, ongoing work is showing us that we can uncover specific molecular mechanisms that may one day allow us to combat addiction with much more success. I for one welcome that.