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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.

Cannabinoids, motor control, and Huntington’s Disease

In the striatum, CB1 receptors (the most common cannabinoid receptors and the main target for THC) are very important in this mechanism of inhibiting output. In fact, there’s some evidence that their activation is important in savings cells from dying in cases of over excitation, an idea we’ll return to shortly. It’s important to note that Huntington’s patients and animal models of the disease have been shown to have reduced levels of CB1 receptors in this area.

A group of researchers in Madrid wanted to examine what exactly the role of this reduced cannabinoid receptors was in the development of Huntington’s Disease. The researchers created transgenic mice that expressed both the human version of the HD gene (called Huntingtin) and reduced levels of CB1 receptors (we’ll call these the combined-type mice). Using a battery of tests that are supposed to assess motor coordination, exploration, and strength, the researchers compared these mice with mice expressing only the Huntingtin gene.

The results were pretty clear: Having reduced CB1 receptors made HD symptoms appear four weeks earlier in the combined-type mice when compared with the HD mice and the disease symptoms also progressed much more quickly. The CB1 deficit was also associated with a greater level of neuron loss in the striatum and a whole mess of other problems with neuron structure. It was clear that these mice were suffering due to the increased absence of cannabinoid receptors.

As a theraputic experiment, the researchers then tried to give THCto the Huntingtin mice (not the combined-type this time, that wouldn’t do much since they don’t have CB1 receptors). The reasoning went that if losing CB1 receptors made things worse then maybe activating those receptors more strongly in HD mice would make their symptoms better – and it worked! Giving HD mice THC improved their motor function, slowed the disease symptom progression, and improved the volume of their striatum.

A deeper look into the mechanism of this revealed that as mentioned earlier, the activation of CB1 receptors by THC apparently served a protective role and helped the HD mice delay, or reduce, the extent of neuron loss in their straitum that was the cause for all their Huntington’s Disease symptoms.

Conclusion, limitations, and the notion of weed for Huntington’s disease

The idea that THC can be used to relieve disease symptoms isn’t a new thing – Glaucoma, HIV, and cancer patients have all benefited from the use of CB1 agonists whether in the form of marijuana leaves or a pharmacologically similar product (like dronabinol). Nevertheless, the idea of using THC or other CB1 agonists for the treatment of HD is pretty new. There have been a small handful of studies but only one well-constructed experiment that used a placebo-controlled crosover design, which yielded some positive results. The results of this study suggest that THC and other CB1 compounds may not only be able to improve symptoms in already symptomatic HD patients, but also slow down the progression of such a devestating disease. Good news all around and a great use of THC as far as I’m concerned (medical use and removal from schedule-1 anyone?!).

Some of you may be asking yourself why I decided to write about a study so focused on Huntington’s Disease for a site called All About Addiction. As far as I’m concerned, discussions of commonly abused drugs generally fit with the concept I have for this site: An information hub having to do with addictions and all related matters. Moreover, the close connection that I see between HD and addictions, in terms of loss of control brought about specifically by compromised brain structures and function, makes this study one that is crucially important for understanding control in general. Add to that the evidence for THC’s use in a medical setting and I think we have a winner, if a slightly unusual one, for A3.

Peggy C. Nopoulos, Elizabeth H. Aylward, Christopher A. Ross, James A. Mills, Douglas R. Langbehn, Hans J. Johnson, Vincent A. Magnotta, Ronald K. Pierson, Leigh J. Beglinger, Martha A. Nance, Roger A. Barker, Jane S. Paulsen, and the PREDICT-HD Investigators and Coordinators of the Huntington Study Group (2011) Loss of striatal type 1 cannabinoid receptors is a key pathogenic factor in Huntington’s disease. Brain 2011 134: 119-136.

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