Thursday, July 8, 2010

Consider the CB(2) Receptor

A different destination for cannabinoids.

THC and its organic cousin, anandamide, do what they do by locking into both the CB1 receptor, discovered in 1988, and the CB2 receptor (as it is commonly written in shorthand), discovered 5 years later. THC and anandamide are CB receptor agonists, meaning they activate the receptors in question. (An antagonist blocks the receptor’s action.)

CB1 is a very common receptor in the central nervous system, and, when stimulated by an agonist, is responsible for the well-known roster of alleged medical effects, such as pain relief and nausea from chemotherapy--along with the typical marijuana high. (For more on this, see the excellent 2007 post by Dr. Joan Bushwell.) Conversely, blocking CB1 activity with an antagonist like rimonabant is one controversial avenue being explored in the search for new weight loss drugs. (CB1 antagonists can also produce anxiety and depression.)

However, CB2 was long considered a “peripheral” cannabinoid receptor, meaning that scientists hadn’t managed to find CB2 receptors in the central nervous system. They were, however, plentiful in the immune system, and seemed to be involved in inflammation as well as pain responses. CB2 receptors were in fact eventually discovered in the central nervous system, and are active in the brain during certain kinds of inflammatory responses.

There is a straightforward commercial incentive for tracking the extent of CB2 expression in brain neurons. As the authors of a cannabinoid receptor study wrote in the June issue of the British Journal of Pharmacology:“As CB(2) is an attractive therapeutic target for pain management and immune system modulation without overt psychoactivity, defining the extent of its presence in neurons will have a significant impact on drug discovery.”

Translated, this means that there are a number of new molecules that are selective for CB2 receptors. Since people don’t get a strong traditional marijuana-style buzz from CB2 receptor activation, and given the active involvement of CB2 receptors in things like immune responses and inflammatory reactions, the possibility exists of finding lucrative spinoffs like pain pills or anti-inflammatory medications.  So drug researchers would like to know exactly where those receptors are, and what they do, in the event that they end up attempting to make a medicine that stimulates or blocks  them artificially. (Credit to Vaughan Bell of Mind Hacks for highlighting this study.) 

The psychologists at Indiana University who produced the paper did their best to shed light on where the CB(2) receptor is hiding, and what, exactly, it does.  But there is still not enough known about how various substances react with this somewhat elusive receptor for cannabinoids. In 2008, scientists at the University of Madrid published research in the Journal of Biological Chemistry indicating that activation of the CB2 receptor reduced nerve cell loss in animals suffering from a disease similar to multiple sclerosis. Researchers point to the possibility that a safe drug for M.S. patients could be one of the results of CB2 research.

Atwood, B., & Mackie, K. (2010). CB2: a cannabinoid receptor with an identity crisis British Journal of Pharmacology, 160 (3), 467-479 DOI: 10.1111/j.1476-5381.2010.00729.x

Graphics Credit:


Lars said...

Casual observer here: Is it possible that CB2 activation might still lead to the dreaded cannabis psychosis while not getting you high, or do you consider that an impossibility?

Dirk Hanson said...

I don't know the answer to that. And I'm not entirely convinced about the cannabis psychosis question. Correlation is not causation. People with existing mental problems, or incipient mental illness like schizophrenia, often turn to drugs.

Neuroskeptic said...

THC, the active ingredient in cannabis, is a combined CB1 and CB2 agonist. We don't really know what proportion of the effects of cannabis are related to CB2 agonism, probably not many given that selective CB1 agonists have similar subjective effects, but CB2 may play a part. If they're in the brain, they must do something...

Dirk Hanson said...

Thanks for the info, Neuroskeptic. We're only just beginning to take apart cannabis and see what makes it tick, in a sense. I calculate that the scientific community lost as much as three decades of research time, relative to other drugs of abuse, due to the Feds putting pot research on hold.

Related Posts Plugin for WordPress, Blogger...