Legalize marijuana? Medicinal or recreational? Is marijuana good or bad for you? These are the questions our society is currently facing when discussing the legal stance on marijuana. Right now, the legal climate is fairly rocky as some states have decided to legalize this drug for recreational use. However, it is still currently illegal under the federal government. This is because we don’t fully understand the impacts and effects of cannabis on the brain/body and how this can effect us long term. The FDA classifies this drug as a schedule I drug which makes research on cannabis nearly impossible. This makes it extremely difficult to learn more about this potentially very beneficial drug. Here is what we do know about how the cannabinoids in our brain impact us right now:
Endocannabinoids:
Endocannabinoids (eCB’s) are the molecules that we find naturally occurring in the brain. The most abundant eCB’s in the brain are N-Arachidonoylethanolamine (anandamide, AEA) and 2-arachidonoylclycerol (2-AG). In the brain, these molecules bind to the CB1 and CB2 receptors. These are also the same receptors that we think exogenous cannabinoids bind to, like THC in marijuana. The CB1 receptor is a g-protein coupled receptor (GPCR) which is paired to a Gi protein. This means that when activated this molecule will decrease the activity of adenylyl cyclase which in turn leads to lower levels of cAMP and PKA which are important molecules for cell functioning and working memory. This pathway also has the ability to activate the ERK, JNK, FAK and p38 pathways along with the control of ceramide and ion concentrations within the cell. I would specifically like to talk about the role of the JNK pathway and the CB1 receptor.
JNK and CB1 activation:
The JNK pathway is normally turned on in response to stress which leads to DNA repair, transcription factor changes or even cell death in extreme cases. Due to the CB1 receptor being coupled to the Gi g-protein, the activation of this GPCR has the ability to turn on Ras (one of the first proteins involved in the activation of the JNK pathway). Ras activates Raf activates MEK activates MKK which activates JNK in the nucleus. All of these molecules phosphorylate the next protein in the chain leading to its activation. It is also interesting to note that MEK is responsible for activating the MAPK pathway and the MEKK pathway. Therefore, the activation of the CB1 receptors can have three different outcomes just from activating the Ras protein. JNK leads to DNA repair and cell apoptosis. This could explain some of the healing effects of marijuana. We see that it has the ability to aid in the decline of growth of cancer cells while also giving patients an appetite needed during treatment.
Figure shows the activation of CB1 which in turn activates the JNK pathway.
Legalize it?
Although we don’t necessarily have enough evidence telling us whether the extended use of medicinal marijuana is bad or good. It has been shown to have remarkable beneficial impacts on diseases like cancer, glaucoma and epilepsy (seizures). Cannabis definitely changes the chemical balances in the brain and can in some cases be seen as addictive which could lead to negative side effects in the future. However, it may be logical to use medical marijuana as a treatment for these diseases to give people pain relief, appetite and relaxation for now.
For more information about the role of eCBs in the body read:
https://moodle.cord.edu/pluginfile.php/625296/mod_resource/content/0/endocannabinoids.pdf
Figure from:
http://molpharm.aspetjournals.org/content/molpharm/58/4/814.full.pdf
Cover Photo from:
https://www.hcillinois.com/learn/endocannabinoid-system/
Cannabinoids in the Body
