Shedding Light on Medical Marijuana: The Endocannabinoid System

Patient Expert

This is the third in our series on medical marijuana for bipolar. In the first piece, we made a conditional case for marijuana to treat bipolar, with some major provisos. The second piece compared the risk/benefits of medical marijuana with prescription drugs.

In this installment, we look at the endocannabis system that marijuana acts upon.

Endocannabinoids (ECs) are naturally occurring compounds throughout the brain and body that regulate cellular signaling and cellular maintenance. They function in a similar fashion to neurotransmitters such as serotonin and dopamine, except they travel backward, against the flow, from the postsynaptic cell to the presynaptic cell.

At the presynaptic cell, the ECs dock to CR1 and CR2 cannabinoid receptors and release their chemical messages. One of the effects may be to inhibit the release of certain neurotransmitters from the presynaptic cell back to the postsynaptic cell.

In effect, the postsynaptic cell restricts the flow of incoming neurotransmitter traffic from its neighbors. Here you are, a neuron in the say hippocampus (involved in memory formation), just wanting some peace and quiet. The neuron next door, however, is drawing a bead on the glutamate receptors on one of your dendrites, about to get off a round.

Glutamate is an "excitatory" neurotransmitter that plays a major role in the stress response. But too much of a good thing can lead to neurotoxicity and cellular damage. This may have the effect of rendering entire neural networks vulnerable to the next stressful event. We may overreact, get anxious, panic, lose sleep.

Glutamate dysregulation has been fingered in bipolar and other mental illnesses. According to Husseini Manji, formally of the NIMH and now at Johnson&Johnson, it may be more accurate to regard bipolar as "atrophic" (characterized by neurons in distress) rather than "symptomatic."

So here you are, your average postsynaptic hippocampal neuron needing to protect yourself. You do this by creating your own endocanniboids on demand and dispatching them to your troublesome neighbor. If everything goes right, your neighbor quiets down and the brain resets to normal.

The EC system plays similar roles throughout the brain and the body. It is involved in the regulation of mood, memory, appetite, pain, and movement, among other things. In appetite regulation, for instance, it is believed that ECs play a major role in "energy homeostasis," in part by encouraging the growth of fat cells.

A system this widespread and so involved in maintaining balance in so many different biological processes is hardly one we want to lightly tamper with. Hence, the concern over recreational marijuana use, particularly in the young when the brain has yet to complete its process of development.

But scientists are quick to note that the endocannabinoid system begs the need to develop specially targeted medical interventions. According to this 2006 review article in Pharmacological Review:

Modulating the activity of the endocannabinoid system turned out to hold therapeutic promise in a wide range of disparate diseases and pathological conditions, ranging from mood and anxiety disorders, movement disorders such as Parkinson's and Huntington's disease, neuropathic pain ...

Likewise, this, from Current Neuropharmacology (2008):

In the brain, endocannabinoid signaling is mostly inhibitory and suggests a role for cannabinoids as therapeutic agents in central nervous system disease. Their ability to modulate synaptic efficacy has a wide range of functional consequences and provides unique therapeutic possibilities.

Unfortunately, because cannabis is classified as a Schedule One controlled substance by the FDA, we know next to nothing about these possibilities.

Depending on what source you read, there are some 60 to 100 different cannabinoids in the marijuana plant. These are chemical cousins of the endocannabinoids found naturally in the brain and the body. The most well-known is THC, which is the psychoactive agent in marijuana. But the other cannabinoids may account for some of the therapeutic benefits, plus a host of unknown ones.

There may well come a day when doctors prescribe "smart cannabinoid" meds, specific agents targeted to achieve specific results for a specific condition. In the meantime, we have do-it-yourself "medical marijuana."

Previous articles:

Medical Marijuana for Bipolar? Getting High is NOT the Object

Medical Marijuana: The User's Dilemma