Downregulation and Upregulation of Receptors

In a previous blog entry, Overview of How the Endocannabinoid System Works, we described how our Endocannabinoid Systems (ECSs) contain three basic sets of components: 

  • Cannabinoid receptors: Receptors on cell membranes that are activated by cannabinoids
  • Cannabinoids: The messengers, or neurotransmitters, that activate cannabinoid receptors
  • Cannabinoid enzymes: The enzymes that break down, or inactivate, cannabinoids

Each type of cell has a particular speed at which new cell receptors are naturally synthesized and then subsequently degraded. However, activation of cell receptors by messengers causes receptors to degrade more quickly.[1]

The number of receptors present on the cell at any given time thus depends on how quickly new receptors are being synthesized, relative to how quickly existing receptors are degrading. If receptors are degrading faster than they’re being synthesized, then the total number of receptors on the cell will decrease, or experience downregulation. Conversely, if receptors are being synthesized faster than they’re degrading, the total number of receptors on the cell will increase, or experience upregulation (see Figure 1).

Introduction to the Endocannabinoid System

I’m a researcher. Just over two years ago, I was introduced to the subject of medical cannabis. My quest was to understand how cannabis works in our bodies to provide medicinal benefits. It’s been a little over two years since I started my research, and I’ve learned quite a bit. 

The more I’ve read, the more overwhelmed I’ve become at how extraordinarily complex the human body is. Our bodies are the product of millions of years of evolution, and it shows. Our bodies are like tremendous orchestras, with more instruments in our bodies (cells) than there are stars in the sky. And not only are there brass and string and percussion instruments – akin to our circulatory and digestive and immune systems – but within each system there are scores of sub-systems. Within the wind instruments are numerous flutes and oboes and clarinets and saxophones and bassoons. 

The average human body contains about 33 trillion cells of about 200 different types, 100,000 miles of blood vessels, and 640 skeletal muscles. Every day, the average adult takes over 20,000 breaths, experiences 100,000 heartbeats, processes about 200 quarts (50 gallons) of blood through the kidneys, and filters out about 2 quarts of waste and water. 

Overview of How the Endocannabinoid System Works

So how does the Endocannabinoid System (ECS) in our bodies work? To understand this, we first have to understand some basics about cells and cell-to-cell communications.

Cells

cell is the smallest unit of life. Cells are often called the "building blocks of life." Our bodies are comprised of trillions and trillions of different cells, approximately 32.7 trillion cells in all, of more than 200 different types

Cells Cluster

Each cell has a particular function to perform. At the same time, however, cells cluster to form tissues, organs, and body systems, where they work together with other cells to serve larger functions (see Figure 1)

Figure 1: Cell Clusters

1 cell clusters

Why Most Doctors Are Reluctant to Recommend Medical Cannabis

My brother has multiple sclerosis (MS). MS is a degenerative disease affecting the brain and spinal cord; it generally causes problems with vision, balance, and muscle control. My brother’s body was deteriorating, but none of the medications his doctors recommended seemed to help. While researching the disease on his own, however, he discovered that stem cell transplants have been successfully used to halt the progression of the disease. He was unable to undergo the procedure in the US; he eventually had it performed in Mexico. It’s been 1,193 days since my brother’s stem cell transplant, and so far, the disease has not progressed (my brother has documented his journey here).

My brother, along with many of the people (from all over the world) who underwent the transplant procedure with him in Mexico, was extremely frustrated that none of his doctors had even mentioned — let alone recommended — having a stem cell transplant. Just recently, one of his doctors, Dr. Timothy West, formerly of UCSF Multiple Sclerosis Center and Sansum Clinic, Santa Barbara, gave a talk that provided some much-needed clarity on the issue.

Dr. West explained that when doctors get their licenses to practice medicine, they take a vow to “first, do no harm.” Doctors take this vow very seriously. In particular, doctors strongly resist recommending any treatment that may cause patients harm. Even if there’s evidence a treatment might work, if there is a risk that the treatment may cause harm to the patient, then doctors will generally refuse to take that risk, regardless of whether or not the patient himself is willing to take the risk. In the case of stem cell transplants, there is a chance that patients may die from the procedure. Consequently, doctors are not willing to recommend stem cell transplants, especially when alternative treatments are available to address the condition. My brother's blogpost describing Dr. West's comments is eye-opening:

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