Adjusting One Brain Chemical May Remove Desire for Chronic Marijuana Use

People who fall into chronic marijuana use may have substantial shortages of a brain chemical linked to depression and anxiety, researchers at Vanderbilt University have discovered.

Marijuana is an increasingly popular recreational drug that produces harmful outcomes for a fairly large percentage of users, especially young users and habitual or chronic users. One of these outcomes is the development of cannabis use disorder, a condition that encompasses dysfunctional, non-addicted cannabis abuse and cannabis addiction. In a study published in November 2014 in the journal Cell Reports, researchers from Vanderbilt used laboratory experiments on mice to explore the possibility of eliminating the basic motivation for chronic marijuana intake by preventing the breakdown of naturally occurring substances in the brain called endocannabinoids.

Chronic Marijuana Consumption

A chronic marijuana user consumes the drug on a daily or near-daily basis; as a rule, consumption takes place multiple times per day. This pattern of intake repeatedly exposes the brain to THC (tetrahydrocannabinol), the main ingredient in marijuana and all other forms of cannabis. When THC reaches a part of the brain known informally as the pleasure center, it triggers chemical changes that result in an intense sensation called euphoria. In a chronic marijuana consumer, recurring alteration of the pleasure center’s chemical environment sets the stage for the ultimate development of physical cannabis dependence and the onset of cannabis addiction. According to data compiled by the National Institute on Drug Abuse, a minimum of 25 percent of habitual marijuana users will develop such an addiction over the course of their lifetimes; however, the addiction rate in habitual users may actually be as high as 50 percent.

Some marijuana consumers initiate a pattern of chronic intake merely because they like the euphoric feeling produced by the drug. However, other users fall into such a pattern because they rely on marijuana as a form of self-medication for anxiety or other generally unpleasant emotional states. Unfortunately, the chemical changes triggered by repeated marijuana consumption can actually make the brain more susceptible to these unpleasant states, not less susceptible.


THC is known as a cannabinoid; this means that the substance reaches the brain through sites, called cannabinoid receptors, located on certain nerve cells. However, these receptors are actually intended to provide brain access for naturally occurring internal chemicals called endocannabinoids. All humans rely on these chemicals for things such as pain relief, inflammation control, breakdown of dietary fat, energy processing and proper control of blood sugar levels. One well-studied endocannabinoid known as anandamide bears a striking resemblance to THC and produces a similar (although far less intense) effect inside the brain. However, the brain and body also contain a much more abundant endocannabinoid called 2-AG, which has a substantial effect on brain function.

Eliminating Marijuana Motivation

In the study published in Cell Reports, the Vanderbilt University researchers used laboratory experiments on mice to look at what happens to the brain when its levels of the endocannabinoid 2-AG are altered. The underlying purpose of these experiments was a desire to see if it’s possible to create a natural internal substitute for the anxiety-relieving effects of THC and thereby eliminate at least some of the motivation that drives chronic marijuana consumption.

During the first phase of the experiments, the researchers chemically manipulated the brains of a group of mice in order to lower these animals’ naturally occurring 2-AG levels. In response to this chemical change, the mice displayed a significant increase in behaviors that mirror anxiety in humans. In addition, some of the female mice exhibited behaviors that mirror the symptoms of depression in humans. In the second phase of the experiments, the researchers reversed the chemical manipulation and allowed the mice’s 2-AG levels to return to normal. In response to this restoration, the animals stopped displaying anxious and depressed behaviors.

The study’s authors believe that their experiments may provide a fairly accurate model of the role that 2-AG plays inside the human brain. They also believe that their findings indicate that at least some people who fall into chronic marijuana use may have substantial shortages of this chemical. If this is true, future pharmaceutical researchers may be able to develop ways to correct 2-AG shortages and thereby ease some of the anxiety and depression that motivate chronic marijuana consumers’ ultimately misguided attempts at self-medication. The Vanderbilt University research team has already started to develop potential medications that increase endocannabinoid levels inside the brain.

Posted on March 11th, 2015
Posted in Drug Addiction

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