1185

Written by:

How THC Impacts Habit Memory

Pharmacology

Habit memory drives much of our unconscious behavior throughout the day. This is regulated by the endocannabinoid system, so how is it impacted by THC?

We all have habits that we stick to throughout our day. In fact, a surprisingly lot of our decisions are made on autopilot by sticking to what we have done dozens or hundreds of times before. Specific situations trigger a specific reaction in us almost automatically. This set of patterns depends on something called habit memory (also called stimulus-response memory).

All habits start as goal-directed behaviors, which are controlled be conscious decisions. For example, you open Facebook on your phone with the intention of checking what time an event starts. However, after being repeated many times, habits start to form. Soon, just seeing a phone will trigger you to open Facebook for no reason in particular. During this process, control of your behavior literally switches from one brain region to an entirely different one.

Although habits can make our lives easier, we also need to be able to change our habits when it benefits us. There are several mental health conditions where we lose the ability to maintain control over our habits. With the ongoing opioid epidemic, addiction is one that we hear about often.

Most people are aware that cannabis can affect our conscious memory,  but few realize that it can also affect habit memory. This is not surprising since it is a completely unconscious process and thus almost impossible to observe in yourself. Yet, the endocannabinoid system plays a crucial role in habit learning and regulating which part of your brain maintains control over your behavior.

This is therefore an opportune time to review the latest research on the link between cannabinoids and habit memories. Much of the information presented below comes from this excellent review article.

How Habit Memory Works

The striatum [Wikimedia commons]

The most important part of your brain for habit memory is the striatum, an area below your cerebral cortex. The striatum coordinates several things, including action planning, decision making, motivation, and reward. The striatum receives input from the cortex and in turn regulates many brain regions below it.

The striatum consists primarily of medium spiny neurons,  These neurons comprise 95% of the neurons in the striatum.

Medium spiny neurons [Wikimedia Commons]

Not every part of the striatum is involved in habit learning. The most important part is the the dorsolateral striatum (DLS). The DLS is regulated by neurons that project from other brain areas, including corticostriatal projection neurons. These neurons originate from different parts of the cortex and utilize the excitatory neurotransmitter glutamate. Glutamate release into the DLS is absolutely necessary for normal acquisition and consolidation of habit memory.

Perhaps the most important neural pathway is the one that controls the switch from conscious, goal-directed behavior to habitual behavior. A recent 2016 study has reported that this switch is regulated by neurons that project from the orbitofrontal cortex (OFC) to the DLS.  Without proper functioning of this pathway, habitual behavior is never activated.

Orbitofrontal Cortex [Wikimedia Commons]

Role of the Endocannabinoid System in Habit Memory

The formation of habit memory depends on your DLS making an association between a stimulus and a specific behavior (for example, seeing your smartphone and then opening Instagram). This learning requires synaptic plasticity. Synaptic plasticity involves short- and long-term changes in how specific synapses release neurotransmitters.

The cannabinoid CB1 receptor is the most important receptor for synaptic plasticity. CB1 receptors in the DLS are located both in the medium spiny neurons and the corticostriatal projection neurons. Through plasticity, temporary activation of the CB1 receptor on these neurons can lead to long-term suppression of neurotransmitter release.

Infusion of a CB1 antagonist directly in the DLS was sufficient to slow development of habit memories in rodents. This is not surprising since a CB1 antagonist will block synaptic plasticity. It didn’t matter if the antagonist was administered after the habit training period was over. Synaptic plasticity occurs during the process of memory consolidation, which occurs in the hours after the training.

In one set of experiments, mice were trained to press a lever for food, which they intermittently received. Then, they were given as much of the food as they could eat and put back in the cage with the lever. The mice continued to press the lever out of habit, even though they were already as full as could be.

Recently checked every social media update…still takes out phone [Wikimedia]

However, mice with an inactivated CB1 receptor (either from an antagonist or through genetic deletion) did not continue to press the lever for food. They only pressed the lever as a goal-directed behavior (i.e. they were hungry and wanted the food) and not as a habitual behavior.

The 2016 study (mentioned in the previous section) refined our knowledge even further. They removed the CB1 receptor specifically from the glutamatergic neurons that project from the OFC. These mice were similarly unable to develop habitual behaviors. It appears that the endocannabinoid system is in control over the “switch” that happens from goal-oriented to habitual behavior!

What THC Does To Habit Memory

The previous section showed that the endocannabinoid system is crucial for forming habit memories. Inactivating the CB1 receptor blocks formation of habit memories and activation of habitual behavior. So then what does activating the CB1 receptor with THC do?

Treatment of rodents with a single dose of a CB1 agonist reduced habit memory formation. Flooding the system and activating CB1 receptors at every synapse had just as much effect as blocking the CB1 receptors.

The above study only dosed during the period of time after the habit training. It probably has little relevance to humans since habits are formed over a longer period of time and a single dose of THC here and there won’t have too much effect.

So what happens with regular cannabis consumption? We know that frequent exposure to THC will cause tolerance to it’s effects. This tolerance involves adaptive changes, including downregulation of CB1 receptors in the DLS. If frequent THC downregulates the CB1 receptor, then does chronic THC consumption reduce habit formation, similar to what happens in the CB1 knockout mice?

Actually, the opposite occurred. Mice given regular THC had stronger habitual responding. This experiment was similar to the study described above where mice were trained to press a lever for food (except in this case, they poked their nose through a hole instead of pressing a lever.)  The mice given vehicle injections (i.e. no THC) stopped the nose poking once they were fed. The THC-tolerant mice continued to perform nose pokes at nearly the same rate whether they had just eaten or not. Their behavior was completely based on habit and was no longer goal-directed.

Obviously we need to question how these rodent studies translate to humans, but there is evidence that regular cannabis users depend more on habit memory than non-users. However, we are still in the early stages of understanding this and more research is needed before we can say what the implications are.

Pathological Habit Memory

[Ellsworth Air Force Base]

So what is the relevance of all of these results to human behavior – that smoking weed will make you habitually check your iPhone more often? Smart phones probably are the greatest naturalistic experiment of habit memory in human history, but it gets more serious than that.

Several mental health disorders have strong habit-like features. These include, obsessive-compulsive disorder, drug addiction and relapse, PTSD, and eating disorders.

In all of these diseases, people become locked into certain habits that they cannot escape. Different parts of their brain are battling for control of behavior. The cortex is trying to maintain goal-directed behavior, but it has lost control over the DLS and its habit-directed behavior.

Since cannabinoids regulate striatal activity and the shift from goal-oriented to habit behavior, they may offer new treatment options for these diseases. I will go into more details on this in future articles.

Want to read more about cannabinoids and memory? Here are the 5 types of memory impacted by THC.

Last modified: September 18, 2017

Leave a Reply

Your email address will not be published. Required fields are marked *