How THC Reduces And Intensifies Anxiety | The Two Poles of THC

How THC Reduces And Intensifies Anxiety

Why do people use marijuana? The main goal, as most of its users declare, is to achieve a state of relaxation — to relax after a hard day or to relieve unpleasant symptoms of stress.

Do these individual opinions find confirmation in scientific data? Which brings us to the main theme of this article ” How THC Reduces And Intensifies Anxiety”

How does THC reduce and intensify anxiety?

A very interesting article was published in the pages of Drug and Alcohol dependence a year ago. It presented the results of a clinical trial, in which attempts were made to determine the effect of tetrahydrocannabinol (THC) on the well-being of healthy volunteers who were subjected to temporary stress. The results are as follows:


After the healthy volunteers were subjected to a temporary stress, they were given a low dose of THC (7.5 mg) which actually reduced the feeling of anxiety often associated with stress. However, when they were given a higher dose of THC (12.5 mg), it intensified their feeling of anxiety.


Now you might wonder why the same substance, although used in different doses, cause such different effects?

The simple answer to that is because the effects of cannabinoid agonists (CB1 receptors) on anxiety is biphasic, meaning they have two phases. Thus, when THC is administered in low doses and combines with CB1 receptors, it is anxiolytic but when administered in high doses they become anxiogenic.

Regions of the brain

Amygdala and hippocampus 

The part of the brain that processes sensory information and relays it to various parts of the brain.

The prefrontal cortex

The area of the brain that exerts control over emotions and behaviours. When it’s functioning properly, it can suppress the anxiety sent by the amygdala.

These three areas of the brain are interconnected, creating a network that receives and integrates the information provided to decide on the final response to a given stimulus, i.e. stress.

However, these different parts of the brain can sometimes send conflicting messages when under influence i.e. THC.

THC induced anxiety

How did scientists determine the role of different brain areas in the modulation of THC-induced anxiety?

They injected THC to each of these areas of the brain in a mice and studied changes in the rodent’s behaviour in a cross-maze labyrinth (the model for anxiety testing in animals).

Cross-maze labyrinth

Cross-maze labyrinth

The method is based on a rodent’s normal preference for a dark room as opposed to exploring open and heavily lit spaces — which “awakens” anxiety in rodents. Before the actual test, the animals undergo an adaptation period – they are placed in a wooden box with appropriate dimensions for a period of 5 minutes. After this time, the rodent is moved to a cross-shaped labyrinth, which has open and closed “arms”.

The central point of the labyrinth is illuminated by a light bulb. Within 5 minutes of the test, the time the animal stays in the open arms of the labyrinth is recorded by two observers, sitting at a suitable distance from the place of the experiment. It is worth mentioning that, the use of anxiolytic drugs in the studied animals caused the animals to stay longer and frequent the open space of the labyrinth.

Let’s get back to our experiment. The administration of small amounts of THC to the amygdala resulted in the mice not even exploring the bright space of the maze. Therefore, the administration of THC to this area of the brain caused great anxiety in these animals. But when low doses of THC was administered directly to the prefrontal cortex and hippocampus, it increased the courage of the mice (to explore bright spaces), but higher doses caused fear, and rodents more often remained in the dark.

The conclusion of the experiment

What conclusions arise from this experiment? Although THC in a small dose can cause anxiety through the amygdala, this effect is probably suppressed by anxiolytic effects in the hippocampus and prefrontal cortex. Furthermore, in response to high doses of THC, all three areas of the brain generate anxiety. Although the above conclusions relate to animal studies, it is difficult to determine if a similar situation also occurs in people who are anxious with a high THC dose.

That being said, it will differ from person to person, our individual bodies will respond differently to THC and stress.

Do not forget about the neurotransmitters present in the central nervous system, which have a significant impact on emotions, i.e. glutaminic acid (excitatory neurotransmitter, enhances anxiety) and gamma-aminobutyric acid GABA (inhibitory neurotransmitter, reduces anxiety).

THC can regulate the release of glutamate and GABA by activating the CB1 receptor that is present in both glutamatergic neurons and GABAergic neurons in the prefrontal cortex.

Low doses of THC reduce the level of glutamic acid (acting directly on glutaminergic neurons). High doses of THC increase the concentration of this neurotransmitter (acting indirectly through GABAergic neurons).

It has been hypothesized that CB1 receptors are more easily activated on glutamatergic neurons than on GABAergic neurons. Low THC doses can activate CB1 receptors only on glutamatergic neurons, which reduces glutamate and anxiety. At higher doses of THC, CB1 receptors are activated on GABAergic neurons. This reduces the release of GABA and ultimately increases glutamate and anxiety.

Wrap up

Issues regarding THC and its pro-anxiolytic activity are a difficult and complex issue, but how fascinating.

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