Mechanism of Action

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THC, the main active ingredient in marijuana, binds to and activates specific receptors, known as cannabinoid receptors. There are many of these receptors in parts of the brain that control memory, thought, concentration, time and depth perception, and coordinated movement. By activating these receptors, THC interferes with their normal functioning.

The cerebellum is a part of the brain involved in balance, posture, and coordination of movement. The cerebellum coordinates the muscle actions ordered by the motor cortex. Nerve impulses alert the cerebellum that the motor cortex has directed a part of the body to perform a certain act. Almost instantly, impulses from that part of the body inform the cerebellum as to how the action is being carried out. The cerebellum compares the actual movement with the intended movement and then signals the motor cortex to make any necessary corrections. In this way, the cerebellum ensures that the body moves smoothly and efficiently.

The hippocampus is involved with memory formation. Studies suggest that marijuana affects memory by decreasing the activity of neurons in this area. Because the hippocampus is involved in new memory formation, someone under the influence of marijuana will have impaired short-term memory, and new learning may be compromised. However, most studies in humans suggest that if a person stops using marijuana, their memory abilities can recover.

Marijuana also affects brain areas responsible for sensory perception (for example, touch, sight, hearing, taste, and smell) in the cerebral cortex. Most sensory information that comes from the body is routed through the thalamus, and then on to appropriate areas of the cerebral cortex. For example, the somatosensory cortex receives messages interpreted as body sensations, such as touch. The somatosensory cortex lies in the parietal lobe of each hemisphere. The somatosensory cortex is organized in such a way that the entire body is represented, so that it can receive and accurately interpret impulses from a specific body part. Other specialized areas of the cerebral cortex receive the sensory impulses related to seeing, hearing, taste, and smell. Impulses from the eyes travel along the optic nerve and then are relayed via the thalamus to the visual cortex in the occipital lobes. Portions of the temporal lobes receive auditory messages from the ears. The area for taste lies buried in the lateral fissure, which separates the frontal and temporal lobes. The center for smell is on the underside of the frontal lobes-smell is the only sense that is not relayed through the thalamus. Olfactory nerves carrying this information go through the olfactory bulb and directly to the cortex. Marijuana activates cannabinoid receptors in these various cortical areas, leading to altered sensory perception that users experience under the influence.

In the late 1980’s, it was discovered that THC acted at specific receptors in the brain, which became known as cannabinoid receptors. It was then hypothesized that, because these receptors exist, there must also be a substance naturally produced in the brain that acts on them. In 1992, scientists discovered a substance that activates the THC receptors and has many of the same physiological effects as THC. The scientists named the substance anandamide, from a Sanskrit word meaning “bliss.” The discovery of anandamide opened whole new avenues of research, which led to the discovery of additional cannabinoid molecules and receptors. One of these, 2-arachidonoglycerol, is similar to anandamide, and helps control pain. Scientists continue to study the functions of anandamide and 2-arachidonoglycerol in the brain, with the hope of understanding not just how marijuana exerts its actions and why it is abused, but also how the cannabinoid system contributes to brain function under normal (non-drug) conditions.

Marijuana’s potential medicinal effects have long been hypothesized. Indeed, oral forms of THC (e.g., marinol) are already currently available to treat nausea associated with chemotherapy and to stimulate appetite in AIDS wasting syndrome. The discovery of the brain's own THC-like substances, and their unique mode of action, should help uncover the mechanisms underlying the therapeutic potential of cannabinoids, which could then lead to the development of more effective and safer treatments for a variety of conditions, including addiction, pain, obesity, multiple sclerosis, etc.

The following activities will help explain to students how these substances change the brain and the body.

This publication is available for your use and may be reproduced in its entirety without permission from NIDA. Citation of the source is appreciated, using the following language: Source: National Institute on Drug Abuse; National Institutes of Health; U.S. Department of Health and Human Services.