Marijuana and the Human Brain

Receptors in the brain

The locations of the cannabinoid receptors are most revealing of the way THC acts on the brain, but the importance of this determination is best understood in comparison with the effects of other drugs on the brain.

Neurons are brain cells which process information. Neurotransmitter chemicals enable them to communicate with each other by their release into the gap between the neurons. This gap is called the synapse. Receptors are actually proteins in neurons which are specific to neurotransmitters, and which turn various cellular mechanisms on or off. Neurons can have thousands of receptors for different neurotransmitters, causing any neurotransmitter to have diverse effects in the brain.

Drugs affect the production, release or re-uptake (a regulating mechanism) of various neurotransmitters. They also mimic or block actions of neurotransmitters, and can interfere with or enhance the mechanisms associated with the receptor.

Dopamine is a neurotransmitter which is associated with extremely pleasurable sensations, so that the neural systems which trigger dopamine release are known as the "brain reward system." The key part of this system is identified as the mesocorticolimbic pathway, which links the dopamine-production area with the nucleus of accumbens in the limbic system, an area of the brain which is associated with the control of emotion and behavior.

Cocaine, for example, blocks the re-uptake of dopamine so that the brain, lacking biofeedback, keeps on producing it. Amphetamines also block the re-uptake of dopamine, and stimulate additional production and release of it.

Opiates activate neural pathways that increase dopamine production by mimicking opioid-peptide neurotransmitters which increase dopamine activity in the ventral tegmental area of the brain where the neurotransmitter originates. Opiates work on three receptor sites, and in effect restrain an inhibitory amino acid, gamma-aminobutyric acid, that otherwise would slow down or halt dopamine production.

All of these substances can produce strong reinforcing properties that can seriously influence behavior. The rewarding properties of dopamine are what accounts for animal studies in which animals will forgo food and drink or willingly experience electric shocks in order to stimulate the brain reward system. It is now widely held that drugs of abuse directly or indirectly affect the brain reward system. The key clinical test of whether a substance is a drug of abuse potential or not is whether administration of the drug reduces the amount of electrical stimulation needed to produce self-stimulation response, or dopamine production. This is an indication that a drug has reinforcing properties, and that an individual's use of the drug can lead to addictive and other harmful behavior.

To be precise, according to the Office of Technological Assessment (OTA): "The capacity to produce reinforcing effects is essential to any drug with significant abuse potential."

Marijuana should no longer be considered a serious drug abuse because, as summarized by the OTA: "Animals will not self-administer THC in controlled studies . . . . Cannabinoids generally do not lower the threshold needed to get animals to self-stimulate the brain regard system, as do other drugs of abuse." Marijuana does not produce reinforcing effects.

The definitive experiment which measures drug-induced dopamine production utilizes microdialysis is live, freely-moving rats. Brain microdialysis has proven that opiates, cocaine, amphetamines, nicotine and alcohol all affect dopamine production, whereas marijuana does not.

This latest research confirms and explains Hollister's 1986 conclusion about cannabis and addiction: "Physical dependence is rarely encountered in the usual patterns, despite some degree of tolerance that may develop."

Most important, the discoveries of Howlett and Devane, Herkenham and their associates demonstrate that the cannabinoid receptors do not influence the dopamine reward system.

Read next part Cannabinoid receptors

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