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Does cannabis affect dopaminergic signaling in the human brain? A systematic review of evidence to date

Add to Mendeley

Abstract

A significant body of epidemiological evidence has linked psychotic symptoms with both acute and chronic use of cannabis. Precisely how these effects of THC are mediated at the neurochemical level is unclear. While abnormalities in multiple pathways may lead to schizophrenia, an abnormality in dopamine neurotransmission is considered to be the final common abnormality. One would thus expect cannabis use to be associated with dopamine signaling alterations. This is the first systematic review of all studies, both observational as well as experimental, examining the acute as well as chronic effect of cannabis or its main psychoactive ingredient, THC, on the dopamine system in man. We aimed to review all studies conducted in man, with any reported neurochemical outcomes related to the dopamine system after cannabis, cannabinoid or endocannabinoid administration or use. We identified 25 studies reporting outcomes on over 568 participants, of which 244 participants belonged to the cannabis/cannabinoid exposure group. In man, there is as yet little direct evidence to suggest that cannabis use affects acute striatal dopamine release or affects chronic dopamine receptor status in healthy human volunteers. However some work has suggested that acute cannabis exposure increases dopamine release in striatal and pre-frontal areas in those genetically predisposed for, or at clinical high risk of psychosis. Furthermore, recent studies are suggesting that chronic cannabis use blunts dopamine synthesis and dopamine release capacity. Further well-designed studies are required to definitively delineate the effects of cannabis use on the dopaminergic system in man.

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Does cannabis affect dopaminergic signaling in the human brain? A systematic review of evidence to date Add to Mendeley Abstract A significant body of epidemiological evidence has linked

The Relationship Between Cannabis and Dopamine

Cannabis contains over 100 active cannabinoids, making it an incredibly complex plant. Every time we consume cannabis in any form, many reactions occur within our body and mind. The purpose of this piece is to educate our readers on the relationship between cannabis and dopamine.

Addiction and Dependence

Although cannabis is not physiologically addictive, its effects have been linked to some forms of psychological dependence. Unlike alcohol, cannabis is not chemically addictive; therefore, it doesn’t have the harsh withdrawal symptoms associated with alcoholism, tobacco smoking, or narcotic substances.

That said, cannabis can impose a form of psychological dependence in long-term users. Regular cannabis users get used to smoking weed, and it becomes a habit that can be hard to quit. This is all down to the relationship between cannabis and a chemical in our brain, known as dopamine.

cannabis can impose a form of psychological dependence in long-term users

What is Dopamine?

Dopamine is a neurotransmitter that helps to process our brains’ natural reward system. It is released in response to pleasurable stimuli. Activities such as sex, sleep, and eating all-cause dopamine to be released in the brain, giving us a feeling of satisfaction and making us feel relaxed and content.

Most illegal narcotics are designed to rapidly increase dopamine levels because it gives us feelings of happiness and pleasure without reason. Dopamine also helps to regulate emotional responses and mood, triggering a feeling of anticipation before we enjoy something. This is one of the reasons that people feel satisfied when they get ‘high’ from smoking cannabis. Your brain is tricked into thinking that you have just done something good for yourself, and in some ways, you did!

Alternatively, a lack of dopamine can be dangerous. Low levels of dopamine are associated with risk-takers and adrenaline junkies. Therefore, if your dopamine levels are low, you’re more likely to become involved in dangerous activities. Lack of dopamine can also be a precursor to serious conditions such as Parkinson’s disease. This progression happens because the disease decreases the levels of dopamine-producing neurons.

How Does Dopamine Interact with Cannabis?

Like most recreational drugs, cannabis increases dopamine levels in the brain for a short period of time. This happens when the THC compound in cannabis binds to the CB1 and CB2 receptors located in the brain.

Dopamine neurons have no cannabinoid receptors present. So, cannabinoids cannot act directly on them. However, GABA neurons limit the amount of dopamine released in our reward pathways. GABA neurons contain no cannabinoid receptors, so they inhibit them, creating a double-negative situation in the brain. When GABA neurons inhibit what inhibits dopamine neurons, cannabinoids increase levels of dopamine in the brain indirectly.

However, this function is already carried out by the endogenous cannabinoids in our bodies. Therefore, a lack of these chemical compounds is dangerous. It can cause symptoms of anxiety and depression. In a paper published in 2013 , mice that were born with no cannabinoid receptors were less enthusiastic about exercise and deemed unhappy compared to normal mice. Researchers concluded that our endocannabinoid system is in charge of the everyday release of dopamine as we carry out activities.

cannabinoid receptors explained in infographic

Short and Long-Term Impact on the Brain

Please note, CBD and THC have very different effects on the brain’s dopamine system. All of the information above was written concerning THC. CBD is non-psychoactive, so it is unlikely to increase dopamine levels or have any significant effects on the brains’ reward system.

However, a 2016 paper clearly stated:

“Acute THC administration causes increased dopamine release and neuron activity, whereas long-term use is associated with blunting of the dopamine system.”

This idea is quite easy to explain. Our bodies slow down their natural production and release of dopamine when it is regularly released by external sources, such as cannabis containing THC.

Not to worry too much though, if you’ve been a regular cannabis smoker for some time and you are trying to quit, The Department of Psychiatry from the New York State Psychiatric Institute compared the brain of previous marijuana consumers with that of a non-consumer, and the results were surprising.

After a period of time, the dopamine receptors in the brain’s reward system had returned to the norm. These could not be differentiated from the control group.

Cannabis contains over 100 active cannabinoids, making it an incredibly complex plant. Every time we consume cannabis in any form, many reactions occur within our body and mind. The purpose of this piece is to educate our readers on the relationship between cannabis and dopamine. Addiction and Dependence Although ca