In part 1 of what marijuana really does to your brain, we traced the discovery of the cannabinoid receptor. Finding the receptor is the first step in determining how smoking causes a high. The next step is to figure out where cannabinoid receptors are and what they’re doing.

In 1989, the year after the cannabinoid receptor was discovered, Miles Herkenham led a group of researchers at the National Institute on Mental Health to find out where cannabinoid receptors were located in the brain. He first collected brains of three deceased humans whose bodies had been donated to science. He sliced the brains so he could quantify how many cannabinoid receptors were in each region. Then he labeled CP-55,990, the same synthetic version of THC used to discover the cannabinoid receptor, with a radioactive form of hydrogen atom called tritium. He squirted the radio-labeled CP-55,990 onto the brain slices and then took pictures of them using film that was sensitive to tritium. He found the receptor in many parts of the brain, but they were most densely packed in the hippocampus, amygdala, striatum and cerebellum. As we will see, it is not surprising that Herkenham identified these four regions—they are responsible for many of the functions that marijuana influences.

1.       Impaired memory

Marijuana may not destroy memories, but it can prevent you from forming new ones. One way researchers test memory is by reading a list of words to someone and later asking them to repeat the list or recognize the original words from a new list. A number of studies have shown that when the researcher read the words before participants smoked, the participants remembered the words just as well if the joint contained marijuana or a placebo. If the researcher read the words after participants smoked, however, they remembered less if the joint contained marijuana. Since we know that marijuana can disrupt memory, the likely target in the brain is the hippocampus, the region most linked to memory formation. When cannabinoid receptors in the hippocampus are activated, they interfere with a cellular process called long term potentiation, a long-lasting booster of cross-talk between neurons. Studying for a test high may not be the best idea because THC disrupts the hippocampus’ cellular process of creating new memories.

2.       Reduced anxiety

A group of multiple sclerosis patients were given marijuana as an experimental treatment, and they reported a consistent side-effect. 89 percent reported reduced anxiety after smoking. Since regular marijuana users tend to have higher than normal anxiety levels, they may smoke in part to ease their worries. The brain produces a chemical, anandamide, that targets the cannabinoid receptor, the body’s own form of THC. Anandamide gets deactivated by an enzyme called FAAH, or fatty acid amide hydrolase. A group of researchers at the National Institute on Alcohol Abuse and Alcoholism injected a chemical into the amygdala region of mice brains to block FAAH from deactivating anandamide, which allows it to have longer-lasting effects. The amygdala has a high concentration of cannabinoid receptors and is the brain region most associated with fear and anxiety. When FAAH was blocked in the amygdala, mice were less afraid of cues previously paired with shocks. The authors found a similar effect in humans. People with a gene that produces a lower functioning version of FAAH, and who consequently have more anandamide, were quicker to learn that a threatening cue was harmless. Marijuana may reduce anxiety because THC binds to cannabinoid receptors in the amygdala, reducing the brain’s threat response.

3.       Disrupted motor control

The greatest concentration of cannabinoid receptors reside in the striatum and substantia nigra, parts of the brain responsible for coordinating movement. These brain regions also deteriorate in Parkinson’s Disease, and like Parkinson’s, one of the signature effects of THC is poor motor control. That’s partly why marijuana, like alcohol, compromises driving ability. A recent study from an emergency room in Canada found that 20 percent of driver’s injured in car accidents had THC in their blood, even though, according to UN estimates, only 4 percent of the population smoked in the past year. A group of researchers asked the marijuana users about their driving habits and determined that the drivers were 4x as likely to crash when they were high compared to when they drove sober at the same time of day. 

4.       Stoked appetite

At Seattle’s 2013 Hempfest, police wanted to remind attendees of the state’s pot laws. To make sure Hempfesters got the message, they attached the rules to bags of Doritos. They capitalized on a long-held belief about marijuana: it boosts desire to eat junk food, also known as the munchies. A 2001 study in the journal Nature offers an explanation. The study found that activating cannabinoid receptors in a part of the brain called the hypothalamus could trigger the release of leptin and neuropeptide Y, hormones that stimulates appetite. You don’t need much coordination to down a handful of Doritos.

5.       Elevated heart rate

"I vaped a bunch of weed last night and I counted my heart rate at 120 beats per minute,” said a user on the message board at Increased heart rate is a common effect of marijuana, often leading to a 50 percent increase in beats per minute. Peak heart rates usually occur 15 minutes after peak THC concentrations. Studies have found that the risk for heart attack is 4.8 times higher in the hour after smoking marijuana compared to the hour before (4.8 times a small number, however, is still a small number). A group of researchers at the National Institute on Drug Abuse led by Marilyn Huestis tested whether the brain’s cannabinoid receptors caused the elevated heart rate. They gave some people a chemical called SR141716 that blocks the brain’s cannabinoid receptors, and other people received a placebo. They then had all participants smoke a joint of marijuana. The group that got a placebo had an average increase of 30 heart beats per minute after smoking. The group that got SR141716 only increased their heart rate by 10 beats per minute. The group who took SR141716 also reported feeling less high than the group smoking marijuana without the antagonist. Based on this evidence, the increase in heart rate after smoking marijuana likely occurs when THC activates cannabinoid receptors in the brain. 

6.       Altered sleep

This is the effect with the least solid evidence. According to pot critic William Breathes, some strains of marijuana help him fall asleep. But research into this has produced mixed findings, with some evidence suggesting that high THC concentrations can even prevent sleep, inducing restlessness instead. The subjects in that study did not have a history of heavy cannabis use, so the effect on sleep may have to do with tolerance. One effect on sleep seems fairly consistent: THC reduces the amount of time a person spends in rapid eye movement sleep, the phase of sleep where most dreaming occurs.    

7.       Reduced pain

Dating back over 1,500 years, one of the earliest recorded uses of marijuana was to numb pain during surgery. They didn’t have microscopes to look at nerve cells back then, but they were already observing something that modern neuroscientists have only explained in the past 20 years. Many of the nerve cells in our body that carry pain signals have cannabinoid receptors, from the body to the spinal cord up into the brain. When researchers activated the cannabinoid receptors in the spinal cords of rats, they would leave their tail on a hot plate for longer before moving it, suggesting that it didn’t hurt as much. One of the brain’s main pathways of pain signals, the periaqueductal gray region, is heavily populated with cannabinoid receptors. Similarly, activating these receptors makes rats less sensitive to pain. Marijuana’s ability to numb pain is one of the reasons some patients seek it to deal with cancer treatment.  

Those are 7 short term effects of THC. Come back for Part 3 to find out about the long term effects of marijuana on the brain.

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