What Does Marijuana Really Do to the Brain?

By Basoodler · Jul 28, 2014 · Updated Dec 2, 2014 · ·
  1. Basoodler
    Around 4% of adults worldwide smoked cannabis at least once in the last year according to a United Nations study. That makes it the most used illegal drug in the world. But it may not remain that way. It’s not that people will use it less, but that cannabis may become legal in more places. Already, two US states and Uruguay have legalized its use.

    Changing laws reflect change in the public perception of the drug. In elementary school, I was taught to just say no to cannabis. Now, legalization supporters say it’s safer than alcohol. While perception may be in flux, one thing hasn’t changed: cannabis’ effects. With those effects cropping up in conversation more frequently as cannabis laws make headlines, it’s high time I found out what cannabis does to the brain.

    We’ve long known how cannabis—the scientific name of the plant often called marijuana or pot—makes us feel. By 100 CE, the Chinese, the first culture to have a historical record of cannabis use, were giving it as an anesthetic before surgeries. Even then, they knew it numbed pain.

    More recently, William Breathes, a pot critic for Denver’s Westword newspaper, described the effects, saying he smokes, “for mellowing out and easing anxiety after a stressful day.” One strain is “definitely great for appetite and all-around mood enhancement” he says, while another, is “naptime ganja…slamming you down, face-first, into a pillow.” But to cause those effects, cannabis must be altering brain function.

    By the 1970s, neuroscientists had isolated molecules in cannabis to test which affect nerve cells. They determined that, of the many molecules contained in cannabis, delta-9 tetrahydrocannabinol, or THC, was the chief one that changed nerve cell function. When they squirted a drop of THC on a nerve cell, the cell’s charge decreased, making it less likely to fire a message its neighbors. For THC to lower charge, cells need a receptor that responds to THC—a cannabinoid receptor—yet no one had ever identified one. At that point, cannabinoid receptors were like gravity: we were pretty sure it was there, but we had never seen it.

    One of the problems with finding a cannabinoid receptor is that THC is lipophilic, meaning it is attracted to fat molecules. This is great if you want to make pot brownies, since fats—like butter and oil—soak up the THC in cannabis leaves and taste good when baked with chocolate. But for a scientist trying to determine how THC affects nerve cells, it’s a problem. A cell’s surface is made almost entirely of fat molecules, so THC seems to interact everywhere, like a guy at a Dave Matthews Band concert offering anyone within arm’s reach a puff of his joint. But all that mingling that makes it hard to find the spot where THC exerts its effects. We needed a new tool to help uncover a cannabinoid receptor.

    In 1974, some chemists at Pfizer developed a tool that might help. They created a molecule that had a similar structure to THC, but preferred water to fat. The fat molecules on a cell’s surface repulsed this water-loving molecule, called CP-55,940. That meant it could only approach a cell in places with a receptor that attracted it, since receptors are proteins, not fats. In 1988, William Devane and Allyn Howlett, pharmacologists at St Louis University, showed that CP-55,940 bound to a receptor on a nerve cell that had never been described. When CP-55,990 did bind to that receptor, it caused the same effects on a cell as THC. Light it up and smoke it, the cannabinoid receptor was found.

    After identifying the cannabinoid receptor, the next step was figuring out how it caused a high.

    Come back for part 2 of this topic to find out about 7 short term effects marijuana has on the brain.

    By Joshua Gowin, Ph.D. on July 27, 2014 - 11:56am


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  1. Basoodler
    Part 2:

    7 Short-term Effects of Marijuana on the Brain

    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% 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% of driver’s injured in car accidents had THC in their blood, even though, according to UN estimates, only 4% 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 4 times 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 cannabis.com. Increased heart rate is a common effect of marijuana, often leading to a 50% 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 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.

    by Joshua Gowin, m.psychologytoday.com
    July 28

  2. Mindless
    It's a pity the source doesn't provide references. Nevertheless, pretty large doses do make me stagger and increase my appetite.

    The comments on use of cannabis in pain control are of great personal interest. I have arthritis, accompanied by reduced mobility of neck and spine, swelling and cramps in fingers and toes, and a high level of pain.

    The most effective opioid analgesic I've tried was buprenorphine. My current prescribed analgesic is tramadol, which was only effective at 300-400 mg daily. Neither opioid analgesic reduced inflammation, pain relief ranged from an estimated 50-75%.

    I have been ingesting full-plant extract of cannabis for around two months. Inflammation is reduced, I have a full range of movement in my neck (as opposed to little or none) and am able to makes a fist. I hadn't been able to use power-tools or screwdrivers for a few months.

    Pain is down by 90%, mobility is increased by 100%. I take tramadol as required, now at 100mg around 3-4 times per week. My mood and concentration seem improved, despite the well-known potential for short-term memory deficits during cannabis intoxication. The evident increased focus may well be due to pain relief.
  3. Basoodler
    NP .. I will get the remaining parts up when he publishes them

    ( My mobile chrome browser is really not
    Jiving on drugs forums today.. The default theme isn't loading correctly and the light weight seems a bit out of sorts (yet functional))

    I read this blog and figured it stood out in terms of detail vs readability.. I figured it might be of use to someone here.

    I can ask the author for the refs.. After I look around the blog for them of course

    Hell its a psychologist who wrote it.. He may like the fact his blog is useful to somebody

    Here are the studies linked in the 2nd post. Attached ones too

    >,March–April 2010, Vol.58(4):758–766, doi:10.1016/j.neuropharm.2009.12.010
    Cannabinoid receptor-mediated antinociception with acetaminophen drug combinations in rats with neuropathic spinal cord injury pain

    > An examination of the central sites of action of cannabinoid-induced
    antinociception in the rat. Martin WJ(1), Patrick SL, Coffin PO, Tsou K, Walker JM.
    (1)Schrier Research Laboratory, Department of Psychology, Brown University,
    Providence, RI 02912, USA.
    PMID: 7776838 [PubMed - indexed for MEDLINE]

    >Smith PB, Martin BR. Spinal mechanisms of delta 9-tetrahydrocannabinol-induced
    analgesia. Brain Res. 1992 Apr 24;578(1-2):8-12. PubMed PMID: 1324767.

    > Schierenbeck T, Riemann D, Berger M, Hornyak M. Effect of illicit recreational
    drugs upon sleep: cocaine, ecstasy and marijuana. Sleep Med Rev. 2008
    Oct;12(5):381-9. doi: 10.1016/j.smrv.2007.12.004. Epub 2008 Mar 3. Review. PubMed
    PMID: 18313952.
  4. Meow Tse Dung
    I do find it interesting that the effect on sleep is the least well documented, but maybe they all fell asleep before they could write the results of the tests. But I do have some mixed feeling about the effect on memory and appetite, I can't deny that my cat does seem to lose the lighter he was just holding from time to time but if he is focused on what he is supposed to remember it doesn't seem to disappear, and when tolerance is high my cat's appetite does seem to be somewhat unaffected (also some french study from yonks ago the pointed to stoners having a lower BMI on average, went hunting around for it but can't find it yet)

    None the less, I'm on the edge of my seat, waiting for part 3 like it's the next episode of my favourite TV show.
  5. Basoodler
    Part 3 (finally)

    Long Term Effects of Marijuana on the Brain

    by Joshua Gowin, m.psychologytoday.com
    September 18

    Some long-term effects are carry-over short-term effects. Since fat attracts THC and cellular walls in your body are composed of fat, THC gets sucked up by cells everywhere. THC then gets re-released gradually, which is why you can test positive for marijuana up to a month after you put down your hash pipe. So many short-term effects, like impaired memory and driving, might endure.

    To test this idea, a recent study compared the short term memory and information processing speed of people who used marijuana in the past 4 weeks to people who had never used it. The recent marijuana users remembered less and processed information more slowly than the people who never smoked, even though the users didn’t smoke that day. Among the marijuana users, those who used more marijuana in the past 28 days performed worse than those who used less. The authors concluded, “cannabis use is associated with cognitive impairments that persist after abstinence.”

    As long as THC remains in the body, it stands to reason, marijuana continues to affect the brain. What’s less clear is whether marijuana can actually change the brain. Once the last traces of THC have been excreted, could brain function remain altered for months, or years, after?

    Few studies have addressed this question and the lack of clarity provides fodder for debate. To remove some ambiguity, Nora Volkow, director of the National Institute on Drug Abuse, recently wrote a summary in the New England Journal of Medicine of the scientific findings on the lasting effects of marijuana use. The entire article is worth reading, but I’ll highlight two key conclusions here.

    1. Risk of addiction

    Smoking marijuana won’t set an irreversible course for addiction, but you must start using marijuana to become addicted. Almost one in ten people who use marijuana will eventually become dependent on it, according to findings from the National Epidemiologic Survey on Alcohol and Related Conditions. Half of the people who eventually met criteria for marijuana dependence did so within four years of their first use.

    A little under half of people who seek treatment for marijuana dependence experience withdrawal when they try to quit, becoming anxious, irritable or depressed. These symptoms can precipitate relapse, making it harder to quit.

    2. Alterations in brain development

    The brain can be molded and developed throughout our lives, but since it is particularly malleable from the months before birth to our twenty-first birthday, researchers have wondered whether smoking marijuana during adolescence could change the brain’s development.

    A team led by Andrew Zalesky from The University of Melbourne, Australia examined this question by performing MRI scans on regular marijuana users who started smoking in adolescence and a comparison group who never smoked. They found that the neural connections between the brain’s left and right hemispheres were impaired in the marijuana users relative to the non-users, which could mean that smokers’ brains have poorer internal communication.

    Zalesky’s study, like much of the human work, compared people who already smoke to those who never smoked, so it doesn’t show that brains changed after the person started smoking. Smokers’ brains may have been different to begin with. The earlier someone started smoking, however, the more pronounced the impairments were, suggesting marijuana may cause changes.

    Zalesky’s study is hardly unassailable proof, but the suggestion is powerful. Especially considering a study in New Zealand that followed over a thousand individuals from birth to age 38, showing that people who started smoking marijuana in their teens had lower IQs in their thirties compared to their childhood.

    The IQ declines were not associated with personality, socioeconomic status, current drug use or presence of psychiatric diseases. The people who started smoking youngest and who smoked most heavily showed the greatest drop in cognitive performance.

    The deficits extended beyond laboratory tests. People who lived with the study participants filled out questionnaires about the memory and smarts of participants. The participants who started smoking marijuana as teens had more memory troubles in daily life, according to the people who knew them best.

    Causal studies of change due to marijuana are, of course, unethical in humans. But existing evidence suggests that marijuana probably won’t scramble your brain, but if you start smoking heavily as a teen, it may slow your brain down.

    Clearly, we still have much to learn about the long-term effects of marijuana on the brain. The few studies available suggest that marijuana may change the brain’s function, especially if used when the brain is still undergoing rapid development. However, more studies need to confirm these suggestions and identify more specific alterations. Any conclusions may be premature, but it makes you wonder.

  6. Basoodler
    Re: (updated: part 3) What Does Marijuana Really Do to the Brain?

    Just a thought,

    This guy's actual blog at psychology today really hasn't received the support or recognition for these posts that it probably deserves. The first post for example has only a few bitchy comments about having to wait for the 2nd. 11 shares on Twitter and one on tumbler.

    Since he started part one the psychological society officially took a left turn on the long term effects of marijuana which probably made it much more difficult to finish the series .

    I figure that it would be nice if we could show some appreciation or thanks in the way of comments. I am willing to bet that the 23k views here is more than he has on psychology today .

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