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Cannabis Study: How THC Affects Learning and Memory at Different Ages

June 13, 2017
Cannabis Study: How THC Affects Learning and Memory at Different Ages(diego_cervo/iStock)

“All diseases run into one, old age.” –Ralph Waldo Emerson

 

A recent study in mice sparked eye-catching headlines like, “Memory Loss From Old Age Could Be Reversed By Smoking Marijuana.” The idea is alluring, especially given the toll cognitive decline takes as we age: instead of leaving you dazed and confused, THC might actually help restore cognitive function in older individuals.

While the study made interesting observations about how THC affects learning and memory in young vs. older mice, it didn’t involve smoking or cannabis consumption. What did the study find, how did it work, and what are the implications for future human research?

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Cannabinoids and Aging: What Did We Already Know?

We knew three basic things going into this recent study. First, young mice have stronger learning and memory abilities than older mice—no surprise there. Second, giving young mice THC generally makes them perform worse on learning and memory tests. Third, the endocannabinoid system influences the progression of aging in the brain, and endocannabinoid levels in the brain decline with age.

Dr. Andras Bilkei-Gorzo, lead author of the recent study, explained the rationale for their experiments. “We had learned from previous work that decreased cannabinoid signaling accelerates brain aging. We asked whether enhancing cannabinoid system activity might slow down—or even reverse—normal cognitive decline that comes with aging.”

The idea was relatively straightforward. If age-related cognitive deficits are due, at least in part, to deficits in the endocannabinoid system, then perhaps exposure to a plant cannabinoid like THC might compensate for this. So, how did their experiments work?

THC, Memory, and Aging Study: Basic Findings and Summary

The study looked at behavioral measures of learning and memory in young vs. old mice. In each age group, some mice received a constant, daily dose of THC for 28 days, while others served as controls (they didn’t receive THC). After their 28-day treatment, their learning and memory abilities were assessed. There was no THC in their system during assessment. The question was how learning and memory were affected after chronic THC exposure.

It turned out that old mice responded differently to chronic THC compared to young mice. Old mice did better on learning and memory tests if they had a 28-day THC treatment beforehand. The behavior of old mice that had a chronic THC treatment looked like the behavior of young mice without a THC treatment.

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There were also molecular changes in a brain area called the hippocampus that paralleled these behavioral changes. Basically, the brains of older mice that had received THC looked more like the brains of young mice without THC; there were more connections between neurons in the hippocampus. There were also some interesting genomic changes. In the THC-treated old mice, genes associated with plasticity and extended lifespan were turned up, while genes associated with age-related cognitive impairment were turned down.

Figure 1: Chronic THC exposure in old mice can increase the number of connections between neurons in the brain. Brain cells often have structures called "spines." Each spine marks a single connection between two brain cells. Compared to young mice (left), neurons in old-mice (middle) tend to have fewer spines. After chronic THC exposure (right), the brain cells of old mice often look more like those of young mice--they have more spines, and therefore more connections to other brain cells.

Figure 1: Chronic THC exposure in old mice can increase the number of connections between neurons in the brain. Brain cells often have structures called “spines.” Each spine marks a single connection between two brain cells. Compared to young mice (left), neurons in old-mice (middle) tend to have fewer spines. After chronic THC exposure (right), the brain cells of old mice often look more like those of young mice–they have more spines, and therefore more connections to other brain cells.

 

Cannabis and Aging: The Role of the Endocannabinoid System

As we age, our endocannabinoid system changes, including changes in CB1 receptor levels. CB1 is the receptor THC needs to activate for the classical effects of cannabis to be felt, and these receptor levels seem to generally decrease as we age. Perhaps chronic THC exposure in old mice restored cognitive function by increasing CB1 activation, compensating for the low overall levels of CB1 receptors. Using genetically engineered mice, researchers found evidence consistent with this idea.

Figure 2: CB1 receptor levels decrease with age, and chronic THC exposure may compensate for this in mice. Compared to young mice (top-left), old mice tend to have fewer CB1 receptors in their brain (top-right). Because THC activates CB1 receptors, chronic exposure to low-dose THC may compensate for this age-related change.

Figure 2: CB1 receptor levels decrease with age, and chronic THC exposure may compensate for this in old mice. Compared to young mice (top-left), old mice tend to have fewer CB1 receptors in their brain (top-right). Because THC activates CB1 receptors, chronic exposure to low-dose THC may compensate for this age-related change in the endocannabinoid system. Each red “V” represents a CB1 receptor. At any given time, some CB1 receptors may be activated (yellow lines) by cannabinoids, while others are not.

 

The broad takeaway from this study is that plant cannabinoids like THC can have very different effects on individuals depending on their age. These differences are likely due to age-related changes in the endocannabinoid system. Elevating cannabinoids levels may help compensate for some of these age-related changes.

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These results should remind us to be cautious about generalizing the results of studies conducted in specific age groups. We should also hesitate to generalize the results of animal studies to humans, as there are important differences in how our bodies process biologically active compounds.

Study Caveat: Mice and Humans Metabolize Compounds Differently

The study’s title is, “A chronic low dose of THC restores cognitive function in old mice.” But how low was the “low dose” that the mice received?

In this study, mice were given 3 milligrams per kilogram (mg/kg) of body weight of THC per day for 28 consecutive days before learning and memory assessments. For a 150-pound person, that would be equivalent to about 204 milligrams of THC. Spread evenly throughout the day, that comes out to about 8.5 mg of THC every hour. A standard THC edible in a legal adult-use state is 10 mg, so the dose these mice were getting would be akin to taking an edible every hour of every day, for an entire month.

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While that’s far from a low dose for a human, mice are a different story. Dr. Bilkei-Gorzo explained, “Humans are much more sensitive to psychoactive substances than rodents. The effective doses of anti-anxiety and anti-depression drugs is roughly 100 times higher in rodents compared to human patients. The same is true for THC—one needs a higher dose in rodents to see effects comparable to humans.”

Rodents and humans metabolize plant cannabinoids, pharmaceuticals, and other compounds at different rates, and sometimes in very different ways. That’s one big reason why we need to careful about jumping to conclusions about how animal studies will translate to humans.

Study Caveat: Cannabis Was Not Consumed, Pure THC Was Administered

The mice in this study were given pure THC through small devices surgically implanted under their skin. This allowed THC to be directly administered at a constant rate. Mice were not inhaling smoke or consuming cannabis products comparable to normal human consumption methods. This is another reason why we should be cautious when thinking about how cannabis consumption will affect learning and memory in older humans.

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Questions for Future Research

Despite these caveats, the results of the study are intriguing and illustrate how plant cannabinoids like THC can have very different effects based on an individual’s age. These are likely due to age-related changes in the endocannabinoid system that unfold naturally over time. This points us to some important questions worth investigating in humans.

The first question is whether similar results would be seen in a human clinical trial. If so, would these results be seen after consumption of cannabis products through traditional consumption methods, or would older individuals need to acquire pure THC?

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Thankfully, the researchers who conducted this animal study are designing experiments to investigate the effects of THC on elderly adults with mild cognitive impairment.  “We are in the very beginning of the study design,” Dr. Bilkei-Gorzo explained. “The best-case scenario is that the clinical trial will start at the end of 2017 or beginning of 2018. The human trials will most likely use THC. This will allow us to precisely dose THC and compare the human results with the animal studies.”

While pure cannabinoid extracts are often used in human studies, there are legitimate reasons for why patients might respond differently to whole plant cannabis. “There are clear differences between cannabis and pure THC. Cannabis has the advantage of being better tolerated by patients, but pure THC can be precisely dosed.”

The Future of Medical Cannabis Research: Which Countries Will Lead the Way?

It’s also worth noting where the latest research is happening. This recent study was led by researchers at the University of Bonn, in Germany, in collaboration with scientists at Hebrew University in Israel. Israel has already established itself as the capital of medical cannabis research, while Germany and Canada are charging forward with federal legalization of medical and adult-use cannabis laws, respectively.

Meanwhile, federal prohibition in the United States means that medical cannabis research moves as slowly as possible. With the prospect of major budget cuts to government research agencies like the NIH looming, countries like Israel, Germany, and Canada may solidify themselves as the world’s medical cannabis research leaders, and be the first to reap the benefits.


References
Bilkei-gorzo A, Albayram O, Draffehn A, et al. A chronic low dose of Δ(9)-tetrahydrocannabinol (THC) restores cognitive function in old mice. Nat Med. 2017 [PDF]
Albayram O, Alferink J, Pitsch J, et al. Role of CB1 cannabinoid receptors on GABAergic neurons in brain aging. Proc Natl Acad Sci USA. 2011;108(27):11256-61.
Jenniches I, Ternes S, Albayram O, et al. Anxiety, Stress, and Fear Response in Mice With Reduced Endocannabinoid Levels. Biol Psychiatry. 2016;79(10):858-68.
Piyanova A, Lomazzo E, Bindila L, et al. Age-related changes in the endocannabinoid system in the mouse hippocampus. Mech Ageing Dev. 2015;150:55-64.

Nick Jikomes's Bio Image

Nick Jikomes

Nick is Leafly's principal research scientist and holds a PhD in neuroscience from Harvard University and a B.S. in genetics from the University of Wisconsin-Madison. He has been a professional cannabis researcher and data scientist since 2016.

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  • Dieter Klum

    Never is it more important for cannabis to be safely tested than when it’s for medical patients! States like Nevada need more integrity! As a consumer I feel cheated by the inflated, phony THC levels, but also I worry for patients who depend on realistic results for their health and wellbeing!

    • AAron

      A little info on THC levels and why there accurate but not correct.
      Phony is the wrong word, deceptive is better, but inaccurate also.
      It’s a slight of hand with the plant. The samples come from the bottom of the plant, where the THC level is the same as the top of the plat or close.
      The difference is, the green matter is much lower on the bottom of the plant allowing for a higher THC level results as posed to the top where the THC is the same and green matter is much higher.
      The tests are squed only buy manipulating the sample taking location.
      The tests are correct and accurate.

      The Medical industry is on it’s way out, sorry to say.
      The definition of Medical as defined by the MM industry has no medical basis to support the term, Medical Marijuana.
      However, the two patents held by the US government do.

      • Jynnifer Brock

        I was put off by your poor spelling/editing/misspellings but appreciated you trying to explain in understandable language (even if a little butchered).
        Because the post appears much less educated than other authors and individuals, it seems MUCH LESS credible. Just saying…

        • Joshua Peterson

          He’s incoherent and incorrect. Medical testing can be standardized for actual patients and will continue to grow more accurate. The industry has proven this already. We live in a society of growth and progress, not regression. With the legalization of recreational cannabis, the medical industry will focus on what it should have all along, patient and strain specific doses along with the furthering of medical research. I really want to know how he believes a blossoming industry will just wilt and die.

          • Jimmy Dean

            He is correct that the current form is dying. It has been under attack since inception. It has been almost completely beaten down in WA and is on it’s way out here in Oregon as well. Big business will control cannabis when it is all settled out. Why would they allow it to be any different than alcohol or big pharma?

          • Joshua Peterson

            While I agree that the “current form” is dying, I don’t think that the current form of medical marijuana is actually accurate to what the industry should be. It was a weak way of working towards decriminalization/legalization under the guise of helping those that need it. It’s a schedule 1 drug still, and as the research comes in that specifies exactly where and how it helps, it’ll eventually be removed. This will lead to the invention of the real MMJ industry which as you point out will probably become Big-Canna. There are tons of venture capitalists that are funding the cannabis revolution right now, and I feel confident saying that medical is about to be renovated, not die.

  • AAron

    I smoke about a quarter a week. Flower 18-27%? Dabs (oil’s) to 90%
    I’m not feeling it. My memory is slowly getting worse every year. I plan to do the oposit and stop consuming THC and see if my memory gets worse, stays the same or gets worse.
    Informative, Thank you.

    • Joshua Peterson

      But is it getting worse at a slower rate than if you weren’t using? That’s the problem with trying to discover science on your own, it’s nearly impossible. We need human research studies so we can adjust our lives accordingly.

    • Jimmy Dean

      That would be way too high compared to the ratios they gave for mice vs humans. If the mice were given 8.5 mg per hour, and that is typically 100 times more than we require to get the same effects (paraphrasing here), you would be way over the ED. Cut it way back brother.

  • Ville Tuomela

    Short time memory go worse after using cannabis, but in long time memory I have notice opposite. And learning without cannabis is hard because it helps with my ADHD, so, I do better in school than before I start to use. I have 15 years experience and have couple of 6months brakes. Now I prefer vaping because it wins smoking 100-0

  • Mark Robert

    Medical marijuana . Not just today , but every day , give thanks for Herb is no doubt the back bone of a people , alcohol is the killer of these people . Recommended for relief and treatment of particular diseases .

    Some of these conditions include:
    1. Treatment for anxiety (White widow , Afghan Kush , Blueberry Kush)
    2. Glaucoma (Sour Diesel , Blue Dream , OG Darth Vader)
    3. Neuropathy (diseases affecting the nerves or nerve cells) Ex.epilepsy(Grand Daddy Purple , Girls Scout
    Cookies)
    4. Nausea and vomiting associated with cancer chemotherapy (Amnesia haze , Purple Urkle , Jack Horror)
    5. Pain caused by structural or psycho-physiological disorders. (Super Skunk, Banana Kush)
    6. Muscular spasticity and limb pain (multiple sclerosis or spinal cord injury) (Bubble Gum, Cotton Candy,
    Lemon Haze)
    7. Symptoms of movement disorders such as Parkinson’s disease,Huntington’s disease, Tourette’s syndrome
    (Alaskan thunderfuck , Grape Ape , Snow white , Trainwreck )
    8. Appetite stimulant for diseases of malnutrition (cachexia or starvation) (Og Kush, Northern Lights, Mr.
    Nice Guy , Super Silver Haze )
    9. Nausea and vomiting (general) (NYC Diesel , Khalifa Kush , Moonrock , AK47 )
    10. Migraine headaches. (Green Crack , Hindu Kush , Grand daddy purple , Sweet tooth )

  • Eddy Sunderland

    I feel like cannabis allows me to open my mind to learning things that would have never sparked my interest without it. Our materialistic world defines our ability to learn as our ability to successfully function in society, which is good. But what about the ability to ponder the beauty of a puddle of mud or trip on the trees as they dance in the breeze. And please let’s learn how to give Peace an chance!

  • Jimmy Dean

    This is simply huge!