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Hate the way cannabis feels? You may be wired to dislike it

August 22, 2018
(CSA-Archive/iStock)
The cannabis experience isn’t great for everyone. For many, THC-rich cannabis provides an enjoyable and euphoric high, but in others, it causes unpleasant dysphoria. In one report, 22% consumers felt anxious or panicked after using cannabis.

For most drugs, the first time experience goes a long way in predicting future use patterns, so your first time matters. But let’s assume that you once enjoyed cannabis but now find it unpleasant. What causes cannabis to be pleasant or unpleasant?

There are three main factors that influence whether we find cannabis good or bad (note that for this discussion, we’re focusing on THC-rich cannabis only and not including the potential influence of terpenes or other cannabinoids).

  • Age — We typically enjoy cannabis more as adolescents than as adults.
  • Opioid receptors — The distribution of opioid receptors in our brains affects how we perceive cannabis.
  • CB1 receptor location — The type of brain cells that have the most CB1 receptors can dictate our enjoyment, or aversion, to cannabis.

Factor #1: Your age

Despite being in a critical time of brain development, adolescents tend to be less sensitive to the aversive effects of cannabis compared to adults. In a study comparing the effects of THC on adolescent versus adult rats, THC caused higher levels of anxiety, spiked their stress hormones, and suppressed their movement to a greater extent than in adolescents. The adult rats found THC to be generally unpleasant and avoided the chamber in which they had experienced THC. Adolescent rats didn’t seem to mind.

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The problem, however, is that cannabis has a more profound and long-lasting impact on the brain in adolescence than in adulthood. THC altered nearly 3 times more genes in the hippocampus, a critical brain region for mood and memory, in adolescent rats than in adult rats. Since these genes influence everything from how energy is created in brain cells, how harmful free radicals are neutralized, and how brain cells look and connect, it’s easy to see how adolescent THC exposure has long-lasting consequences on brain function.

Factor #2: Your opioid system

The interaction between the cannabinoid and opioid systems not only contributes to cannabis’ pain-relieving effects, but it also contributes to whether you find cannabis pleasant or aversive. Like the different cannabinoid receptors (i.e., CB1 and CB2), the opioid system also has different of receptors that cause different effects when activated by drugs or the body’s own chemicals. The relevant players in the opioid system are the μ-opioid receptors and the κ-opioid receptors.

Activation of μ-opioid receptors makes you feel good, and these receptors are largely responsible for the pain-relieving effects of morphine and prescription opioids. κ-opioid receptors, on the other hand, can have the opposite effect, and are responsible for some of the aversive properties of taking prescription opioid medications.

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THC increases the level of the brain’s endogenous opioid chemicals in brain regions involved in mood and reward processing. This proposes that the difference between the presence of μ-opioid receptors versus κ-opioid receptors can influence whether THC has positive and rewarding effects. If you’re activating more μ-opioid receptors, you’ll enjoy THC more than if you were activating more κ-opioid receptors. Indeed, when genetically engineered mice cannot create κ-opioid receptors, or produce the brain’s own chemical that activates them, THC is no longer aversive, and instead, mice seem to really enjoy it!

Factor #3: Your CB1 receptors

In the most recent attempt to understand what underlies preference versus aversion to cannabis, scientists honed in on the CB1 receptors—the receptors that interact with THC to cause a high.

The scientists revealed that CB1 receptors on excitatory brain cells are responsible for THC’s aversive properties.

They focused their attention to a critical brain region for the rewarding properties of drugs, called the ventral tegmental area (for all you brain science nerds, the VTA is where many of the cells that make dopamine come from). Specifically, they asked whether CB1 receptors found on either excitatory brain cells (i.e., those that increase communication between brain cells) or inhibitory brain cells (i.e., those that reduce communication between brain cells) determined whether mice find THC good or bad.

The scientists revealed that CB1 receptors on excitatory brain cells are responsible for THC’s aversive properties. This fits with the idea that CB1 receptors on inhibitory brain cells are responsible for the rewarding properties of THC. From this, we can speculate that someone who initially doesn’t enjoy cannabis may have more CB1 receptors on their excitatory brain cells in the VTA than someone who enjoys cannabis.

In a complex human, it’s not one single mechanism that determines whether we like or dislike cannabis, but instead is likely the net effect of all these factors. And of course, nothing is set in stone. The way our DNA is expressed changes as we age and is influenced by life events or cannabis use patterns. These factors can alter our brain’s chemical systems, including where CB1 receptors are located. Therefore, the way we perceive cannabis can change, for better or worse.

Josh Kaplan's Bio Image

Josh Kaplan

Josh Kaplan, Ph.D., is an Assistant Professor of Behavioral Neuroscience at Western Washington University. He is a passionate science writer, educator, and runs a laboratory that researches cannabis' developmental and therapeutic effects.

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  • How about factor 4? The growers have focused on increasing the levels of THC in the modern strains instead of trying to keep a good THC:CBD ratio. I personally like to buy a CBD only strain and a THC rich strain and grind them up together in a 1:1 ratio. My experiences are just as enjoyable in my 50’s as they were my 20’s.

    • James Kelly

      Nice, been grinding Mixes lately here, so I think i will try that.

      • Yeah, I smoked pretty regularly in the 80’s, then stopped and didn’t smoke again until around 4 years ago and it was a very unpleasant experience. Did some research and found out the “why” of it. The 50/50 blend works extremely well!

  • David Yoseph Schreiber

    The issue of dysphoria is a big one and requires much investigation. My take that is that cannabis and psychedelics in general facilitate the emotion of humility and attack egotism. This is particularly true of the pleasure from THC and triptamines. Consequently somebody who is vain, domineering, or brutal will not like the high. Another issue is that cannabis strengthens the emotions of guilt and fear. The older a person is, the more likely they’ve done something that bothers them. As a result cannabis is more likely to hang a guilt trip on an older person than an adolescent. There also is the issue of innocence. Cannabis tends to be charitable towards people who don’t quite know what’s going on and have not become too clever.

    • Austin Konrad

      Very true, when I smoke I feel immense guilt for my life choices and it’s one of many reasons I hate smoking, however eating a low dose edible is pure heaven.

    • Xavier Guzman

      I find your position quite refreshing and agree that cannabis tends to provide (for myself, at least) a vacuum of self, wherein I’m gifted with an incredibly humiliating perspective of my position in our universe. The effect curtails my arrogance to a socially tolerable level.

    • Renee Vespa

      If I use a higher THC strain, I get extremely dizzy and unable to walk or move my body. Sometimes I get so dizzy I will vomit, which clearly is not pleasant. However I need something that will calm nerve pain and help me sleep. I’m having a very hard time finding the right balance. I am not domineering, and I’m in my 50’s. I don’t particularly feel guilty about anything, I just get really physically ill. It’s like the difference between a glass or two of wine, and being waterboarded with a gallon of tequila when I use a high THC low cbd product.

      • Josh Clark

        Have you given a more cbd rich strain a shot? I tried adding a 1:1 cbd ratio strain, Pennywise, to my normal indica strain, 9# Hammer, and its helped me out. i think leafly has an article about some of the best CBD strains available.

    • James Kelly

      Uhm, No. Ok, so at first thought, mine is that you are just making stuff up.
      But you probably are not. You may even be a smart MF.
      You were making sense on vain peple though, then you typed that last sentence, dude, you need to rethink your words and thoughts. Do some research. Look at the entire picture… Especially the world of cannabias users that are clever and are out there making stuff happen for good. Ya, just because some people don’t know, does not mean you know everything and more specifically does not mean your opinion is anyone elses word of any god. You just sound high and mighty to this audience.

      Now if you have some proof, bring it!

    • Sheryl

      If you consider cannabis like a medicine, then dysphoria could be considered an adverse side effect. Like all medications, people don’t respond the same way, and side effects can vary a lot. But, most of the time, honestly, science doesn’t really know why some ppl have certain responses and not others, only speculation. So, to say that all ppl who experience dysphoria from thc are “vain, domineering and brutal” is definitely an unscientific statement.

      • rich1051414

        For me, the two MAJOR adverse side effects are muscle spasms and a racing mind. These two side effects are precisely what makes me not like weed. Having adhd, I don’t need anything that makes me anxious, and the side effects do that to me. I don’t like muscle spasms(even if they tickle), and I don’t like a racing mind as I need to keep my racing mind under control to think clearly. For me, weed doesn’t do me any good, I need the opposite of that.

    • rich1051414

      Sounds like you are directly attacking people who chose not to smoke. How about, go f yourself man. I don’t care you smoke, don’t label me as something I am not if I don’t want to myself. There is no us vs them. Smoke if you want, if I chose not to it is not because I am scared of my ego being attacked, it is because I simply don’t like it. It gives me muscle spasms and a racing mind to the point that I can’t think clearly. To put it bluntly, it makes me feel stupid, and I don’t like that.
      I already have a racing mind, as I have ADD. Weed makes it worse FOR ME, but it may help someone else. To each their own man.

      • Maya west

        Chill TF out. I also choose not to smoke weed for many reasons and I don’t feel personally attacked by this guys comment. Hes not trying to push an us vs them narrative, he’s simply sharing the relevant insight of his experience. And I completely agree with him, drugs like weed and psychedelics do attack the ego and thats why they can be so uncomfortable for people who are not yet ready to let go of their ego, identity, and vain material pursuits and desires. These drugs require a sort of spiritual surrender, and the instinctive mental grapple to remain in control likely contributes to the dysphoric hell of being high. Its ok to have a hard time with this process, it doesn’t mean you are less than those who smoke. This may not be your personal experience or reason for not smoking but that does not mean that your experience supersedes or disproves his. As I said everyone has an ego, and everyone has to eventually go through the painful process of shedding it and letting go of worldy attachments- I too believe that this is a big reason for many peoples aversion to weed. So chill the hell out. No one is attacking you, or non smokers in general like me.

  • Etidorhpa

    It just makes me feel terrible. First I get this vibration all over my body then , things go all ridged. Then I start thinking about females .It’s the worst.

    • K_Hart

      I hope I’m not being insensitive….your post really cracked me up! 🙂

      • Etidorhpa

        HAHHA

      • j m

        How cum everything’s a joke to you, Mr Hart?

    • James Kelly

      What? Females? Huh.

      • Josh Clark

        i believe they are implying past relationships…?

  • Chutney

    I’m strictly a medical user. I absolutely hate smoking cannabis. I get a strange electrified sensation that I can easily do without. I prefer CBD oil on a piece of dried mango, or prepared in some kind of edible, anything other than smoking it. That said, I have fibromyalgia and terrible PTSD and cannabis helps a lot. I won’t use opioids, except in an absolute emergency.

  • Two Bears

    Never touched weed till I was almost 58.

    First time I used it I literally felt as if I were dying.

    Have NEVER enjoyed it and probably never will.

    I have this love/hate relationship with the plant.

    Love it controls my Crohn’s disease.

    Hate the high with a passion

    This is why I microdose.

    I ONLY use concentrates such as hash and hash oil.

    I tried buds but could not get consistent relief from them.

    Using concentrates I can go 6-8 months between minor flares. With buds I could only get 3-4 weeks between flares. Way better than the 3-4 days of respite I could get with pharmaceuticals between major flares.

  • rwscid

    Possibly the best Leafly article I have ever read. Thx.

    • Satan McLucifer

      You don’t get out enough.

  • j m

    As a teenager I found weed to be entertaining and fun (it was also low end shake). Later on the strengths and strains became unpleasant to me. “I don’t want to be disabled… where’s the fun weed?” I eventually found a mix that was perfect for me: 0% THC, and 100% opiate. Works great!! But alternately, some friends and relatives hate the opiate high, to the point of totally avoidance, but would jump over a barbed wire fence to retrieve a joint. It’s all just individual physiology and personality. Nothing to sweat over… Peace 😉

    • Seize_The_Means_Of_Production

      Opiate? You mean CBD?

      • Mma

        No, it was a silly way of saying “no weed, lots of opiate”.

  • j m

    Leafly is weak

  • Satan McLucifer

    Trump steals dirty panties from Ivanka’s hamper for his late-night “sniffy time”. Melania doesn’t care, do you?

  • Zach Ward

    Anyone and everyone can feel anxious on weed. Anyone and everyone can pull themselves out of that mindset as well. People who have learned to avoid those feeling because they are fake/wrong/dangerous/stupid are the people who enjoy using marijuana. Everyone has felt that way before, it’s about overcoming that and stepping into the freedom getting high allows.

    It is my “peel-away” from reality. I get a birds eye view of life, its problems and a lot of the time – solutions. Worries melt and you find yourself living in the moment and loving the world around despite its decaying nature.

    Stop worrying, start living, people. Good luck out there.