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THC Tolerance: Here’s Why T-Breaks Work So Quickly

May 17, 2018
Cannabis doesn’t kill brain cells like methamphetamine. Unlike alcohol, it doesn’t cause the connections between these cells to wither away. Instead—cue scary music—repeated cannabis consumption leads to a diminished effect better known as “tolerance.”

If you stop using cannabis, the brain can recover. And it does so impressively quickly, generally within weeks.

The reason for a consumer’s tolerance to THC can be explained by cannabinoid type I (CB1) receptors in the brain, which decrease with continued cannabis use. That is, you need to consume more of the high-inducing THC to get your buzz. Over time and with continued use, it may seem impossible to get high at all.

But here’s the thing: if you stop, the brain can recover. And it does so impressively quickly, generally within weeks.

What Is “Tolerance”?

THC activates CB1 receptors to make you feel stoned. The high is essentially an abnormal increase in the activity of CB1 receptors. Once THC is gone, this activity usually returns to normal.

But if you repeatedly expose the brain to THC over a couple days or weeks, the brain takes action to minimize the increase in CB1 receptor activity; the brain fights back so that normal CB1 activation patterns are preserved. To do so, CB1 receptors are reduced, their effects weakened, or genetic expression altered. These mechanisms work to dampen the impact of THC so that in order to achieve the initial high, one must consume more. This is tolerance.


Can a Tolerance Break Rejuvenate the Effects of Cannabis?

How Tolerance to THC Develops

THC causes tolerance through repeated activation of CB1 receptors. Repeated activation of CB1 receptors initiates events inside the brain cell that at first leads to desensitization, which is the weakening of the response to THC, followed by internalization, which is the removal of CB1 receptors from the cell’s surface. You’ll be able to detect when these processes occur because you’ll need to consume more THC to get high. 

If you continue to consume THC, it will have less of an effect on brain functioning because there are fewer receptors for it to act on.

The difference between the two is that desensitized receptors are still available for THC to bind, but when it does bind, its impact is lower than it once was. Internalized receptors are no longer available for THC to bind since they’re brought into the brain cell from the surface where they stay or get broken down into smaller parts.

The activation of CB1 receptors by THC initiates these processes. As CB1 receptors get frequently activated, they become less associated with the components that carry out the receptors effects. CB1 receptors are like a baseball pitcher who throws a lot of pitches. Eventually, the pitcher’s muscles can’t carry out the task of throwing the ball as hard as it once could. This weakening strength is observed by the coach who then pulls the pitcher out of the game.


How Does Cannabis Consumption Affect the Brain?

Similarly, there are proteins in the cell that act like the coach to detect weak receptors and pull them from the game. Desensitized CB1 receptors are detected by components within the cell that tag the receptor with a phosphate group. This is like the pitcher telling the coach to take them out of the game. This phosphate group signals to  additional components within the cell to remove the receptor from the cell’s surface. At this point, both the pitcher and the CB1 receptor are no longer active players.

As a result, if you continue to consume THC, it will have less of an effect on brain functioning because there are fewer receptors for it to act on.

The Timeline of Tolerance

If you’re a regular cannabis user, how quickly you become tolerant to THC (which reflects CB1 receptor internalization) depends on the dose and frequency you consume, your use history, and your DNA. Obviously, these factors vary greatly across individuals, so our best understanding of the time course for tolerance development comes from studies in mice.

Mice who were given twice daily injections of THC at 10 mg/kg developed tolerance to THC’s pain-relieving and sedative effects after 36 hours (i.e., 3 THC injections). Tolerance to THC’s sedative effects were stronger than to its pain-relieving effects, suggesting that different brain regions or brain cells are more susceptible to tolerance than others.


How Does Cannabis Affect Your Memory?

After a week of THC exposure, the THC injections stopped, and the rate of recovery was measured. Behavior normalized in less than two weeks, and tolerance to THC’s sedative effect recovered quicker than its effect on pain. So the brain mechanisms that promote quicker tolerance are also most resilient and recover quicker from a period of abstinence.

Tolerance to THC Soon Disappears With Abstinence

Compared to other recreational drugs, cannabis is unique in the speed at which the brain “recovers” following a period of abstinence. Recovery is notably difficult to measure, but we can look at changes in behavior, brain function, and brain chemical receptor levels as a proxy.

A study of daily cannabis users reported that users had reduced CB1 receptors compared to non-users, which increased to around-normal after just two weeks of abstinence. Importantly, this study didn’t assess whether CB1 receptors remained desensitized. However, additional studies demonstrated that withdrawal is more intense when there are fewer available CB1 receptors for THC to bind, suggesting that tolerance is indeed the internalization of CB1 receptors. 

Since internalization of CB1 receptors is the predominant consequence of excessive THC consumption, it helps explain why there’s faster brain recovery with cannabis abstinence than many other drugs of abuse. At worst, CB1 receptors become internalized and broken down, in which case they must be reproduced and sent back up to the cell’s surface to recover normal brain function (it should be noted that there can be additional repercussions with substantial use on other brain chemical systems).


Cannabis Is Exactly 114 Times Less Toxic Than Alcohol

When you compare it to alcohol, cannabis doesn’t seem so bad. Excessive alcohol consumption can be toxic to the brain, causing injury or death to the brain cells themselves. Abstaining from alcohol can lead to some recovery, but it takes longer than cannabis and is often less complete.

With methamphetamine, there’s little recovery of brain functioning in the critical brain regions involved in reward processing even after a year of abstinence. To add to the reduced brain activity, meth is toxic and repeated use can trick the brain into thinking it’s injured, leading to persistent activation of repair cells that impair brain function. Meth can even kill brain cells.

You’re better off sticking with cannabis.

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.

View Josh Kaplan's articles

  • Mark Skinner

    I regularly have a two day break from smoking dope (there goes the addiction bullshit) and after a break the next joint I smoke will really buzz me.

    • Bebo

      Please don’t call cannabis “dope”. Where I’m from dope is anything other than cannabis.

      • yes it is cannabis and there are those of us who need it medicinally I cannot take a two day break it helps me get through the night seizures

  • David Branstetter

    I thought this is an excellent article on marijuana, the endocannabinoid system blood pressure and tolerance.I have used marijuana for 45 years to relieve severe muscle spasms resulting from a spinal cord injury in 1969.In 1980 I participated in a double blind clinical study on the effectiveness of THC on muscle spasms in paraplegics and quadriplegics. The study concluded that Marinol,the government’s THC pill, enters the body through multiple synaptic pathways rather than exerting it’s influence on the excitibility of the alpha beta neurons! With all the studies in the past 30 years, there needs to be even more.If possible,i would like to communicate with Dr.Josh Kaplan to initiate future studies This was an excellent article, but we need to learn more about marijuana and CBD-oils effect on so many medical problems. Thank you,

    • Robyn Solski

      i agree David. I was under the impression that since cannabis is (ridiculously) Schedule 1 drug, human trials could not be conducted in the U.S. until it is federally re-scheduled. Countries like Israel have been able to do human trials. Like you, I have info that falls on deaf ears. I have reached out twice to my Assemblyman, who never responded. I just don’t get it.

      • David Branstetter

        Thank you for your comment. I guess time will is long overdue.

    • pixman55

      Israel have done Years of Research into Cannabis Medicinal Use. Google Israel Cannabis Research ? i have Seen Youtube Doco on A Professor who said Proudly he was the First Person to Legally take cannabis From the Police.;-) He used Confiscated Hashish and Plant Material .He Isolated the THC and CBD compounds every one of them. He Tested them on People and it is now Prescribed Some smoke a joint others eat it or use oil drops.

  • The Resistance

    Great piece, as always Dr. Kaplan! This is a very clear explanation to the informed Leafly audience that even contains a basic description of how kinases work. Kudos!

  • Mick Healy

    Ahhh when I started eating decarb & peanut butter, followed by canna cake and endless pipes about 4 weeks ago after harvest I was geting high, semi tripping state, yet now despite consuming and smoking with gusto i cant quite get to the same level.. now i understand why.. I simply need more.. oh good//

  • alacrity

    My experience over 5 decades suggests that the tolerance issue is influenced more by sativa use than Indica- we noticed back in the early 80’s that Thai stick would kick ass for the first few doses then taper down, but when switched to an indica, we’d be back to altitude in short order. Cannabis phenos have distinctly unique properties- it seems the only generality that they share is that they start as seed- and that each terpine combination has a different total effect.

    • it is Indica too….unfortunately…I need for sleep seizures …I read some research that CBD from Hemp helps but I have not had any results from Hemp.

  • Christian Safaii

    Consuming strains with higher than 2 % CBD allows me to never develop a thc tolerance

  • HipJipC

    About 40 or so years ago, we called this effect “smoking yourself straight”. I learned long ago that breaks were necessary. That never seemed to be a problem as breaks happened because we either couldn’t find any to purchase (dry spell) or we had no money. Now it’s just the not enough money for me since going legal in my state of Massachusetts. I don’t see any “dry spells” in the near future except for the possibility of shriveled up, white-haired, majority white skinned Neanderthals in the federal government who honestly need to drink tons of brain laxative and go extinct already, continuing their pathetic “evil” classification of cannabis. Makes them look like morons. I guess they don’t mind that side effect from taking money from the other Neanderthals to keep cannabis under the “Devil” column federally. Bah freaking hum bug to all those with the greed gene. Happy to see your houses of cards falling down. Slowly, buy falling nevertheless.

    • Patrick Shae Connolly

      What a bizarre understanding of how the world works some people have these days.

    • disqus_vGUqLSa646

      Ah and once again heres the left bringing its racism and politics into things that dont need it

    • Marius Streicher

      8 people agreed enough to upvote this, I hope they where all to high to think properly.

  • Talira K.

    Come on! Enough with the ads at the end of the comments! This seems to lessen your integrity.

    • Talira K.

      The ones for the Florida Dr. that are masquerading as viable “comments”!

      • Talira K.

        And now–2 new huge, obvious ads!? What’s up?

  • Black Harvey

    I’ve never had a problem with this. I’ve been smoking everyday for over 800+ days straight. I like to smoke indica at night as it helps with my PTSD for sleeping at night. Sativa in the day helps with my High Anxiety. My consumption is at least 3 – 7 grams a day depending on work. I must admit there have been times when I didnt feel as if I was getting high but when I switched strains I would get right back where I left off. I do believe keeping a variety of different strains helps to withstand tollerance, along with smoking according to your day.

    • Etidorhpa

      You’ll probably get Cannabinoid hyperemesis syndrome soon. So keep going.

      • what is that? I too have a tolerance.

        • Don’t think so never heard of it and I don’t have any of those bogus side effects

          • SplitAces

            never heard of it in my 27 years of smoking and basically everyone i know friends and family are as much of a smoker as i am.

      • SirKingHoff

        Thats so rare you’re likely to develop alcoholism and need a new liver before you come down with this.

        • Jim Trebowski

          I’ve had it four times in the last two years.

          • SirKingHoff

            Then you should clearly stop smoking and be smarter

          • Jim Trebowski

            I was only diagnosed last week. You’re hardly one to suggest people should be “smarter”.

          • SirKingHoff

            You said that you had it 4 times in the past 2 years…. Doesnt that suggest that marijuana may not be the best thing for you?? Think smarter.

          • Jim Trebowski

            The first three times were immediately after eating food at restaurants.. Why are so angry?

          • SirKingHoff


          • Jim Trebowski

            Excuse you? The only way you could make an accusation like that is if you’re stalking me. I was looking for informed opinions, and you’ve proven yourself just the opposite.

          • Jim Trebowski

            The first few times were after eating at restaurants. Why are you so angry?

      • Jim Trebowski

        I’ve had it four times in the last two years with my last bout just ladt week. It was so bad the first two times, I had to spend three nights in the hospital. They told me I would have to quit altogether, but I’m hoping a two week t-break then keeping usage lower after that will work. What is your opinion?

        • SplitAces

          never heard of it in my 27 years of smoking and basically everyone i know friends and family are as much of a smoker as i am

          • Jim Trebowski

            Thankfully it’s still quite rare, but becoming more prevalent. Some articles suggest it may be due to some people not being able to tolerate certain pesticides. There are still many theories.

  • torry nerheim

    I believe that using every day doe’s indeed cause a level of tolerance to the effect of THC, I have always taken breaks eating consuming or smoking cannabis, although I use a very high CBD types of Cannabis, mostly hybrid Indica.
    Funny but true I have always had a very high tolerance to ingesting cannabis but a very low tolerance to smoking or vaping even dabbing cannabis.
    From the start of my most recent injury Nov of 2012, I have been using in all methods, with exception to smoking or vaping dabbing, I still take breaks with all methods but less breaks ingesting.
    This week I have taken two days off from ingesting and three day off from dabbing or smoking, which I’m about to change.
    Tonight I will dab and eat cannabis about three hours apart ingesting being the last before bed.
    I have been sick with cold, chest now and earlier head cold for about a week, so smoking has been a problem, but eating a canna treat is still fine.
    For the best good of mankind, I can only hope that research will help bring more light into this great herb, to benefit mankind and even animals.
    Thanks for your time research,
    Torry Nerheim

  • I have a friend selling CBD from Hemp I read it is not of any use without at least a trace of THC any thoughts?

    • Floyd Pool

      I joined a company last year with hemp based cbd, in my opinion the thc is needed for best results. I guess if in a non legal state hemp cbd may be your only choice to be legal. Yes joined the company but I don’t promote their product, I do believe the company I joined does have one of the best hemp cbd out there. I’d stay with the cannaibis based cbd with a ratio of thc. Just my opinion.

      • I agree I have read research that one needs THC to get certain cabinoids.

  • MobyDick123

    I´m a little bit confused, I´ve been smoking cannabis for 40 years, I am now on my 65 birthday. and i have never experienced a need to increase my dosage. Instead I tend to use smaller amounts then before to get the same high. Ofcourse I sometimes need to adjust the dose depending on the quality of the cannabis. But if it is good I never had to take a bigger dose than before. For the record I add that I mostly been using Hashish because this have been the most commun in my country (not the US). I have smoked every day for the latest 30 years. Many years ago it was described that some people developed an decreased tolerance level. maybe I´m one of them ?

  • Neoclassicalguy

    I hadn’t used cannabis since a bad experience with a (most likely PCP) laced bag when I was 17. At 43 I decided that the health benefits (I have severe OCD and annoying arthritis) outweighed my fear of the leaf since I now have a trustable source. About a month and a half ago I began smoking instead of using edibles. I’ve smoked almost every night this month and a half and have been noticing a change in my high. Sometimes I think I could be a little higher, but smoking more does very little. Am I building a tolerance? I only smoke half-three quarters of a joint a night. Is that too little to build a tolerance? Do I need a T break, or just a break to better appreciate my weed? I do notice a 2-4 day break helps me get back to where I was the next time.

  • Dmember

    All I said was that nobody ever tells us how long it takes to build up a tolerance again after finishing a tolerance break and using again…so we can know in general how often we’ll need a tolerance break. Every 3 days? Every week? Longer than that? Who knows. Nobody I think.

    • ray dock

      Whenever u have to smoke several blunts to get a slight buzz

    • Asmodeus1971

      That is because it varies from person to person. It actually kind of did cover that, you just can’t give a definitive answer because metabolisms changes from person to person, along with other things that deal with how the body handles and reacts to THC. So you need to monitor your own use.

  • When it comes to cannabis choose KanaRelief.

  • William Rain

    I guess i got a High Tolerance because before i started smoking/vaping Medical Marijuana i took CBD Oil with 0.3% THC and i would take High dosages such as 0.75ML under the tongue once per hour up to 6 hours. So basically i would take roughly 6.0ML everyday for 5 work days to get through work and it got me super high. Once i started taking Medical Marijuana and got off the CBD Oil the High from the Medical Marijuana has been Weak and i’ve tried many different Sativa strains and non of them seem to give me a rough high like i used to get from recreational weed i used to smoke nearly 10 years ago so I figure that because i took the CBD Oil for over a year that my High Tolerance will take abit longer to trickle down.