CBD can reduce activation of the cannabinoid CB1 receptor in cell experiments. Does this mean that it can actually prevent you from getting high?

Cannabidiol (CBD) is the second most common cannabinoid after the more famous THC. Although CBD levels in most strains of cannabis are low (and have been dropping for decades), it is currently gaining in popularity as a treatment for a number of conditions.

The high from cannabis is primarily from THC activating the CB1 receptor. In cells, CBD is able to block THC activation of the CB1 receptor. It logically follows then that CBD should block the psychoactive effects of THC (although also therapeutic effects of THC mediated by the CB1 receptor, such as the analgesic and anti-nausea effects).

With the surge in CBD popularity,  there have been questions about whether taking CBD may block the high you get from THC. There are specific side effects of THC that CBD does block (anxiety, psychotic effects, and certain cognitive deficits). Those are important, and I will cover those in subsequent articles. However, I am covering just one thing here: can CBD reduce your high?

The CB1 Receptor Gets You High

The first thing to understand in this story is that THC gets you high by activating the CB1 receptor in your brain. Although THC also has activities at other receptors, getting high 100% depends on the CB1 receptor. It is also responsible for the increase in heart rate caused by THC.

How can we be so sure about this?  Because in clinical studies, 3 different CB1 receptor antagonists (rimonabant, TM38837, and tetrahydrocannabivarin) could reduce both the THC-induced high and the increase in heart rate.

CBD Reduces CB1 Receptor Activation in Cells

CBD is capable of blocking THC activation of the CB1 receptor in cells. For a long time, it was thought to be a weak antagonist. However, this weak affinity for the THC binding site didn’t fully explain the effects of CBD in cells.

Only recently, a 2015 study showed that CBD actually functions as a negative allosteric modulator by binding to a site on the CB1 receptor distinct from the THC binding site. From this secondary site, CBD is able to change the shape of the receptor in a way that there is less THC binding and less activation of the CB1 receptor. Reduced THC potency was seen at CBD concentrations as low as 100 nM – which can definitely be achieved in humans.

Conflicting Reports of CBD’s Effects in Animals

From the cell data, we would expect that CBD is capable of blocking the effects of THC in animal studies. In reality, the results are all over the place. In some cases, CBD reduces the effects of THC and in other cases it potentiates the effects of THC.

The reason for the conflicting results? There are multiple mechanisms through which CBD can interact with THC. [Read more about the 3 Mechanisms of the Cannabis Entourage Effect]. Rodents appear to be much more susceptible to a pharmacokinetic interaction where CBD boosts THC blood and brain levels. One hypothesis is that the timing matters: giving CBD before THC will maximize the pharmacokinetic interaction (potentiating THC) and giving them concurrently will maximize the pharmacodynamic interaction (inhibiting THC).

Clinical Studies of THC and CBD

A 1974 study was the first to combine THC and CBD in a controlled setting. Eight groups of subjects (n=5) were given placebo or 30 mg oral THC combined with placebo, 15 mg, 30 mg, or 60 mg of oral CBD.

This study showed that both 30 and 60 mg of CBD could reduce THC-induced increases in heart rate back to baseline. The psychological rating scale (from 0-4 points) they used showed that CBD brought the effects of THC from a 4 (practically a psychotic state on this scale) down to a 2 (a pleasant high).

The title of the paper says it all: “Cannabidiol interferes with the effects of delta9-tetrahydrocannabinol in man.” This report started the notion that CBD could block the effects of THC. It was highly cited and still continues to be cited today, over 40 years later.

The problem is that this study is wrong. I will show you below that almost all clinical studies done since then have contradicted it.

How can one study manage to stubbornly influence people for decades, even after it is contradicted? Well sadly, this isn’t the only example: One short letter’s huge impact on the opioid epidemic.

Subsequent Clinical Studies:

  • 1975: A study of 20 mg oral THC and 40 mg oral CBD or placebo. No effect of CBD on heart rate or total intensity of high was seen.
  • 1976: A study of 25 ug/kg (~1.75 mg) smoked THC and 150 ug/kg (~10.5 mg) smoked CBD or placebo. There was no effect of CBD on heart rate, but the rating of psychological high was reduced from 5.7 to 4.5. When the CBD was smoked 30 min before THC, no effect was seen.
  • 1981: A study of 2 mg intravenous THC with placebo or 1500 mg oral CBD given over the previous 8 hours. No effect of CBD was seen on heart rate or self-rated high.
  • 1982: A study of 0.5 mg/kg (~35 mg) oral THC wit 1 mg/kg (~70 mg) oral CBD or placebo. No effect of CBD was observed on heart rate, but there was no self-rating of the high. CBD did reduce some responses on a standardized questionnaire of drug effects.
  • 2010: A “naturalistic” study where people could bring their own cannabis.  No difference in the ratings of being high between people with low-CBD and high-CBD cannabis.
  • 2011: Two studies were published comparing dronabinol (synthetic oral THC) with Sativex (a standardized cannabis extract oral spray with 1:1 THC and CBD). These studies are difficult to interpret since the THC pharmacokinetics were different between the two formulations. However, no obvious effects on heart rate or ratings of feeling high were seen with CBD.
  • 2015: A study of 8 mg vaporized THC with 16 mg vaporized CBD or placebo. No effects were seen on ratings of feeling stoned.
  • 2016: A study of 5.5% smoked cannabis (~22 mg) with placebo, 200, 400, or 800 mg oral CBD 90 minutes prior. There were no effects of CBD on heart rate or ratings of feeling high.

Clinical study results of whether CBD blocks the high of THC

I have shown the best studies in this figure. To be included, they needed to be double-blind, placebo-controlled randomized crossover studies with self-reported ratings of the THC high. Five studies fit these criteria, although one could not be included since it didn’t report the ratings of feeling high (they only stated that there was no difference with CBD).

Out of these 5 studies, only one (from 1976) showed a significant reduction in the THC high when it was taken with CBD. This study was repeated again, but with smoking the CBD 30 min before THC and there was no difference in feeling high.

Does CBD Block the High of THC?

So does CBD reduce the high from THC by blocking CB1 receptors? The answer is no, CBD will not reduce the high you get from THC. Despite CBD blocking the activation of the CB1 receptor in cell experiments, it does not appear to do this in people.

Although a few studies showed a reduction in psychological effects from CBD, most showed no significant difference in the THC high. This was demonstrated even at very high CBD doses up to 1500 mg (much higher than most people take). I could not identify any trend for the few reports that did see an effect of CBD, looking at THC dose, CBD dose, cannabinoid ratio, or route of administration

The lack of CB1 antagonism was further confirmed by heart rate measurements. CBD did not affect increases in heart rate from THC, an effect also mediated by the CB1 receptor.

Regardless of the cell experiments showing that CBD is a negative allosteric modulator of CB1, we are not seeing much evidence that CBD blocks this receptor in humans. This also means that if you take THC therapeutically, you generally don’t need to worry that adding CBD will block these effects.

[Featured image credit: Wikimedia Commons]

Last modified: June 22, 2017

8 Responses to " Does CBD Block the High of THC? "

  1. Steve Short says:

    CBD doesn’t reduce the THC high but I sure know what does. That is beta-caryophyllene (BCP) as in Copaiba Oil. Even d-limonene (Orange Oil) has a similar effect but weaker. BCP is a strong CB2 agonist, d-limonene a weaker one. Amazed that so few seem to know this.

    • Prof of Pot says:

      Interesting, I hadn’t heard before that CB2 agonists decrease the high. Did you discover this through personal experience?

      • Steve Short says:

        Yes I verified it for myself 3 years back but I had vague memories of having read it somewhere earlier. FYI have been taking 10 – 15 drops/day of Copaiaba Oil for the last 2.5 years to suppress the daily ache of arthritis in the 6 vertebrae of my lower back (osteophytes). It works very well provided I keep the Copaiba Oil upside down in a jar in the refrigerator as BCP oxidizes readily to BCPO (beta caryophyllene oxide). I find it remarkable that not only BCP but the even more readily available d-limonene (Orange Oil) also suppresses the THC high. I have patients fighting cancer who find that very useful e.g. for driving.

  2. Mike Petereit says:

    The question I have is what would be the minimum or ideal ratio of THC to CBD to give the maximum health benefit?

    • Prof of Pot says:

      This probably won’t be a very satisfying answer, but here goes: It all depends on what condition you would like to treat. And even then, the ideal ratio (if there is one) for most conditions has not yet been established. Finally, it can vary depending on the person. People can metabolize THC and CBD differently, and so would need different ratios. We are still at an early stage where most people need to experiment with different ratios to see what works best for them. I think this will change in the future with more research, but it is still a ways off.

  3. Maciej says:

    This is a very interesting, in depth article… however on the same website it goes against the article found in different section on this website:


    Can you please clarify if one of them is outdated, or am I missing something.

    • Prof of Pot says:

      I agree with you that the two articles seem to conflict. I am writing an article soon that will clarify this. CBD does reduce certain effects of high THC doses, such as anxiety. However, it appears to do this not through reducing CB1 receptor activation, but through acting at a serotonin receptor.

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