woman lighting a joint

What do you remember about your first time with cannabis?

This happens to a lot of people. You finally get around to trying this special herb and … nothing.

Although there have never been any formal studies into the question, an estimated 41 percent of first-time cannabis consumers experience what experts call “reverse tolerance.”

Indeed, for some people it can take several times to finally experience the effects of cannabis.

On the other hand, some people have the opposite experience with a very strong first-time effect!

So what’s behind this common yet widely-overlooked occurrence? Well, nobody seems to be sure, but there are some intriguing theories out there.

Do some people just not inhale right?

Mandee smoking a joint

For some people inhaling cannabis smoke or vapor can become second nature. But it can definitely take some getting used to!

Think about it: many first-time consumers are complete novices when it comes to smoking of any kind. The concept of fully inhaling and holding tickly smoke in the lungs may not exactly come naturally.

Even for cigarette smokers, the style of inhalation is a little different, as cigarettes are better smoked in short, light puffs, whereas cannabis is widely thought to be more effective when inhaled deeper into the lungs.

Whether or not this is actually the case is interesting in its own right, but it really doesn’t add up that incorrect inhalation is the reason so many first-time consumers report feeling nothing at all. There are dozens of reports on forums and message boards from people who claim to have eaten whole space-cakes or ripped giant bongs and still felt nothing!

And yet there are also plenty of folks out there who do a pretty poor job of inhaling the first few times, but yet still manage to get super high. So, there is clearly something else at work. Let’s take a look at the next possibility.

Does the brain just not know that it’s high?

woman smoking a joint

Do you think it’s possible that cannabis newbies could be high and simply not realize it?

Now this is an intriguing and certainly more likely possibility. There is a theory that the first few times some people try cannabis, they are so unfamiliar with the altered state of mind it brings on that they fail to recognize any subjective change at all!

It may seem ridiculous, but there is a certain logic to this line of thought. After all, consciousness is subjective, and awareness of an altered mind state is also entirely subjective.

Another fact that may give some credence to this possibility is this: a brief, cursory Google search for the same effect with other psychoactive substances (LSD, mushrooms, cocaine) shows instantly that it’s an effect that’s not limited to cannabis. Given that these substances all have different (although often related) mechanisms of action, it seems plausible that the effect is more psychological than physiological.

However, this explanation seems unsatisfying, perhaps because most people that take psychoactive substances expect to experience an altered mind state. You’d think that if someone is looking out for any sign of altered consciousness in themselves, they would be less likely to miss any such signs.

But then that also leads us to the possibility that some people simply may not realize the cannabis high until they’ve grown accustomed to its effects. Confused yet? So were we, so we put the question to the renowned cannabinoid scientist Dr. Ethan Russo to see what light he could shed on the matter.

Dr. Russo states, “Many initiates find the effects of cannabis to be subtle at first, and then, upon recognition, appreciate the effects with lesser exposure.”

So yes, perhaps subjective awareness of the effects of cannabis is at the heart of why some people don’t feel anything their first time. But there is one last possibility to consider, so pay attention!

So maybe the brain just can’t get high at first?

This really is an intriguing concept. The ability to get high from cannabis (specifically, from THC, which is the psychoactive ingredient in cannabis) depends on the availability of cannabinoid receptors in the brain. Specifically, the high requires CB₁-receptors, which bind to THC and regulate its psychoactive effect.

CB1 receptor chart

We are still learning new things about how cannabis interacts with the brain and the rest of the body.

Even more specifically, this process requires CB₁-receptors in the areas of the brain related to psychoactivity, stimulus and reward—areas such as the hippocampus and amygdala. If these areas are low in CB₁-receptors, then there may not be enough binding sites to process sufficient THC to produce a noticeably altered state of consciousness.

There are various possibilities to account for why an individual may be lacking in CB₁-receptors. Perhaps presence of certain compounds (such as medications, dietary supplements, or other psychoactive drugs) could cause low CB₁-receptor density, or perhaps pre-existing medical conditions could play a role, or perhaps it’s down to individual genetics, or even a combination of multiple factors.

There’s one study out there showing that CB₁-receptor density in key brain areas is reduced when certain hormones are present. In this case, the study investigated a steroid hormone known as glutocorticoid, which has various medical applications including treatment of asthma, allergies, and inflammation.

Another study has shown that low CB₁-receptor density figures heavily in Huntington’s disease, and while no-one would suggest that everyone who didn’t get high the first time must have Huntington’s, it opens the door to other similar neurological abnormalities having a part to play.

It also implies that after just a few uses of cannabis, the density of the CB₁-receptors must significantly increase. That sounds somewhat far-fetched, but astonishingly, there is actually a piece of research out there that shows exactly that. In this study, CB₁-receptors exhibited a “drastic increase” when exposed to THC for just 48 hours! Admittedly, this study was looking at immune cells, not brain cells, but the same logic may very well apply in both cases.

Dr. Russo tells us that “low doses of THC may jump-start the endocannabinoid system, which becomes more sensitive subsequently.” Perhaps this is the process at work here — as Dr. Russo puts it, a form of “reverse tolerance”, whereby the individual becomes more sensitized to cannabis over time.

So why doesn’t it happen to everyone?

Well, if this phenomenon occurs due to abnormally low CB₁-receptor levels, individuals with healthy levels should be spared. It may also be possible that individual genetics plays some role, as is the case for so many cannabis-related phenomena. On this note, Dr. Russo says that “people also vary tremendously in their ‘endocannabinoid tone,’ and this will obviously affect the dose necessary to produce a given effect.”

But if it’s not due to that, and it’s something more to do with the subjective experience of getting high, then perhaps it’s simply down to how self-aware one is. After all, if you don’t know yourself, how do you know if you are or aren’t feeling your usual self?

Want to learn more interesting insights into the effects of cannabis? Be sure to sign up for Green Flower’s VIRTUAL Cannabis Health Summit, where you can watch 20+ experts talking about cannabis for free from the comfort of your own home. Register free here.