The Why of the High: Tolerance Explained
Ever Wonder Why Some People Who Smoke All Day Function Better Than You?
The concept of tolerance has always baffled me. In the three years I spent reporting and writing Brave New Weed I was always curious how the growers and serious cannabists could imbibe massive amounts of weed all day long and get through very busy days coherently and competently. That amount of THC would knock me flat.
But once I learned about the endocannabinoid system, the galaxy of receptors that snake through our bodies and brains, things started to make more sense. It turns out that heavy smokers are not getting as high because their endocannabinoid receptors are filled to the brim.
To understand this, it’s useful to understand the way dopamine, another neurotransmitter in the body works. Dopamine stimulates the brain’s “happy” area. Drugs including heroin, cocaine, amphetamines, alcohol, and nicotine, make us feel well by increasing production of this pleasure juice, which in turn titillates the brain’s reward receptors. Heroin is so addictive because the brain quickly learns to treasure that pleasure and maximizes the amount of dopamine it produces. This drives us to take more heroin, until the body requires those elevated levels to maintain homeostasis. If the body doesn’t get its fix, a physiological storm moves in and certain systems go berserk, which is why addicts in withdrawal suffer cramps, diarrhea, and other wretchedness.
We know a lot about opiate addiction because the dopamine neurotransmitter system was discovered in the 1970s. But cannabinoid receptors inside the human body weren’t identified until the 1990s, and scientists simply assumed that cannabis worked in the same way — and they trumpeted their mistaken assumptions to the world. Those proclamations helped to solidify some of the unfounded myths about so called cannabis “addiction.”
Wake and bakers say that their tolerance reduces side effects, such as loss of coordination and short term memory. It’s counterintuitive that smoking more could reduce unwanted effects, but this was demonstrated in a little noticed 1995 experiment by Dr. Miles Herkenham, a principal investigator at the National Institute of Mental Health.
Herkenham’s group gave mice different levels of radioactively labeled synthetic THC for two weeks. The strongest doses were “the equivalent of smoking a thousand joints a day,” Herkenham told me. At first, the superstoned mice were catatonic, so docile that the scientists could arrange their tiny limbs in different yoga positions with no resistance. But after a few days they noticed that the mice hit with the highest doses began to regain motor control most quickly.
When the scientists dissected the mice’s brains, they saw those exposed to extreme THC had the fewest available cannabinoid receptors. The body, in its infinite wisdom, had reduced the number of receptors that THC could bind to so the animals couldn’t get as high.
This process of reducing cannabinoid receptors is called “down regulating” and it is the body’s way of placing a ceiling on every high. It also explains how heavy users can smoke all day and go about their business, while more casual users would be on the floor.
And the reason cannabis causes virtually no withdrawal? There are no receptors in tissues that trigger those symptoms (just as there are no cannabinoid receptors in the brain areas that control the heart or lungs). “That’s one of the nicest things about working with cannabinoids,” Herkenham told me. “You can give 10,000 times a typical dose and it won’t kill the animal.” Or a human.
But here’s the possible bad news: the effects of long-term down regulation are as yet unknown. If you’re constantly supplementing the endocannabinoid system, the body’s main regulating structure, with a large supply of THC and your body isn’t producing as many endocannabinoids, there’s a chance that you could tip your body into a state of endocannabinoid deficiency. This is speculative, but other neurotransmitter systems have diseases associated with deficiencies: dementia in Alzheimer’s disease is correlated with a loss of acetylcholine; Parkinsonism is associated with low levels of dopamine; and depression is associated with low levels of serotonin. Why should the endocannabinoid system, which has the greatest receptor density of all, be the exception?
As to what those unforeseen effects of down regulation might be, it’s anyone’s guess, but I have found that people who oversmoke for years on end without stopping do seem to exhibit some form of cognitive dulling. They lose some of their brightness and become disconnected from their inner lives (cannabis takes away dreams, which might explain this disconnection).
These issues are the same with any substance, and the consequences differ depending on the drug. The writer Adam Hanft published an unforgettable article about the contributions anti-depressants made to the financial crisis of 2008. He found that prescriptions for Lexapro, Prozac, and Seroquil, the drugs that so many white collar professionals rely on to fight off depression and to power through their days, spiked in the years leading up to the recession and possibly numbed the ability of the managers to assess risk. In other words, derivatives look really good if you don’t care about the results. I’m not drawing a parallel between cannabis and anti-depressants, but as we learn more about how the ECS functions, it would be reckless to ignore what we know about dose, tolerance, and what it means to smoke smart.
Sorry, stoners. Now that we’re in the post prohibitionist era, it’s time to get real.