If only studying marijuana's effects on the brain were as easy as researching alcohol.

Throw back a shot of whiskey or tequila or vodka, and you’ll feel a bit buzzed. After 5 shots, you’ll be drunk. With spirits, it’s all about the ethanol content. The more ethanol you consume, the drunker you become. It doesn’t matter if you have 5 shots of 80 proof vodka or of 80 proof whiskey, ethanol is going to have the same effect on brain function regardless of the distillation process.

This makes studying alcohol in the lab straightforward. When mice get drunk on 190 proof ethanol mixed with water, or mixed with sugar water (think Smirnoff Ice), scientists can generalize the effects to those from humans pounding drinks at the company Christmas party.

Marijuana isn’t that simple. Over 100 phytocannabinoids have been discovered in marijuana, and some have actions in the brain. When people talk about “brain actions”, they’re often referring to acting on a receptor, which influences how neurons communicate. It doesn’t imply that these actions make you high. Cannabinoids that make you high are termed “psychoactive” or “psychotomimetic.”

The challenging part of studying cannabis, is that some phytocannabinoids are psychoactive while others are not. Some will counteract psychoactive actions while others enhance them. It can be a mess. So when you take a hit, it’s not just one cannabinoid that affects brain function, but a complex interaction between numerous cannabinoids that produce your state of mind.

Looking Beyond THC

Traditionally, THC (more specifically referred to as Δ9-THC) has gotten all the press. Ever since it was first discovered in the ‘60s, THC has been the primary focus of recreational marijuana research. Justifiably so! THC gets you high.

It’s not surprising that cultivation efforts have led to an increase in THC levels over time. A study that analyzed nearly 39,000 cannabis samples found that in THC potency jumped from ~4% on 1994 to 12% by 2014. The 2016 Cannabis Cup even saw four medical grade Indica strains topping the 30% THC potency mark.

Coinciding with the increase in THC potency, there has been a decrease in cannabidiol (CBD) potency. CBD is a phytocannabinoid that can counteract THC’s psychoactive effect, so strains with a high THC:CBD ratio will lead to a more intense high than those with a low THC:CBD ratio. The average THC:CBD ratio increased from 14 in 1994 to around 80 by 2014. The intensity of people’s high can now be higher than ever.

This rapid escalation in the THC potency signals that we’ve entered uncharted territory for understanding marijuana’s short- and long-term impacts on the brain. Conclusions gleaned from early human studies may no longer be valid in today’s high-THC environment. How do you study the long-term consequence of a drug whose composition is constantly changing? It would be like trying to make conclusions about the safety of today’s highways by including data gathered before airbags were invented.

And don’t forget, an increase in THC potency means that other cannabinoid levels will also be altered (as exemplified by the reduction in CBD levels). This shift in cannabinoid concentrations greatly impacts a strain’s effect on the initial high, and its prolonged effect. The high THC potency levels common in today’s weed are thought to be so overpowering that subjective differences must be based on additional distinguishing features. These other features of the subjective experience result from the presence of additional cannabinoids present in the strain and the terpenes they’re dissolved in (terpenes are the fragrant oils that add flavorful qualities to a strain).

And this is where things get a bit complicated.

Marijuana's Multifaceted High

With whiskey, if you evaporate out the ethanol, it no longer gets you drunk. It doesn’t matter if it still retains the oakey, chocolatey notes it once had; the whiskey flavor doesn’t affect how drunk you get. Similarly with marijuana, if you breed out the THC (and consequently its psychoactive metabolites), and crank up the CBD levels, you don’t get stoned.

But with marijuana, the additional cannabinoids can impact how stoned you get, how long it lasts, and the long-term impacts on the brain. While a shot of 80 proof whiskey will you get you equally as intoxicated as a shot of a different brand of 80 proof whiskey, a hit of one strain of weed with a 15% THC potency may have a vastly different effect as a hit of a different strain also with 15% THC potency.

How can two strains with the same THC levels have different effects?

Part II will discuss cannabinoid actions in the brain.