Why THC Isn’t The Only Thing In Weed That Matters

Marijuana may still be illegal according to the federal government, but that hasn't stopped the hype machine from claiming it can work wonders. One variety of pot in particular has been getting some considerable press because it can supposedly help with everything from seizures to schizophrenia — all without actually getting you high. While desperate patients see it as miraculous, actual studies into its effectiveness are still lagging. There are two compounds in marijuana responsible for almost all of its effects. The one you probably already know about is tetrahydrocannabinol (THC). But the other, cannabidiol (CBD), is becoming more well-known in the medical marijuana community for both its potential medical benefits and because, on its own, it doesn’t produce the same psychoactive effects that THC does. As David Casarett, MD, author of Stoned: A Doctor’s Case For Medical Marijuana told us last month, there are dozens of other cannabinoids in pot, but THC and CBD are the two we know the most about. For instance, we know that THC mainly activates CB1 receptors in brain areas that are associated with memory and coordinated movement. We also know that CB1 receptor activation can interact with the release of another well-known neurotransmitter: dopamine. This all causes a lot of those classic stoner effects — altered thinking patterns, euphoria, and a not-so-great memory, to name a few. However, unlike THC, CBD interacts with CB2 receptors, which are found more often in various immune system tissues in your body than in the brain (although they are there in smaller amounts). But CBD interacts with and can block both CB1 and CB2 receptors, meaning that it may sometimes block THC’s actions. So, CBD on its own tends to produce effects more along the lines of anti-inflammation and reducing pain. And, crucially, CBD doesn’t cause the same “high” that THC does. This is one reason why different strains can produce noticeably different effects. There are exceptions of course. But sativas, which are thought to give users more of an energetic, creative vibe, are usually high in THC and relatively low in CBD. Indica strains, on the other hand, known for putting users “in da couch,” tend to have more equal THC and CBD concentrations. Most modern strains, though, are selectively bred to have a high THC content because that’s what most customers are after.

That's a huge reason why THC's gotten the majority of the public and research attention — good and bad. But we haven't seen the same level of investigation into CBD’s effects. The studies we do have are often in animals or aren’t placebo-controlled. So far, these haven’t provided enough evidence to make it through the Food and Drug Administration’s regulatory process into an actual, approved medication. But that doesn’t mean CBD has been totally ignored. “Initially, CBD was of great interest,” says Philippe Lucas, VP of patient research and services at Canadian medical cannabis manufacturer Tilray. “But as CBD began to be bred out of recreational cannabis, there was less concern about looking at the potential health impacts of CBD...for a long time, it was thought that both the negative and therapeutic effects of cannabis could largely be attributed to THC.” The compound CBD was first identified in the '40s. And in the '70s and '80s, scientists first started to notice it could calm seizures in rodents. From there, it faded from the scene until around 2006, when researchers discovered CB2 receptors in the brain, causing many to question whether or not CBD was really as non-psychoactive as first thought. The past few decades' push for medical (and recreational) marijuana legislation also helped renew scientific interest in both THC and its left-behind little sibling. The other major roadblock has been and still is legality: Since the Controlled Substances Act was introduced in 1970, the federal government has called marijuana a Schedule 1 drug — meaning it’s considered to be highly addictive and to have no medical value. Despite pretty much constant protests since the early '70s, there pot has stayed, along with everything derived from it.

“It’s not the CBD that’s necessarily illegal," explains Amanda Reiman, manager of marijuana law and policy at the nonprofit Drug Policy Alliance, “It’s the fact that it’s extracted from the plant that makes it illegal.” This comes with very strict requirements for researchers who want to study CBD, which means that few get to actually do that work. To get around this issue, some companies have opted for synthetic versions of the cannabinoid, which may or may not come with less-restrictive scheduling (a murky issue in itself). Much of the CBD oil you can currently buy online is actually derived from imported hemp, which also contains CBD in smaller amounts, says Reiman. It’s totally legal to sell this, but it’s also totally unregulated. Which is why getting the research necessary for FDA approval is so important. A 2014 Cochrane review found four clinical trials (including a total of only 48 participants) looking into the antiepileptic effects of CBD. According to the review, all the studies were pretty low-quality, so the review’s authors concluded there wasn’t enough evidence to recommend CBD for the treatment of seizures just yet. By now, however, Epidiolex, a CBD-based oil manufactured by GW Pharmaceuticals, has received orphan drug status for the treatment of Dravet and Lennox-Gastaut syndromes, which both cause severe, treatment-resistant childhood seizures. This status (given to drugs in development to treat very rare conditions) gives researchers some legal wiggle room to figure things out. So far, they’ve been allowed to give Epidiolex to about 200 people (including kids) as part of a pilot program. Daniel Friedman, MD, one of the scientists working on Epidiolex’s clinical trials at New York University’s Langone Comprehensive Epilepsy Center, says the oil is 98-99% CBD and is created in "a tightly-controlled, pharmaceutical-grade fashion." And, with FDA approval, Dr. Friedman says the cost of Epidiolex will ideally be covered under insurance. For desperate parents who are already spending upwards of $600 a month buying highly concentrated (but unregulated) CBD oil online, this could be a huge improvement. The results of the recent pilot study were promising, and there are now two double-blind Epidiolex trials underway. But, because Epidiolex is derived from the marijuana plant, it is still considered a Schedule I drug during the trial phase. While CBD may provide relief for those suffering from seizures (without pot's characteristic high), evidence for the compound's other potential uses is a little more complicated. For instance, research has shown that patients with inflammatory bowel disease may find relief with medical marijuana, but find the psychoactive effects limiting. So CBD seemed like a natural option to look into. A 2012 double-blind, placebo-controlled trial began to do just that, but so far results are inconclusive. Another GW Pharmaceuticals phase-2 trial that examined the treatment of diabetes with marijuana turned out negative — no significant differences between the treatment and control groups. But, the company says it’s still working on both THC- and CBD-based compounds for Type 2 diabetes-related conditions.

While THC is known to make us feel good, CBD doesn’t seem to have the same rewarding properties. Instead, in animal studies, CBD administration has reduced drug-seeking behavior, which got researchers thinking it might be able to curb addiction. In particular, a trial conducted by researchers at Mount Sinai is currently looking into whether CBD could help prevent heroin addicts from relapsing. And a small 2013 study found CBD may help curb nicotine addiction as well. After researchers shed light on a controversial relationship between marijuana use and worsened symptoms of schizophrenia, other scientists started looking at whether or not CBD on its own would show anything similar. So far, it doesn’t seem like it. In one small 2006 study, people with schizophrenia either show mild improvements or nothing with CBD. But, importantly, there aren’t any major adverse effects. GW Pharmaceuticals is also currently trying its hand at developing a CBD-based drug for the treatment of schizophrenia (alongside current medications). Complicating everything is that there are conditions, such as chemotherapy-related nausea, for which high-THC drugs may be the best option. And in other cases, like with sleep disorders, a mix of THC and CBD seems to be the most effective. The point is that this research is still early, and it’s complicated. Although it’s tempting to assign beneficial qualities to a single component of pot — as with vitamin supplements — we can’t always take the part from the whole and expect the best results. Though CBD may not come with the classic psychoactive effects we normally associate with marijuana, the more we learn about it, the more it seems like it may have been the secret star all along. And, as the case for medical marijuana continues to face the necessary scientific scrutiny, we’ll have our eyes on this one. Correction: An earlier version of this article incorrectly stated that, if Epidiolex were approved by the FDA, it would still be a Schedule 1 drug. However, if approved, it would have to be moved to a less restrictive schedule.