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What Is the Endocannabinoid System?

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In 1964, Israeli scientist Raphael Mechoulam isolated tetrahydrocannabinol, or THC, from a cannabis plant. Hundreds of chemicals exist in cannabis, not just the high-inducing THC and supposed-wellness-hero CBD (cannabidiol) that most are familiar with today. Still, this isolation opened new opportunities for scientists to study how cannabis affects the human body.

Our bodies must have receptors for anything that impacts us—from what we eat and drink to what we inhale. And given that we don’t need cannabis to survive, scientists could assume that we have naturally occurring compounds that connect with these receptors, too, Yasmin Hurd, PhD, a neuroscientist and director of the Addiction Institute at Mount Sinai in New York, tells Well+Good. These receptors are protein molecules in and on the surface of our cells that bind with particular substances (think: hormones, drugs, etc.) to help influence the activity of the cell. In 1992, nearly three decades after the isolation of THC, a Czech chemist on Mechoulam’s research team isolated the first known endocannabinoid, a compound similar in structure to the chemicals in cannabis but naturally occurring in our bodies. This discovery led to a revelation: Humans have a whole system of endocannabinoids and endocannabinoid receptors.

What is the endocannabinoid system

The endocannabinoid system consists of endocannabinoids, receptors, and enzymes that work together to act as a regulator in our bodies, helping to keep us in a kind of balance. Endocannabinoid receptors are especially abundant in the brain, says Dr. Hurd, who was interviewed in the PBS documentary called The Cannabis Question that looks at the science of cannabis, which is still in its infancy.

Endocannabinoids and their receptors control the release of almost every neurotransmitter in the body. They regulate how much dopamine floods our brain with a happy, giddy feeling as well as our response to stress, among many other brain communications. “Any kind of upregulation of signaling will turn on the synthesis of these endocannabinoids,” Susan Ingram, PhD, an associate professor of neurosurgery in the OHSU School of Medicine, says. For example, stress will activate the production of endocannabinoids which try to reduce the overall amount of stress hormones in your brain.

“[Endocannabinoids] are a critical part of fundamental biological processes, from metabolism to immune regulation,” says Dr. Hurd. “In the brain, they regulate cognitive function, motor function, mood, and memory.”

This system is complicated, so we don’t know everything about it yet, but we know that humans have two primary endocannabinoid receptors: CB1 and CB2. CB1 is found mostly throughout the central nervous system, Dr. Ingram says. The other, CB2, is primarily found in our immune system and therefore helps to regulate our immune response.

Do endocannabinoids act like cannabis in our bodies

Although they’re named after cannabis, our endocannabinoids don’t act quite the same way as THC and CBD. “You’re not feeling stoned every day,” Dr. Hurd says. Our natural endocannabinoids don’t make us feel high because they’re at a much, much lower concentration in our bodies than when we flood our systems with THC. The cannabinoids that enter our brains when we ingest marijuana are like a “hammer” on our receptors, Dr. Hurd says. THC and CBD compete with our natural endocannabinoids and therefore alter the way our neurotransmitters fire. One of the most significant effects you’ll feel with THC is a change in dopamine. “When THC binds to the CB1 receptor, it causes a domino effect that causes the increase of dopamine. That’s one of the ways in which it causes a high,” Dr. Hurd says.

So, is cannabis helpful or harmful

It’s still unclear to scientists how marijuana helps or hurts the brain, especially given the variables involved. Dr. Ingram lives in Oregon, where recreational marijuana is legal, but the THC she would legally study in her lab would be pure. At dispensaries in her city, people can buy from many variations of the marijuana plant and different combinations of THC and CBD extracts. “It was very clear to me [upon visiting a dispensary] that it would be hard to study what people were taking,” she says.

However, the FDA has already approved an epilepsy drug that has CBD as its active ingredient. Medical marijuana has been legal for decades and has, at least anecdotally, been effective for treating cancer patients, people with PTSD and other mental health conditions, as well as chronic pain (which Dr. Ingram studies). “We find that with inflammation, the CB1 receptor function goes down,” Dr. Ingram says. “So I do wonder why it’s useful. We’re trying to understand in which synapses these regulatory changes happen and what THC is doing that seems to be beneficial for people.”

While it’s still unclear when cannabis can help and when it can hurt, it seems related to how the endocannabinoid system functions. Perhaps people who have chronic anxiety have an endocannabinoid system that isn’t properly regulating stress hormones. And cannabis can help bring them back on track.

We do know that chronic cannabis use, which Dr. Hurd defines as daily use, can disrupt the natural function of our endocannabinoid system. “It definitely changes brain circuitry,” Dr. Ingram says. “When you see how many different circuits these receptors work in, it just seems like you don’t want to be messing with them quite so much.”

There is some evidence that your endocannabinoid system can bounce back if you stop using marijuana every day—at least if you started using cannabis as an adult after your brain had finished growing. But, in the short term, with chronic use, the THC “hammer” seems to make endocannabinoid receptors retreat, therefore messing with your body’s universal regulator.

Scientists still have a lot to discover about how, when, in what quantities, and in what forms marijuana can be helpful and how recreational use affects us long term. Dr. Ingram holds hope for the future of research as recreational marijuana becomes more legal. “I honestly am hoping that the legalization will help people do the gold standard clinical studies that are necessary,” she says. “The placebo-controlled, double-blind type of studies to really understand what cannabis is useful for, so that people are taking it for the right reasons.”

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