Film critic Matt Zoller Seitz describes Paul Thomas Anderson’s new film, Inherent Vice, as “A film about a stoner which itself seems stoned.” An adaptation of Thomas Pynchon’s 1970-set hardboiled-detective pastiche, Inherent Vice follows the adventures of a pothead private eye named Larry “Doc” Sportello (played by Joaquin Phoenix) who sets out to investigate the disappearance of an ex-girlfriend’s lover, but uncovers a broader swath of conspiratorial intrigue.

While neither the book nor the movie aspires to be a faithful depiction of the drug culture of its era, the story nevertheless features several stereotypes associated with marijuana, from its stumbling slacker protagonist and rambling narrative to its paranoid vibe and mild hallucinations.

From 1936’s Reefer Madness to 1969’s Easy Rider to 2004’s Harold & Kumar Go to White Castle, marijuana-fueled stories are ubiquitous in popular cinema. But what exactly do we know about the effects of marijuana on the brain, and is it accurately portrayed in movies like Inherent Vice? Sloan Science and Film spoke with Dr. Daniele Piomelli, a professor of anatomy, neurobiology and pharmacology at the University of California Irvine, about the effects of long-term pot smoking, pot usage and paranoia, and the natural marijuana-like substances that exist in abundance in our brain. At UCI, Dr. Piomelli's lab has focused on, among other things, developing various classes of pharmacological agents that target this cannabis-like brain compound (called endocannabinoids), producing analgesic, anxiolytic and antidepressant effects.

Sloan Science and Film: What do we know about how marijuana affects the brain?

Daniele Piomelli: The basic idea is that marijuana contains many cannabinoids, and one of them is, of course, delta-9-tetrahydrocannabinol or THC. THC is able to recognize the receptors in our brain, which are on the surface of a lot of the brain’s neurons. So the THC binds to these receptors, and it changes the shape of the receptors. And this affects the activity of the neurons. It’s become very clear that these cannabinoid receptors are involved in a variety of neurological activities and functions in the brain. And they are all modulated by these cannabinoid receptors.

SSF: So what are the consequences when THC interacts with these receptors?

DP: The consequences are multiple and variable. Because the effects on the cannabinoid receptor will depend very much on how you activate it and the quantity of THC that goes into the blood and the timing—does it go fast, does it go slowly. That’s why people respond so differently to THC.

The cannabinoid receptors in the brain have a variety of functions, so to give you a broad sense, it can activate receptors as an analgesic; or if activates other receptors, it can cause loss of memory; in others, it creates the opposite effect and increases memory; and in another part of the brain, it effects hormone release. All these different things can happen. They don’t happen every time someone takes a puff of marijuana, but they can happen.

SSF: Let’s talk about a few of the popular conceptions of what happens when you smoke marijuana. What about paranoia? Is that scientifically proven?

DP: Yes, there are individuals who experience anxiety and paranoia and unpleasant and negative effects. Has that been established in double-blinded controlled experiments? No. But we know from anecdotal evidence that the vast majority of people who smoke marijuana don’t have that experience. Most people who smoke it invariably have a pleasant experience. It lowers anxiety. If anything, it has a general calming effect, because of the brain centers it controls. This is the reason why so many people smoke it, because it helps people wind down. But if you take an inexperienced individual who smokes a whole lot of marijuana, it’s likely they could develop anxiety or paranoia. These are all effects of higher doses of marijuana.

SSF: So is the difference between creating anxiety and paranoia versus a tranquilizer effect about the dose?

DP: Particularly in the field of the pharmacology of the brain, everything depends on the dose. But another important component is context. Psychological context is crucial. Our brain is not empty. It’s not like THC comes into a virgin brain, and all of a sudden, these receptors are activated. We make our own cannabinoids, called endocannabinoids, and we make tons of them. So depending on whether you have these endocannabinoids, and they’re engaged already, or if these endocannabinoids are empty and essentially waiting for something to activate them, and then comes this flood of THC, either would create very different situations. So what determines the amount of cannabinoids that are activated? And what is the context? Are you relaxed? Are you stressed? These are all different psychological contexts where THC can have a different impact.

SSF: Marijuana is not a hallucinogenic, but can it cause hallucinations?

DP: There are certain strands of marijuana that have very high doses of THC. If, for example, you took an intravenous injection of THC, it can cause cognitive abnormalities in high doses. Many years ago, at the end of the 19th century, people would put marijuana in tea or coffee, and swallow the whole thing and that would cause a massive activation in the brain and that would create hallucinations. But, of course, it’s a completely different ballpark from the true hallucinogenics, which activate on different receptors within the brain.

With marijuana, many people don’t feel anything. Another group might experience anxiety and paranoia, but the majority of the people experience decreased anxiety, relaxation, or change in the perception of time or increase in appetite. These are the most standard effects.

SF: What about long term versus short-term effects? There’s this idea that if you smoke a lot, you become a slacker pothead, for instance.

DP: It depends. It’s about dose and how often. Once a week over fifty years, versus someone who smokes three times a day for a year—that’s a very different thing. If you’re an infrequent user, the chances that it would cause side effects are minimal. I’m not saying they’re zero. It’s a drug, and it does things to your body. But if you smoke marijuana three or four times a day, and you can’t relax or go to sleep without marijuana, then you have a problem. And it is an addictive drug. It’s not very addictive, like tobacco or cocaine, and lots of people become fooled because it’s not very addictive. But it’s not harmless. Taking it in excess will cause addiction, and it will also cause a slowing down of a variety of cognitive abilities, because the receptor for marijuana, which is termed CB1, is located in one particular spot of the brain, the hippocampus, and it has a very important role in memory. There are a ton of receptors in that region, so if you activate that receptor too much, you will negatively cause losses in the ability to learn new material and to retain material and possibly a loss of motivation.

SSF: Are there other myths in the popular culture that you’d like to dispel, or things that you feel people don’t understand about marijuana?

DP: The scientific community has been working on marijuana for more than twenty years, working hard to understand what the cannabinoid receptors are doing in the brain, what the endocanniboids are, and what marijuana does in the brain. But because it’s been around for so long, people think we know what it does. But we still don’t know a lot. We know much more now, but we still don’t know very important things. We still don’t know much about how our own endocannabinoid system works, what it does, and why it does what it does. We don’t know how much to manipulate this system to our own advantage. We don’t know how much marijuana is useful as a therapeutic drug. We have strong clinical data that shows marijuana helps patients suffering from chronic neuropathic pain. But we don’t have the data for lots of other problems, such as epilepsy. There is a whole universe of knowledge out there, and I think the public is becoming cognizant of this, and I think we’re seeing this is something that we can tap into for our own health. But before that, we need to understand it and we need to prove it will work.