Drugs the CIA Has Used, Ranked by How Much Fun They Are

uncle sam drugs america
Jason Hoffman/Thrillist
Jason Hoffman/Thrillist

In the early aughts, my idea of a good Friday night involved chewing a tab of ecstasy and huffing ether at a rave in an abandoned former Mexican restaurant. I'm older and wiser now, with a felony arrest and stint in court-ordered rehab under my belt, so I have absorbed many a life lesson.

Among them: drugs are fun. They made me more outgoing and better at dancing -- even though they cost me thousands of dollars and took a metaphorical ice cream scoop to my neocortex.

Drug-induced personality changes were revelatory to me, but you know who's been hip to them for decades? The OG druggie of the Western world: Uncle Sam. In the aftermath of World War II, a simultaneous explosion of pharmaceutical research and Cold War tensions led the CIA to try many drugs in its hunt for a truth serum and/or espionage weapon. Here are a few of those drugs, ranked by how fun they are.

Mescaline peyote cactus
Wikimedia/Peter A. Mansfeld

5. Mescaline

Boy, did I have a nightmarish trip on mescaline back in the day. That's one reason the semi-synthetic extract of cactus peyote ranks low. But also this: in 1947, mescaline became one of the first drugs the newly formed CIA decided to fuck with. It heard about mescaline from Nazis, who'd drugged Dachau concentration camp prisoners as one of their mind-control experiments. Obviously, this did not yield a truth serum. But the CIA figured they could succeed where Nazis had failed, laying the groundwork for MK-ULTRA, its Cold War-era research project.

"MK-ULTRA used psychedelics for mind control or interrogation tactics or other weaponized purposes,"  says Brad Burge, director of communications and marketing at the Multidisciplinary Association for Psychedelic Studies (MAPS). Spoiler alert: "Those weren't successful."

cocaine lines

4. Cocaine

The CIA latched on to cocaine and its derivatives in the early 1950s. It quickly proved itself a worthless truth serum that made users feel incredible. I was never that into cocaine, but a lot of people are, and it's easy to see why.

"Cocaine hijacks the reward pathway in the brain, which is governed by a chemical called dopamine," says Dr. Justin Dragna, who holds a PhD in organic chemistry from the University of Texas at Austin and could make really good meth if he wanted to. (He doesn't want to.)

"The reward center of the human brain is a primitive place with a pleasure switch that is turned on by dopamine," Dr. Dragna says. "It doesn't matter whether that dopamine exists because you finally got that promotion or if it’s there because you just did a fat line of cocaine -- your brain just knows it did something great and it wants to let you know you should do it again."

So basically, cocaine makes you a human god... and then it makes you a teeth-grinding, hollow-eyed fiend waiting for 10am to roll around so you can pawn your amp and buy an eight ball. Not the greatest drug. Not the worst. But definitely not the greatest.

woman swallowing pill


MDMA, or molly, as the kids say, is the first drug I ever did and it was definitely the most life-changing. Pre-MDMA, I was an angsty misanthrope. Post-MDMA, I was a hugging, dancing glitter-bomb of peace, love, unity, and respect. Here's the chemical explanation for that:

"The unique feeling of closeness and connection people on MDMA feel with others is because of the serotonin being released in the brain, which triggers a release of oxytocin," Dr. Dragna says. "MDMA is unique as a psychoactive drug in its ability to create the experience of total emotional vulnerability without fear between two strangers."

MDMA was first synthesized in 1912 by German pharmaceutical company Merck, Burge says, and became a useful tool for psychotherapists. "MDMA in particular was used in therapy for PTSD, couples counseling, anxiety... all the way up to 1985, when it was criminalized by the DEA," Burge says. Fortunately (or unfortunately?) the CIA only tested MDMA on animals.

The downside of MDMA, though, is that it actually depletes your stores of serotonin and can lead to some pretty bleak mid-week depression. So try not to overdo it.

Marijuana cannabis jar

2. Marijuana

Of all the drugs on this list, cannabis is the only one I still use. In the 1940s, the OSS (the CIA's precursor) put marijuana through a process called esterification, which makes it into a potent, odorless, tasteless, clear liquid. There was a snappy nickname for it: Truth Drug (TD). OSS agents used TD for operations, but super-stoned targets weren't any more likely to spill the beans.

I don't think I need to go into detail about why marijuana is great, do I? The sooner I finish this article, the sooner I can smoke up, so let's move on to the most fun drug.

LSD drug

1. LSD

The CIA thought this drug was the greatest, devoting the lion's share of the MK-ULTRA's resources to its study. First these guys thought it was a truth serum. Then they thought it was a lie serum -- useful for agents undergoing interrogation, because who can tell the truth when they're tripping balls? Then they considered it a "madness-mimicking" or brainwashing agent. And throughout all these years, they did plenty of it; they also slipped it to unknowing citizens, which makes the irony of the war on drugs even heavier.  

So let's lighten the mood and talk about why LSD is actually the most fun drug. To do that, you need to understand how neurotransmitters work. "Neurotransmitters are the molecules used for communication within and between neurons in the brain," Dr. Dragna says. "The neurotransmitters are like keys, and the neurons have little molecular doors with locks that can only be opened by little molecular neurotransmitter keys."

LSD poses as both dopamine and serotonin, he says. "In the locks in the brain where serotonin or dopamine would fit like keys, LSD will stick instead," Dr. Dragna says. "LSD isn't shaped exactly like dopamine or serotonin. It doesn't fit into the locks the same way dopamine and serotonin do. Imagine a lock with a key that doesn't really fit. And now imagine jamming that key into the lock anyway. It's going to deform the lock."

When LSD jams itself into a molecular lock, the lock gets deformed. And since that lock we're talking about is a cell in your brain, and since your brain is how you perceive the world, everything looks very different when its cells change shape. "Collectively, this somehow causes a change in how we experience consciousness," Dr. Dragna says.

Altering the way we perceive reality is a lot of fun. It's also, I would argue, a fundamental part of being human. And that's why LSD is No. 1.

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Missy Wilkinson asks you not to judge her just because she once drank cough syrup recreationally. Follow her on Twitter at @missy_wilkinson.