Hacking the immune system to fight cocaine addiction
The problem
Anyone who's ever been a habitual user of a drug like cocaine can tell you that once you start, it can be a slippery slope to addiction. Tim Deloughery from Peterborough, Ontario, knows that all too well. He first tried cocaine decades ago when he was in his 20s. At first he was a casual user. But he remembers when that changed. "After a few years maybe in my late 20s somehow at a party somebody had a large quantity and were up all night using cocaine. So it was after that binge sort of where it seemed like something changed."
'[W]hat I came to realize is that once I started using again I couldn't stop. So even in early recovery after treatment, I knew that if I gave in I'd be right back where I came from.- Tim Deloughery
Deloughery found himself thinking about cocaine a lot — from the time he'd wake up until he'd go to bed. It became a bit of a mental obsession for him. And he found himself using by himself, every day. After his family gave him an ultimatum, he tried to quit, but struggled with it until he got himself into treatment. "There were many attempts to stop," he says. "[It'd] last a week and maybe a couple of months. At one point [I] had six months. But what I came to realize is that once I started using again I couldn't stop. So even in early recovery after treatment, I knew that if I gave in I'd be right back where I came from."
Deloughery is now drug free. He even works as an addiction counsellor, but he's one of the lucky ones. Even with treatment, about a quarter of addicts relapse within a year. And that's partly because we really don't have good ways of coping with the powerful chemistry of cocaine addiction. Now research may be changing that.
Dialing back cravings
A new study out in Nature Communications this week describes how scientists, led by Dr. Drew Kiraly, an assistant professor of psychiatry and neuroscience at the Icahn School of Medicine at Mount Sinai in New York City, investigated how cocaine and the immune system conspire together to make the drug more addictive.
They exposed mice to long-term cocaine and looked to see if cytokines, which are proteins in our immune system, went up or down in correlation with the cocaine addiction. They narrowed it down to one protein, which Kiraly calls, "G-CSF," otherwise known as granulocyte-colony stimulating factor.
It seems like there may be a bit of a vicious cycle to it where we're taking this drug increases this protein, which increases the rewarding value of the drug.- Dr. Drew Kiraly
When Kiraly injected that protein into mice, it hit their brains' addiction centre and their cocaine cravings became more intense. Kiraly says, "It seems like there may be a bit of a vicious cycle to it where we're taking this drug increases this protein, which increases the rewarding value of the drug."
Kiraly then injected an antibody to that protein into the mice and found that if they inject it into the mice's periphery, it reduced the cravings by about a third. But when they injected it directly into the brain, the cocaine cravings completely disappeared. The hope is that eventually they can target this protein with an antibody in people to dial back the cravings. He's currently working to see what effect this protein, G-CSF, might have opiate use in animals.
A vaccine to block the high
Another approach scientists are working on is a cocaine vaccine. Dr. Ronald Crystal, the chairman of genetic medicine at Weill Cornell Medical College in New York City, is the lead scientist working on the cocaine vaccine. He says that since cocaine is a small molecule, our immune systems don't normally see it. "To be able to develop a vaccine, we have to trick the immune system," says Crystal. "The way we did that was by taking a cold virus, called the adenovirus, one of the causes of the common cold. And we know that that evokes a great deal of immunity against the virus itself. So we attach cocaine to the cold virus. And we ripped it apart, so that it wouldn't cause harm."
If we vaccinated the animals, they stopped tapping the bar for cocaine and switched to the M&Ms.- Dr. Ronald Crystal
The idea behind this vaccine is that if a vaccinated person were to sniff cocaine, the antibodies in their blood would recognize and neutralize it.
They tested this cocaine vaccine on experimental animals that were given a choice of tapping a bar to get some cocaine or tapping a bar to get some M&Ms. Crystal says, "If we vaccinated the animals, they stopped tapping the bar for cocaine and switched to the M&Ms."
This vaccine is currently in a blinded human clinical trial. Crystal says he hopes to find out the results from that trial in about a year to a year in a half.
Crystal says this method they used to develop this vaccine is what he calls a "platform strategy." Theoretically it could work with any addictive drug. They are currently testing another version of this vaccine for nicotine.