Cocaine addiction: Scientists discover ‘back door’ into the brain

Individuals addicted to cocaine may have difficulty in controlling their addiction because of a previously-unknown ‘back door’ into the brain, circumventing their self-control, suggests a new study led by the University of Cambridge.

A second study from the team suggests that a drug used to treat paracetamol overdose may be able to help individuals who want to break their addiction and stop their damaging cocaine seeking habits.

Although both studies were carried out in rats, the researchers believe the findings will be relevant to humans.

Cocaine is a stimulant drug that can lead to addiction when taken repeatedly. Quitting can be extremely difficult for some people: around four in ten individuals who relapse report having experienced a craving for the drug – however, this means that six out of ten people have relapsed for reasons other than ‘needing’ the drug.

“Most people who use cocaine do so initially in search of a hedonic ‘high’,” explains Dr David Belin from the Department of Pharmacology at the University of Cambridge. “In some individuals, though, frequent use leads to addiction, where use of the drug is no longer voluntary, but ultimately becomes a compulsion. We wanted to understand why this should be the case.”

Drug-taking causes a release in the brain of the chemical dopamine, which helps provide the ‘high’ experienced by the user. Initially the drug taking is volitional – in other words, it is the individual’s choice to take the drug – but over time, this becomes habitual, beyond their control.

Previous research by Professor Barry Everitt from the Department of Psychology at Cambridge showed that when rats were allowed to self-administer cocaine, dopamine-related activity occurred initially in an area of the brain known as the nucleus accumbens, which plays a significant role driving ‘goal-directed’ behaviour, as the rats sought out the drug. However, if the rats were given cocaine over an extended period, this activity transferred to the dorsolateral striatum, which plays an important role in habitual behaviour, suggesting that the rats were no longer in control, but rather were responding automatically, having developed a drug-taking habit.

The brain mechanisms underlying the balance between goal-directed and habitual behaviour involves the prefrontal cortex, the brain region that orchestrates our behaviour. It was previously thought that this region was overwhelmed by stimuli associated with the drugs, or with the craving experienced during withdrawal; however, this does not easily explain why the majority of individuals relapsing to drug use did not experience any craving.

Chronic exposure to drugs alters the prefrontal cortex, but it also alters an area of the brain called the basolateral amygdala, which is associated with the link between a stimulus and an emotion. The basolateral amygdala stores the pleasurable memories associated with cocaine, but the pre-frontal cortex manipulates this information, helping an individual to weigh up whether or not to take the drug: if an addicted individual takes the drug, this activates mechanisms in the dorsal striatum.

However, in a study published in the journal Nature Communications, Dr Belin and Professor Everitt studied the brains of rats addicted to cocaine through self-administration of the drug and identified a previously unknown pathway within the brain that links impulse with habits.

The pathway links the basolateral amygdala indirectly with the dorsolateral striatum, circumventing the prefrontal cortex. This means that an addicted individual would not necessarily be aware of their desire to take the drug.

“We’ve always assumed that addiction occurs through a failure or our self-control, but now we know this is not necessarily the case,” explains Dr Belin. “We’ve found a back door directly to habitual behaviour.

“Drug addiction is mainly viewed as a psychiatric disorder, with treatments such as cognitive behavioural therapy focused on restoring the ability of the prefrontal cortex to control the otherwise maladaptive drug use. But we’ve shown that the prefrontal cortex is not always aware of what is happening, suggesting these treatments may not always be effective.”

In a second study, published in the journal Biological Psychiatry, Dr Belin and colleagues showed that a drug used to treat paracetamol overdose may be able to help individuals addicted to cocaine overcome their addiction – provided the individual wants to quit.

The drug, N-acetylcysteine, had previously been shown in rat studies to prevent relapse. However, the drug later failed human clinical trials, though analysis suggested that while it did not lead addicted individuals to stop using cocaine, amongst those who were trying to abstain, it helped them refrain from taking the drug.

Dr Belin and colleagues used an experiment in which rats compulsively self-administered cocaine. They found that rats given N-acetylcysteine lost the motivation to self-administer cocaine more quickly than rats given a placebo. In fact, when they had stopped working for cocaine, they tended to relapse at a lower rate. N-acetylcysteine also increased the activity in the brain of a particular gene associated with plasticity – the ability of the brain to adapt and learn new skills.

“A hallmark of addiction is that the user continues to take the drug even in the face of negative consequences – such as on their health, their family and friends, their job, and so on,” says co-author Mickael Puaud from the Department of Pharmacology of the University of Cambridge. “Our study suggests that N-acetylcysteine, a drug that we know is well tolerated and safe, may help individuals who want to quit to do so.”

High cocaine doses ‘can cause brain to eat itself’

A study of mice found that the drug can trigger out-of-control “autophagy”, a process by which cells digest themselves.

When it is properly regulated, autophagy provides a valuable cleanup service – getting rid of unwanted debris that is dissolved away by enzymes within cell “pockets”.

Dr Prasun Guha, from Johns Hopkins University School of Medicine in the US, who led the research published in the journal Proceedings of the National Academy of Sciences, said: “A cell is like a household that is constantly generating trash. Autophagy is the housekeeper that takes out the trash – it’s usually a good thing. But cocaine makes the housekeeper throw away really important things, like mitochondria, which produce energy for the cell.”

The scientists carried out postmortems that showed clear signs of autophagy-induced cell death in the brains of mice given high doses of cocaine. They also found evidence of autophagy in the brain cells of mice whose mothers received the drug while pregnant.

The scientists showed that an experimental drug called CGP3466B was able to protect mouse nerve cells from cocaine death due to autophagy. Since the drug has already been tested in clinical trials to treat Parkinson’s and motor neurone disease, it is known to be safe in humans. But much more research is needed to find out whether the drug can prevent the harmful effects of cocaine in people, said the team.

Co-author Dr Maged Harraz said: “Since cocaine works exclusively to modulate autophagy versus other cell death programs, there’s a better chance that we can develop new targeted therapeutics to suppress its toxicity.”

Image: There were clear signs of autophagy-induced cell death in the brains of mice given high doses of cocaine. Credit: OJO Images/Alamy

Source: Guardian 

anonymous asked:

Take a mechanical pencil and take out the lead then tape the front and take out the eraser and put cocaine in the pencil and when you're ready to snort it untape it and the cocaine will come out of the front and you can snort a line then tape it back up.

thank u for this advice

“Oh, dear heart-throb of YouTube…”

So I was scrolling through the tumbs and I found the profile picture of @septickat and I had charcoal and yeah. 

SepticEye Hell? Yeah, I jumped INTO it. What a fuhkin’ idiot.
Fuck tagging OG on here he’s not gonna see this anyway. fuck.
High doses of cocaine cause mouse brain cells to eat themselves
"Out-of-control autophagy."
By Fiona MacDonald

Research in mice has shown that high doses of cocaine can trigger “out-of-control autophagy” in the brain - which means that the drug causes brain cells to literally digest themselves at an unprecedented rate. And that’s not great news, considering around 1.9 million people in the US admit to regularly taking cocaine.

Although it sounds scary, autophagy is actually a totally normal way for our cells clean up their waste and stay healthy. But when mice are given a hefty dose of cocaine, that process goes dangerously into overdrive, a team from the Johns Hopkins University School of Medicine has discovered.

“A cell is like a household that is constantly generating trash,” said lead author of the study, Prasun Guha. “Autophagy is the housekeeper that takes out the trash - it’s usually a good thing. But cocaine makes the housekeeper throw away really important things, like mitochondria, which produce energy for the cell.”

Re-watch tonight everyone?

8:30 est on Slack. Once more, with feeling! We’re starting from the very beginning with “Cocaine Blues”. I hope as many of you as possible can join us. [Maybe default to one ep. per week + convo after since we have an entire year to get through - maybe, hopefully, please.]

Meet you all in John Andrews bathroom!

anonymous asked:

Florida kilo's is all about selling and doing coke. I believe it bc she describes it really accurately

Anybody can describe cocaine accurately. Theres the internet lol

also i miss running my radio show and i’ve been thinking of songs to play, i’ve discovered so many since the last show and there’s always always a reason why i play a song and i love just talking about music that means something to me and radio just gives me a platform to do that even tho i only have like 4 listeners

Funhaus Starters ( part 1 )

“Praise him.” 
“You stay away from him!” 
“Oh my god look at all those scrobbles.” 
“YOU GOT ME, _______” 
“Am I in your head yet, ______?” 
“As expected.” 
“Perfect! This is exactly where we wanted to be.”
“Just go to Hell. God I can’t believe you’d ask me that.” 
“Yeah well, you’re already sinning in the eyes of the lord 
you son of a bitch.” 
“Are you really drinking alcohol, right now, while I’m talking about 
“I was pouring alcohol while you were talking. Now I’m drinking
“Cocaine is all natural.” 
“You just activated my GET FUCKED card.” 
“I can’t see. I’m blinded by the glitz and glamour.” 
“Everybody has to bring a nice bottle of wine to fight club.”
“Why is it never normal sex?” 
“No one’s gonna keep me straight.” 
“Go down on her.” 
“Either you burn out or fade away. I did both.” 

Lexa : Clarke ?

Clarke : What now ?

Lexa : I feel like a hero and you’re my cocaine.

Clarke : What the fuck Lexa ?!

Lexa : This was supposed to make you smile and maybe even flush, it should have been romantic.

Clarke : Wait… Don’t tell me anything. Raven ?

Lexa : She said cocaine was the same as heroine.

Clarke : I can’t believe she did this…