5 ms·

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

68 points by Libertatea 11y ago

aidos 11y ago
Fascinating. Would something like this connection be cocaine specific?
- danieltillett 11y ago
  I kind of doubt it. It would be very interesting to see if N-actly-cystine would help control in other addictive behaviour. Of course there is the slight issue that this is just in rats, but the fact that NAC is an over the counter supplement makes it easy to test.
  - randomname2 11y ago
    NAC has been shown to help with compulsive hair-pulling (trichotillomania)
- peteretep 11y ago
  Tobacco and heroin too, apparently: http://www.nature.com/npp/journal/v37/n1/full/npp2011164a.html http://www.nature.com/npp/journal/v37/n1/full/npp2011164a.ht...
- alderz 11y ago
  Probably not. Quoting from the article: 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.
- tyingq 11y ago
  Ibogaine, and it's effect on GDNF (a brain protein), is reported to have a similar effect[1] on both alcohol and heroin addictions. [1] at least to a layperson like me.
peteretep 11y ago
Hrm, it's for sale on Amazon as an anti-antioxidant dietary supplement. Gwern?
- ry_ry 11y ago
  Interesting, the article mentions it failing clinical human trials but not why, presumably there was no significant health aspect if it's available as a supplement. Perhaps this will finally help me kick my 10-page-a-day HN habit?
poelzi 11y ago
right... http://www.ted.com/talks/johann_hari_everything_you_think_you_know_about_addiction_is_wrong http://www.ted.com/talks/johann_hari_everything_you_think_yo...
rurban 11y ago
Uh, press releases. There is no back-door. What they found is the plain old habituation effect, circumventing the cortex directly through the hypothalamus, and in this case linking the basolateral amygdala (the pleasure centre) with the dorsolateral striatum (the main centre for unaware behavior). This is a normal effect, not everything can go through the consciousness (the cortex), otherwise it will be overloaded. In fact 80% of all senses and motoric effects are eventually bypassed this way.
- padobson 11y ago
  It sure took them a long time to get to this point. Here's the pivot line from the release: 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.
- brenfrow 11y ago
  Can you give me a link on more information on this? I'm very interested in including this type of research into one of my future presentations.
  - joveian 11y ago
    Here is one recent review article with further references: http://www.sciencedirect.com/science/article/pii/S1074742714000860 http://www.sciencedirect.com/science/article/pii/S1074742714... That is "From ventral-medial to dorsal-lateral striatum: Neural correlates of reward-guided decision-making" by Burton et al. They have a nice summary picture. The first paper that this press release talks about is about amygdala contribution to this process (at least for cocaine addition), where the basolateral amygdala (BLA) is involved as neural involvement in behavior shifts from the ventral to anterior dorsolateral striatum (DLS) and then the amygdala contribution changes to the central nucleus. It looks like the BLA pathway to the anterior DLS they describe is through the core of the nucleus accumbens to the substantia nigra. The central amygdala projects directly to the substantia nigra. I found this paper exploring the connection of the central nucleus and the DLS ("Amygdala central nucleus interacts with dorsolateral striatum to regulate the acquisition of habits" by Lingawe and Balleine): https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3711777/ https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3711777/ Another interesting paper that talks more about the hippocampal system and DLS is "Factors That Influence the Relative Use of Multiple Memory Systems" by Packard and Goodman [pdf]: https://www.researchgate.net/profile/Jarid_Goodman/publication/255715967_Factors_that_influence_the_relative_use_of_multiple_memory_systems/links/54d82aca0cf2970e4e76bf28.pdf https://www.researchgate.net/profile/Jarid_Goodman/publicati... For one view of the possible role of the amygdala, see Pessoa's 'Emotion and Cognition and the Amygdala: From “what is it?” to “what’s to be done?”' https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2949460/ https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2949460/ Another interesting paper I found argues that the basic function of the DLS could be "action chunking". "Investigating habits: strategies, technologies and models" by Smith and Graybiel: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3921576/ https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3921576/ ETA: I also noticed this paper the other day concerning value judgements in the nucleus accumbens ("Dissecting components of reward: ‘liking’, ‘wanting’, and learning." by Berridge et al.): https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2756052/ https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2756052/
blazespin 11y ago
Neat, but even looking at this http://www.nature.com/npp/journal/v37/n1/pdf/npp2011164a.pdf http://www.nature.com/npp/journal/v37/n1/pdf/npp2011164a.pdf I see absolutely no numerical measurements of how much it "reduced craving". No experiments against a placebo control or anything.
enkephalin 11y ago
More than 20 clinical trials have employed NAC as an adjunctive treatment in various psychiatric disorders. These include methamphetamine and cannabis dependence, nicotine and cocaine addiction, pathological gambling, obsessive–compulsive disorder, trichotillomania, nail biting and skin picking, schizophrenia, bipolar disorder, autism, and AD. In most of these studies, NAC had positive effects on clinical outcomes (Gere-Paszti and Jakus 2009; Samuni et al. 2013). http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3967529/ http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3967529/ edit: NAC = N-acetylcysteine
amelius 11y ago
There's also a substance called citicoline (CDP-choline), that has been used as a partial treatment for addictive disorders, [1]. > Furthermore, citicoline appears to decrease craving and is associated with a reduction in cocaine use, at least at high doses in patients with both bipolar disorder and cocaine dependence. [1] http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4139283/ http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4139283/
elwell 11y ago
Apparently /classic isn't a sufficient filter for HN anymore.
ommunist 11y ago
Ha! I 'd like very much to see the results of clinical trials of N-acetylcysteine to cure Internet (especially Facebook) addiction and game addiction.

68 points by Libertatea 11y ago

aidos 11y ago

Fascinating. Would something like this connection be cocaine specific?

danieltillett 11y ago
I kind of doubt it. It would be very interesting to see if N-actly-cystine would help control in other addictive behaviour. Of course there is the slight issue that this is just in rats, but the fact that NAC is an over the counter supplement makes it easy to test.
- randomname2 11y ago
  NAC has been shown to help with compulsive hair-pulling (trichotillomania)
peteretep 11y ago
Tobacco and heroin too, apparently: http://www.nature.com/npp/journal/v37/n1/full/npp2011164a.html http://www.nature.com/npp/journal/v37/n1/full/npp2011164a.ht...
alderz 11y ago
Probably not. Quoting from the article: 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.
tyingq 11y ago
Ibogaine, and it's effect on GDNF (a brain protein), is reported to have a similar effect[1] on both alcohol and heroin addictions. [1] at least to a layperson like me.

peteretep 11y ago

Hrm, it's for sale on Amazon as an anti-antioxidant dietary supplement. Gwern?

ry_ry 11y ago
Interesting, the article mentions it failing clinical human trials but not why, presumably there was no significant health aspect if it's available as a supplement. Perhaps this will finally help me kick my 10-page-a-day HN habit?

poelzi 11y ago

right... http://www.ted.com/talks/johann_hari_everything_you_think_you_know_about_addiction_is_wrong http://www.ted.com/talks/johann_hari_everything_you_think_yo...

rurban 11y ago

Uh, press releases. There is no back-door. What they found is the plain old habituation effect, circumventing the cortex directly through the hypothalamus, and in this case linking the basolateral amygdala (the pleasure centre) with the dorsolateral striatum (the main centre for unaware behavior). This is a normal effect, not everything can go through the consciousness (the cortex), otherwise it will be overloaded. In fact 80% of all senses and motoric effects are eventually bypassed this way.

padobson 11y ago
It sure took them a long time to get to this point. Here's the pivot line from the release: 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.
brenfrow 11y ago
Can you give me a link on more information on this? I'm very interested in including this type of research into one of my future presentations.
- joveian 11y ago
  Here is one recent review article with further references: http://www.sciencedirect.com/science/article/pii/S1074742714000860 http://www.sciencedirect.com/science/article/pii/S1074742714... That is "From ventral-medial to dorsal-lateral striatum: Neural correlates of reward-guided decision-making" by Burton et al. They have a nice summary picture. The first paper that this press release talks about is about amygdala contribution to this process (at least for cocaine addition), where the basolateral amygdala (BLA) is involved as neural involvement in behavior shifts from the ventral to anterior dorsolateral striatum (DLS) and then the amygdala contribution changes to the central nucleus. It looks like the BLA pathway to the anterior DLS they describe is through the core of the nucleus accumbens to the substantia nigra. The central amygdala projects directly to the substantia nigra. I found this paper exploring the connection of the central nucleus and the DLS ("Amygdala central nucleus interacts with dorsolateral striatum to regulate the acquisition of habits" by Lingawe and Balleine): https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3711777/ https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3711777/ Another interesting paper that talks more about the hippocampal system and DLS is "Factors That Influence the Relative Use of Multiple Memory Systems" by Packard and Goodman [pdf]: https://www.researchgate.net/profile/Jarid_Goodman/publication/255715967_Factors_that_influence_the_relative_use_of_multiple_memory_systems/links/54d82aca0cf2970e4e76bf28.pdf https://www.researchgate.net/profile/Jarid_Goodman/publicati... For one view of the possible role of the amygdala, see Pessoa's 'Emotion and Cognition and the Amygdala: From “what is it?” to “what’s to be done?”' https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2949460/ https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2949460/ Another interesting paper I found argues that the basic function of the DLS could be "action chunking". "Investigating habits: strategies, technologies and models" by Smith and Graybiel: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3921576/ https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3921576/ ETA: I also noticed this paper the other day concerning value judgements in the nucleus accumbens ("Dissecting components of reward: ‘liking’, ‘wanting’, and learning." by Berridge et al.): https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2756052/ https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2756052/

blazespin 11y ago

Neat, but even looking at this http://www.nature.com/npp/journal/v37/n1/pdf/npp2011164a.pdf http://www.nature.com/npp/journal/v37/n1/pdf/npp2011164a.pdf I see absolutely no numerical measurements of how much it "reduced craving". No experiments against a placebo control or anything.

enkephalin 11y ago

More than 20 clinical trials have employed NAC as an adjunctive treatment in various psychiatric disorders. These include methamphetamine and cannabis dependence, nicotine and cocaine addiction, pathological gambling, obsessive–compulsive disorder, trichotillomania, nail biting and skin picking, schizophrenia, bipolar disorder, autism, and AD. In most of these studies, NAC had positive effects on clinical outcomes (Gere-Paszti and Jakus 2009; Samuni et al. 2013). http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3967529/ http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3967529/ edit: NAC = N-acetylcysteine

amelius 11y ago

There's also a substance called citicoline (CDP-choline), that has been used as a partial treatment for addictive disorders, [1]. > Furthermore, citicoline appears to decrease craving and is associated with a reduction in cocaine use, at least at high doses in patients with both bipolar disorder and cocaine dependence. [1] http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4139283/ http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4139283/

elwell 11y ago

Apparently /classic isn't a sufficient filter for HN anymore.

ommunist 11y ago

Ha! I 'd like very much to see the results of clinical trials of N-acetylcysteine to cure Internet (especially Facebook) addiction and game addiction.