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Dr. Bob is Robert Hsiung, MD,
bob@dr-bob.orgShown: posts 1 to 22 of 22. This is the beginning of the thread.
Posted by linkadge on January 18, 2009, at 20:07:28
Linkadge
Posted by Phillipa on January 19, 2009, at 0:47:02
In reply to Nicotine increases GAD67 levels in schizophrenia, posted by linkadge on January 18, 2009, at 20:07:28
Link I found that the schizophrenics that I had as patients when working in locked unit in psych all smoked like crazy and they fingers were strained brown. Said it relaxed them. So they knew something none of the docs did as they wanted them to stop smoking. Love Phillipa
Posted by mav27 on January 19, 2009, at 1:10:47
In reply to Nicotine increases GAD67 levels in schizophrenia, posted by linkadge on January 18, 2009, at 20:07:28
So if i've read that right ( and i won't be suprised if i didn't) the main thing is people with schizophrenia can find that nicotine helps by increasing GABA via GAD67 ? With GABA being the important part in the end result ?
Posted by SLS on January 19, 2009, at 8:19:53
In reply to Re: Nicotine increases GAD67 levels in schizophrenia, posted by mav27 on January 19, 2009, at 1:10:47
> So if i've read that right ( and i won't be suprised if i didn't) the main thing is people with schizophrenia can find that nicotine helps by increasing GABA via GAD67 ? With GABA being the important part in the end result ?
The effects of nicotine are complex and involve dopamine, glutamate, GABA, and opioids as well. I can barely make heads or tails of it without studying more thoroughly all the systems and receptors involved.
The net effect of nicotine on GABA and dopamine release appears to be phasic; with GABA release and dopamine inhibition occurring first and GABA reduction and an extended period of dopamine increase occurring thereafter. My guess is that the GABA release and dopamine inhibition helps with the positive symptoms of schizophrenia while the extended dopamine increase helps with the positive symptoms. Understanding the circuity involved and the differential loci of these effects on neurotransmission is important.
http://www.drugabuse.gov/NIDA_Notes/NNVol17N6/DoubleEffect.gif
While I was a client in a PH program, the hospital, after years of allowing smoking at the program changed their policy to make the entire hospital smoke-free. I considered this to be a disaster, and through our member council, lobbied the hospital to change their mind on the basis of the therapeutic effects of smoking on our schizophrenics. We were not given a special accommodation. So now, people can leave the grounds without impediment to smoke. Luckily, there is an abandoned lot across the street to accommodate the many smokers who represent a majority of clients there.
- Scott
Posted by SLS on January 19, 2009, at 8:31:20
In reply to Re: Nicotine increases GAD67 levels in schizophrenia, posted by SLS on January 19, 2009, at 8:19:53
Made a mistake.
This passage should read:
"My guess is that the GABA release and dopamine inhibition helps with the POSITIVE symptoms of schizophrenia while the extended dopamine increase helps with the NEGATIVE symptoms."
- Scott
Posted by seldomseen on January 19, 2009, at 10:20:27
In reply to Re: Nicotine increases GAD67 levels in schizophrenia, posted by SLS on January 19, 2009, at 8:19:53
What amazes me about nicotine is that it is anxiolytic and promotes alertness and cognitive ability.
I think when one consider nicotine however, one shouldn't ignore it's primary target - the nicotinic acetylcholine receptors. Acetylcholine is, in my opinion, such an underappreciated neurotransmitter.
Nicotine has also been studied pretty extensively in Alzheimer's patients and seems to provide both neuroprotective effects as well as increases in cognitive function.
Now, having said that, I will also say (perhaps it goes without saying) that the methods we have to deliver nicotine need some serious improvement. It's effects on the cardiovascular system are profound and induce significant morbidity. Of course, there is the threat of cancer that looms large among tobacco users. If only we had a form of nicotine that targeted the brain only....
Okay, now I'm only dreaming.
Seldom.
Posted by SLS on January 19, 2009, at 11:03:46
In reply to Re: Nicotine increases GAD67 levels in schizophrenia » SLS, posted by seldomseen on January 19, 2009, at 10:20:27
Hi Seldom
> Now, having said that, I will also say (perhaps it goes without saying) that the methods we have to deliver nicotine need some serious improvement.
I had suggested to the doctors at the PH program that perhaps nicotine lozenges could become a viable palliative treatment for schizophrenia. They smiled and understood, but... I guess there are some ethical questions about prescribing such an addictive substance, especially if it is only mildly palliative. I don't know. I felt somehow naive.
These schizophrenic folks would probably still continue smoking, as the behavioral component is so strong, and the delivery of the nicotine so immediate and potent - 10 seconds to the brain.
- Scott
Posted by seldomseen on January 19, 2009, at 12:31:02
In reply to Re: Nicotine increases GAD67 levels in schizophrenia » seldomseen, posted by SLS on January 19, 2009, at 11:03:46
Me? I would happily and without reserve apply a nictotine delivery patch directly to my brain. ;)
Given all we do know about the addictive potential of nicotine it's a hard drug to study. (I know that I would have some *serious* reservations about forming a cohort of patients to be given nicotine in any form). Therefore, I wonder if we fully understand its palliative OR curative effects in a variety of situations. I agree with your contention however, and suspect that we will never know.
All I can say is that, as a bona fide, direhard, committed smoker, I'm much much much better with nicotine on board. However, I also have some serious questions regarding how I would be IF i never started smoking. Would I be the same just not addicted? I don't know.
This is only my personal experience and clearly I do not advocate that anyone start smoking. Not only is it bad for you, but it is expensive.
Seldom
Posted by linkadge on January 19, 2009, at 18:22:13
In reply to Re: Nicotine increases GAD67 levels in schizophrenia » SLS, posted by seldomseen on January 19, 2009, at 10:20:27
>Now, having said that, I will also say (perhaps >it goes without saying) that the methods we have >to deliver nicotine need some serious >improvement. It's effects on the cardiovascular >system are profound and induce significant >morbidity.
There is very little research to suggest that nicotine replacement therapy is infact associated with cardiovascular disease. I remember reading one study in which low-moderate dose nicotine actually lowered blood pressure.
>Of course, there is the threat of cancer that >looms large among tobacco users. If only we had >a form of nicotine that targeted the brain >only
Nicotine is not carcinogenic. It does increase angiogenesis which some have theorized could promote tumor growth, but angiognesis can also be beneficial in heart disease and some forms of brain injury.
Linkadge
Posted by linkadge on January 19, 2009, at 18:27:54
In reply to Re: Nicotine increases GAD67 levels in schizophrenia » seldomseen, posted by SLS on January 19, 2009, at 11:03:46
>I guess there are some ethical questions about >prescribing such an addictive substance, >especially if it is only mildly palliative. I >don't know. I felt somehow naive.
We know that smoking is addictive, but we have far less evidence of the extend to which nicotine is addictive. Mice don't really self administer nicotine in the way that they do other drugs of abuse.
Some studies call into question the notion that nicotine is infact a euphoriant at all:
http://biopsychiatry.com/cigarettes-pleasure.htm
People generally find a steady number of cigarettes that does it for them. There is not a steady dose escalation like there is with other drugs.
Furthermore, because of the fact that smoking is often comorbid with depresson/schizophrenia whose to say that people simply can't stop smoking because it controlls their symptoms. I.e. is nicotine any more addictive than zyprexa is, or paxil ?
I think the main thing is that nicotine cannot be patented.
Linkadge
Posted by linkadge on January 19, 2009, at 18:36:25
In reply to Re: Nicotine increases GAD67 levels in schizophrenia » SLS, posted by seldomseen on January 19, 2009, at 12:31:02
I think that many people's view of nicotine is considerably skewed. Nicotine has been painted such a negative picture mainly because of anti-smoking campaigns. Unlike other drugs of abuse, long term nicotine adminstration actualy increases the responsiveness of the reward system. That is, like antidepressants and ECT administration, the brain d3 receptors actually become more (not less) responsive after long term admintration.
I think that nicotine is no more addictive than SSRI's or benzodiazapines. I have gone on and off nicotine many times and the withdrawl is nothing in comaprison to that of SSRI's. Ritalin and amphetamiens can be very addictive for some, but that is not used a reason to not prescribe it to children and adults with ADHD. So really, WFT?
I am happy that nicotine is being studied and that the experineces of many schizophrenic patients are actually being listened to. I hope it is is further studied in the future.
Linkadge
Posted by SLS on January 19, 2009, at 19:02:46
In reply to Re: Nicotine increases GAD67 levels in schizophrenia, posted by linkadge on January 19, 2009, at 18:27:54
> >I guess there are some ethical questions about >prescribing such an addictive substance, >especially if it is only mildly palliative. I >don't know. I felt somehow naive.
>
> We know that smoking is addictive, but we have far less evidence of the extend to which nicotine is addictive. Mice don't really self administer nicotine in the way that they do other drugs of abuse.
>
> Some studies call into question the notion that nicotine is infact a euphoriant at all:
>
> http://biopsychiatry.com/cigarettes-pleasure.htm
>
> People generally find a steady number of cigarettes that does it for them. There is not a steady dose escalation like there is with other drugs.
>
> Furthermore, because of the fact that smoking is often comorbid with depresson/schizophrenia whose to say that people simply can't stop smoking because it controlls their symptoms. I.e. is nicotine any more addictive than zyprexa is, or paxil ?
>
> I think the main thing is that nicotine cannot be patented.
>
> Linkadge
Nicotine is not addictive in the same way as are cocaine or amphetamines. That makes it no less addictive. Mice can be Pavlovian conditioned to anticipate nicotine administration and demonstrate hyperactivity in between doses, especially when it is withheld. Mice also demonstrate conditioned place-preference with nicotine. Self-administration is therefore not the right paradigm to assay nicotine addiction.
- Scott
Posted by SLS on January 19, 2009, at 19:28:10
In reply to Re: Nicotine increases GAD67 levels in schizophrenia, posted by SLS on January 19, 2009, at 19:02:46
> Nicotine is not addictive in the same way as are cocaine or amphetamines. That makes it no less addictive. Mice can be Pavlovian conditioned to anticipate nicotine administration and demonstrate hyperactivity in between doses, especially when it is withheld. Mice also demonstrate conditioned place-preference with nicotine. Self-administration is therefore not the right paradigm to assay nicotine addiction.
When nicotine is administered IV, things change:
"Further, self-administration studies with rats consistently report that IV nicotine maintains instrumental responding over a range of doses (e.g., Corrigall & Coen 1989; DeNoble & Mele 2006; Donny et al. 1995; Rauhut et al. 2003; Shoaib et al. 1996) indicating that IV nicotine has some reinforcing properties."
http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=2248701
I think Linkadge makes a valuable observation that nicotine is significantly different from most other drugs of abuse (I believe cannabis is another exception). I don't know for sure that someone can become addicted to nicotine replacement products if they were nicotine-naive. I never looked into it.
I think any definition of addiction must include the presence of cravings. People don't crave Zyprexa or Effexor.
- Scott
Posted by Phillipa on January 19, 2009, at 20:02:10
In reply to Re: Nicotine increases GAD67 levels in schizophrenia, posted by SLS on January 19, 2009, at 19:28:10
When I smoked hated it as it made me dizzy and anxious almost fainted one morning first time every had a cigarette unless night and drinking beer. Used it as a stimulant for defacation. Seriously. Phillipa
Posted by seldomseen on January 19, 2009, at 20:15:46
In reply to Re: Nicotine increases GAD67 levels in schizophrenia » seldomseen, posted by linkadge on January 19, 2009, at 18:22:13
Nicotine is a profound vaso-constrictor. But like most agents that work in the vasculature, it depends on which vascular bed as to the exact role of vaso-dilation vs vaso-constriction.
One also has to consider the role of nicotine as an anxiolytic when one looks at blood pressure.
Again, I think what is called for looking at the preponderance of evidence.
As far as nicotine being a carcinogen, I didn't say it was. I said the use of *tobacco* was associated with the development of cancer.
Seldom.
Posted by SLS on January 20, 2009, at 10:06:01
In reply to Re: Nicotine increases GAD67 levels in schizophrenia » SLS, posted by Phillipa on January 19, 2009, at 20:02:10
> When I smoked hated it as it made me dizzy and anxious almost fainted one morning first time every had a cigarette unless night and drinking beer. Used it as a stimulant for defacation. Seriously. Phillipa
I remember my first cigar. I smoked it in the vestibule between two cars on the train. I got through half of it and felt dizzy and nauseous. I swear I almost fell off the train. It took me awhile to go back in the car and find a seat.
- Scott
Posted by linkadge on January 20, 2009, at 12:29:39
In reply to Re: Nicotine increases GAD67 levels in schizophrenia, posted by SLS on January 19, 2009, at 19:02:46
Mice demonstrate withdrawl effects from SSRI's too, so whats your point?
Linkadge
Posted by linkadge on January 20, 2009, at 12:34:33
In reply to Re: Nicotine increases GAD67 levels in schizophrenia » linkadge, posted by seldomseen on January 19, 2009, at 20:15:46
Nicotine promotes angiogenesis, which theoretically could hasten recovery in certain paradigms of cardiac hypoxia.
Serotonin is also a vasoconstrictor and I believe some studies suggest SSRI's like the triptans can cause vasoconstricton.
Linkadge
Posted by desolationrower on January 23, 2009, at 2:02:58
In reply to Re: Nicotine increases GAD67 levels in schizophrenia, posted by linkadge on January 20, 2009, at 12:34:33
I think that the upregulation of d3 clearly can have long-term addictive potential, but the biggest thing that causes addiction is how fast something gets in to your system. with lozenges, they take forever. Also it has effects on expression and affinity states of the nicotinic receptors. problem is few of the studies have been ver long term, they are all looking at "how does addiction form' with the presumption that it does happen.
-d/r
Posted by raisinb on January 24, 2009, at 0:27:57
In reply to Nicotine increases GAD67 levels in schizophrenia, posted by linkadge on January 18, 2009, at 20:07:28
Interesting thread. I've never read anything about the therapeutic effects of nicotine. I don't smoke often--more when stressed or upset--but I sure do love it.
I'd always assumed (half-remembered from reading something a long time ago) that it's not the nicotine that causes cancer. It's the fillers in most modern filtered cigarettes. Again, probably a rather incorrect memory, but I think that the incidence of lung cancer in 1900--when there were many more smokers--was a fraction of what it is today. The hypothesis of that study was that most people back then smoked pure unfiltered tobacco in pipes or rolled their own, and it's what the companies today add that is so destructive to the cardiovascular system.
Posted by raisinb on January 24, 2009, at 0:35:08
In reply to Re: Nicotine increases GAD67 levels in schizophren » linkadge, posted by raisinb on January 24, 2009, at 0:27:57
Freud's beloved cigars were the death of him (oral cancer that metastasized).
Posted by desolationrower on January 25, 2009, at 1:52:09
In reply to of course, posted by raisinb on January 24, 2009, at 0:35:08
its the products of combustion mainly; nice pure tobbacco is bad too, although it tastes better than pre-rolled cigarettes
-d/r
This is the end of the thread.
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