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Dr. Bob is Robert Hsiung, MD,
bob@dr-bob.orgShown: posts 1 to 13 of 13. This is the beginning of the thread.
Posted by MrBrice on September 20, 2006, at 11:58:15
dear Bobbers,
i have a somewhat burn-out, with anxiety and social phobia.
I use dosulepin and klonopin and it relaxes me and relieves me from my anxiety.But now i founf out that smoking actually makes me feel 'like i used to', ie normal!
I've been smoking since i was 14 and quit on mu 19th birthday cause it made me feel sad after my 'burn out'.Now that my anxiety is under control it seems that i can enjoy cigarettes again, and weirdly enough they have an energizing and uplifting effect for me.
how can this be explained?
Are there medicines that can give me the same witheout smoking?greetings,
Brice
Posted by Tomatheus on September 20, 2006, at 12:53:37
In reply to Nicotine works :s, posted by MrBrice on September 20, 2006, at 11:58:15
> how can this be explained?
It could be possible that the stimulating the nicotinic acetylcholine receptors provides some sort of therapeutic benefit for you. Or perhaps the compounds in tobacco that have been demonstrated to reversibly inhibit MAO-A and MAO-B might be contributing to your "response" to smoking. After all, comparative studies have found the "old" Nardil (an MAOI) to be the most effective medication in the treatment of social anxiety disorder.
Of course, there are other explanations. And it's possible that your response could be explained by a combination of factors.
> Are there medicines that can give me the same witheout smoking?
The nicotine in over-the-counter gum and transdermal patches should be equivalent to the nicotine in tobacco. However, there is no available medication that combines nicotine with MAO-inhibiting compounds in tobacco and any of tobacco's other compounds that might have some sort of therapeutic benefits.
I suppose you could try combining nicotine gum or patches with an MAOI, but it's difficult to say to what extent the effects of such a combo would be comparable to those of smoking.
Tomatheus
Posted by linkadge on September 20, 2006, at 15:14:38
In reply to Re: Nicotine works :s » MrBrice, posted by Tomatheus on September 20, 2006, at 12:53:37
I have tried nicotine alone and in combination with certain MAOI inhibiting herbs.
The best combination I found was with nicotine and a herb called FO-TI. You can get it at most health food stores or online. Supposedly it is a stronger MAO-B inhibitor than MAO-A inhibitor.
I noticed that the effect from nicotine was prolonged, and that I needed less of it to have a positive effect.
Nicotine and a MAO-I may replicate the effect of smoking with substantially less health risk.
Another option may be nicotine + low dose selegeline.
Linkadge
Posted by MrBrice on September 21, 2006, at 9:05:58
In reply to Re: Nicotine works :s, posted by linkadge on September 20, 2006, at 15:14:38
Thanks for the respons guys.
i'm thinking probably the nicotine releases dopamine in the head, relieving me from a 'dopamine deficiency'.
I HAVE tried selegiline in the past, and it work to some extend, but i think i should maybe try a 'stronger' maoi to get the result i hope for.nardil maybe?
grtz
Posted by linkadge on September 21, 2006, at 9:28:32
In reply to Re: Nicotine works :s, posted by MrBrice on September 21, 2006, at 9:05:58
Did you ever try nicotine in combination with selegeline. Tobacco smoke isn't that powerful an MAOI. HEavy smokers my only have a ~50% inhibition of MAOA/B, but it is really the synergy between nicotine induced dopamine release, and MAOI induced metabolism slowing.
Linkadge
Posted by SLS on September 21, 2006, at 12:44:34
In reply to Re: Nicotine works :s, posted by linkadge on September 21, 2006, at 9:28:32
I wish the authors of the following study took their jobs more seriously. They had a good idea - to study nicotine as an antidepressant - but made the results worthless. The results were that nicotine was no better than placebo after chronic administration after 4 weeks. I happen to believe that this would be the outcome in a properly-designed study, but this one has some glaring weaknesses that make it impossible to draw any conclusions.
1. Only 11 subjects?2. The CES-D rating scale does not consider a score of 10 to be depressed. The scale ranges 0-60, with higher scores indicating more severe depression. This study allowed people in with scores as low as 10. It is possible that only mild depressions are being studied here.
3. The amount of nicotine given did not remain constant throughout the trial. No reason was given for this. It was identified as a confounding variable in interpreting results.
4. The abstract declined to report the results at day 21.
* It is interesting to note that they did not report any improvement in mood from nicotine when given acutely.I believe that nicotine can produce improvements in mood from acute and sub-chronic administration (8 days), but not from chronic administration. I just don't believe that its effects can be sustained. I don't think it is a matter of MAOI inhibition protecting DA supply. I don't think there is the type of second-messenger induced changes in gene expression occurring with nicotine that is probably necessary in producing a true antidepressant response. I think it takes a minimum of 2 weeks for this to occur, not the 1 week (8 days) seen here. The reason the nicotine pooped-out was probably because of receptor reregulation, not because of neurotransmitter depletion or a drop in nicotine administration.
I think this study got the right answers, despite its shortcomings.
- Scott
------------------------------------------------------
Psychopharmacology (Berl). 2006 Sep 15; [Epub ahead of print] Related Articles, Links
Click here to read
Transdermal nicotine attenuates depression symptoms in nonsmokers: a double-blind, placebo-controlled trial.McClernon FJ, Hiott FB, Westman EC, Rose JE, Levin ED.
Department of Psychiatry and Behavioral Sciences, Duke University Medical Center, Durham, NC, USA, mccle011@mc.duke.edu.
RATIONALE: Despite established links between nicotine dependence and depression, little research has examined the effects of nicotine on depression symptoms. OBJECTIVE: This study evaluated the acute and chronic effects of transdermal nicotine in nonsmokers with baseline depression symptoms during a 4-week, double-blind, placebo-controlled trial. METHODS: Nonsmokers with scores >/=10 on the Center for Epidemiological Studies Depression scale (CES-D) were recruited from the community. Mood and cognitive performance were measured at baseline (day 0) and at 1, 8, 21, and 28 days. Participants were randomly assigned to wear a placebo or nicotine patch for 4 weeks (3.5 mg/day during weeks 1 and 4; 7 mg/day during weeks 2 and 3). The final sample consisted of 11 nonsmokers with a mean baseline CES-D score of 27.36 (SD=10.53). RESULTS: Salivary nicotine levels indicated the majority of participants were compliant with treatment. Acute nicotine did not alter mood. After adjusting for baseline values, chronic nicotine resulted in a significant decline in CES-D scores at day 8 (3.5 mg/day), but returned to placebo levels by the last visit. This return to baseline levels was coincident with a decrease in nicotine administration from 7 to 3.5 mg/day. A similar trend for improved response inhibition as measured by the Conners Continuous Performance Task was also observed. Reported side effects were infrequent and minimal. CONCLUSION: These findings suggest a role for nicotinic receptor systems in the pathophysiology of depression and that nicotinic compounds should be evaluated for treating depression symptoms.
PMID: 16977477 [PubMed - as supplied by publisher]
Posted by linkadge on September 21, 2006, at 16:03:02
In reply to Re: Nicotine works :s, posted by SLS on September 21, 2006, at 12:44:34
If nicotine doesn't help your mood long term, then thats fine. But, what is the use in setting out to discredit those who do find help from the substance. Addictive? What speficically do you mean by that? No more addictive than effexor, and if so, explain in what way?
One study is really insufficiant to conclude anything. I'd at least require one failed study for each of ones used in support of nicotine therapy. Nicotine has already undergone studies in ADHD and Tourettes' syndrome with some promising results. It is very important to understand that depression can be caused by a whole array of varying biochemical abnormalities.
To say that, for instance, activation of second messenger systems, is required for an antidepressant response is not entirely acurate, since we have many effective antidepressants which probably do not activate second messenger systems. Drugs like, substance P inhibitors, NK-1 antagonists, NDMA antagonists, lithium, trimipramine, etc etc. have antidepressant effects but do not really directly elevate second messenger systems. Perhaps a more significant underlying effect of antidepressant treatments is an amelioration of overactive HPA axis function. Perhaps overactive CRF in the amygdala is one of the key underpinnings of learned helplessness.
Since, we don't really have any clue as to the exact mechanisms of antidepressant action, I find it kind of strange that one would be able to directly conclude that a certain agent will or will not have long term antidepressant effect.
We know that nicotine can directly and significantly lower cortisol, as well as reducing neurogenic inflammation. Even these actions by themselves warrent further investigation for psychiatric purposes. Nicotine based nuroprotection is another avenue for research.
>I believe that nicotine can produce improvements >in mood from acute and sub-chronic >administration (8 days), but not from chronic >administration.We simply need more data to show either way. A hunch about a drug is really no proof. DA release is clearly only one effect of the drug. Reduction of neural inflamation, for instance, is likely independant of DA release effects.
>true antidepressant response. I think it takes a
>minimum of 2 weeks for this to occur, not the 1 >week (8 days) seen here. The reason the nicotine >pooped-out was probably because of receptor >reregulation, not because of neurotransmitter >depletion or a drop in nicotine administration.Or just the fact that it may not work for some people. Its just like how wellbutrin can be pure poison for some people, and yet for others be the best drug.
>I think this study got the right answers, >despite its shortcomings
I think that we need more than one study to conclude anything at all.
I don't understand what you've got against the substance. It would seem to me that this is a potential avenue for a theraputic drug research.
In terms of abuse potential, nicotine is misunderstood. Nicotine has only limited reinforcement effect in animals. Animals do not self administer nicotine like they do cocaine, amphetamines, heroin etc. Even smokers will find a fixed dose of the substance, and maintain that for years.
So, I say go ahead and experiment. If it doesn't work for you then taper off of it slowly. Its not like you're going to start robbing banks to support the habbit or something.
Posted by SLS on September 21, 2006, at 18:29:25
In reply to Re: Nicotine works :s, posted by linkadge on September 21, 2006, at 16:03:02
> If nicotine doesn't help your mood long term, then thats fine. But, what is the use in setting out to discredit those who do find help from the substance.
Gosh. This is indeed an interesting turn of events. That is a very balanced way of looking at things.
Over the last 5 years, I have spent time around perhaps 200 actively smoking people diagnosed with depression in an outpatient partial hospitalization program. These people smoke 2-3 packs a day regardless of their mood state. The only things that get these people well are standard psychopharmacology and psychological support. No amount of smoking seems to help. I am reporting a personal observation. I guess one could argue that they could have been more severely depressed without smoking or that they were not getting enough nicotine.
> Addictive? What speficically do you mean by that? No more addictive than effexor, and if so, explain in what way?
Where did you see the word "addictive" in my post?
> One study is really insufficiant to conclude anything. I'd at least require one failed study for each of ones used in support of nicotine therapy.I think that one bad study got good results. No big deal. They reported what they found. I don't think we are going to find dozens of clinical trials of nicotine as an antidepressant to compare it to.
> Nicotine has already undergone studies in ADHD and Tourettes' syndrome with some promising results.
I am not trashing nicotine as a pharmacological agent. It is a rather elegant drug. I am just saying that it is not an antidepressant. You can theorize why it is. I can theorize why it is not. Those things don't matter one bit. What matters is whether or not the stuff works robustly and persistently.
As for the rest, you are right, there is indeed quite a bit of interest in the potential of nicotine to yield therapeutic benefits in disorders other than MDD. It is a rather elegant drug. However, at this point, I think the few studies indicating antidepressant-like effects with nicotine are somewhat illusory. I could be wrong. It would be great if I were.
I never thought nicotine was the devil.
- Scott
Posted by SLS on September 22, 2006, at 1:42:30
In reply to Re: Nicotine works :s » linkadge, posted by SLS on September 21, 2006, at 18:29:25
> I never thought nicotine was the devil.
http://www.dr-bob.org/babble/20051003/msgs/562922.html
- Scott
Posted by linkadge on September 23, 2006, at 9:25:11
In reply to Re: Nicotine works :s » linkadge, posted by SLS on September 21, 2006, at 18:29:25
>Over the last 5 years, I have spent time around >perhaps 200 actively smoking people diagnosed >with depression in an outpatient partial >hospitalization program. These people smoke 2-3 >packs a day regardless of their mood state. The >only things that get these people well are >standard psychopharmacology and psychological >support. No amount of smoking seems to help.
I've seen handfulls of people who have been taking antidepressants and still seem very depressed. They know that the drugs do *something*, but they just havn't found drugs that are sufficiant.
They're people like you for instance, You're on a number of medications that you know help *some*, but they're not fully cutting the mustard. To the untrained eye, they appear to be doing nothing (am i right?) but that doesn't mean we dismiss the agents.
>I guess one could argue that they could have >been more severely depressed without smoking or >that they were not getting enough nicotine.
For some people, nicotine may not be a direct antidepressant, but it could have other properties which are in some way helping the mood disorder. For instance, pychiatric patients who smoke do not have the upregulated postsynaptic 5-ht1a receptors that nonsmoking depressives have.
The drug may be acting like buspar, which is not a powerful antidepressant, but can relieve some of the symptoms of depression.>Where did you see the word "addictive" in my post?
I just assumed that you must have seen some inherent evil in nicotine in order to be discouraging people from trying it.
>I think that one bad study got good results. No >big deal. They reported what they found. I don't >think we are going to find dozens of clinical >trials of nicotine as an antidepressant to >compare it to.I think there could be a growing number of them. There is talk about developing nicotine like drugs for depressive/smoking/adhd disorder, if so, companies might want to know beforehand, on just how nicotine affects these populations.
>What matters is whether or not the stuff works >robustly and persistently.I agree, I think we just need the studies to show either way.
Like any other antidepressant, I don't think it will work for every depression.
Linkadge
Posted by SLS on September 23, 2006, at 9:51:42
In reply to Re: Nicotine works :s, posted by linkadge on September 23, 2006, at 9:25:11
> pychiatric patients who smoke do not have the upregulated postsynaptic 5-ht1a receptors that nonsmoking depressives have.
> The drug may be acting like buspar, which is not a powerful antidepressant, but can relieve some of the symptoms of depression.This I would like to see more on. Do you recall where you saw this? I am not disputing it, I am just interested to know more.
- Scott
Posted by linkadge on September 23, 2006, at 17:12:16
In reply to Re: Nicotine works :s, posted by SLS on September 23, 2006, at 9:51:42
I'll keep looking for the exact study I am looking for.
Apparently nicotine acts as an agonist of 5-ht1a autorecpeotrs, especially sensitive to those in the dorsal raphia neucleus. Long term administration may downregulate autoreceptor function.
I got this hit when searching, but I can't acess find the abstract, this may have been the one I was looking for:
Depression and Nicotine: Preclinical and Clinical Evidence for ...Another action of nicotine, which may be analogous to that of some serotonergic antidepressants, is that nicotine downregulates the expression of 5HT1A ...
www.current-reports.com/article.cfm?PubID=PR03-6-1-05&Type=Article&KeyWords= -
Posted by MrBrice on September 26, 2006, at 5:46:18
In reply to Re: Nicotine works :s, posted by linkadge on September 23, 2006, at 17:12:16
I'm trying nicotine pills now and they boost up my energy way high!
It's nice actually...makes me more talkatiive.BUT the dopamine-release is not there i think, wich is a pitty...
grtz
This is the end of the thread.
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