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Dr. Bob is Robert Hsiung, MD,
bob@dr-bob.orgShown: posts 1 to 25 of 25. This is the beginning of the thread.
Posted by Hugh on December 10, 2014, at 10:26:11
Nitrous oxide, or laughing gas, has shown early promise as a potential treatment for severe depression in patients whose symptoms don't respond to standard therapies. The pilot study, at Washington University School of Medicine in St. Louis, is believed to be the first research in which patients with depression were given laughing gas.
In 20 patients who had treatment-resistant clinical depression, the researchers found that two-thirds experienced an improvement in symptoms after receiving nitrous oxide. In comparison, one-third of the same patients reported improved symptoms after treatment with a placebo. The patients were evaluated on the day of and day after each treatment.
"It's kind of surprising that no one ever thought about using a drug that makes people laugh as a treatment for patients whose main symptom is that they're so very sad," Nagele said.
The complete article is here:
http://medicalxpress.com/news/2014-12-gas-depression-treatment.html
Posted by ed_uk2010 on December 10, 2014, at 19:09:31
In reply to Laughing gas studied as depression treatment, posted by Hugh on December 10, 2014, at 10:26:11
Shame it's follow by nausea and vomiting. What goes up must come down....
Posted by Hugh on December 10, 2014, at 20:20:19
In reply to Re: Laughing gas studied as depression treatment, posted by ed_uk2010 on December 10, 2014, at 19:09:31
I've had laughing gas and it didn't make me nauseous. I felt wonderful while I was on it. I don't remember if I felt any less depressed in the following days, since this was years ago.
Posted by Phillipa on December 10, 2014, at 20:38:26
In reply to Re: Laughing gas studied as depression treatment » ed_uk2010, posted by Hugh on December 10, 2014, at 20:20:19
I had it once also years ago for wisdom tooth extraction. At that time in my life had never had anxiety. It caused me to become sexually suggestive in what I said to the Dentist. That was it. And no nothing went on it was how I was thinking was in 20's then. Phillipa
Posted by ed_uk2010 on December 10, 2014, at 20:58:07
In reply to Re: Laughing gas studied as depression treatment, posted by ed_uk2010 on December 10, 2014, at 19:09:31
>What goes up must come down....
Apologies if that was misinterpreted. It was intended entirely for purposes of amusement :) The study is clearly interesting but requires some context (in my opinion).
Bearing in mind that nitrous oxide (N20) is a known euphoriant.... I do tend to feel that any allegedly persistent 'antidepressant' effects found in trials such as this should be questioned very carefully. Patients may feel better briefly after treatment, perhaps as a result of remembering what it's like to feel pleasure (?). The issue as I see it is that it seems highly unlikely that any apparent benefits would continue long-term. Problems, on the other hand, seem likely. The same applies to other euphoriant drugs sometimes purported to exert antidepressant effects. Depression of mood is likely in the long run... amongst many other issues related to addiction.
Posted by ed_uk2010 on December 10, 2014, at 20:59:11
In reply to Re: Laughing gas studied as depression treatment » ed_uk2010, posted by Hugh on December 10, 2014, at 20:20:19
> I've had laughing gas and it didn't make me nauseous. I felt wonderful while I was on it. I don't remember if I felt any less depressed in the following days, since this was years ago.
I expect your experience is very common.
Posted by Lamdage22 on December 11, 2014, at 14:01:33
In reply to Re: Laughing gas studied as depression treatment, posted by ed_uk2010 on December 10, 2014, at 20:59:11
Hm,
the big question, as always for me is:
Can it cause or worsen psychosis?
Posted by Lamdage22 on December 11, 2014, at 14:04:12
In reply to Re: Laughing gas studied as depression treatment, posted by Lamdage22 on December 11, 2014, at 14:01:33
And the answer as so often is YES.
No go.
Posted by BrainDamage on December 11, 2014, at 17:14:01
In reply to Re: Laughing gas studied as depression treatment, posted by Lamdage22 on December 11, 2014, at 14:04:12
This might be part of the reason for its affects
Posted by SLS on December 11, 2014, at 19:36:52
In reply to Re: Laughing gas-NMDA antagonist, posted by BrainDamage on December 11, 2014, at 17:14:01
> This might be part of the reason for its affects
Interesting.
- Scott
Posted by linkadge on December 12, 2014, at 20:21:08
In reply to Caution » ed_uk2010, posted by ed_uk2010 on December 10, 2014, at 20:58:07
Ketamine, Nicotine and scopolamine are also euphoriants which are proving to be faster acting antidepressants than the nonsense they prescribe now.
Linkadge
Posted by SLS on December 12, 2014, at 20:35:09
In reply to Re: Caution » ed_uk2010, posted by linkadge on December 12, 2014, at 20:21:08
> Ketamine, Nicotine and scopolamine are also euphoriants which are proving to be faster acting antidepressants than the nonsense they prescribe now.
>
> Linkadge
Yes to all three!I remember arguing with you about nicotine many years ago. You were right (as usual).
HNK and alpha-7 nicotinic receptors:
"A compound, hydroxynorketamine (HNK), has been identified by researchers that may treat symptoms of depression just as effectively and rapidly as ketamine, without the unwanted side effects associated with the psychoactive drug, according to a study. "
http://www.sciencedaily.com/releases/2014/06/140617093820.htm
Perhaps NMDA receptor blockade is not the mechanism by which ketamine produces antidepressant effects. That would be very convenient.
- Scott
Posted by ed_uk2010 on December 13, 2014, at 5:55:50
In reply to Re: Caution » ed_uk2010, posted by linkadge on December 12, 2014, at 20:21:08
>ketamine, nicotine and scopolamine....
Ketamine - early days. Not exactly an ideal first line treatment ready to use on a widespread basis :) I have to say, despite its potential benefits, I can't see ketamine replacing the likes of sertraline or citalopram for general use. I can see it being used as an alternative to ECT in some situations.
Scopolamine - high doses are deliriant as much as euphoric, and can be intensely unpleasant. Same applies to various other central anticholinergics. The anticholinergic effects of TCAs may be relevant to producing a response in some people. Amitriptyline, for example, is exceptionally anticholinergic. I find all strong anticholinergics intolerable, including scopolamine, but I do believe some may respond. Of course, central anticholinergics can produce a high incidence of cognitive and memory impairment at anything above the smallest doses. In the elderly, even tiny doses can cause acute confusional states and are contra-indicated in dementia. Drugs which elevate acetylcholine, eg. the acetylcholinesterase inhibitors (donepezil, Aricept and so on) are the main pharmacological treatment for dementia, with limited success. Their side effects are the opposite of anticholinergics, and on combination cancel each other out. Peripherally acting anticholingergics, eg. Buscopan, the lipid-insoluble form of scopolamine, may be of some use in treating the GI side effects of donepezil due to poor absorption and poor CNS penetration. Combining standard scopolamine (eg. Scopoderm) or amitriptyline with donepezil would cancel out the benefits. Donepezil can be 'depressing', but some dementia pts experience an improvement in mood associated with a reduction in confusion. Confusion is no fun, certainly not on a long-term basis....
Nicotine - I've heard of the nicotine patch being used with some success on occasion. Again, I wouldn't say it's first line, or that it will replace anything. Nicotine products tend to cause a high incidence of side effects in non-smokers, and can actually be dysphoric in anything more than tiny amounts eg. 1mg gum. Only very low doses of nicotine temporarily enhance calmness and concentration. Higher doses frequently cause nausea, dizziness, some degree of agitation and worsened cognitive performance.
>the nonsense they prescribe now...
Well, none of the treatment we have are anywhere near ideal, including those discussed above :)
Posted by Lamdage22 on December 13, 2014, at 5:57:15
In reply to Re: Caution » linkadge, posted by ed_uk2010 on December 13, 2014, at 5:55:50
Hey linkadge,
is scopolamine pro psychotic at all?
Posted by ed_uk2010 on December 13, 2014, at 6:18:38
In reply to Re: Caution » linkadge, posted by SLS on December 12, 2014, at 20:35:09
>I remember arguing with you about nicotine many years ago.
Interesting that bupropion (Wellbutrin, Zyban) binds to certain nicotinic receptors, I believe as an antagonist but not at all nicotinic receptor subtypes. Another 'anti smoking' drug, varenicline (Champix, Chantix), a nicotinic partial agonist, has been associated with possibly inducing psychiatric disturbances including depression. Having said that, so has bupropion and so have most common ADs. Nothing is simple...
>HNK and alpha-7 nicotinic receptors:
>
> "A compound, hydroxynorketamine (HNK), has been identified by researchers that may treat symptoms of depression just as effectively and rapidly as ketamine, without the unwanted side effects associated with the psychoactive drug, according to a study.Very interesting, thanks for the link.
>Perhaps NMDA receptor blockade is not the mechanism by which ketamine produces antidepressant effects. That would be very convenient.
NMDA antagonists confuse me. I mean, memantine is used to treat Alzheimer's... and then other NMDA antagonists are dissociatives. I suppose most of them have a variety of neuropharmacological actions.
Posted by linkadge on December 13, 2014, at 9:26:56
In reply to Re: Caution » linkadge, posted by ed_uk2010 on December 13, 2014, at 5:55:50
But, here is the problem.....
Citalopram makes me feel like an apathetic zombie for months at a time, until it kicks in... And after it 'kicks in' I still feel like an apathetic zombie for months at a time. I'm tired of asking myself....is this how I have to feel just to rid myself of menacing anxiety and depression? I'm tired of being impaired by the drugs that are suppose to help. I'm tired of not being able to concentrate, or sit still (or sleep) on SSRIs.
Now, when I feel that my depression is starting to become overwhelming, I can put on a 1.5mg scopolamine patch and chew 0.5-1mg of nicotine and literally feel better in about 10 minutes.
Everything improves, my anxiety, my depression, my appetite, my insomnia.I can feel the depression disappear. Its like the brain circuits and pathways are redirected. Even when I take off the patch, I feel better for maybe 3-6 days later.
During that 3-6 day period, I have no side effects and I am not on anything. I am far more productive than I would be in the SSRI haze.
I don't think that this constitutes a simple euphoria. To me, you're getting a rapid alteration in the brain circuitry that regulates mood.
The notion that an antidepressant needs to be taken for weeks and months to produce an effect is nonsense IMHO. Depression is nothing more than stress and a crappy life making it difficult for somebody to feel pleasure.
Is it really any surprise that regular coffee drinkers have lower rates of depression and suicide?
Linkadge
Posted by linkadge on December 13, 2014, at 9:37:21
In reply to Re: Caution - with anything » SLS, posted by ed_uk2010 on December 13, 2014, at 6:18:38
Depression appears to be associated with upregulation of certain nicotinergic receptors. Nicotine causes a rapid downregulation of certain nicotinergic receptors. I assume that nicotinergic antagonists could also cause receptor downregulation or upregulation. I remember reading studies on how TCA's will alter nicotinergic rececptors over the course of weeks.
Nicotine initially produces catecholamine release, but tolerance to this effect is rapid.There is also interaction between nicotinergic receptors, sigma receptors, dopamine and serotonin reuptake.
Nicotine administration acutely inhibits dopamine and enhances serotonin reuptake transporters respectively.
Nicotine also rapidly activates AKT and inhibits GSK-3 which are mechanisms associated with the rapid antidepressant effects of ketamine, lithium, zinc etc. Activating AKT is also neuroprotective. Nicotine displays significant neuroprotective effects in certain models. Nicotine also interacts with mTOR. Blocking mTOR receptors blocks the antidepressant effects of ketamine and scopolamine (as well as the rapid induction of BDNF and synaptogenesis).
Linkadge
Posted by ed_uk2010 on December 13, 2014, at 10:49:42
In reply to Re: Caution » ed_uk2010, posted by linkadge on December 13, 2014, at 9:26:56
Hi Link,
>Citalopram makes me feel like an apathetic zombie for months at a time, until it kicks in... And after it 'kicks in' I still feel like an apathetic zombie for months at a time. I'm tired of asking myself....is this how I have to feel just to rid myself of menacing anxiety and depression? I'm tired of being impaired by the drugs that are suppose to help. I'm tired of not being able to concentrate, or sit still (or sleep) on SSRIs.
I hear you. I wasn't saying our meds are great, far from it..... just that citalopram is probably more suitable for general use than say ketamine :)
>Now, when I feel that my depression is starting to become overwhelming, I can put on a 1.5mg scopolamine patch and chew 0.5-1mg of nicotine and literally feel better in about 10 minutes.
> Everything improves, my anxiety, my depression, my appetite, my insomnia.That's impressive. I must admit I've never tried Scopoderm because the tablets make me feel unwell. I imagine I would feel unwell in a long-acting form: Unwell XL?
>I can feel the depression disappear. Its like the brain circuits and pathways are redirected.
So, do you use it as your only med? And how do you do on other anticholinergic drugs?
>euphoria
I wouldn't generally class Scopoderm as a euphoriant. Some people 'get high' on anticholinergics, often Artane - it seems to happen in areas and situations where they are the only drug available. They are 'liked' by some people with schizophrenia, and 'misused' by some. I would hazard a guess that a proportion of people in this situation are trying to cover up the dysphoric side effects of high dose antipsychotics, often depots.
Posted by ed_uk2010 on December 13, 2014, at 10:57:22
In reply to Re: Caution - with anything, posted by linkadge on December 13, 2014, at 9:37:21
Thanks Link. There's a lot I didn't know there. Interestingly enough, nortriptyline, a TCA, has been shown in trials to be an effective aid to smoking cessation. It appears to be similar in effectiveness to the nicotine patch... overall. Obviously, some people will do better on one than the other.
> Depression appears to be associated with upregulation of certain nicotinergic receptors. Nicotine causes a rapid downregulation of certain nicotinergic receptors. I assume that nicotinergic antagonists could also cause receptor downregulation or upregulation. I remember reading studies on how TCA's will alter nicotinergic rececptors over the course of weeks.
>
>
> Nicotine initially produces catecholamine release, but tolerance to this effect is rapid.
>
> There is also interaction between nicotinergic receptors, sigma receptors, dopamine and serotonin reuptake.
>
> Nicotine administration acutely inhibits dopamine and enhances serotonin reuptake transporters respectively.
>
> Nicotine also rapidly activates AKT and inhibits GSK-3 which are mechanisms associated with the rapid antidepressant effects of ketamine, lithium, zinc etc. Activating AKT is also neuroprotective. Nicotine displays significant neuroprotective effects in certain models. Nicotine also interacts with mTOR. Blocking mTOR receptors blocks the antidepressant effects of ketamine and scopolamine (as well as the rapid induction of BDNF and synaptogenesis).
>
> Linkadge
>
>
>
Posted by linkadge on December 14, 2014, at 20:12:40
In reply to Re: Caution » linkadge, posted by ed_uk2010 on December 13, 2014, at 10:49:42
Hi Ed,
I actually prefer a pure anticholinergic to something like amitriptyline. Amitriptyline is a good medication, but it really whacks you out (antihistamine + anticholinergic + all the rest).
I think its the M1 receptors that exert inhibitory control over the mesolimbic dopaminergic system. Mice lacking the M1 receptors display a depression resistant phenotype. The M1 receptors are important the consolation of emotional memory. For instance, blocking the m1 receptors will prevent the enhanced REM response in mice to predator exposure - as well as subsequent emotional disturbance.
AFAIK, Cogentin (benztropine) is also a dopamine reuptake inhibitor, which probably contributes to its abuse liability.
Posted by ed_uk2010 on December 14, 2014, at 23:36:25
In reply to Re: Caution, posted by linkadge on December 14, 2014, at 20:12:40
Hi Link,
Great post.
True about amitriptyline - very messy drug!
.....
Muscarinic receptors are confusing in general.
I think you could be right about M1 receptors. I know they are thought to be involved in memory. M1 receptors also have a role in gastric acid and salivary secretion. I believe all the anticholinergics used in Parkinson's/antipsychotic side effects are M1 antagonists, but not selective.
M2 receptors are important in regulating heart rate. In certain areas of the brain, they are apparently autoreceptors inhibiting further acetylcholine release.
M3 receptors control contraction and secretion respectively in the bronchi, bladder and salivary glands. In the brain they may regulate nausea/vomiting/motion sickness. I assume Scopoderm and various other anticholinergic and combined antihistamine/anticholinergic antiemetics work here!
M4 receptors are thought to be involved in motor control.
M5 - Don't know.
>AFAIK, Cogentin (benztropine) is also a dopamine reuptake inhibitor, which probably contributes to its abuse liability.
I've read that too. May also apply to other anticholinergic antiparkinson drugs.
> Hi Ed,
>
> I actually prefer a pure anticholinergic to something like amitriptyline. Amitriptyline is a good medication, but it really whacks you out (antihistamine + anticholinergic + all the rest).
>
> I think its the M1 receptors that exert inhibitory control over the mesolimbic dopaminergic system. Mice lacking the M1 receptors display a depression resistant phenotype. The M1 receptors are important the consolation of emotional memory. For instance, blocking the m1 receptors will prevent the enhanced REM response in mice to predator exposure - as well as subsequent emotional disturbance.
>
> AFAIK, Cogentin (benztropine) is also a dopamine reuptake inhibitor, which probably contributes to its abuse liability.
>
Posted by Lamdage22 on December 15, 2014, at 13:17:24
In reply to Re: Caution - with anything » linkadge, posted by ed_uk2010 on December 13, 2014, at 10:57:22
Sorry to disappoint you guys. I take all the nicotine in the world and i am still depressed.
My environment leaves me no choice, or so it seems.
My therapist encourages me to voice this to others.
Posted by linkadge on December 15, 2014, at 19:01:43
In reply to Re: Caution - with anything, posted by Lamdage22 on December 15, 2014, at 13:17:24
>I take all the nicotine in the world and i am >still depressed....
It may be all the other stuff you are taking. Maybe the dopamine antagonist effects of antipsychotics may be blocking the nicotine effect....
Posted by Jeroen on December 16, 2014, at 11:14:15
In reply to Laughing gas studied as depression treatment, posted by Hugh on December 10, 2014, at 10:26:11
too many laughing + gass can kill you i've read : )
Posted by Lamdage22 on December 18, 2014, at 15:11:15
In reply to too many laughing + gass can kill you i've read, posted by Jeroen on December 16, 2014, at 11:14:15
Are the scientists becoming bored?
They should be working for our remission.
This is the end of the thread.
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