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Dr. Bob is Robert Hsiung, MD,
bob@dr-bob.orgShown: posts 1 to 25 of 30. This is the beginning of the thread.
Posted by SLS on July 23, 2006, at 8:47:51
Remeron makes me feel like crap, so this combination really doesn't apply to me. However, I saw an abstract on Medline which reported giving non-responders to Remeron adjunctive reboxetine. I thought that giving a NE reuptake inhibitor in this situation was a pretty smart idea, although I wouldn't have selected reboxetine as the agent to fill this role. So, I was wondering if anyone has tried combining Remeron with a tricyclic antidepressant, particularly desipramine. It might be worth trying.
- Scott
Posted by JahL on July 23, 2006, at 9:02:49
In reply to Combining Remeron + TCA, posted by SLS on July 23, 2006, at 8:47:51
> Remeron makes me feel like crap, so this combination really doesn't apply to me. However, I saw an abstract on Medline which reported giving non-responders to Remeron adjunctive reboxetine.
Hi Scott.
This is an established combination used by some of the teaching establishments in the UK (specifically, Newcastle Univ, which is, interestingly for me, pioneering work on cannabinoid use in Bipolar). It's not for everyone; I became very ill on it, as I did with Effexor. I don't think my brain likes the dual-action concept.
However, I was told that for some treatment-resistant folk people it is a genuinely effective treatment.
J.
Posted by SLS on July 23, 2006, at 9:05:25
In reply to Re: Combining Remeron + TCA » SLS, posted by JahL on July 23, 2006, at 9:02:49
Hi J.
> pioneering work on cannabinoid use in Bipolar
Can you elaborate?
Thanks.
- Scott
Posted by JahL on July 23, 2006, at 9:42:46
In reply to Re: Combining Remeron + TCA, posted by SLS on July 23, 2006, at 9:05:25
> Hi J.
>
> > pioneering work on cannabinoid use in Bipolar
>
> Can you elaborate?
This is the abstract doing the rounds:"The cannabinoids....may exert sedative, hypnotic, anxiolytic, antidepressant, antipsychotic and anticonvulsant effects."
This paper - which first appeared in The Journal of Psychopharmacology - goes some way to vindicating my own heavy drug use. I have been serially condemned by various pdocs, who were convinced that my marijuana use is in some way responsible for my depression. Now studies are beginning to crop up which suggest depression often precedes drug use, which is then simply a form of self-medication. I smoke MJ for one reason only - it makes me feel better.
The Good Drug Guide states:
"Experiments with stoned rats suggest that cannabis use reduces the amount of corticotrophin-releasing factor (CRF) in the amygdala. Excess secretion of CRF is associated with abnormalities in the HPLA axis and depression."
...so it's a very crude (and weak) version of the much-anticipated CRF-antagonists?
J.
Posted by SLS on July 23, 2006, at 9:49:27
In reply to Re: Cannabinoids » SLS, posted by JahL on July 23, 2006, at 9:42:46
> The Good Drug Guide states:
>
> "Experiments with stoned rats suggest that cannabis use reduces the amount of corticotrophin-releasing factor (CRF) in the amygdala. Excess secretion of CRF is associated with abnormalities in the HPLA axis and depression."
>
> ...so it's a very crude (and weak) version of the much-anticipated CRF-antagonists?
Hmmm.I'm sure Linkadge will have a few words to add here. This actually deserves a separate thread.
- Scott
Posted by Phillipa on July 23, 2006, at 12:13:32
In reply to Re: Cannabinoids, posted by SLS on July 23, 2006, at 9:49:27
Lar's in a study of mj for his chronic shoulder pain in Canada. Love Phillipa
Posted by linkadge on July 23, 2006, at 16:08:12
In reply to Re: Cannabinoids » SLS, posted by JahL on July 23, 2006, at 9:42:46
"so it's a very crude (and weak) version of the much-anticipated CRF-antagonists?"
Yes, hypericum too also has some direct CRF antagonist effect.
Linkadge
Posted by linkadge on July 23, 2006, at 16:31:53
In reply to Re: Cannabinoids » SLS, posted by Phillipa on July 23, 2006, at 12:13:32
Yes, marajuanna seems to house growing reports of efficacy in bipolar disorder. There are quite a few reports I have heard now of bipolar individuals gaining superior symtpom releif in all domains as compared to traditional agents.
Marajuanna has anti conflict, anti agression, antidepressant, and antimanic, antihyperlocomotion, properties. "Stoned" can often a very stable state.
With the recent evidence that cannabanoid agents actually promote neurogenesis, (unlike other agents of abuse), there is growing reason to believe an antidepressant effect is real, and not completely explained by a "high".
Cannabanoid compounds exert multiple binding effects to the serotonin system. They are not as blunt as an SSRI, and the result may be a more natural effect on hippocampal formation and function.
Cannabanaoids and dopamine also seem to work on an axis, where cannabanoids can turn off certain dopaminergic circutry. Some agents are being tested for hyperactivity disorders, as they do have the ability to reduce hyperlocomotion.
Certain cannabanoids have antipsychotic effects in their ablity to reduce dopamine in certain limbic circutry.People with schizophrenia may be using it for multiple reasons, one being to counteract prefrontal hypofunction.
There are some reports of MJ inducing paranoia. I would argue that this may be an effect of excessive anticholinergic action. I had a slight effect in this regard for perhaps 10 minautes. It did not last too long, and I never had it the second time (when I used it when free from pharmacudical ADs' etc). So, I can't recomend it in combination with prescription drugs.
Essentially, if you're exercising for too long, and the brain wants you to stop exercising, it activates the endocannabanoid system, which can make you hungary, tired, satisfied, etc.
The evidence is growing that anorexic disorders may be linked to dysfunctional endocannabanoid systems.
Omega-3, in particular DHA, has the ability to enhance the activity of the endocannabanoid system. Low DHA levels have been associated with bipolar disorder in some studies, so it makes one wonder if the stabalizing effects are not a result of (in part) an enhancement of the endocannabanoid system.
The reports that marajuanna creates apathy, are fairly irrelevant in comparison to the apathy syndromes that can be a product of SSRI's, AP's and lithium. This too may manifest itself differently in a bipolar individual.
Marajuanna never created apathy in me to any degree, infact it did the opposite. It certainly curtailed my locomotion (Ie I didn't have to exercise for 5 hours a day to be satisfied). The reduction of locomotion may be confused with apathy by some researchers.
I've heard of a few people who are doing well treating their "resistant" mood disorders with combinations of fish oil and marajuanna.
In addition, there is an anandamide reuptake inhibitor in the pipelines. Anandamide is the brains own version of THC. It seems to show promise as an antianxiety agent.
Linkadge
Posted by SLS on July 24, 2006, at 7:07:16
In reply to Re: Cannabinoids, posted by linkadge on July 23, 2006, at 16:31:53
The "MAOI" of Cannabinoids:
It appears that the inhibition of the catabolization of anandamide produces antidepressant effects throught the moduclation of monoaminergic systems. This mechanism obviates the need to get "high" because it doesn't use agonist ligands.
- Scott-----------------------------------------------
Proc Natl Acad Sci U S A. 2005 Dec 20;102(51):18620-5. Epub 2005 Dec 13.* Proc Natl Acad Sci U S A. 2006 Feb 14;103(7):2465.
Antidepressant-like activity and modulation of brain monoaminergic transmission by blockade of anandamide hydrolysis.Gobbi G, Bambico FR, Mangieri R, Bortolato M, Campolongo P, Solinas M, Cassano T, Morgese MG, Debonnel G, Duranti A, Tontini A, Tarzia G, Mor M, Trezza V, Goldberg SR, Cuomo V, Piomelli D.
Department of Psychiatry, McGill University, Montreal, QC, Canada H1N 3V2.
Although anecdotal reports suggest that cannabis may be used to alleviate symptoms of depression, the psychotropic effects and abuse liability of this drug prevent its therapeutic application. The active constituent of cannabis, delta9-tetrahydrocannabinol, acts by binding to brain CB1 cannabinoid receptors, but an alternative approach might be to develop agents that amplify the actions of endogenous cannabinoids by blocking their deactivation. Here, we show that URB597, a selective inhibitor of the enzyme fatty-acid amide hydrolase, which catalyzes the intracellular hydrolysis of the endocannabinoid anandamide, exerts potent antidepressant-like effects in the mouse tail-suspension test and the rat forced-swim test. Moreover, URB597 increases firing activity of serotonergic neurons in the dorsal raphe nucleus and noradrenergic neurons in the nucleus locus ceruleus. These actions are prevented by the CB1 antagonist rimonabant, are accompanied by increased brain anandamide levels, and are maintained upon repeated URB597 administration. Unlike direct CB1 agonists, URB597 does not exert rewarding effects in the conditioned place preference test or produce generalization to the discriminative effects of delta9-tetrahydrocannabinol in rats. The findings support a role for anandamide in mood regulation and point to fatty-acid amide hydrolase as a previously uncharacterized target for antidepressant drugs.
PMID: 16352709 [PubMed - indexed for MEDLINE]
Posted by linkadge on July 24, 2006, at 20:46:12
In reply to The MAOI of Cannabinoids, posted by SLS on July 24, 2006, at 7:07:16
Yeah, I was reading about URB597.
There are two methods for anandamide metabolism, one being the fatty acid transport, and the other being FAAH, (fatty acid anandamide hydroxylase) (or something). In addition to the FAAH inhibitor URB-597, there are a few other compounds coming out that seem to work as inhibitors of anandamide uptake.
Anyhow, the researchers who immediately discredit the antidepresant effects of cocoa based on the fact that it contains too little anandamide, are not taking into account that cocoa also conatins inhibitors of anandamide uptake.
There are some FAAH inhibitors already available to us. OTC Ibuprofen actually has some FAAH inhibiting properties. If you combine Ibuprofen and dark chocolate (As I was mentioning on the alternative board), you can get quite a buzz.
Also, if you go for some long aerobic exercise, you can extend the blissfull effects by taking an advil aftarwards.
Exercise can boost anandamide levels several fold.
I'd like to get my hands on a URB-597. I really hope this one comes to the market, and doesn't get stopped by some stupid relitively inconsequential hold up.
I don't understand it. Drugs for ADHD have some abuse potential, yet they are still dispensed to children everywhere.
So what if cannabanoid agonists have a small abuse potential, can we not take that risk in order to get some people better for real?
I'd rather be addicted to a drug that works instead of being addicted to paxil.
Linkadge
Posted by linkadge on July 24, 2006, at 20:47:22
In reply to Re: The MAOI of Cannabinoids, posted by linkadge on July 24, 2006, at 20:46:12
That being said, I do hope that inhibiting the metabolism of anandamide really pans out to have the same clinical effect as cannabanoid agonists.
Linkadge
Posted by JahL on July 24, 2006, at 21:32:45
In reply to Re: Cannabinoids, posted by linkadge on July 23, 2006, at 16:31:53
Thanks for an excellent post Linkadge.
It's pleasing to see my intuitive beliefs concerning MJ use validated in some way, and in a non-judgemental fashion.
As you suggest, MJ can help ameliorate a wide range of symptoms. MJ is helpful to me not just for its AD properties; it also dampens Lamictal hypomania, keeps me and my filthy temper out of trouble ('anti-conflict') and creates an appetite which would otherwise not exist.
> There are some reports of MJ inducing paranoia.
There is no doubt in my mind that MJ can induce mild paranoia in certain susceptible individuals - I've seen it happen. It actually exacerbates my social phobia somewhat, but this is a fair trade-off for the AD properties it imparts.
> The reports that marajuanna creates apathy, are fairly irrelevant in comparison to the apathy syndromes that can be a product of SSRI's, AP's and lithium. This too may manifest itself differently in a bipolar individual.
I have noticed that the Bipolar brain can exhibit a number of atypical responses to various psychotropics. For example, in order to lift weights I must be stoned. Low-dose Methadone helps in this regard also. That's just strange.
All you neglected to mention was MJ's superior sedative qualities. Chronic insomnia was the original inspiration for my regular consumption. My brothers, both of whom are Bipolar, use it for the same reason.
Anyway, very interesting post,
J.
Posted by linkadge on July 25, 2006, at 16:33:22
In reply to Re: Cannabinoids » linkadge, posted by JahL on July 24, 2006, at 21:32:45
Yes, that is true. I have taken every seditive antidepressant out there. Amitryptaline, Trazodone, Remeron, benzo's etc.
None providing the relief from insomnia I got from marajuanna.
The amount somebody needs in order to produce a desired effect can be very small too.
Just a few puffs can relieve bad insomnia, and loss of appetite in myself.
Doctors are looking for a magic bullit. They want a drug that relieves symtpoms and has no abuse potental.
I'd like to see medicinal marajuanna with an indication for insomnia etc. Wishfull thinking ?
Linkadge
Posted by JahL on July 25, 2006, at 17:53:20
In reply to Re: Cannabinoids » JahL, posted by linkadge on July 25, 2006, at 16:33:22
> I'd like to see medicinal marajuanna with an indication for insomnia etc. Wishfull thinking ?Possibly. Things were looking up here in the UK when MJ was downgraded to a Class C drug (equivalent to prescription medications) 3 years ago.
However TheWarOnDrugsters have recently made much of the Cannabis-Schizophrenia Connection:
http://news.bbc.co.uk/1/hi/health/4486548.stm
Obviously schizophrenia is a very serious condition and so this issue deserves attention.
Less justifiable is the huge capital being made out of this tragic but freakish incident:
http://www.timesonline.co.uk/article/0,,8122-1922744,00.html
I wonder how many years that fatality has put back MJ research?
J.
Posted by linkadge on July 25, 2006, at 18:31:52
In reply to Re: Cannabinoids » linkadge, posted by JahL on July 25, 2006, at 17:53:20
Its a shame. I'm not asking that doctors have marajuanna dispense to everbody for a particular complaint. I'm just asking that those who have used it and use it regularly for a particular condition, and know how they're going to react, might be able to obtain the substance in a legitamite and safe way.
Linkadge
Posted by laima on July 26, 2006, at 14:08:40
In reply to The MAOI of Cannabinoids, posted by SLS on July 24, 2006, at 7:07:16
Does this all mean, theoretically speaking, that cannabis and MAOI are something of the same? IE, is marijuana itself something along the lines of an MAOI, or is that an over-simplification?
I wonder if that's how the research idea came up. I read about this new drug that is being developed, too- but alas, the blurb I saw said so far it's only been tested in "mice". Sounds like we'll be waiting a long time for a chance to try this one:(
Very interesting.
Posted by laima on July 26, 2006, at 14:12:26
In reply to Re: Cannabinoids, posted by linkadge on July 23, 2006, at 16:31:53
>The reports that marajuanna creates apathy, are fairly irrelevant in comparison to the apathy syndromes that can be a product of SSRI's, AP's and lithium.
Wish someone warned me about the ssris once upon a time. I believe that part.
Posted by linkadge on July 26, 2006, at 16:07:15
In reply to Re: The MAOI of Cannabinoids » SLS, posted by laima on July 26, 2006, at 14:08:40
I think that "The MAOI of Cannabinoids" was referring to the drug URB-597, a new compound that does to anandamide what an MAOI does to sertonin, norepeinephrine, and dopamine.
Linkadge
Posted by linkadge on July 26, 2006, at 16:10:01
In reply to Re: Cannabinoids » linkadge, posted by laima on July 26, 2006, at 14:12:26
Yeah, I can't imagine that cannabis produces an apathy any more severe than that of a high dose of SSRI, not to mention in combination with a AP.
Linkadge
Posted by laima on July 26, 2006, at 16:46:01
In reply to Re: The MAOI of Cannabinoids, posted by linkadge on July 26, 2006, at 16:07:15
Oh yes, I got that part- I was wondering if there was a more literal connection, or if this is semantics. Thanks for clarifying.> I think that "The MAOI of Cannabinoids" was referring to the drug URB-597, a new compound that does to anandamide what an MAOI does to sertonin, norepeinephrine, and dopamine.
>
>
>
> Linkadge
>
Posted by linkadge on July 26, 2006, at 17:48:08
In reply to Re: The MAOI of Cannabinoids » linkadge, posted by laima on July 26, 2006, at 16:46:01
> Oh yes, I got that part
Sorry. I didn't mean to come off sounding..
Linkadge
Posted by laima on July 26, 2006, at 18:48:23
In reply to Re: The MAOI of Cannabinoids, posted by linkadge on July 26, 2006, at 17:48:08
Not at all! There is nothing to apologize over. I think we both understood each other's sincere responses clearly, and everything is well.Fondly,
Laima
> > Oh yes, I got that part
>
> Sorry. I didn't mean to come off sounding..
>
> Linkadge
Posted by laima on July 26, 2006, at 19:10:05
In reply to Re: The MAOI of Cannabinoids » linkadge, posted by laima on July 26, 2006, at 18:48:23
Dear Linkadge,Now I feel a bit squeemish over the chance of a misunderstanding or even a civility rule infraction-
this:
> > > Oh yes, I got that part
was nothing more than my casual speaking voice, intended as "friendly, casual".
I type as almost as fast as I speak, so it blurs easily.
No offense of any sort, from me, was meant to be implied.
No offense ever crossed my mind. Never conceived that my response might even be possibly interpreted as "offended".I was in fact very glad to read your clarification detailing your understanding of what I was speculating and asking about.
I was delighted that you took the time to respond, and so soon after I asked, too.I 'm thinking perhaps communication is easier when people can see each other face to face-maybe the same voice can sound vaguer and more open to various interpretations in type than when actually spoken "in person" and animated with expression and tone.
Very sincerely,
Laima
> Not at all! There is nothing to apologize over. I think we both understood each other's sincere responses clearly, and everything is well.
>
> Fondly,
>
> Laima
>
> > > Oh yes, I got that part
> >
> > Sorry. I didn't mean to come off sounding..
> >
> > Linkadge
>
>
Posted by wacky on July 27, 2006, at 8:56:56
In reply to Re: The MAOI of Cannabinoids » laima, posted by laima on July 26, 2006, at 19:10:05
Wow. I am just amazed at all the info re MJ!! Is everybody on this site a biochemist or something???? I too have found HUGE benefits from MJ for insomnia. And truly, it doesn't take much. It's such a shame that the paranoia surrounding it's use precludes more research and open usage. When I contrast it's "horrible" side effects with the withdrawal effects of Effexor, I wonder what they are thinking! I get totally obnoxious when I drink. I get very calm and compliant when I smoke. And if alcohol exacerbates depression - and alchohol is legal - it leads me to the conclusion that those in charge of the "war on drugs" have a very low IQ.
I'm thinking about using MJ to quit drinking. I'll take the risk - if I need to grow my own plant - I will. Geez - I'm a fr*gging lawyer - representing public agencies (INCLUDING SEVERAL POLICE DEPARTMENTS) - can you imagine what would happen if I got caught? I'd have to leave my firm. But I don't care - the value outweighs the risk. When I smoke at night, it's done more than Trazadone and Rezorem combined. And it just so happens that when I really sleep at night - I am better at work! Imagine that.
Sorry for the long post - I had to vent.
Nancy
Posted by laima on July 27, 2006, at 9:36:05
In reply to Re: The MAOI of Cannabinoids, posted by wacky on July 27, 2006, at 8:56:56
Quite some politics around drugs of all kinds, isn't there?
I suspect politics and myths that remain unchallenged due to legal restrictions on research.I've thought about the irony with alcohol being legal, while marijuana isn't, too. Both can certainly be damaging and/or dangerous when used irresponsabley, or be considered "social problems"--but I personally never heard anything about a bunch of stoned people go out on any violent rampages, get into viscious arguments, or anything like that. Usually, the *worst* I ever hear is that they are on the couch watching tv or something :) (Hey, I like tv-in case anyone is wondering what I mean by that.) But, I have heard of very drunk people getting rowdy, argumentative, and disruptive...you know? I live in an area with a number of bars, and late at night, when they close, there is a lot of yelling, fighting, bottle smashing, etc. outside. So I find it all very ironic indeed, and don't understand the logic to the laws either.
>>And truly, it doesn't take much. It's such a shame that the paranoia surrounding it's use precludes more research and open usage. When I contrast it's "horrible" side effects with the withdrawal effects of Effexor, I wonder what they are thinking! I get totally obnoxious when I drink. I get very calm and compliant when I smoke. And if alcohol exacerbates depression - and alchohol is legal - it leads me to the conclusion that those in charge of the "war on drugs" have a very low IQ.
>
> I'm thinking about using MJ to quit drinking. I'll take the risk - if I need to grow my own plant - I will. Geez - I'm a fr*gging lawyer - representing public agencies (INCLUDING SEVERAL POLICE DEPARTMENTS) - can you imagine what would happen if I got caught? I'd have to leave my firm. But I don't care - the value outweighs the risk. When I smoke at night, it's done more than Trazadone and Rezorem combined. And it just so happens that when I really sleep at night - I am better at work! Imagine that.
>
> Sorry for the long post - I had to vent.
>
> Nancy
>
>
>
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