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Dr. Bob is Robert Hsiung, MD,
bob@dr-bob.orgShown: posts 1 to 25 of 35. This is the beginning of the thread.
Posted by shasling on May 11, 2009, at 22:24:31
The page has tons of stuff,so i choose to just copy and paste the relevant part.
Low doses had a potent anti-depressant effect, but when we increased the dose, the serotonin in the rats' brains actually dropped below the level of those in the control group. So we actually demonstrated a double effect: At low doses it increases serotonin, but at higher doses the effect is devastating, completely reversed.
The McGill researchers are concerned that marijuana smokers may not be able to judge their dosage amounts properly. They claim that smoking joints doesnt offer the best quantitative measure of marijuana dosage. Instead, Dr. Gobbi and her colleagues are focusing their research on a new type of drug which enhances the effects of the brains natural endo-cannabinoids.
Posted by chumbawumba on May 11, 2009, at 22:32:00
In reply to Little more, posted by shasling on May 11, 2009, at 22:24:31
Of course they are looking for a "drug that enhances the brain's own endocannibinoids"
They couldn't just say go out and get stoned now could they. Astra Zeneca wouldn't profit from that
Actually before I ever took antidepressants I smoked a lot of weed. I think I was self medicating. Fairly effectively too. It's probably just as effective as any SSRI, SNRI, ABCD or PDQ that I ever took. Cannabis kinda puts me in a strange state of mind these days though. I try to avoid it.
Posted by bleauberry on May 12, 2009, at 5:36:20
In reply to Little more, posted by shasling on May 11, 2009, at 22:24:31
In my opinion pot is the best all around medicinal herb on the planet. Insomnia, depression, anxiety, nervousness, boredome, apathy, mania, muscle wasting, nausea, low appetite...whatever is needed, it does it and does it fast.
The trick though is very low controlled doses. If the user gets high, the dose was too high. When the dose is too high it can result in psychotic-like, delusional-like, and paranoia-like responses.
I would think that since technology can get meds to absorb in controlled precise doses through the skin (such as Ensam or Evoclin (Clindamycin foam), surely they can construct a deliver device for marijuana that gives a specific dose. I mean, maybe just as a rough example, the prescription includes a kind of pipe, and the pot comes in preformed pill shapes that are inserted in the pipe, and each pill is manufactured to be exactly like every other.
They've noticed all these good things with pot and yet hunt for ways to duplicate it in the lab synthetically? I don't understand that kind of humanistic egotism, economics, greed, and negligence.
By the way, I have tried pure pharmaceutical THC prescribed by my doctor. It is crap. Nothing at all like marijuana. Good for munchies and sleep, yes. For mood it is very depressing lethargic stuff. While everyone assumes it is THC in pot with all the goodness, I am here to say, it is not. It is more likely an orchestra of several different mechanisms, of which THC is a minor player having effects primarily on appetite and sleep.
For sure someone will get a lot more high with pot that has a higher THC content. But, I believe that is because the other unidentified mechanisms in the plant are also higher. It is not just THC. I know instinctively without a doubt.
The evils of pot and its bad name come from two things:
1. It is illegal which causes criminal behavior and greed.
2. It is used to get high.Unlike alcohol or prescription medicines of all kinds, I have never seen in a newspaper cases of car accidents, murders, rages, or cancers caused by pot. If anything, it tends to make someone more safe and more peaceful.
As a medicine in low controlled doses, I have never known a better substance for psychiatric uses of nearly any pscyhiatric condition.
I haven't smoked in over 3 years. I live in a state where it is medically legal with a doctor's prescription to grow it for medical use under specific conditions. However, there is not a single doctor that prescribes it in this state. Even if they did, it is still illegal by Federal law.
It amazes me how with the assumed high intelligence of the human race we come up with the most stupid laws, stupid research, and stupid approaches to some things. Such as medicianl marijuana.
All said here is purely personal opinion. I was a longtime user of pot, an abuser at times, and a heavy researcher of it. I know how this herb behaves and what it does.
Posted by Larry Hoover on May 12, 2009, at 6:09:27
In reply to Re: Little more, posted by bleauberry on May 12, 2009, at 5:36:20
I agree that the dose needs to be small enough that there is no real high. The key to that, IMHO, is oral use of standardized products. They can do it with St. John's wort, so why not cannabis?
I'm a user of medicinal marijuana products for a chronic pain condition. Although I can readily obtain bud for smoking, I purchase a product that has been made up analogous to a simple chocolate bar, only instead of cocoa butter, the cook uses cannabis butter. My dosing is something on the order of $.50 to $1.00 worth, and I use that pricing because everything is more or less tied to street pricing. You don't get much pot for 50 cents. From one-half to a full small square of chocolate is all I need, and I generally don't get much of a buzz, if any. But that is the most effective dose. Just as with opiates, the best dose for pain is that amount that just skirts the buzz effect. IMHO. And I use the buzz response as feedback with respect to the amount I chose as my dose. The whole thing is now almost intuitive. With oral preps, moreover, you don't have to deal with any lung injury issues.
FAAH inhibitors might be useful, but then again, they might not. We have no idea what chronic use might do to other inter-related regulatory systems. In other words, the chronic effects might be very different than the acute effects in humans, and we won't know about that from rodent studies.
Lar
Posted by SLS on May 12, 2009, at 6:45:49
In reply to Re: Little more, posted by Larry Hoover on May 12, 2009, at 6:09:27
> FAAH inhibitors might be useful, but then again, they might not.
Hi Larry.
What are FAAH inhibitors? Do they affect the metabolism of endogenous anandamide?
Never mind. I looked it up on Google. Good guess.
Do you feel that these drugs would be less effective therapeutically than marijuana? Also, if THC were removed from a marijuana preparation, would it still maintain its therapeutic effects through the presence of other cannabinoids?
- Scott
Posted by Phillipa on May 12, 2009, at 12:35:13
In reply to Re: Little more » Larry Hoover, posted by SLS on May 12, 2009, at 6:45:49
The one time I smoked it lasted over 24 hours think it was laced as felt like I was flying an airplane all senses where incredibly stimulated scarey. Phillipa
Posted by Larry Hoover on May 12, 2009, at 12:58:52
In reply to Re: Little more » Larry Hoover, posted by SLS on May 12, 2009, at 6:45:49
I don't know enough to answer your questions, Scott. Myco sent me a bunch of literature a few weeks back, but I haven't found time to read it yet. Maybe I'll get on it.
Lar
Posted by linkadge on May 12, 2009, at 16:09:27
In reply to Little more, posted by shasling on May 11, 2009, at 22:24:31
>So we actually demonstrated a double effect: At >low doses it increases serotonin, but at higher >doses the effect is devastating, completely >reversed
I don't understand the use of the word devastating in this context. Why is lowering serotonin 'devastating'? Tianeptine lowerse serotonin and the effect isn't devastating. Usually people don't use this kind of word when describing scientific findings. It is almost, as you suggest, an attempt to demonize the effects of marajuanna.
Linkadge
Posted by SLS on May 12, 2009, at 20:43:25
In reply to Re: Little more, posted by linkadge on May 12, 2009, at 16:09:27
> Tianeptine lowerse serotonin and the effect isn't devastating.
Maybe you can point me in the direction of where I might find this information. Right now, I am only aware of one reported property of tianeptine, which is simply that its acute effect is to accelerate the reuptake of serotonin. I am uncertain as to what are the effects on serotoninergic neurotransmission after chronic exposure. It is quite possible that serotoninergic activity is enhanced rather than suppressed.
- Scott
Posted by linkadge on May 12, 2009, at 21:58:25
In reply to Re: Little more » linkadge, posted by SLS on May 12, 2009, at 20:43:25
>I am uncertain as to what are the effects on >serotoninergic neurotransmission after chronic >exposure. It is quite possible that >serotoninergic activity is enhanced rather than >suppressed.
I suppose thats possible, although I havn't seen studies either way. I just personally don't think that enhancement of serotonin neurotransmission has a whole lot to do with antidepressant action. Take the most effective antidepressant (ECT), some of the most recent and comprehensive studies that ECT has not appreciable or measurable effect on serotonergic neurotransmission. I guess I am just arguing with the logic: "if it doesn't increase serotonin, it can't be an antidepressant".
Linkadge
Posted by Sigismund on May 13, 2009, at 2:59:24
In reply to Re: Little more, posted by linkadge on May 12, 2009, at 21:58:25
>Take the most effective antidepressant (ECT)
That's interesting to hear you say that.
Posted by SLS on May 13, 2009, at 6:42:01
In reply to Re: Little more, posted by linkadge on May 12, 2009, at 21:58:25
> >I am uncertain as to what are the effects on >serotoninergic neurotransmission after chronic >exposure. It is quite possible that >serotoninergic activity is enhanced rather than >suppressed.
>
> I suppose thats possible, although I havn't seen studies either way. I just personally don't think that enhancement of serotonin neurotransmission has a whole lot to do with antidepressant action. Take the most effective antidepressant (ECT), some of the most recent and comprehensive studies that ECT has not appreciable or measurable effect on serotonergic neurotransmission. I guess I am just arguing with the logic: "if it doesn't increase serotonin, it can't be an antidepressant".I am in complete agreement with you.
I think it is helpful to think of depression as a diagnosis fraught with a heterogeneity of etiologies that demand a heterogeneity of treatments. It might be that the SSRIs are the best choice for some people - regardless of how they work. As you indicate, it may still have little to do with serotonin. Still, it is becoming a more common finding that 5-HT1a receptors are subsensitive in at least some cases of major depressive disorder (MDD).
Antidepressants don't seem to work in 5-HT1a receptor knockout mice with respect to anxiety related behavior.
- Scott
Posted by desolationrower on May 13, 2009, at 10:34:01
In reply to Re: Little more, posted by SLS on May 13, 2009, at 6:42:01
well its probably related to 5ht1a receptors, since they can have biphasic effects on anxiety/mood. I forgot or never really knew their complete effects, and haven't found a good usmmary yet.
i know tianeptine causes 5htergic branching from extended use, similar to sris.
last time i got high (way high, i had time running backwards and noone was speaking english and i was god and all quarks and had fractured my timeline and had to reassemble it like a puzzle or i'd be alone forever) i had 90% of my anxiety go away for about a week and a half. I had forgotten abotu that, really the only time i can remember anxiety reduced.
-d/r
Posted by linkadge on May 13, 2009, at 20:14:18
In reply to Re: Little more » linkadge, posted by Sigismund on May 13, 2009, at 2:59:24
Well, to be honest, I don't know if I believe that ECT is the most effective antidepressant, but according to the medical establishment it is.
Basically I am showing that if you assume once piece of psychiatry's logic you reach a contradiction.
Linkadge
Posted by linkadge on May 13, 2009, at 20:21:06
In reply to Re: Little more, posted by SLS on May 13, 2009, at 6:42:01
Check out this study.
Linkadge
Posted by Jimmyboy on May 13, 2009, at 23:27:21
In reply to Re: Little more, posted by desolationrower on May 13, 2009, at 10:34:01
Well.. THC is a partial Kappa opoid agonist, if you really hammered those receptors it could have caused KOR downregulation --> less anxiety.
Posted by desolationrower on May 14, 2009, at 1:37:44
In reply to Re: Little more, posted by Jimmyboy on May 13, 2009, at 23:27:21
not seen this in kidb...where did you see it
-d/r
Posted by SLS on May 14, 2009, at 6:23:44
In reply to Re: Little more » SLS, posted by linkadge on May 13, 2009, at 20:21:06
> Check out this study.
>
> http://www.ncbi.nlm.nih.gov/pubmed/17429410?ordinalpos=41&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_DefaultReportPanel.Pubmed_RVDocSum
>
> Linkadge
Thanks.Interesting. That is the second abstract I have seen that casts doubt on the need for 5-HT1a receptor upregulation to produce an antidepressant response.
It is an easy argument to make that the probable heterogeneity of diatheses of phenotypic depressions allows for multiple mechanisms to be contributory to a therapeutic effect across the population. Post mortem studies of humans with MDD have demonstrated reduced 5-HT1a binding.
There are so many different reported biological correlates of Axis I affective disorders, it is difficult to invest in any one of them.
- Scott
Posted by linkadge on May 14, 2009, at 8:27:34
In reply to Re: Little more » linkadge, posted by SLS on May 14, 2009, at 6:23:44
>Interesting. That is the second abstract I have >seen that casts doubt on the need for 5-HT1a >receptor upregulation to produce an >antidepressant response.
>It is an easy argument to make that the probable >heterogeneity of diatheses of phenotypic >depressions allows for multiple mechanisms to be >contributory to a therapeutic effect across the >population. Post mortem studies of humans with >MDD have demonstrated reduced 5-HT1a binding.
And some studies have demonstrated increased binding.
http://www.futurepundit.com/archives/001768.html
>There are so many different reported biological >correlates of Axis I affective disorders, it is >difficult to invest in any one of them.True
Linkadge
Posted by SLS on May 14, 2009, at 10:25:40
In reply to Re: Little more, posted by linkadge on May 14, 2009, at 8:27:34
> And some studies have demonstrated increased binding.
>
> http://www.futurepundit.com/archives/001768.htmlThis can make sense. I almost hate to say something so simplistic, but a chronic decrease in available serotonin might force these 5-HT1a somatodendritic autoreceptors to become upregulated. I don't know. I don't know enough about the dynamics of this receptor to be certain. However, if this is true, then you have a positive feedback loop that allows the severity of symptoms to worsen over time.
- Scott
Posted by Jimmyboy on May 14, 2009, at 11:02:41
In reply to Re: Little more - thc/kappa or, posted by desolationrower on May 14, 2009, at 1:37:44
Well this is from wikipedia
Cannabis sativa
"The active component of cannabis, THC, is a partial kappa-opioid agonist and may account for the aversive affects of "paranoia" experienced during its use as well as some non-addictive properties of cannabis.[53][54]"
These are what they cite:
Smith PB, Welch SP, Martin BR (March 1994).
"Interactions between delta 9-tetrahydrocannabinol and kappa opioids in mice". The Journal of pharmacology and experimental therapeutics 268 (3): 13817. PMID 8138952.
http://jpet.aspetjournals.org/cgi/content/abstract/268/3/1381
^
Hampson RE, Mu J, Deadwyler SA (November 2000)."Cannabinoid and kappa opioid receptors reduce potassium K current via activation of G(s) proteins in cultured hippocampal neurons". Journal of neurophysiology 84 (5): 235664.
PMID 11067978http://jn.physiology.org/cgi/content/abstract/84/5/2356
As well as this:
The Journal of Neuroscience, February 1, 2002, 22(3):1146-1154
Motivational Effects of Cannabinoids Are Mediated by µ-Opioid and -Opioid Receptors
Sandy Ghozland1, Hans W. D. Matthes2, Frederic Simonin2, Dominique Filliol2, Brigitte L. Kieffer2, and Rafael Maldonado1"...protocols that reveal both THC rewarding and aversive properties. Absence of µ receptors abolishes THC place preference. Deletion of receptors ablates THC place aversion and furthermore unmasks THC place preference. Thus, an opposing activity of µ- and -opioid receptors in modulating reward pathways forms the basis for the dual euphoric-dysphoric activity of THC. "
I got this from a thread at mind and muscle which has more info
http://www.mindandmuscle.net/forum/index.php?showtopic=36315&st=0&gopid=550105&#entry550105
Posted by linkadge on May 14, 2009, at 17:53:23
In reply to Re: Little more, posted by SLS on May 14, 2009, at 10:25:40
There are a lot of new studies which are challenging old theories.
Originally they though that 5-ht2a receptors were upregulated in depression. Some new research is suggesting that they are downregulated or at least less responsive in depression than normal controls.
There is some evidence of an insensitivity to serotonin in mood disorders, especially those with comorbid diabetes. Agents like chromimum actually increase insulin sensitivity as well as serotonin sensitivity.
There is a decrease in temporal lobe 5-ht1a binding in depression in temporal lobe epilepsy. This is interesting because post synaptic 5-ht1a receptors exert anticonvulsant effects in animal models of epilepsy. ECT apparently increases the sensitivty of limbic 5-ht1a receptors (which may play a role in its anticonvulsant effect).
The problem with SSRI's is that by agonizing all the serotionin receptors they don't really exert a single clean effect. I think some of the work with monoaminergic or neuropeptide agonists/antagonists is going to slowly give us a better pictue of what is relavent in mood disorders.
Theraputic serotonergic targets (that I know of) include 5-ht1a,b,d 5-ht2a,c 5-ht3 5-ht7.
I'd personally like to see some more work on the development of selective serotoniergic modulators without the dopamine effect. We need drugs like rianserin and gepirone.
Linkadge
Posted by linkadge on May 14, 2009, at 17:55:01
In reply to Re: Little more - thc/kappa or » desolationrower, posted by Jimmyboy on May 14, 2009, at 11:02:41
Interesting, although I never noticed paranoia as a side effect of the potent kappa agonist salvoin-a. I mean, it did some strange things, but I don't really remember pot like paranoia.
Linkadge
Posted by Jimmyboy on May 14, 2009, at 19:52:36
In reply to Re: Little more, posted by linkadge on May 14, 2009, at 17:53:23
Hmm.. that is interesting, if 5ht2a receptors are actually downregulated in depression it seems strange that 5ht2a antagonism helps so much with panic /anxiety.
Posted by desolationrower on May 15, 2009, at 5:29:29
In reply to Re: Little more » linkadge, posted by Jimmyboy on May 14, 2009, at 19:52:36
> Hmm.. that is interesting, if 5ht2a receptors are actually downregulated in depression it seems strange that 5ht2a antagonism helps so much with panic /anxiety.
another good thread now on 5ht1a/2 and axiety vs. panic
http://www.mindandmuscle.net/forum/index.php?showtopic=38047&hl=interesting the kappa/thc thing, i wonder how much of thc's hallucinagenic effects are from that.
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