I'm interested in Rimbonant for several reasons;weight loss and its application towards drug abuse.Specifically,smoking nicotine and lessening my apparent need for liberal/heavy handed stimulant usage.
The addition of SEA (acts on a different CB1 receptor,apparently)looks promising as a synergystic agent,the cut and paste of my post on this from another rimbonant thread is below.I'll be using the nootropic stack listed below,I may bump dosing up in increments of 5mg up to 20 if side effects aren't very pronounced.
I don't have the SEA now but am placing an order for at least 150 grams from BN so I expect to have it within the next several days.
.........
IOW I would like to take less stimulants and be functional (not feel like shit,lethargic etc) when I'm off caffiene and what not.
WRT upping fish oil dosage;I do not think higher intake of fish oil would be sufficient (by itself) to prevent suicidal ideation induced by 20mg of rimbonant.
Hell,I'm really not all that convinded that anything would.
I was thinking of a much more comprehensive noot stack of 6 grams epa/dha along with established therapuetical dosages of pir,ani,ALCAR,rhodilia,ash,bacopa...and something else.The something else would be the novel drug I refered to in the title,but this is likely just over reaching as a compound that exerts the polar opposite of the effect that weed has on me probably cannot be defeated in any form.When I smoke weed (which is raely,once a month if that)I tend to get pro-social,relatively optimistic and generally care free.Obviously,the polar effect of weed,in my case,is highly undesirable.But I don't smoke on a chronic basis,opposed to taking rimbonant would be,and smoking e/d would likely have a detrimental effect as far as apathy/motivation is concerned.
I've used SEA (amount present in LipidFX) and double dosage at that,with only minimal appetite supression.It was enough to tolerate 1500-2000kcals for over a month though,which I'd love to be able to get now.I think I may have been using other appetite supressents at the time(besides the usual shit like GTE,caffiene) but can't recall.
WRT SEA though,it looks like,( if I'm interpreting this study correctly) that perhaps 5mg rimbonant and at least 250mg SEA twice per day) would be good for appetite and PERHAPS,PERHAPS,PERHAPS, kicking drug addiction(smoking cigs,excessive caffiene):
Binding, degradation and apoptotic activity of stearoylethanolamide in rat C6 glioma cells.
Maccarrone M, Pauselli R, Di Rienzo M, Finazzi-Agrò A.
Department of Experimental Medicine and Biochemical Sciences, University of Rome Tor Vergata, Via Montpellier 1, 00133, Rome, Italy. Maccarrone@med.uniroma2.it
Stearoylethanolamide (SEA) is present in human, rat and mouse brain in amounts comparable with those of the endocannabinoid anandamide (arachidonoylethanolamide; AEA). Yet, the biological activity of SEA has never been investigated. We synthesized unlabelled and radiolabelled SEA to investigate its binding, degradation and biological activity in rat C6 glioma cells. We report that SEA binds to a specific site distinct from known cannabinoid or vanilloid receptors, and that AEA and capsazepine partly (approx. 50%) antagonized this binding. Treatment of C6 cells with SEA inhibits cellular nitric oxide synthase and does not affect adenylate cyclase, whereas treatment with cannabinoid type 1 agonist 2-arachidonoylglycerol activates the former enzyme and inhibits the latter. C6 cells also have a specific SEA membrane transporter, which is inhibited by NO, and a fatty acid amide hydrolase capable of cleaving SEA. In these cells, SEA shows pro-apoptotic activity, due to elevation of intracellular calcium, activation of the arachidonate cascade and mitochondrial uncoupling. NO further enhances SEA-induced apoptosis. Moreover, the cannabinoid type 1 receptor-mediated decrease in cAMP induced by AEA in C6 cells is potentiated by SEA, suggesting that this compound also has an 'entourage' effect. Taken together, this study shows that SEA is an endocannabinoid-like compound which binds to and is transported by new components of the endocannabinoid system. It seems noteworthy that degradation and pro-apoptotic activity of SEA are regulated by NO in a way opposite to that reported for AEA.
PMID: 12010121 [PubMed - indexed for MEDLINE]
Here is what I find pretty damn interesting:
"We report that SEA binds to a specific site distinct from known cannabinoid or vanilloid receptors, and that AEA and capsazepine partly (approx. 50%) antagonized this binding"
So it's a different site from no known cannabanoid receptors (assuming this includes rimbonant's action) then a low dose of 5mg rimbonant(shown to have mild positive effect and the higher dose of 20mg correlates with more reports of depression/anxiety) so it looks like we can cleave at the very least,the appetite supression from rimbonant(possibly the anti-addictive aspect as well,which would be fucking awesome) by taking 5mg once per day with SEA at 250-350mg 2x e/d.
This is all going under the premise that SEA and 5mg rimbonant would have a synergystic effect,as they hit different CB1 pathways.Of course,even if I'm right,avoidance of the 20mg related side effects would also have to be in line with 5mg rim + SEA.
Edit:
Just popped the first 5mg dose.I've got 24 days's worth at 5mg a day,will buy 28 of the 20mg tabs from CN/UN before this runs out,after I gauge the effects from 5 and 10mg dosages.
Also,started back up on a 1/4 hydergine tab to day after not taking it consistently for the past few weeks.I believe my test levels to be quite subpar ATM so I'll also add in sizable edy + tribulus dosing to bring T up to normal levels.I did start on higher dose forskolin recently,mostly for T elevation,but as edy+trib haven't any possible detrimental effect I'll add them in.I've got an excess stash of them regardless.In speculation,this should help with any negative effect on mood get from rimbonant.
EPA/DHA will be split up into two divided dosages,ending up around 6 grams total epa/dha.Despite the established fact that epa/dha is ideally taken at two seperate intervals per day I've always dosed it pre bed with a meal in order to avoid oxidation through physical acitivity.Lately I've been using around 2 grams epa/dha per day but have used 6 grams epa/dha daily for months on end with negligible effect (if any at all) on mood and body composition.
Full Version: Rimonabant
Well,this may be the novel compound I alluded to in my first post.So far as it may exert an anxiogenic effect,distinctly aligned against rimbonant's cb1 antagonism.
Capsaican is a big player,which I'm ordering from BN,but sourcing
1: Cereb Cortex. 2007 Oct 5 [Epub ahead of print]Click here to read Links
Role in Anxiety Behavior of the Endocannabinoid System in the Prefrontal Cortex.
Rubino T, Realini N, Castiglioni C, Guidali C, Viganó D, Marras E, Petrosino S, Perletti G, Maccarrone M, Di Marzo V, Parolaro D.
DBSF, Pharmacology Section and Center of Neuroscience, University of Insubria, via A. da Giussano 10, 21052 Busto Arsizio (VA), Italy.
In the present study we explored with a multidisciplinary approach, the role of anandamide (AEA) in the modulation of anxiety behavior at the level of the prefrontal cortex (PFC). Low doses of the metabolically stable AEA analog, methanandamide, microinjected into the PFC, produced an anxiolytic-like response in rats, whereas higher doses induced anxiety-like behaviors. Pretreatment with the selective antagonist of CB1 or TRPV1 receptors (AM251 and capsazepine respectively) suggested that the anxiolytic effect evoked by AEA might be due to the interaction with the CB1 cannabinoid receptor, whereas vanilloid receptors seem to be involved in AEA anxiogenic action. When AEA contents in the PFC were increased by microinjecting the selective inhibitor of fatty acid amide hydrolase (FAAH), URB597, we observed an anxiolytic response only at low doses of the compound and no effect or even an anxiogenic profile at higher doses. In line with this, a marked decrease of AEA levels in the PFC, achieved by lentivirus-mediated local overexpression of FAAH, produced an anxiogenic response. These findings support an anxiolytic role for physiological increases in AEA in the PFC, whereas more marked increases or decreases of this endocannabinoid might lead to an anxiogenic response due to TRPV1 stimulation or the lack of CB1 activation, respectively.
PMID: 17921459 [PubMed - as supplied by publisher] methanandamide,which I've never heard of,will probably be difficult.Administration is also an issue,obviously injecting into my precortex isn't a viable solution.
I'll order the SEA + cap from BN immediately,roll the dice and stay at 5mg for the next week while adding them in as soonas they show up.Guess I'll have 3 days on them,enough to gauge effect on appetite,but anti-addictoon potential won't be realized this route.
I'm toying with the idea of adding in one of the following;5mg bromo,300mg XR bupropion or 2.5 mg selegeline.All of which I have on hand but I clearly have to look into them more,as any or all of them could be horrible concepts.
I'll likely end up trying to ride out 20mg with a lot of epa/dha and assorted noots,knowing full well that any potential depressive mindset is merely drug induced.
OTOH,with any luck I may have stumbled upon a new application for anti-addiction and weight loss virtually free of the negative sides of rimbonant,via a lowered dose of 5mg rimbonant with these additives.Then again,I barely know how to interpret half the shit I read on Pubmed so this whole pseudo-venture of mine may be fucked from the start.
Capsaican is a big player,which I'm ordering from BN,but sourcing
1: Cereb Cortex. 2007 Oct 5 [Epub ahead of print]Click here to read Links
Role in Anxiety Behavior of the Endocannabinoid System in the Prefrontal Cortex.
Rubino T, Realini N, Castiglioni C, Guidali C, Viganó D, Marras E, Petrosino S, Perletti G, Maccarrone M, Di Marzo V, Parolaro D.
DBSF, Pharmacology Section and Center of Neuroscience, University of Insubria, via A. da Giussano 10, 21052 Busto Arsizio (VA), Italy.
In the present study we explored with a multidisciplinary approach, the role of anandamide (AEA) in the modulation of anxiety behavior at the level of the prefrontal cortex (PFC). Low doses of the metabolically stable AEA analog, methanandamide, microinjected into the PFC, produced an anxiolytic-like response in rats, whereas higher doses induced anxiety-like behaviors. Pretreatment with the selective antagonist of CB1 or TRPV1 receptors (AM251 and capsazepine respectively) suggested that the anxiolytic effect evoked by AEA might be due to the interaction with the CB1 cannabinoid receptor, whereas vanilloid receptors seem to be involved in AEA anxiogenic action. When AEA contents in the PFC were increased by microinjecting the selective inhibitor of fatty acid amide hydrolase (FAAH), URB597, we observed an anxiolytic response only at low doses of the compound and no effect or even an anxiogenic profile at higher doses. In line with this, a marked decrease of AEA levels in the PFC, achieved by lentivirus-mediated local overexpression of FAAH, produced an anxiogenic response. These findings support an anxiolytic role for physiological increases in AEA in the PFC, whereas more marked increases or decreases of this endocannabinoid might lead to an anxiogenic response due to TRPV1 stimulation or the lack of CB1 activation, respectively.
PMID: 17921459 [PubMed - as supplied by publisher] methanandamide,which I've never heard of,will probably be difficult.Administration is also an issue,obviously injecting into my precortex isn't a viable solution.
I'll order the SEA + cap from BN immediately,roll the dice and stay at 5mg for the next week while adding them in as soonas they show up.Guess I'll have 3 days on them,enough to gauge effect on appetite,but anti-addictoon potential won't be realized this route.
I'm toying with the idea of adding in one of the following;5mg bromo,300mg XR bupropion or 2.5 mg selegeline.All of which I have on hand but I clearly have to look into them more,as any or all of them could be horrible concepts.
I'll likely end up trying to ride out 20mg with a lot of epa/dha and assorted noots,knowing full well that any potential depressive mindset is merely drug induced.
OTOH,with any luck I may have stumbled upon a new application for anti-addiction and weight loss virtually free of the negative sides of rimbonant,via a lowered dose of 5mg rimbonant with these additives.Then again,I barely know how to interpret half the shit I read on Pubmed so this whole pseudo-venture of mine may be fucked from the start.
Well,this may be the novel compound I alluded to in my first post.So far as it may exert an anxiogenic effect,distinctly aligned against rimbonant's cb1 antagonism.
Capsaican is a big player,which I'm ordering from BN,but sourcing
1: Cereb Cortex. 2007 Oct 5 [Epub ahead of print]Click here to read Links
Role in Anxiety Behavior of the Endocannabinoid System in the Prefrontal Cortex.
Rubino T, Realini N, Castiglioni C, Guidali C, Viganó D, Marras E, Petrosino S, Perletti G, Maccarrone M, Di Marzo V, Parolaro D.
DBSF, Pharmacology Section and Center of Neuroscience, University of Insubria, via A. da Giussano 10, 21052 Busto Arsizio (VA), Italy.
In the present study we explored with a multidisciplinary approach, the role of anandamide (AEA) in the modulation of anxiety behavior at the level of the prefrontal cortex (PFC). Low doses of the metabolically stable AEA analog, methanandamide, microinjected into the PFC, produced an anxiolytic-like response in rats, whereas higher doses induced anxiety-like behaviors. Pretreatment with the selective antagonist of CB1 or TRPV1 receptors (AM251 and capsazepine respectively) suggested that the anxiolytic effect evoked by AEA might be due to the interaction with the CB1 cannabinoid receptor, whereas vanilloid receptors seem to be involved in AEA anxiogenic action. When AEA contents in the PFC were increased by microinjecting the selective inhibitor of fatty acid amide hydrolase (FAAH), URB597, we observed an anxiolytic response only at low doses of the compound and no effect or even an anxiogenic profile at higher doses. In line with this, a marked decrease of AEA levels in the PFC, achieved by lentivirus-mediated local overexpression of FAAH, produced an anxiogenic response. These findings support an anxiolytic role for physiological increases in AEA in the PFC, whereas more marked increases or decreases of this endocannabinoid might lead to an anxiogenic response due to TRPV1 stimulation or the lack of CB1 activation, respectively.
PMID: 17921459 [PubMed - as supplied by publisher] methanandamide,which I've never heard of,will probably be difficult.Administration is also an issue,obviously injecting into my precortex isn't a viable solution.
I'll order the SEA + cap from BN immediately,roll the dice and stay at 5mg for the next week while adding them in as soonas they show up.Guess I'll have 3 days on them,enough to gauge effect on appetite,but anti-addictoon potential won't be realized this route.
I'm toying with the idea of adding in one of the following;5mg bromo,300mg XR bupropion or 2.5 mg selegeline.All of which I have on hand but I clearly have to look into them more,as any or all of them could be horrible concepts.
I'll likely end up trying to ride out 20mg with a lot of epa/dha and assorted noots,knowing full well that any potential depressive mindset is merely drug induced.
OTOH,with any luck I may have stumbled upon a new application for anti-addiction and weight loss virtually free of the negative sides of rimbonant,via a lowered dose of 5mg rimbonant with these additives.Then again,I barely know how to interpret half the shit I read on Pubmed so this whole pseudo-venture of mine may be fucked from the start.
Capsaican is a big player,which I'm ordering from BN,but sourcing
1: Cereb Cortex. 2007 Oct 5 [Epub ahead of print]Click here to read Links
Role in Anxiety Behavior of the Endocannabinoid System in the Prefrontal Cortex.
Rubino T, Realini N, Castiglioni C, Guidali C, Viganó D, Marras E, Petrosino S, Perletti G, Maccarrone M, Di Marzo V, Parolaro D.
DBSF, Pharmacology Section and Center of Neuroscience, University of Insubria, via A. da Giussano 10, 21052 Busto Arsizio (VA), Italy.
In the present study we explored with a multidisciplinary approach, the role of anandamide (AEA) in the modulation of anxiety behavior at the level of the prefrontal cortex (PFC). Low doses of the metabolically stable AEA analog, methanandamide, microinjected into the PFC, produced an anxiolytic-like response in rats, whereas higher doses induced anxiety-like behaviors. Pretreatment with the selective antagonist of CB1 or TRPV1 receptors (AM251 and capsazepine respectively) suggested that the anxiolytic effect evoked by AEA might be due to the interaction with the CB1 cannabinoid receptor, whereas vanilloid receptors seem to be involved in AEA anxiogenic action. When AEA contents in the PFC were increased by microinjecting the selective inhibitor of fatty acid amide hydrolase (FAAH), URB597, we observed an anxiolytic response only at low doses of the compound and no effect or even an anxiogenic profile at higher doses. In line with this, a marked decrease of AEA levels in the PFC, achieved by lentivirus-mediated local overexpression of FAAH, produced an anxiogenic response. These findings support an anxiolytic role for physiological increases in AEA in the PFC, whereas more marked increases or decreases of this endocannabinoid might lead to an anxiogenic response due to TRPV1 stimulation or the lack of CB1 activation, respectively.
PMID: 17921459 [PubMed - as supplied by publisher] methanandamide,which I've never heard of,will probably be difficult.Administration is also an issue,obviously injecting into my precortex isn't a viable solution.
I'll order the SEA + cap from BN immediately,roll the dice and stay at 5mg for the next week while adding them in as soonas they show up.Guess I'll have 3 days on them,enough to gauge effect on appetite,but anti-addictoon potential won't be realized this route.
I'm toying with the idea of adding in one of the following;5mg bromo,300mg XR bupropion or 2.5 mg selegeline.All of which I have on hand but I clearly have to look into them more,as any or all of them could be horrible concepts.
I'll likely end up trying to ride out 20mg with a lot of epa/dha and assorted noots,knowing full well that any potential depressive mindset is merely drug induced.
OTOH,with any luck I may have stumbled upon a new application for anti-addiction and weight loss virtually free of the negative sides of rimbonant,via a lowered dose of 5mg rimbonant with these additives.Then again,I barely know how to interpret half the shit I read on Pubmed so this whole pseudo-venture of mine may be fucked from the start.
There's a slew of srudies on AEA/anandamide kicking in anxiolytic benefit via CB1 business,but dosage varies and higher amounts are anxiogenic.That along with it being injected into the rat's fucking brains makes for a pretty big variable when accounting for method and amount of human dosing.
http://www.ncbi.nlm.nih.gov/sites/entrez?D..._RVAbstractPlus
http://www.ncbi.nlm.nih.gov/sites/entrez?D..._RVAbstractPlus
Applied a 21mg nicotine patch last night,awoke feeling sickly this morning.I may just ride it out with the patches that I have(2 weeks worth) by that time,the higher dose rimbonant will have fully kicked in and nicotine/food cravings should be much less pronounced.
I'm bumping up the rimbonant to 10mg tomorrow and will be at 20mg per day by the end of this week.
Adding in uridine and kappa shortly.
I'm bumping up the rimbonant to 10mg tomorrow and will be at 20mg per day by the end of this week.
Adding in uridine and kappa shortly.
I've been feeling tired on a notably more consistent basis than before using this drug.
No unexplainable,weird mood swings to note other than the one I mentioned above.
Despite the one episode I noted above,if depression has manifested itself yet it is not along the lines of severe and suicidal ideations are absent.
The only depression that I feel since starting on this is more pf a physical sensation of tiredness and apathy.WRT training,I've little desrire to do so and taking liberal amounts of caffiene(Scorch and a 24oz wawa coffeee) barely mitigate the haze.However,I was laid off from work(hardscape contruction) last week which coincided with a wrist injury so those two things haven't had me feeling all that great.
I have been training 4+ days per week,mostly squatting and abs.It could be said that that squatting,which I primarily do in 20 rep sets(lighter to heavier sets 20x225ATG,20x315 paralell and a couple 1/2-esque singles with 405 the other day) could be leading to the lethargy,but I don't think this is the case.It just feels more chemically induced and basically,all I feel like doing is lying in deb.
FWIW,I smoked around 1/2 a pack last night but I'm working at a bar part time now,and it's chock full of preppy/pretty boy types and girls with those trendy,winter like boots that have that fluffy shit coming out of the top of them.Urge to smoke while not in such an environment is fairly controllable.
I decoded not to bump dosage up to 10mg today as I only have 5 20mg caps left and am just compiling an order for UN tonight.
No unexplainable,weird mood swings to note other than the one I mentioned above.
Despite the one episode I noted above,if depression has manifested itself yet it is not along the lines of severe and suicidal ideations are absent.
The only depression that I feel since starting on this is more pf a physical sensation of tiredness and apathy.WRT training,I've little desrire to do so and taking liberal amounts of caffiene(Scorch and a 24oz wawa coffeee) barely mitigate the haze.However,I was laid off from work(hardscape contruction) last week which coincided with a wrist injury so those two things haven't had me feeling all that great.
I have been training 4+ days per week,mostly squatting and abs.It could be said that that squatting,which I primarily do in 20 rep sets(lighter to heavier sets 20x225ATG,20x315 paralell and a couple 1/2-esque singles with 405 the other day) could be leading to the lethargy,but I don't think this is the case.It just feels more chemically induced and basically,all I feel like doing is lying in deb.
FWIW,I smoked around 1/2 a pack last night but I'm working at a bar part time now,and it's chock full of preppy/pretty boy types and girls with those trendy,winter like boots that have that fluffy shit coming out of the top of them.Urge to smoke while not in such an environment is fairly controllable.
I decoded not to bump dosage up to 10mg today as I only have 5 20mg caps left and am just compiling an order for UN tonight.
QUOTE(Colin @ Dec 15 2007, 07:10 PM) [snapback]442748[/snapback]
FWIW,I smoked around 1/2 a pack last night but I'm working at a bar part time now,and it's chock full of preppy/pretty boy types and girls with those trendy,winter like boots that have that fluffy shit coming out of the top of them.Urge to smoke while not in such an environment is fairly controllable.
This cracked me up.
Yeah,the absurdity of that statement also made me a laugh a bit as I posted it.
I received the bulk SEA and capped cayyene earlier today and have added them in to potentiate CB1 agonism,see this thread for my reasoning:
Binding, degradation and apoptotic activity of stearoylethanolamide in rat C6 glioma cells.
Maccarrone M, Pauselli R, Di Rienzo M, Finazzi-Agrò A.
Department of Experimental Medicine and Biochemical Sciences, University of Rome Tor Vergata, Via Montpellier 1, 00133, Rome, Italy. Maccarrone@med.uniroma2.it
Stearoylethanolamide (SEA) is present in human, rat and mouse brain in amounts comparable with those of the endocannabinoid anandamide (arachidonoylethanolamide; AEA). Yet, the biological activity of SEA has never been investigated. We synthesized unlabelled and radiolabelled SEA to investigate its binding, degradation and biological activity in rat C6 glioma cells. We report that SEA binds to a specific site distinct from known cannabinoid or vanilloid receptors, and that AEA and capsazepine partly (approx. 50%) antagonized this binding. Treatment of C6 cells with SEA inhibits cellular nitric oxide synthase and does not affect adenylate cyclase, whereas treatment with cannabinoid type 1 agonist 2-arachidonoylglycerol activates the former enzyme and inhibits the latter. C6 cells also have a specific SEA membrane transporter, which is inhibited by NO, and a fatty acid amide hydrolase capable of cleaving SEA. In these cells, SEA shows pro-apoptotic activity, due to elevation of intracellular calcium, activation of the arachidonate cascade and mitochondrial uncoupling. NO further enhances SEA-induced apoptosis. Moreover, the cannabinoid type 1 receptor-mediated decrease in cAMP induced by AEA in C6 cells is potentiated by SEA, suggesting that this compound also has an 'entourage' effect. Taken together, this study shows that SEA is an endocannabinoid-like compound which binds to and is transported by new components of the endocannabinoid system. It seems noteworthy that degradation and pro-apoptotic activity of SEA are regulated by NO in a way opposite to that reported for AEA.
PMID: 12010121 [PubMed - indexed for MEDLINE]
I'm still on 5mg per day and the depression has manifested itself as a sort of previously unreached apathy,laziness and desire to pretty much fuck off and do nothing.No anorectic effect has been noticed since I started last week,quite the contrary,I've been eating very poorly(pizza,milkshakes etc) so yeah,not good.Quitting this behavior today.
I received the bulk SEA and capped cayyene earlier today and have added them in to potentiate CB1 agonism,see this thread for my reasoning:
Binding, degradation and apoptotic activity of stearoylethanolamide in rat C6 glioma cells.
Maccarrone M, Pauselli R, Di Rienzo M, Finazzi-Agrò A.
Department of Experimental Medicine and Biochemical Sciences, University of Rome Tor Vergata, Via Montpellier 1, 00133, Rome, Italy. Maccarrone@med.uniroma2.it
Stearoylethanolamide (SEA) is present in human, rat and mouse brain in amounts comparable with those of the endocannabinoid anandamide (arachidonoylethanolamide; AEA). Yet, the biological activity of SEA has never been investigated. We synthesized unlabelled and radiolabelled SEA to investigate its binding, degradation and biological activity in rat C6 glioma cells. We report that SEA binds to a specific site distinct from known cannabinoid or vanilloid receptors, and that AEA and capsazepine partly (approx. 50%) antagonized this binding. Treatment of C6 cells with SEA inhibits cellular nitric oxide synthase and does not affect adenylate cyclase, whereas treatment with cannabinoid type 1 agonist 2-arachidonoylglycerol activates the former enzyme and inhibits the latter. C6 cells also have a specific SEA membrane transporter, which is inhibited by NO, and a fatty acid amide hydrolase capable of cleaving SEA. In these cells, SEA shows pro-apoptotic activity, due to elevation of intracellular calcium, activation of the arachidonate cascade and mitochondrial uncoupling. NO further enhances SEA-induced apoptosis. Moreover, the cannabinoid type 1 receptor-mediated decrease in cAMP induced by AEA in C6 cells is potentiated by SEA, suggesting that this compound also has an 'entourage' effect. Taken together, this study shows that SEA is an endocannabinoid-like compound which binds to and is transported by new components of the endocannabinoid system. It seems noteworthy that degradation and pro-apoptotic activity of SEA are regulated by NO in a way opposite to that reported for AEA.
PMID: 12010121 [PubMed - indexed for MEDLINE]
I'm still on 5mg per day and the depression has manifested itself as a sort of previously unreached apathy,laziness and desire to pretty much fuck off and do nothing.No anorectic effect has been noticed since I started last week,quite the contrary,I've been eating very poorly(pizza,milkshakes etc) so yeah,not good.Quitting this behavior today.
SEA and 5mg rim have made appetite pretty dull today,this is after I dropped cayenne as I interpreted one of the studies incorrectly.Cayenne makes the action weaker,not stronger,as I had thought.
I definitely am feeling the decrease in appetite now,opposed to yesterday.I went to the gym several hours after waking (no food yet) and ate a third of a Muscle Milk bar between sets.I've been awake for 7 hours now with negligible hunger,downing a low cho pro shake as I type this and I feel relatively full.
The depression-esque feeling remains,it is a strange sensation to try to describe.I'm not depressed as in emo'ed out,no suicidal ideations have kicked in suddenly etc.
Interest and drive is remarkably down as I have to force myself to engage in much of anything.A sense of feeling consistently tired,despite popping stism which usually give me a immediate sense of drive and/or manic energy.The stims(sulbutiamine,liberal amounts of caffiene and racetams) have some impact but not a Hell of a lot.
Apathy is the word of the day.
I can only do leg oriented shit WRT weights ATM, as I don't want to take the chance of permanently banging up my still healing left wrist and did some squats a little while ago.Managed a decent w/o but despite working up a good sweat and squatting 405 for 20( well,partial squats as I can't get 405 ATG) the session,for lack of a better word,sucked.
I definitely am feeling the decrease in appetite now,opposed to yesterday.I went to the gym several hours after waking (no food yet) and ate a third of a Muscle Milk bar between sets.I've been awake for 7 hours now with negligible hunger,downing a low cho pro shake as I type this and I feel relatively full.
The depression-esque feeling remains,it is a strange sensation to try to describe.I'm not depressed as in emo'ed out,no suicidal ideations have kicked in suddenly etc.
Interest and drive is remarkably down as I have to force myself to engage in much of anything.A sense of feeling consistently tired,despite popping stism which usually give me a immediate sense of drive and/or manic energy.The stims(sulbutiamine,liberal amounts of caffiene and racetams) have some impact but not a Hell of a lot.
Apathy is the word of the day.
I can only do leg oriented shit WRT weights ATM, as I don't want to take the chance of permanently banging up my still healing left wrist and did some squats a little while ago.Managed a decent w/o but despite working up a good sweat and squatting 405 for 20( well,partial squats as I can't get 405 ATG) the session,for lack of a better word,sucked.
Why would you take a CB antagonist to lose weight?
QUOTE(Sprinkles @ Dec 21 2007, 09:54 PM) [snapback]444082[/snapback]
Why would you take a CB antagonist to lose weight?
Because it works.
QUOTE(SteveSliwa @ Dec 21 2007, 11:00 PM) [snapback]444083[/snapback]
Because it works.
http://www.ncbi.nlm.nih.gov/sites/entrez?D...Pubmed_RVDocSum
Cannabinoids elicit antidepressant-like behavior and activate serotonergic neurons through the medial prefrontal cortex.Bambico FR, Katz N, Debonnel G, Gobbi G.
Neurobiological Psychiatry Unit, Department of Psychiatry, McGill University, Montréal, Quebec, Canada H3A 1A1.
Preclinical and clinical studies show that cannabis modulates mood and possesses antidepressant-like properties, mediated by the agonistic activity of cannabinoids on central CB1 receptors (CB1Rs). The action of CB1R agonists on the serotonin (5-HT) system, the major transmitter system involved in mood control and implicated in the mechanism of action of antidepressants, remains however poorly understood. In this study, we demonstrated that, at low doses, the CB1R agonist WIN55,212-2 [R(+)-[2,3-dihydro-5-methyl-3-[(morpholinyl)]pyrrolo[1,2,3-de]-1,4-benzoxazinyl]-(1-naphthalenyl) methanone mesylate] exerts potent antidepressant-like properties in the rat forced-swim test (FST). This effect is CB1R dependent because it was blocked by the CB1R antagonist rimonabant and is 5-HT mediated because it was abolished by pretreatment with the 5-HT-depleting agent parachlorophenylalanine. Then, using in vivo electrophysiology, we showed that low doses of WIN55,212-2 dose dependently enhanced dorsal raphe nucleus 5-HT neuronal activity through a CB1R-dependent mechanism. Conversely, high doses of WIN55,212-2 were ineffective in the FST and decreased 5-HT neuronal activity through a CB1R-independent mechanism. The CB1R agonist-induced enhancement of 5-HT neuronal activity was abolished by total or medial prefrontocortical, but not by lateral prefrontocortical, transection. Furthermore, 5-HT neuronal activity was enhanced by the local microinjection of WIN55,212-2 into the ventromedial prefrontal cortex (mPFCv) but not by the local microinjection of WIN55,212-2 into the lateral prefrontal cortex. Similarly, the microinjection of WIN55,212-2 into the mPFCv produced a CB1R-dependent antidepressant-like effect in the FST. These results demonstrate that CB1R agonists possess antidepressant-like properties and modulate 5-HT neuronal activity via the mPFCv.
QUOTE(Sprinkles @ Dec 21 2007, 10:31 PM) [snapback]444085[/snapback]
http://www.ncbi.nlm.nih.gov/sites/entrez?D...Pubmed_RVDocSum
Cannabinoids elicit antidepressant-like behavior and activate serotonergic neurons through the medial prefrontal cortex.Bambico FR, Katz N, Debonnel G, Gobbi G.
Neurobiological Psychiatry Unit, Department of Psychiatry, McGill University, Montréal, Quebec, Canada H3A 1A1.
Preclinical and clinical studies show that cannabis modulates mood and possesses antidepressant-like properties, mediated by the agonistic activity of cannabinoids on central CB1 receptors (CB1Rs). The action of CB1R agonists on the serotonin (5-HT) system, the major transmitter system involved in mood control and implicated in the mechanism of action of antidepressants, remains however poorly understood. In this study, we demonstrated that, at low doses, the CB1R agonist WIN55,212-2 [R(+)-[2,3-dihydro-5-methyl-3-[(morpholinyl)]pyrrolo[1,2,3-de]-1,4-benzoxazinyl]-(1-naphthalenyl) methanone mesylate] exerts potent antidepressant-like properties in the rat forced-swim test (FST). This effect is CB1R dependent because it was blocked by the CB1R antagonist rimonabant and is 5-HT mediated because it was abolished by pretreatment with the 5-HT-depleting agent parachlorophenylalanine. Then, using in vivo electrophysiology, we showed that low doses of WIN55,212-2 dose dependently enhanced dorsal raphe nucleus 5-HT neuronal activity through a CB1R-dependent mechanism. Conversely, high doses of WIN55,212-2 were ineffective in the FST and decreased 5-HT neuronal activity through a CB1R-independent mechanism. The CB1R agonist-induced enhancement of 5-HT neuronal activity was abolished by total or medial prefrontocortical, but not by lateral prefrontocortical, transection. Furthermore, 5-HT neuronal activity was enhanced by the local microinjection of WIN55,212-2 into the ventromedial prefrontal cortex (mPFCv) but not by the local microinjection of WIN55,212-2 into the lateral prefrontal cortex. Similarly, the microinjection of WIN55,212-2 into the mPFCv produced a CB1R-dependent antidepressant-like effect in the FST. These results demonstrate that CB1R agonists possess antidepressant-like properties and modulate 5-HT neuronal activity via the mPFCv.
Cannabinoids elicit antidepressant-like behavior and activate serotonergic neurons through the medial prefrontal cortex.Bambico FR, Katz N, Debonnel G, Gobbi G.
Neurobiological Psychiatry Unit, Department of Psychiatry, McGill University, Montréal, Quebec, Canada H3A 1A1.
Preclinical and clinical studies show that cannabis modulates mood and possesses antidepressant-like properties, mediated by the agonistic activity of cannabinoids on central CB1 receptors (CB1Rs). The action of CB1R agonists on the serotonin (5-HT) system, the major transmitter system involved in mood control and implicated in the mechanism of action of antidepressants, remains however poorly understood. In this study, we demonstrated that, at low doses, the CB1R agonist WIN55,212-2 [R(+)-[2,3-dihydro-5-methyl-3-[(morpholinyl)]pyrrolo[1,2,3-de]-1,4-benzoxazinyl]-(1-naphthalenyl) methanone mesylate] exerts potent antidepressant-like properties in the rat forced-swim test (FST). This effect is CB1R dependent because it was blocked by the CB1R antagonist rimonabant and is 5-HT mediated because it was abolished by pretreatment with the 5-HT-depleting agent parachlorophenylalanine. Then, using in vivo electrophysiology, we showed that low doses of WIN55,212-2 dose dependently enhanced dorsal raphe nucleus 5-HT neuronal activity through a CB1R-dependent mechanism. Conversely, high doses of WIN55,212-2 were ineffective in the FST and decreased 5-HT neuronal activity through a CB1R-independent mechanism. The CB1R agonist-induced enhancement of 5-HT neuronal activity was abolished by total or medial prefrontocortical, but not by lateral prefrontocortical, transection. Furthermore, 5-HT neuronal activity was enhanced by the local microinjection of WIN55,212-2 into the ventromedial prefrontal cortex (mPFCv) but not by the local microinjection of WIN55,212-2 into the lateral prefrontal cortex. Similarly, the microinjection of WIN55,212-2 into the mPFCv produced a CB1R-dependent antidepressant-like effect in the FST. These results demonstrate that CB1R agonists possess antidepressant-like properties and modulate 5-HT neuronal activity via the mPFCv.
Sigh we get more newbies everyday.
QUOTE
Rimonabant (also known as SR141716, Acomplia, Riobant, Slimona, Rimoslim, and Zimulti) is an anorectic anti-obesity drug. It is a CB1 cannabinoid receptor inverse agonist. Its main avenue of effect is reduction in appetite.
Rimonabant is the first selective CB1 receptor blocker to be approved for use anywhere in the world. In Europe, it is indicated for use in conjunction with diet and exercise for patients with a body mass index greater than 30 kg/m², or patients wih a BMI greater than 27 kg/m² with associated risk factors, such as type 2 diabetes or dyslipidaemia. In the UK, it has been available since the end of July 2006. As of 2007, the drug was available in 38 countries.
Rimonabant is the first selective CB1 receptor blocker to be approved for use anywhere in the world. In Europe, it is indicated for use in conjunction with diet and exercise for patients with a body mass index greater than 30 kg/m², or patients wih a BMI greater than 27 kg/m² with associated risk factors, such as type 2 diabetes or dyslipidaemia. In the UK, it has been available since the end of July 2006. As of 2007, the drug was available in 38 countries.
QUOTE(SteveSliwa @ Dec 21 2007, 11:37 PM) [snapback]444086[/snapback]
Sigh we get more newbies everyday.
You're a fucking idiot.
I mean, if you don't understand - i'm not going to spell it out for you. The concept is a crystal.
QUOTE(Sprinkles @ Dec 21 2007, 10:41 PM) [snapback]444089[/snapback]
You're a fucking idiot.
I mean, if you don't understand - i'm not going to spell it out for you. The concept is a crystal.
I mean, if you don't understand - i'm not going to spell it out for you. The concept is a crystal.
Hello "Sprinkles"
Your rat study has little to do with the drug's proven effectiveness in weight loss in human studies.
I understand the rat study just fine.
You may want to work on your anger issues. I would suggest Picamilon.
QUOTE(SteveSliwa @ Dec 21 2007, 11:58 PM) [snapback]444091[/snapback]
Hello "Sprinkles"
Your rat study has little to do with the drug's proven effectiveness in weight loss in human studies.
I understand the rat study just fine.
You may want to work on your anger issues. I would suggest Picamilon.
Your rat study has little to do with the drug's proven effectiveness in weight loss in human studies.
I understand the rat study just fine.
You may want to work on your anger issues. I would suggest Picamilon.
Guess again.
QUOTE(Sprinkles @ Dec 21 2007, 11:11 PM) [snapback]444092[/snapback]
Guess again.
Human studies proven it works. It's been approved for this purpose and several human studies have been done.
Unless you can somehow disprove this (and you would need alot more than 1 rat study) I don't see you going anywhere.
Stop wasting our time with your immaturity. I know far more about this subject than you.
QUOTE(Colin @ Dec 21 2007, 09:25 PM) [snapback]444077[/snapback]
SEA and 5mg rim have made appetite pretty dull today,this is after I dropped cayenne as I interpreted one of the studies incorrectly.Cayenne makes the action weaker,not stronger,as I had thought.
I definitely am feeling the decrease in appetite now,opposed to yesterday.I went to the gym several hours after waking (no food yet) and ate a third of a Muscle Milk bar between sets.I've been awake for 7 hours now with negligible hunger,downing a low cho pro shake as I type this and I feel relatively full.
The depression-esque feeling remains,it is a strange sensation to try to describe.I'm not depressed as in emo'ed out,no suicidal ideations have kicked in suddenly etc.
Interest and drive is remarkably down as I have to force myself to engage in much of anything.A sense of feeling consistently tired,despite popping stism which usually give me a immediate sense of drive and/or manic energy.The stims(sulbutiamine,liberal amounts of caffiene and racetams) have some impact but not a Hell of a lot.
Apathy is the word of the day.
I can only do leg oriented shit WRT weights ATM, as I don't want to take the chance of permanently banging up my still healing left wrist and did some squats a little while ago.Managed a decent w/o but despite working up a good sweat and squatting 405 for 20( well,partial squats as I can't get 405 ATG) the session,for lack of a better word,sucked.
I definitely am feeling the decrease in appetite now,opposed to yesterday.I went to the gym several hours after waking (no food yet) and ate a third of a Muscle Milk bar between sets.I've been awake for 7 hours now with negligible hunger,downing a low cho pro shake as I type this and I feel relatively full.
The depression-esque feeling remains,it is a strange sensation to try to describe.I'm not depressed as in emo'ed out,no suicidal ideations have kicked in suddenly etc.
Interest and drive is remarkably down as I have to force myself to engage in much of anything.A sense of feeling consistently tired,despite popping stism which usually give me a immediate sense of drive and/or manic energy.The stims(sulbutiamine,liberal amounts of caffiene and racetams) have some impact but not a Hell of a lot.
Apathy is the word of the day.
I can only do leg oriented shit WRT weights ATM, as I don't want to take the chance of permanently banging up my still healing left wrist and did some squats a little while ago.Managed a decent w/o but despite working up a good sweat and squatting 405 for 20( well,partial squats as I can't get 405 ATG) the session,for lack of a better word,sucked.
This should be interesting.
QUOTE(SteveSliwa @ Dec 22 2007, 12:19 AM) [snapback]444094[/snapback]
Human studies proven it works. It's been approved for this purpose and several human studies have been done.
Unless you can somehow disprove this (and you would need alot more than 1 rat study) I don't see you going anywhere.
Stop wasting our time with your immaturity. I know far more about this subject than you.
Unless you can somehow disprove this (and you would need alot more than 1 rat study) I don't see you going anywhere.
Stop wasting our time with your immaturity. I know far more about this subject than you.
I don't really give a shit what you know or don't know regarding a drug and its ability to produce results in human studdies. It proves nothing to me and further exemplifies a thought process that is primitive. The issue is that cannabinoid antagonism will produce depressant like effects that are deleterious to psyche and the organism as a whole, and its desired outcome, weightless, is not an end that would justify the means. Until you show an understanding of the organism that is beyond pubmed studies, which i do not believe you will ever be capable of, further replies to your stupidity are not warranted.
If anyone is still fooled by your stupidity, the only explanation is their own.
Sprinkles:
I'm taking the cb antagonists (two of them,actually-SEA and rimbonant) not only to lose weight but for other reasons as well,all explained in the first post I made in this thread.
Steve:
Yes,interesting is a way of putting it.For further effect (and to make smoking a distinct impossibility) I'm adding in 5mg bromo tomorrow.
As soon as I receive the generic rim tabs I ordered from your site I'll bump up the dosage to 20mg,I only placed the order several days ago though.I had planned on titrating dosage slowly by increments of 5mg but considering after seeing how 5mg effects me I''d rather get shis over with within a shorter period of time.I'm hoping that 6 weeks at 20mg with the liberal SEA dosing and 5mg bromo will be sufficient.
I'm taking the cb antagonists (two of them,actually-SEA and rimbonant) not only to lose weight but for other reasons as well,all explained in the first post I made in this thread.
Steve:
Yes,interesting is a way of putting it.For further effect (and to make smoking a distinct impossibility) I'm adding in 5mg bromo tomorrow.
As soon as I receive the generic rim tabs I ordered from your site I'll bump up the dosage to 20mg,I only placed the order several days ago though.I had planned on titrating dosage slowly by increments of 5mg but considering after seeing how 5mg effects me I''d rather get shis over with within a shorter period of time.I'm hoping that 6 weeks at 20mg with the liberal SEA dosing and 5mg bromo will be sufficient.
QUOTE(Colin @ Dec 22 2007, 12:55 AM) [snapback]444099[/snapback]
Sprinkles:
I'm taking the cb antagonists (two of them,actually-SEA and rimbonant) not only to lose weight but for other reasons as well,all explained in the first post I made in this thread.
Steve:
Yes,interesting is a way of putting it.For further effect (and to make smoking a distinct impossibility) I'm adding in 5mg bromo tomorrow.
As soon as I receive the generic rim tabs I ordered from your site I'll bump up the dosage to 20mg,I only placed the order several days ago though.I had planned on titrating dosage slowly by increments of 5mg but considering after seeing how 5mg effects me I''d rather get shis over with within a shorter period of time.I'm hoping that 6 weeks at 20mg with the liberal SEA dosing and 5mg bromo will be sufficient.
I'm taking the cb antagonists (two of them,actually-SEA and rimbonant) not only to lose weight but for other reasons as well,all explained in the first post I made in this thread.
Steve:
Yes,interesting is a way of putting it.For further effect (and to make smoking a distinct impossibility) I'm adding in 5mg bromo tomorrow.
As soon as I receive the generic rim tabs I ordered from your site I'll bump up the dosage to 20mg,I only placed the order several days ago though.I had planned on titrating dosage slowly by increments of 5mg but considering after seeing how 5mg effects me I''d rather get shis over with within a shorter period of time.I'm hoping that 6 weeks at 20mg with the liberal SEA dosing and 5mg bromo will be sufficient.
There are more effective ways to deal with drug addiction.
a) meditation / yoga
mental exercise ie studyingc) lsd / psilocybin
Stop trying to look for the easy way out because it doesn't exist.
QUOTE(Sprinkles @ Dec 21 2007, 09:50 PM) [snapback]444098[/snapback]
I don't really give a shit what you know or don't know regarding a drug and its ability to produce results in human studdies. It proves nothing to me and further exemplifies a thought process that is primitive. The issue is that cannabinoid antagonism will produce depressant like effects that are deleterious to psyche and the organism as a whole, and its desired outcome, weightless, is not an end that would justify the means. Until you show an understanding of the organism that is beyond pubmed studies, which i do not believe you will ever be capable of, further replies to your stupidity are not warranted.
If anyone is still fooled by your stupidity, the only explanation is their own.
If anyone is still fooled by your stupidity, the only explanation is their own.
The drug is a double edged sword.
I've found no evidence to suggest that there may be permanent changes in behavorial patterns,the here and now is the only manner in which this drug can be effective.The concern I have is the large spike in depression/anxiety it induces in most users(high 80%'s of US trial participants reported extreme depression and/or suicidal ideations,IIRC) and my expierience is that even a lower dose of the drug makes you depressed/apathetic.However,considering it's potential in reducing cravings,reward for food,smoking and other drugs I think this is not quite the poor choice most have deemed it to be.However,time on the drug will certainly prove to be difficult and taxing.
To reinterate,there is a lot more potential to this drug than just weight loss.
QUOTE(Colin @ Dec 22 2007, 01:07 AM) [snapback]444101[/snapback]
The drug is a double edged sword.
I've found no evidence to suggest that there may be permanent changes in behavorial patterns,the here and now is the only manner in which this drug can be effective.The concern I have is the large spike in depression/anxiety it induces in most users(high 80%'s of US trial participants reported extreme depression and/or suicidal ideations,IIRC) and my expierience is that even a lower dose of the drug makes you depressed/apathetic.However,considering it's potential in reducing cravings,reward for food,smoking and other drugs I think this is not quite the poor choice most have deemed it to be.However,time on the drug will certainly prove to be difficult and taxing.
To reinterate,there is a lot more potential to this drug than just weight loss.
I've found no evidence to suggest that there may be permanent changes in behavorial patterns,the here and now is the only manner in which this drug can be effective.The concern I have is the large spike in depression/anxiety it induces in most users(high 80%'s of US trial participants reported extreme depression and/or suicidal ideations,IIRC) and my expierience is that even a lower dose of the drug makes you depressed/apathetic.However,considering it's potential in reducing cravings,reward for food,smoking and other drugs I think this is not quite the poor choice most have deemed it to be.However,time on the drug will certainly prove to be difficult and taxing.
To reinterate,there is a lot more potential to this drug than just weight loss.
Uh, dude, it reduces all reward. This is NOT a desirable outcome.
Yes,I know.I didn't say it was desirable and if it proves to be that extreme,yes it would be horrible.
However,it may very well not ber as Hellish as it sounds and looking at the trade off of a rather short period of time,there's much to be gained.Of course,it could also be said with merit that there is much to be lost as well.
This is why I'm keeping a log on this.
However,it may very well not ber as Hellish as it sounds and looking at the trade off of a rather short period of time,there's much to be gained.Of course,it could also be said with merit that there is much to be lost as well.
This is why I'm keeping a log on this.
QUOTE(Colin @ Dec 22 2007, 01:23 AM) [snapback]444104[/snapback]
Yes,I know.I didn't say it was desirable and if it proves to be that extreme,yes it would be horrible.
However,it may very well not ber as Hellish as it sounds and looking at the trade off of a rather short period of time,there's much to be gained.Of course,it could also be said with merit that there is much to be lost as well.
This is why I'm keeping a log on this.
However,it may very well not ber as Hellish as it sounds and looking at the trade off of a rather short period of time,there's much to be gained.Of course,it could also be said with merit that there is much to be lost as well.
This is why I'm keeping a log on this.
Don't get caught in the game of despair because once you're in it's difficult to rationalize out.
QUOTE(Colin @ Dec 22 2007, 12:23 AM) [snapback]444104[/snapback]
Yes,I know.I didn't say it was desirable and if it proves to be that extreme,yes it would be horrible.
However,it may very well not ber as Hellish as it sounds and looking at the trade off of a rather short period of time,there's much to be gained.Of course,it could also be said with merit that there is much to be lost as well.
This is why I'm keeping a log on this.
However,it may very well not ber as Hellish as it sounds and looking at the trade off of a rather short period of time,there's much to be gained.Of course,it could also be said with merit that there is much to be lost as well.
This is why I'm keeping a log on this.
You're doing a great job. This will hopefully open the door for more people to log it.
QUOTE(Colin @ Dec 21 2007, 09:25 PM) [snapback]444077[/snapback]
Interest and drive is remarkably down as I have to force myself to engage in much of anything.A sense of feeling consistently tired,despite popping stism which usually give me a immediate sense of drive and/or manic energy.The stims(sulbutiamine,liberal amounts of caffiene and racetams) have some impact but not a Hell of a lot.
Apathy is the word of the day.
Apathy is the word of the day.
Seems like quite a trade-off between positive and negative effects. The CB1 receptor is a very novel site of action, but the overall role of the endocannabinoid system in motivation, drive, hunger, sleep, etc are far from being fully understood. I'm surprised that stimulants were of no avail WRT your experienced apathy/lethargy wile on Rimbonant, but the psychiatric side effects have been described as "severe" (in the following case very recenty).
QUOTE
Lancet. 2007 Nov 17;370(9600):1706-13.
Efficacy and safety of the weight-loss drug rimonabant: a meta-analysis of randomised trials.
Christensen R, Kristensen PK, Bartels EM, Bliddal H, Astrup A.
The Parker Institute, Musculoskeletal Statistics Unit, Frederiksberg Hospital, Frederiksberg, Denmark.
BACKGROUND: Since the prevalence of obesity continues to increase, there is a demand for effective and safe anti-obesity agents that can produce and maintain weight loss and improve comorbidity. We did a meta-analysis of all published randomised controlled trials to assess the efficacy and safety of the newly approved anti-obesity agent rimonabant. METHODS: We searched The Cochrane database and Controlled Trials Register, Medline via Pubmed, Embase via WebSpirs, Web of Science, Scopus, and reference lists up to July, 2007. We collected data from four double-blind, randomised controlled trials (including 4105 participants) that compared 20 mg per day rimonabant with placebo. FINDINGS: Patients given rimonabant had a 4.7 kg (95% CI 4.1-5.3 kg; p<0.0001) greater weight reduction after 1 year than did those given placebo. Rimonabant caused significantly more adverse events than did placebo (OR=1.4; p=0.0007; number needed to harm=25 individuals [95% CI 17-58]), and 1.4 times more serious adverse events (OR=1.4; p=0.03; number needed to harm=59 [27-830]). Patients given rimonabant were 2.5 times more likely to discontinue the treatment because of depressive mood disorders than were those given placebo (OR=2.5; p=0.01; number needed to harm=49 [19-316]). Furthermore, anxiety caused more patients to discontinue treatment in rimonabant groups than in placebo groups (OR=3.0; p=0.03; number needed to harm=166 [47-3716]). INTERPRETATION: Our findings suggest that 20 mg per day rimonabant increases the risk of psychiatric adverse events--ie, depressed mood disorders and anxiety-despite depressed mood being an exclusion criterion in these trials. Taken together with the recent US Food and Drug Administration finding of increased risk of suicide during treatment with rimonabant, we recommend increased alertness by physicians to these potentially severe psychiatric adverse reactions.
PMID: 18022033.
Efficacy and safety of the weight-loss drug rimonabant: a meta-analysis of randomised trials.
Christensen R, Kristensen PK, Bartels EM, Bliddal H, Astrup A.
The Parker Institute, Musculoskeletal Statistics Unit, Frederiksberg Hospital, Frederiksberg, Denmark.
BACKGROUND: Since the prevalence of obesity continues to increase, there is a demand for effective and safe anti-obesity agents that can produce and maintain weight loss and improve comorbidity. We did a meta-analysis of all published randomised controlled trials to assess the efficacy and safety of the newly approved anti-obesity agent rimonabant. METHODS: We searched The Cochrane database and Controlled Trials Register, Medline via Pubmed, Embase via WebSpirs, Web of Science, Scopus, and reference lists up to July, 2007. We collected data from four double-blind, randomised controlled trials (including 4105 participants) that compared 20 mg per day rimonabant with placebo. FINDINGS: Patients given rimonabant had a 4.7 kg (95% CI 4.1-5.3 kg; p<0.0001) greater weight reduction after 1 year than did those given placebo. Rimonabant caused significantly more adverse events than did placebo (OR=1.4; p=0.0007; number needed to harm=25 individuals [95% CI 17-58]), and 1.4 times more serious adverse events (OR=1.4; p=0.03; number needed to harm=59 [27-830]). Patients given rimonabant were 2.5 times more likely to discontinue the treatment because of depressive mood disorders than were those given placebo (OR=2.5; p=0.01; number needed to harm=49 [19-316]). Furthermore, anxiety caused more patients to discontinue treatment in rimonabant groups than in placebo groups (OR=3.0; p=0.03; number needed to harm=166 [47-3716]). INTERPRETATION: Our findings suggest that 20 mg per day rimonabant increases the risk of psychiatric adverse events--ie, depressed mood disorders and anxiety-despite depressed mood being an exclusion criterion in these trials. Taken together with the recent US Food and Drug Administration finding of increased risk of suicide during treatment with rimonabant, we recommend increased alertness by physicians to these potentially severe psychiatric adverse reactions.
PMID: 18022033.
It would be interesting to see if, in a clinical study, whether modafinil, another novel but "wake-promoting" drug, would in any way diminish the very undesirable side-effects. Not to mention the fact that (obviously) no long-term longitudinal data is available on rimonabant WRT actual suicide rates, and possible heightened incidence of mental health disorders lasting long after discontinuation of the drug. I salute your biochemical pioneer spirit, but I recommend you rethink your use of this drug, especially after reading the side effects you have experienced.
Damnit,right upon entering a rather extensive and well thought out post,I inadvertently deleted it.
I'll post my thoughts in a bit but for now I wanted to thank the three of you for the words and sentiments expressed.
I'll post my thoughts in a bit but for now I wanted to thank the three of you for the words and sentiments expressed.
QUOTE(Colin @ Dec 22 2007, 03:43 PM) [snapback]444166[/snapback]
Damnit,right upon entering a rather extensive and well thought out post,I inadvertently deleted it.
I'll post my thoughts in a bit but for now I wanted to thank the three of you for the words and sentiments expressed.
I'll post my thoughts in a bit but for now I wanted to thank the three of you for the words and sentiments expressed.
Gotta hate when that happens.
Still on 5mg rim + SEA,added in 5mg bromo several days ago.
Urge to smoke has been minimal and fleeting.I kind of want a cig right now but the instant motivation not to smoke via induced vomiting from the combination of bromo and nicotine is enough.
I seem to be acclimating to the aforementioned apathy and lethargy.I attribute a large part of these emotions,or lack thereof to a recently well shafted sleep structure.I should have noted this before but was too preoccupied with the bullshit ruminations from/about the rimbonant,I suppose.
I was recently laid off of work for the end of the season and I somehow ended up staying up til 6 in the morning whilst being absolutely as non-productive as possible during my waking hours,consequently sleeping the bulk of the day.I've also drastically cut back on my stimulant usage as I'm no longer working so heavy handed drug use isn't a requisite,this in itself is also a culplrit.I slept 2 hours or so last night in order to reconfigure my sleeping pattern,with any luck the package from UN will arrive shortly and I can bump the rimbonant up to 20mg ED.
Urge to smoke has been minimal and fleeting.I kind of want a cig right now but the instant motivation not to smoke via induced vomiting from the combination of bromo and nicotine is enough.
I seem to be acclimating to the aforementioned apathy and lethargy.I attribute a large part of these emotions,or lack thereof to a recently well shafted sleep structure.I should have noted this before but was too preoccupied with the bullshit ruminations from/about the rimbonant,I suppose.
I was recently laid off of work for the end of the season and I somehow ended up staying up til 6 in the morning whilst being absolutely as non-productive as possible during my waking hours,consequently sleeping the bulk of the day.I've also drastically cut back on my stimulant usage as I'm no longer working so heavy handed drug use isn't a requisite,this in itself is also a culplrit.I slept 2 hours or so last night in order to reconfigure my sleeping pattern,with any luck the package from UN will arrive shortly and I can bump the rimbonant up to 20mg ED.
Do you think it may be better to titrate up to 20mg, perhaps sitting on 10mg for a week in the event that the side effects ramp up significantly?
I had planned on increasing dosage by increments of 5mg per week and that probably is the wiser play to make but I'm too fucking impatient to get this in full swing.
And yes,I fully realize how loaded with irony that statement is.
OTOH,I think the high 80% of rimbonant trial participants who reported severe depression/anxiety simply did not expect it and therefore were consumed by it.If one is cogniscent of a drug's high likelihood of a side effect on mood e.g. outlook,by that same token,I think it can be dealt with.
I just can't imagine being helplessly compelled towards thinking about snuffing it,all such strong negativity (delusion,whatever else is applicable) stemming from popping a prescription drug in the morning.
And yes,I fully realize how loaded with irony that statement is.
OTOH,I think the high 80% of rimbonant trial participants who reported severe depression/anxiety simply did not expect it and therefore were consumed by it.If one is cogniscent of a drug's high likelihood of a side effect on mood e.g. outlook,by that same token,I think it can be dealt with.
I just can't imagine being helplessly compelled towards thinking about snuffing it,all such strong negativity (delusion,whatever else is applicable) stemming from popping a prescription drug in the morning.
QUOTE(Colin @ Dec 27 2007, 05:00 PM) [snapback]444862[/snapback]
I had planned on increasing dosage by increments of 5mg per week and that probably is the wiser play to make but I'm too fucking impatient to get this in full swing.
And yes,I fully realize how loaded with irony that statement is.
OTOH,I think the high 80% of rimbonant trial participants who reported severe depression/anxiety simply did not expect it and therefore were consumed by it.If one is cogniscent of a drug's high likelihood of a side effect on mood e.g. outlook,by that same token,I think it can be dealt with.
I just can't imagine being helplessly compelled towards thinking about snuffing it,all such strong negativity (delusion,whatever else is applicable) stemming from popping a prescription drug in the morning.
And yes,I fully realize how loaded with irony that statement is.
OTOH,I think the high 80% of rimbonant trial participants who reported severe depression/anxiety simply did not expect it and therefore were consumed by it.If one is cogniscent of a drug's high likelihood of a side effect on mood e.g. outlook,by that same token,I think it can be dealt with.
I just can't imagine being helplessly compelled towards thinking about snuffing it,all such strong negativity (delusion,whatever else is applicable) stemming from popping a prescription drug in the morning.
Perhaps weight loss without proper exercise and diet can contribute to depression and anxiety. Just a thought.
I agree with that to an extent but there is certainly more to thi,due consideration given to the heavy handed fact that such a high percentage of people who previously had shown little to no history of major depression nor anxiety exhibited such emotions on a seemingly profound level.
Some brief updates:
The lethargy/apathy has been mitigated successfully.I returned to training today after a 2 week lay off due to an injuredf wrist and hit all muscle groups via a two hour-esque work out.Towards the end of the w/o I did some deads and worked up to a conventional with 405 off the floor,then held it in full lockout for 30 seconds.I did a drop set of 15 with the bar in the rack(pinds at knees) and managed a static on the last rep,but fell shy of the 30 second mark by a few seconds.Also did some heavier ATG squatting and Oly lifts as well as chest and bi's and HS back rows + pulldowns.I'm mentioning the w/o #'s etc as I really hadn't fel;t the capacity/drive to lift at all (see aforementioned apathetic/lazy fuck sentiment) and after dosing Scorch before going to the gym and feeling the kick from the caffiene,I decided to drive back home a minute after entering the parking lot.Popped a Venom after getting home and weny back,still feeling some residual CNS over stimulation now,an hours post w/o.
Strange as it seems,this drug may actually be confering an unexpected nootropic-esque effect as it seems to just about completely crush over rumination and therefore,irrational thought patterns are truly seen for what they are.
Memeticists's feedback on this very thing is as close to dead on as possible,given it is another person at hand,I belive he stated that the world on this drug becomes flat and grey,and if I am able to articulate this thought to others successfully,this is a good thing as one clearly sees their own shortcomings.This,I believe,is where the application for drug abuse lies,with this drug.
A distinctly unpleasant side effect I've been having since the addition of 5mg bromo is nasua,such as feeling the need to vomit leaading to dry heaves,deep belching or small amounts of food.This happened twice today while lifting,both times i had to hit the bathroom in order to dry heave several times and then vomit the capped supplements(cissus+fucoxathin,sam-e) I ingested shortly before training.However,I've been having the dry heaves occasionally for the past 6 weeks or so and did vomit a few weeks back but that was likely due to too much caffiene + nicotine in a short span of time.
I haven't been smoking since on bromo,at least not for 10-12 hours after dosing it.I have smoked 3 or 4 cigs over the past few days,late at night well after the half life of bromo is gone.IOW,the unavoidable sickly/violent vomiting induced by the combination of nicotine+bromo (I exp'd this previously while smoking on bromo and Loki posted he did also,I forget the pathway etc it happens through though) is not an issue,as far as I can see.
As of tomorrow I'll drop the bromo,feeling like throwing up is not condusive to good times.
I've got an arsenal of other drugs(which I would use one of only) to take its place as a anti-nicotine tool-deprenyl,bupropion and nicotine patches.I'm leaing towards trying deprenyl with a decent amount of choline,apparently this may avoid the need for dep-naps,accoridng to some anecdotal feedback I read.
Some brief updates:
The lethargy/apathy has been mitigated successfully.I returned to training today after a 2 week lay off due to an injuredf wrist and hit all muscle groups via a two hour-esque work out.Towards the end of the w/o I did some deads and worked up to a conventional with 405 off the floor,then held it in full lockout for 30 seconds.I did a drop set of 15 with the bar in the rack(pinds at knees) and managed a static on the last rep,but fell shy of the 30 second mark by a few seconds.Also did some heavier ATG squatting and Oly lifts as well as chest and bi's and HS back rows + pulldowns.I'm mentioning the w/o #'s etc as I really hadn't fel;t the capacity/drive to lift at all (see aforementioned apathetic/lazy fuck sentiment) and after dosing Scorch before going to the gym and feeling the kick from the caffiene,I decided to drive back home a minute after entering the parking lot.Popped a Venom after getting home and weny back,still feeling some residual CNS over stimulation now,an hours post w/o.
Strange as it seems,this drug may actually be confering an unexpected nootropic-esque effect as it seems to just about completely crush over rumination and therefore,irrational thought patterns are truly seen for what they are.
Memeticists's feedback on this very thing is as close to dead on as possible,given it is another person at hand,I belive he stated that the world on this drug becomes flat and grey,and if I am able to articulate this thought to others successfully,this is a good thing as one clearly sees their own shortcomings.This,I believe,is where the application for drug abuse lies,with this drug.
A distinctly unpleasant side effect I've been having since the addition of 5mg bromo is nasua,such as feeling the need to vomit leaading to dry heaves,deep belching or small amounts of food.This happened twice today while lifting,both times i had to hit the bathroom in order to dry heave several times and then vomit the capped supplements(cissus+fucoxathin,sam-e) I ingested shortly before training.However,I've been having the dry heaves occasionally for the past 6 weeks or so and did vomit a few weeks back but that was likely due to too much caffiene + nicotine in a short span of time.
I haven't been smoking since on bromo,at least not for 10-12 hours after dosing it.I have smoked 3 or 4 cigs over the past few days,late at night well after the half life of bromo is gone.IOW,the unavoidable sickly/violent vomiting induced by the combination of nicotine+bromo (I exp'd this previously while smoking on bromo and Loki posted he did also,I forget the pathway etc it happens through though) is not an issue,as far as I can see.
As of tomorrow I'll drop the bromo,feeling like throwing up is not condusive to good times.
I've got an arsenal of other drugs(which I would use one of only) to take its place as a anti-nicotine tool-deprenyl,bupropion and nicotine patches.I'm leaing towards trying deprenyl with a decent amount of choline,apparently this may avoid the need for dep-naps,accoridng to some anecdotal feedback I read.
QUOTE(Colin @ Dec 28 2007, 07:08 PM) [snapback]445034[/snapback]
I agree with that to an extent but there is certainly more to thi,due consideration given to the heavy handed fact that such a high percentage of people who previously had shown little to no history of major depression nor anxiety exhibited such emotions on a seemingly profound level.
Some brief updates:
The lethargy/apathy has been mitigated successfully.I returned to training today after a 2 week lay off due to an injuredf wrist and hit all muscle groups via a two hour-esque work out.Towards the end of the w/o I did some deads and worked up to a conventional with 405 off the floor,then held it in full lockout for 30 seconds.I did a drop set of 15 with the bar in the rack(pinds at knees) and managed a static on the last rep,but fell shy of the 30 second mark by a few seconds.Also did some heavier ATG squatting and Oly lifts as well as chest and bi's and HS back rows + pulldowns.I'm mentioning the w/o #'s etc as I really hadn't fel;t the capacity/drive to lift at all (see aforementioned apathetic/lazy fuck sentiment) and after dosing Scorch before going to the gym and feeling the kick from the caffiene,I decided to drive back home a minute after entering the parking lot.Popped a Venom after getting home and weny back,still feeling some residual CNS over stimulation now,an hours post w/o.
Strange as it seems,this drug may actually be confering an unexpected nootropic-esque effect as it seems to just about completely crush over rumination and therefore,irrational thought patterns are truly seen for what they are.
Memeticists's feedback on this very thing is as close to dead on as possible,given it is another person at hand,I belive he stated that the world on this drug becomes flat and grey,and if I am able to articulate this thought to others successfully,this is a good thing as one clearly sees their own shortcomings.This,I believe,is where the application for drug abuse lies,with this drug.
A distinctly unpleasant side effect I've been having since the addition of 5mg bromo is nasua,such as feeling the need to vomit leaading to dry heaves,deep belching or small amounts of food.This happened twice today while lifting,both times i had to hit the bathroom in order to dry heave several times and then vomit the capped supplements(cissus+fucoxathin,sam-e) I ingested shortly before training.However,I've been having the dry heaves occasionally for the past 6 weeks or so and did vomit a few weeks back but that was likely due to too much caffiene + nicotine in a short span of time.
I haven't been smoking since on bromo,at least not for 10-12 hours after dosing it.I have smoked 3 or 4 cigs over the past few days,late at night well after the half life of bromo is gone.IOW,the unavoidable sickly/violent vomiting induced by the combination of nicotine+bromo (I exp'd this previously while smoking on bromo and Loki posted he did also,I forget the pathway etc it happens through though) is not an issue,as far as I can see.
As of tomorrow I'll drop the bromo,feeling like throwing up is not condusive to good times.
I've got an arsenal of other drugs(which I would use one of only) to take its place as a anti-nicotine tool-deprenyl,bupropion and nicotine patches.I'm leaing towards trying deprenyl with a decent amount of choline,apparently this may avoid the need for dep-naps,accoridng to some anecdotal feedback I read.
Some brief updates:
The lethargy/apathy has been mitigated successfully.I returned to training today after a 2 week lay off due to an injuredf wrist and hit all muscle groups via a two hour-esque work out.Towards the end of the w/o I did some deads and worked up to a conventional with 405 off the floor,then held it in full lockout for 30 seconds.I did a drop set of 15 with the bar in the rack(pinds at knees) and managed a static on the last rep,but fell shy of the 30 second mark by a few seconds.Also did some heavier ATG squatting and Oly lifts as well as chest and bi's and HS back rows + pulldowns.I'm mentioning the w/o #'s etc as I really hadn't fel;t the capacity/drive to lift at all (see aforementioned apathetic/lazy fuck sentiment) and after dosing Scorch before going to the gym and feeling the kick from the caffiene,I decided to drive back home a minute after entering the parking lot.Popped a Venom after getting home and weny back,still feeling some residual CNS over stimulation now,an hours post w/o.
Strange as it seems,this drug may actually be confering an unexpected nootropic-esque effect as it seems to just about completely crush over rumination and therefore,irrational thought patterns are truly seen for what they are.
Memeticists's feedback on this very thing is as close to dead on as possible,given it is another person at hand,I belive he stated that the world on this drug becomes flat and grey,and if I am able to articulate this thought to others successfully,this is a good thing as one clearly sees their own shortcomings.This,I believe,is where the application for drug abuse lies,with this drug.
A distinctly unpleasant side effect I've been having since the addition of 5mg bromo is nasua,such as feeling the need to vomit leaading to dry heaves,deep belching or small amounts of food.This happened twice today while lifting,both times i had to hit the bathroom in order to dry heave several times and then vomit the capped supplements(cissus+fucoxathin,sam-e) I ingested shortly before training.However,I've been having the dry heaves occasionally for the past 6 weeks or so and did vomit a few weeks back but that was likely due to too much caffiene + nicotine in a short span of time.
I haven't been smoking since on bromo,at least not for 10-12 hours after dosing it.I have smoked 3 or 4 cigs over the past few days,late at night well after the half life of bromo is gone.IOW,the unavoidable sickly/violent vomiting induced by the combination of nicotine+bromo (I exp'd this previously while smoking on bromo and Loki posted he did also,I forget the pathway etc it happens through though) is not an issue,as far as I can see.
As of tomorrow I'll drop the bromo,feeling like throwing up is not condusive to good times.
I've got an arsenal of other drugs(which I would use one of only) to take its place as a anti-nicotine tool-deprenyl,bupropion and nicotine patches.I'm leaing towards trying deprenyl with a decent amount of choline,apparently this may avoid the need for dep-naps,accoridng to some anecdotal feedback I read.
Bromo made me sick as hell I'll never take it again.
Rimonabant is suppose to have some memory enhancing effects.
QUOTE
Behav Pharmacol. 2007 Sep;18(5-6):571-80. Links
Short-term memory is modulated by the spontaneous release of endocannabinoids: evidence from hippocampal population codes.Deadwyler SA, Goonawardena AV, Hampson RE.
Department of Physiology and Pharmacology, Wake Forest University Health Sciences, Winston-Salem, North Carolina 27157-1083, USA. sdeadwy@wfubmc.edu
Population codes derived from ensembles of hippocampal neurons were assessed to determine whether endocannabinoids were active when rats performed a delayed-nonmatch-to-sample (DNMS) short-term memory task. Multivariate discriminant analyses of the firing patterns of ensembles of CA1 and CA3 hippocampal neurons extracted representations of information encoded at the time of the sample response (SmR codes) during individual DNMS trials. The 'strength' or distinctiveness of trial-specific SmR codes in normal sessions was compared with sessions in which either rimonabant, the well-characterized cannabinoid CB1 receptor antagonist, or WIN 55212-2 (WIN-2), a cannabinoid CB1 receptor agonist, were administered. Results show that performance on trials with delay intervals longer than 10 s was facilitated by rimonabant (2.0 mg/kg) owing to a significantly increased frequency of trials with stronger SmR codes. In contrast, WIN-2 (0.35 mg/kg) suppressed the strength of SmR codes necessary to perform trials with delays greater than 10 s. The positive influence of rimonabant on performance indicated that the action of endocannabinoids was to reduce SmR code strength, resulting in trials that were at risk for errors if the delay exceeded 10 s. Thus endocannabinoids, like exogenously administered cannabinoids, reduced hippocampal encoding necessary to perform long-delay trials. The findings therefore indicate a direct relationship between the actions of endocannabinoids on hippocampal processes and the ability to encode information into short-term memory.
Short-term memory is modulated by the spontaneous release of endocannabinoids: evidence from hippocampal population codes.Deadwyler SA, Goonawardena AV, Hampson RE.
Department of Physiology and Pharmacology, Wake Forest University Health Sciences, Winston-Salem, North Carolina 27157-1083, USA. sdeadwy@wfubmc.edu
Population codes derived from ensembles of hippocampal neurons were assessed to determine whether endocannabinoids were active when rats performed a delayed-nonmatch-to-sample (DNMS) short-term memory task. Multivariate discriminant analyses of the firing patterns of ensembles of CA1 and CA3 hippocampal neurons extracted representations of information encoded at the time of the sample response (SmR codes) during individual DNMS trials. The 'strength' or distinctiveness of trial-specific SmR codes in normal sessions was compared with sessions in which either rimonabant, the well-characterized cannabinoid CB1 receptor antagonist, or WIN 55212-2 (WIN-2), a cannabinoid CB1 receptor agonist, were administered. Results show that performance on trials with delay intervals longer than 10 s was facilitated by rimonabant (2.0 mg/kg) owing to a significantly increased frequency of trials with stronger SmR codes. In contrast, WIN-2 (0.35 mg/kg) suppressed the strength of SmR codes necessary to perform trials with delays greater than 10 s. The positive influence of rimonabant on performance indicated that the action of endocannabinoids was to reduce SmR code strength, resulting in trials that were at risk for errors if the delay exceeded 10 s. Thus endocannabinoids, like exogenously administered cannabinoids, reduced hippocampal encoding necessary to perform long-delay trials. The findings therefore indicate a direct relationship between the actions of endocannabinoids on hippocampal processes and the ability to encode information into short-term memory.
Sweet find,thanks Steve.
This brings up conflicting information WRT hypothetically potential long term adverse psychological effects e.g.the depression/anxiety expirienced by trial participants.
WRT bromo sickness,I have actually taken bromo before for several months on end,with no such sides.With no bromo today I still had a mini-sessionof almost vomiting earlier several minutes ago,I think the bromo compounded whatever unknown shit I have going on already as all this began before well before rimbonant was introduced.As of roughly 6 weeks ago I have occasionally felt like vomiting (general stomach discomfort with a persistent gag reflex) and have vomited small amounts on several occasions.I do have a doctor's appointment scheduled for the 7th of January which will establish WTF actually is wrong with me,in turn this log will have more weight as variables WRT speculation on my part will be eliminated.
The doctor has been a family freind for decades and is well respected in his field(cardio) so he'll have no problems giving me a thorough work up,as far as heart,liver and even stomach and joint problems are concerned.
This brings up conflicting information WRT hypothetically potential long term adverse psychological effects e.g.the depression/anxiety expirienced by trial participants.
WRT bromo sickness,I have actually taken bromo before for several months on end,with no such sides.With no bromo today I still had a mini-sessionof almost vomiting earlier several minutes ago,I think the bromo compounded whatever unknown shit I have going on already as all this began before well before rimbonant was introduced.As of roughly 6 weeks ago I have occasionally felt like vomiting (general stomach discomfort with a persistent gag reflex) and have vomited small amounts on several occasions.I do have a doctor's appointment scheduled for the 7th of January which will establish WTF actually is wrong with me,in turn this log will have more weight as variables WRT speculation on my part will be eliminated.
The doctor has been a family freind for decades and is well respected in his field(cardio) so he'll have no problems giving me a thorough work up,as far as heart,liver and even stomach and joint problems are concerned.
Brief update:
I rec'd the rimbonant stash from UN today,so I've got 42 days worth of this drug at 20mg,41 as of today as I bumped up to 20mg this afternoon.
Misc. thoughts:
I'll be experimenting tonight with PEA,deprenyl and DLPA,hoping to get some MDMA lke effect.Board feedback,from several posters,confirms this to be what's up with that 'lil trifecta of chemical goodness.
I have a limited amount of dep on hand (7 10 mg tabs from a blister sheet I bought from masters or UN a couple years back,assuming they're still potent as no exp date is given on the sheet)and hadn't decided on using it in along with rim intil I realized how shitty bromo+ rim actually makes me feel.I could place an order now for dep but am looking at a two week wait,which obviously sucks or start on generic wellbutrinXL.This drug,OTOH,I have a script for so i can pick it up on the cheap-cheap immediately and will do so monyanna.
I'll probably use it for the duration of the rim run,starting at 300mg in the morning.....close enough for a Kubrick's Shining reference,anyone?
I've always wanted to try dep but the whole nap thing seems totallly fucked as takeing a siesta isn't possible for most.
I stumbled upon a post by AvantGarde in which he stated that he had tried dep and had to deal with napping but after adding DMAE (or some source of choline,can't recall ATM) into the mix he no longer needed a dep-nap.No other alterations took place e.g.no variables to account for.
Course that is only n=1 but it's DAMN GOOD EFF'ING NEWS to me.I'm going to try to find a study (been preoccupied with other things and am not going to use dep for a while anyway) that supports choline eliminating this whole dep-nap bullshit and if I find one,it'll be posted over in Neuroscience.Hell of motherfucking yes.
I have spoken with Dopamine via PM and I would like to take a second to thank him for his advice on dep+wellbutrin with rim.Well,I'd like to thank and honor him for a lot more as wellas I appreciate his pro-consumer,unwavering Ralph Nader-esque approach to the world of nootropics and I strongly believe it is guys like him who contribute to this board(ATB,Frangible,Section8,Ras,Nightop and several others) who do a lot to keep up what Mind & Muscle has always represented.
That being,a place relegated to the advancement of the mind and body via well reasoned discourse on not only the integral,basic concepts of weight and aerobic training (sans typical bro-bot misinformation seen in the inane bodybuilding world) and supplementation but advanced theory of all that is truly relevant in bettering oneself.This would be the threads deeply delving into philosophy at its core.Sadly,much of this has all but vanished or is present only fleetingly.
Well,this was relatively off topic and I should have dedicated a thread to this but I'll let it stand as is for now.
I rec'd the rimbonant stash from UN today,so I've got 42 days worth of this drug at 20mg,41 as of today as I bumped up to 20mg this afternoon.
Misc. thoughts:
I'll be experimenting tonight with PEA,deprenyl and DLPA,hoping to get some MDMA lke effect.Board feedback,from several posters,confirms this to be what's up with that 'lil trifecta of chemical goodness.
I have a limited amount of dep on hand (7 10 mg tabs from a blister sheet I bought from masters or UN a couple years back,assuming they're still potent as no exp date is given on the sheet)and hadn't decided on using it in along with rim intil I realized how shitty bromo+ rim actually makes me feel.I could place an order now for dep but am looking at a two week wait,which obviously sucks or start on generic wellbutrinXL.This drug,OTOH,I have a script for so i can pick it up on the cheap-cheap immediately and will do so monyanna.
I'll probably use it for the duration of the rim run,starting at 300mg in the morning.....close enough for a Kubrick's Shining reference,anyone?
I've always wanted to try dep but the whole nap thing seems totallly fucked as takeing a siesta isn't possible for most.
I stumbled upon a post by AvantGarde in which he stated that he had tried dep and had to deal with napping but after adding DMAE (or some source of choline,can't recall ATM) into the mix he no longer needed a dep-nap.No other alterations took place e.g.no variables to account for.
Course that is only n=1 but it's DAMN GOOD EFF'ING NEWS to me.I'm going to try to find a study (been preoccupied with other things and am not going to use dep for a while anyway) that supports choline eliminating this whole dep-nap bullshit and if I find one,it'll be posted over in Neuroscience.Hell of motherfucking yes.
I have spoken with Dopamine via PM and I would like to take a second to thank him for his advice on dep+wellbutrin with rim.Well,I'd like to thank and honor him for a lot more as wellas I appreciate his pro-consumer,unwavering Ralph Nader-esque approach to the world of nootropics and I strongly believe it is guys like him who contribute to this board(ATB,Frangible,Section8,Ras,Nightop and several others) who do a lot to keep up what Mind & Muscle has always represented.
That being,a place relegated to the advancement of the mind and body via well reasoned discourse on not only the integral,basic concepts of weight and aerobic training (sans typical bro-bot misinformation seen in the inane bodybuilding world) and supplementation but advanced theory of all that is truly relevant in bettering oneself.This would be the threads deeply delving into philosophy at its core.Sadly,much of this has all but vanished or is present only fleetingly.
Well,this was relatively off topic and I should have dedicated a thread to this but I'll let it stand as is for now.
can you expand on the crushing of the ruminations?
I'd be interested in trying this stuff just to see if it reset my own ec system. That rumination you say was crushed sounds like the kind of rumination I beleive I've gotten through years of pot smoking.
I'd be interested in trying this stuff just to see if it reset my own ec system. That rumination you say was crushed sounds like the kind of rumination I beleive I've gotten through years of pot smoking.
Brian,I'll try to describe this transition.I do hope my references and so on are not so cloudy nor obscure to render the sentiments expressed incomprehensible.I also hope that others reading this find this helpful as that is largely the reason i am detailing my time here.
The drug has flattened my hypervigilance,a trait of seemingly unexplicable anxiety which I had developed around my later teen years to early twentys.The root of which lies in largely distancing myself from both friends and family to the point of dissocosiative behavior*A couple years ago I actually had a girl friend,who while breaking up with me,labeled me as such and suggested I get myself checked out for this,that anecdote should show the severity as to how thoroughly fucked up my head was.This has been worsened through liberal intake of CNS stimulants for the past ten years or thereabouts.The stimulant use was prompted by a self-disgust I had developed during that time period,of what is probably best described as a prolonged nervous breakdown,in which I felt driven to run eight or more miles per day in order to get lean.Shortly after this,I began using various sedatives to deal with the insomnia that began from all of this,which only required the need for more stimulants to mitigate the residual feelings of sedation,hence drastically subpar functioning the next morning.
In essense,the world shifts into a state of grey in which there are no overwhelming distractions to blind you.Thereby making one rush towards over thinking or obsessing over the most minute of details a thing of the past.
For the first week or so on the lower dose of 5mg (which was likely potentiated to some degree by the SEA/other CB1 agonist I was using) this change manifested itself ascomplete apathy,as far as I would think of things that formerly would drive me asridiculous and wasteful.Such as the overwhelming compulsion to physically push myself to the point of utter fatigue every single work out or work day,which led me to do nearly nothing but lie around for upwards of a week inwhat could be called a state of disbelief or shock.
I firmly belive that this drug has these positive mental benefits on those who have some sort of pre-existing psychological issues or set of them.The flattening and greyness of the world that I spoke of above is what I think induced feelings of sevre depression and unmitigated anxiety in upwards of 90% of the US trial participants,as they previously had their world in a set of color and were unable to grasp onto such a fundamental change due to their apparently,and this is as relative and ironic term as can possibily exist,normal state of mind with no histry of depression nor anxiety.
I still feel a deep sadness but this is not due to any fault of mine as this world and society we live in is inherently screwed up to what seems to be beyond reproach.This emotion is not all consuming of my day (refer to the basis of Buddism that life is disapointing) and I see that life can be exquisitely beautiful but,oh so fragile this beauty is.
I now view reality as living the remainder of my life,in lieu of wasting my time as I have been aware of doing in one manner or extent to another every single day for years on end.
*A couple years ago I had a girl friend,who while breaking up with me,labeled me as such and suggested I get myself checked out for this.That anecdote should show the severity as to how thoroughly fucked up my head was.Even my mother,as recently as a year or so ago,said to me I had a dissacociative personality.Of course this was all self evident but suffice to say,when you're borderline suicidal and all around mentally unstable,unless one has the will to power so to speak,you are fucked.
The drug has flattened my hypervigilance,a trait of seemingly unexplicable anxiety which I had developed around my later teen years to early twentys.The root of which lies in largely distancing myself from both friends and family to the point of dissocosiative behavior*A couple years ago I actually had a girl friend,who while breaking up with me,labeled me as such and suggested I get myself checked out for this,that anecdote should show the severity as to how thoroughly fucked up my head was.This has been worsened through liberal intake of CNS stimulants for the past ten years or thereabouts.The stimulant use was prompted by a self-disgust I had developed during that time period,of what is probably best described as a prolonged nervous breakdown,in which I felt driven to run eight or more miles per day in order to get lean.Shortly after this,I began using various sedatives to deal with the insomnia that began from all of this,which only required the need for more stimulants to mitigate the residual feelings of sedation,hence drastically subpar functioning the next morning.
In essense,the world shifts into a state of grey in which there are no overwhelming distractions to blind you.Thereby making one rush towards over thinking or obsessing over the most minute of details a thing of the past.
For the first week or so on the lower dose of 5mg (which was likely potentiated to some degree by the SEA/other CB1 agonist I was using) this change manifested itself ascomplete apathy,as far as I would think of things that formerly would drive me asridiculous and wasteful.Such as the overwhelming compulsion to physically push myself to the point of utter fatigue every single work out or work day,which led me to do nearly nothing but lie around for upwards of a week inwhat could be called a state of disbelief or shock.
I firmly belive that this drug has these positive mental benefits on those who have some sort of pre-existing psychological issues or set of them.The flattening and greyness of the world that I spoke of above is what I think induced feelings of sevre depression and unmitigated anxiety in upwards of 90% of the US trial participants,as they previously had their world in a set of color and were unable to grasp onto such a fundamental change due to their apparently,and this is as relative and ironic term as can possibily exist,normal state of mind with no histry of depression nor anxiety.
I still feel a deep sadness but this is not due to any fault of mine as this world and society we live in is inherently screwed up to what seems to be beyond reproach.This emotion is not all consuming of my day (refer to the basis of Buddism that life is disapointing) and I see that life can be exquisitely beautiful but,oh so fragile this beauty is.
I now view reality as living the remainder of my life,in lieu of wasting my time as I have been aware of doing in one manner or extent to another every single day for years on end.
*A couple years ago I had a girl friend,who while breaking up with me,labeled me as such and suggested I get myself checked out for this.That anecdote should show the severity as to how thoroughly fucked up my head was.Even my mother,as recently as a year or so ago,said to me I had a dissacociative personality.Of course this was all self evident but suffice to say,when you're borderline suicidal and all around mentally unstable,unless one has the will to power so to speak,you are fucked.
QUOTE(Colin @ Jan 1 2008, 12:32 PM) [snapback]445484[/snapback]
Brian,I'll try to describe this transition.I do hope my references and so on are not so cloudy nor obscure to render the sentiments expressed incomprehensible.I also hope that others reading this find this helpful as that is largely the reason i am detailing my time here.
The drug has flattened my hypervigilance,a trait of seemingly unexplicable anxiety which I had developed around my later teen years to early twentys.The root of which lies in largely distancing myself from both friends and family to the point of dissocosiative behavior*A couple years ago I actually had a girl friend,who while breaking up with me,labeled me as such and suggested I get myself checked out for this,that anecdote should show the severity as to how thoroughly fucked up my head was.This has been worsened through liberal intake of CNS stimulants for the past ten years or thereabouts.The stimulant use was prompted by a self-disgust I had developed during that time period,of what is probably best described as a prolonged nervous breakdown,in which I felt driven to run eight or more miles per day in order to get lean.Shortly after this,I began using various sedatives to deal with the insomnia that began from all of this,which only required the need for more stimulants to mitigate the residual feelings of sedation,hence drastically subpar functioning the next morning.
In essense,the world shifts into a state of grey in which there are no overwhelming distractions to blind you.Thereby making one rush towards over thinking or obsessing over the most minute of details a thing of the past.
For the first week or so on the lower dose of 5mg (which was likely potentiated to some degree by the SEA/other CB1 agonist I was using) this change manifested itself ascomplete apathy,as far as I would think of things that formerly would drive me asridiculous and wasteful.Such as the overwhelming compulsion to physically push myself to the point of utter fatigue every single work out or work day,which led me to do nearly nothing but lie around for upwards of a week inwhat could be called a state of disbelief or shock.
I firmly belive that this drug has these positive mental benefits on those who have some sort of pre-existing psychological issues or set of them.The flattening and greyness of the world that I spoke of above is what I think induced feelings of sevre depression and unmitigated anxiety in upwards of 90% of the US trial participants,as they previously had their world in a set of color and were unable to grasp onto such a fundamental change due to their apparently,and this is as relative and ironic term as can possibily exist,normal state of mind with no histry of depression nor anxiety.
I still feel a deep sadness but this is not due to any fault of mine as this world and society we live in is inherently screwed up to what seems to be beyond reproach.This emotion is not all consuming of my day (refer to the basis of Buddism that life is disapointing) and I see that life can be exquisitely beautiful but,oh so fragile this beauty is.
I now view reality as living the remainder of my life,in lieu of wasting my time as I have been aware of doing in one manner or extent to another every single day for years on end.
*A couple years ago I had a girl friend,who while breaking up with me,labeled me as such and suggested I get myself checked out for this.That anecdote should show the severity as to how thoroughly fucked up my head was.Even my mother,as recently as a year or so ago,said to me I had a dissacociative personality.Of course this was all self evident but suffice to say,when you're borderline suicidal and all around mentally unstable,unless one has the will to power so to speak,you are fucked.
The drug has flattened my hypervigilance,a trait of seemingly unexplicable anxiety which I had developed around my later teen years to early twentys.The root of which lies in largely distancing myself from both friends and family to the point of dissocosiative behavior*A couple years ago I actually had a girl friend,who while breaking up with me,labeled me as such and suggested I get myself checked out for this,that anecdote should show the severity as to how thoroughly fucked up my head was.This has been worsened through liberal intake of CNS stimulants for the past ten years or thereabouts.The stimulant use was prompted by a self-disgust I had developed during that time period,of what is probably best described as a prolonged nervous breakdown,in which I felt driven to run eight or more miles per day in order to get lean.Shortly after this,I began using various sedatives to deal with the insomnia that began from all of this,which only required the need for more stimulants to mitigate the residual feelings of sedation,hence drastically subpar functioning the next morning.
In essense,the world shifts into a state of grey in which there are no overwhelming distractions to blind you.Thereby making one rush towards over thinking or obsessing over the most minute of details a thing of the past.
For the first week or so on the lower dose of 5mg (which was likely potentiated to some degree by the SEA/other CB1 agonist I was using) this change manifested itself ascomplete apathy,as far as I would think of things that formerly would drive me asridiculous and wasteful.Such as the overwhelming compulsion to physically push myself to the point of utter fatigue every single work out or work day,which led me to do nearly nothing but lie around for upwards of a week inwhat could be called a state of disbelief or shock.
I firmly belive that this drug has these positive mental benefits on those who have some sort of pre-existing psychological issues or set of them.The flattening and greyness of the world that I spoke of above is what I think induced feelings of sevre depression and unmitigated anxiety in upwards of 90% of the US trial participants,as they previously had their world in a set of color and were unable to grasp onto such a fundamental change due to their apparently,and this is as relative and ironic term as can possibily exist,normal state of mind with no histry of depression nor anxiety.
I still feel a deep sadness but this is not due to any fault of mine as this world and society we live in is inherently screwed up to what seems to be beyond reproach.This emotion is not all consuming of my day (refer to the basis of Buddism that life is disapointing) and I see that life can be exquisitely beautiful but,oh so fragile this beauty is.
I now view reality as living the remainder of my life,in lieu of wasting my time as I have been aware of doing in one manner or extent to another every single day for years on end.
*A couple years ago I had a girl friend,who while breaking up with me,labeled me as such and suggested I get myself checked out for this.That anecdote should show the severity as to how thoroughly fucked up my head was.Even my mother,as recently as a year or so ago,said to me I had a dissacociative personality.Of course this was all self evident but suffice to say,when you're borderline suicidal and all around mentally unstable,unless one has the will to power so to speak,you are fucked.
Very interesting retrospective. The first hypothesis that came to mind when reading your experience was the relationship between dissociative emotional states and CB1 agonism (i.e. in the case of tetrohydrocannibinol). It could be the case that excess CB1 receptor stimulation results in particular emotional states associated with a kind of psychological "detachment." A covariance of factors are involved in the development of personality (an aggregation of emotional experience) cross the sectional elements of neurotransmission, but the involvement of endocannabinoids in emotion is far from understood.
so the greyness is rather depressing but the rumination has ceased?
QUOTE(eclypz @ Jan 2 2008, 08:39 AM) [snapback]445596[/snapback]
so the greyness is rather depressing but the rumination has ceased?
The greyness isn't all that depressing and in fact I'd say that I'm no more depressed than usually am due to the winter season e.g. a minor bit of SAD.
The greyness is correlated with the ending of the pointless,self defeating rumination.
QUOTE(Dopamine @ Jan 1 2008, 03:53 PM) [snapback]445538[/snapback]
Very interesting retrospective. The first hypothesis that came to mind when reading your experience was the relationship between dissociative emotional states and CB1 agonism (i.e. in the case of tetrohydrocannibinol). It could be the case that excess CB1 receptor stimulation results in particular emotional states associated with a kind of psychological "detachment." A covariance of factors are involved in the development of personality (an aggregation of emotional experience) cross the sectional elements of neurotransmission, but the involvement of endocannabinoids in emotion is far from understood.
I've nothing of all that much signifigance,that can be substantiated either way,to add other than this drug seems to be having a paradoxical effect on my mood.The first week on 5mg with 1600mg SEA twice daily pretty much sucked,as previously detailed.Gradually mood has improved but specifically this is attributed in my eyes as a sense of overall awareness previously absent.I'd lie to be able to articulate my thoughts better regarding this but it's difficult to express what feels like the onset of a profound change.This may very well be bollocks on my part though and excessive self absorption can lead to being Oprah-fied.Two bits are due to Nightop for stealing the Oprah reference.
OTOH,the two studies below I found while trolling an old SEA thread do not paint a flattering picture of CB1 agonism.As I see it it's difficult to extrapolate much of anything concrete with all the studies on endo-cannabanoids as the role that they play in the mind hasn't been established.There are studies showing detrimental benefit opposed to the study Steve posted which showed improvement in short term memory.This improvement in memory does not correlate with brain cell death,the conflicting information makes it all even harder to wrap your hands around this.
Title: The '''Dark Side''' of Endocannabinoids: A Neurotoxic Role for Anandamide.
Authors: Ibolja Cernak1
Source: Journal of Cerebral Blood Flow & Metabolism; May2004, Vol. 24 Issue 5, p564-578, 15p
Document Type: Article
Subject Terms: *BRAIN -- Diseases
*CELL death
*CELLS
*DEATH (Biology)
*DIAGNOSTIC imaging
*GENES
*MAGNETIC resonance imaging
*PACKED towers
NAICS/Industry Codes: 621512 Diagnostic Imaging Centers
Abstract: Endocannabinoids, including 2-arachidonoylglycerol and anandamide (N-arachidonoylethanolamine; AEA), have neuroprotective effects in the brain through actions at CB1 receptors. However, AEA also binds to vanilloid (VR1) receptors and induces cell death in several cell lines. Here we show that anandamide causes neuronal cell death in vitro and exacerbates cell loss caused by stretch-induced axonal injury or trophic withdrawal in rat primary neuronal cultures. Administered intracerebroventricularly, AEA causes sustained cerebral edema, as reflected by diffusion-weighted magnetic resonance imaging, regional cell loss, and impairment in long-term cognitive function. These effects are mediated, in part, through VR1 as well as through calpain-dependent mechanisms, but not through CB1 receptors or caspases. Central administration of AEA also significantly upregulates genes involved in pro-inflammatory/microglial-related responses. Thus, anandamide produces neurotoxic effects both in vitro and in vivo through multiple mechanisms independent of the CB1 receptor. [ABSTRACT FROM AUTHOR]
Author Affiliations: 1*Department of Neuroscience, Georgetown University Medical Center, Washington D.C., U.S.A.; and '''Department of Pathology, University of Adelaide, Australia
ISSN: 0271-678X
Accession Number: 13057283
Persistent link to this record: http://search.epnet.com/login.aspx?direct=...amp;an=13057283
Database: Academic Search Premier
And....
http://www.mindandmuscle.net/forum/index.p...ost&id=3703
Great detail, I'm following along.
QUOTE(asianbabe @ Jan 5 2008, 04:53 PM) [snapback]446304[/snapback]
Great detail, I'm following along.
Your the star Colin.
QUOTE(SteveSliwa @ Jan 5 2008, 02:56 PM) [snapback]446307[/snapback]
Your the star Colin.
That is just super-terrific,I really am a special person.
How about sending me a slew of complimentary nootropics along with a sheet of sticky,little shiny yellow stars on account of this?
QUOTE(Colin @ Jan 5 2008, 05:22 PM) [snapback]446313[/snapback]
That is just super-terrific,I really am a special person.
How about sending me a slew of complimentary nootropics along with a sheet of sticky,little shiny yellow stars on account of this?
How about sending me a slew of complimentary nootropics along with a sheet of sticky,little shiny yellow stars on account of this?
I think that can be arranged.
I was actually just joking in that request (the yellow gold start think I thought would make it overt) and wasn't asking for free supplements.If you're willing to send me free supplements though I'm not quite thick enough to pass.
Many thanks
Many thanks
Hey Hey, where's my thanks for getting you hooked up 
jk
Steve are you the stockist for rimbonant?
jkSteve are you the stockist for rimbonant?
My apologies but I haven't taken Steve up on the "offer".
I bought the drug from Steve at retail,he isn't sponsoring this trial.
Well,I just came across this bit linked below,which doesn't look good as far as heart health is concerned.
I've an appointment with a cardiologist tomorrow and will show this to him for his feedback.I do have an enlarged heart,hah...blah blah.No further comment right now as I read a few paragraphs and lost my focus.I'm not capable of rational thought ATM due to my pre-bed insomnia stack of xanax and trazadone,I feel punch fucking drunk.Ah,bollocks.
http://arstechnica.com/journals/science.ars/2006/7/6/4543
I bought the drug from Steve at retail,he isn't sponsoring this trial.
Well,I just came across this bit linked below,which doesn't look good as far as heart health is concerned.
I've an appointment with a cardiologist tomorrow and will show this to him for his feedback.I do have an enlarged heart,hah...blah blah.No further comment right now as I read a few paragraphs and lost my focus.I'm not capable of rational thought ATM due to my pre-bed insomnia stack of xanax and trazadone,I feel punch fucking drunk.Ah,bollocks.
http://arstechnica.com/journals/science.ars/2006/7/6/4543
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