54 replies to this topic

[medievil]

Ive recently made a thread about this on bluelight, there were a few very interesting experiences posted in my thread including my own experience.
http://www.bluelight...ad.php?t=503184

I'm gonna quote my own experience:

I know there's also a thread about the antidepressant properties of them, but it seems they also have alot of potential as study aids, energy boosts or as a motivational boost in low treshold doses.

I personally have found this property with 5mg of 2CD, before i went to work yesterday i barely had any sleep (3 hours) and would have been exhausted at my job, however after taking the 2CD i found that i was full of energy, and the physical work as my job went very well, i noted very little fatigue at a task that would have made me tired rather easily.

What is interesting is that it didnt drain me at all while the effects seemed to be very potent in a natural way, hard to describe, you barely felt it, but the energy was there.

Also take a look at the following few reports:

Been taking low ~3-5mg morning doses of 2C-E recently mostly as an exercise / weight-training companion.

Highly recommended.

A little Theobromine and Creatine Ethyl Esther for energy, low doses of Phenibut and Diphenhydramine as recommended here to reduce general Phenethylamine discomfort, add some Whey Protein, and I've been making some pretty good progress.

I find low-dose 2C-E to be a smooth, almost trance-inducing way to ensure lasting motivation during physical exertion.

About a million times more useful/safe than real stimulants.

~1 mg 2C-P does the trick for me!

I'm an artist and I often have trouble forcing myself to work and be productive... But 5 minutes after a speck of 2cp I am drawing furiously for hours... good stuff too! Then I go to bed feeling satisfied, sleep well with great dreams, and wake up totally refreshed!

Modulate with hashish to your taste

I have done this extensively... in fact it's become my main usage of psychedelics. My favorite booster, so to speak, is DOC, though DOM also works nearly as well. I take .5 to 1mg and it brings on the plateau stage effects, which for me are energy, mood boost and extreme mood stabilization, cognitive enhancement, empathy, and a sort of a general feel that everything is easier and goes with the flow. Low doses like this allow me to sleep at the end of the day easily and they really don't drain me at all... there's a slight tolerance build-up so I generally wouldn't do it 2 days in a row but I have done it up to 4 or 5 days in a row with reduced effects but without burnout.

Ive taken both low doses of 2ce and 2ci on separate occasions. 2C-I gave me a boost of energy and a mood lift, it was perfect for just riding my bike. I was able to exercise a lot longer, as I didn't feel fatigued. I've also taken extremely low doses at work, and its usually enjoyable. Have to be careful cuz it hits me a lot harder in that environment.

2C-E on the other hand doesn't really offer stimulation, so I got tired of riding my bike pretty quick. I was just left wanting more.

While i'm not really interested in psychedelic experiences, those properties of the psychedelic phenethylamines are very interesting to me, and will definatly do some further experimenting with them.
Those compounds arent neurotoxic nor addictive and may be very usefull for an occasional boost.

[medievil]

Also would like to add that ive been taking low doses of 2CD for the past few days with good results, no sign of tolerance occuring, while it works amazingly well for my anhedonia. I'm taking it in combination with memantine. I havent tried studying on it yet so i dont know about its nootropic properties much yet.

For those interested, this is a interesting read:
http://www.erowid.or...artpills1.shtml

[Guacamolium]

Most efficacious, or most potent, because DMT is the tryptaminergic king experience-wise on efficacy, but it's a tryptamine. I thought 2CT7 was the king of the phenylethylamine class, but I never had a chance to try it before some dumbass insufflated it and died from doing so, but you're suggesting a low dose PEA class with hallucinogenic properties as most potent, rather than efficacious? That's kind of hard to tell, as Shulgin never completed the whole class, leaving new little "Shulgins" to take on the cathinone quadrant that Shulgin left alone, so the phenylethylamine drug class is still incomplete regardless. I would say 2CT7 though, never even had the chance to try it...

I always found the tryptaminergics and ergot amide classes low dose to be "nootropic" and the phenylethylamine hallucinogens to be a reverse or null of that, but, whatever.

[medievil]

DMT is indeed a very potent psychedelic, but is it also a potent nootropic? Ive read about ppl taking daily low doses to lift depression but never saw any experiences regarding as a study aid, but it could be interesting.

but you're suggesting a low dose PEA class with hallucinogenic properties as most potent, rather than efficacious?

Not sure what you mean, i'm referring to low doses wich arent psychedelic at all, i'm talking about the nootropic properties.

I found the affinities of DOM, the alpha methylated version of 2CD:

DOM: 4.00 5ht2b, 3.38 Beta2, 2.75 5ht1d, 2.36 5ht2a, 2.30 Alpha2A, 2.13 Alpha2B, 2.10 Alpha2C, 1.87 5ht7, 1.56 Alpha1A, 1.52 5ht1e, 1.51 5ht1a, 1.47 5ht2c, 1.16 5ht6;

http://www.plosone.o...al.pone.0009019

5HT2B agonism can be problemetic in the long run as that could cause fibrosis. 5HT1A agonism explains the potent antidepressant effect adn 5HT2A agonism can have a nootropic effect by increasing glutamate and dopamine in the mesolimbic regions, altough 5HT1A agonism has the opposite effect on glutamate. Not sure what agonism of the other receptors does tough, 5HT2C agonism can be expected to decrease the release of monoamines. Altough the end result of combined agonism can have a way differend effect.

Edited by medievil, 15 May 2010 - 08:16 PM.

[Lestat Rett]

DMT is unlikely to be nootropic, given its a 5HT1a agonist, and as such is anxiolytic and analgesic, but 5HT1a agonists cause working memory impairment (while under the effects, not permanent) notably the potent 5HT1a agonist (and 5HT releaser) 8-OH-DPAT causes memory impairment.

Antidepressive though certainly.

[Guacamolium]

I'm going over all the phenylethylamine hallucinogens that I've done and I can't really pinpoint one that would work as a LD noot. From my own experience 2C-I underdosed just doesn't feel like anything at all - could be wrong though. There's no way mescaline would work well as a low dose noot for me.

If I were to suggest a different drug class entirely, maybe for more options, I'd say to try out low dose naphyrone, since it inhibits the SERT, DAT, and NAT.

[Animal]

Prolonged 5HT2A agonism would likely lead to permanent negative dissociative side effects, including HPPD. Oh and the phenethylamine alkaloids are highly psychologically addictive and can result in constitutive dependence because of the anxiolytic effects. Anyone who thinks that you can take low doses of this class over an extended period and not suffer adverse effects is deluding themselves.

Hell, I know people who take cocaine in order to get up in the morning, or high dose amphetamines to work out, does that mean it's safe because some individuals have used it without any fatalities?

Ergot derivatives would be a far more appropriate nootropic agent, although they are certainly not ideal.

Edited by Animal, 16 May 2010 - 03:57 AM.

[medievil]

Prolonged 5HT2A agonism would likely lead to permanent negative dissociative side effects, including HPPD. Oh and the phenethylamine alkaloids are highly psychologically addictive and can result in constitutive dependence because of the anxiolytic effects. Anyone who thinks that you can take low doses of this class over an extended period and not suffer adverse effects is deluding themselves.

Hell, I know people who take cocaine in order to get up in the morning, or high dose amphetamines to work out, does that mean it's safe because some individuals have used it without

Why? Just because they are in the class of "drugs" doesnt mean they are addictive. Both dopamine and glutamate play a major role in addiction and wanting, psychedelics have a completely differend pharmacological profile.
Selective 5HT1A agonists would also be anxiolytic, this doesnt mean they are addictive.

Prolonged 5HT2A agonism would likely lead to permanent negative dissociative side effects, including HPPD.

Do you have a source for that? I doubt that low agonism wich doesnt cause any dissociative/psychoactive effects causes HPPD.

Serotonine agonism is a very interesting target for analgesia, anxiolytics, nootropics, antidepressants etc, why not explore the low dose benefits of psychedelics?

Hell, I know people who take cocaine in order to get up in the morning, or high dose amphetamines to work out, does that mean it's safe because some individuals have used it without any fatalities?

Sure, but what does this have to do with serotonine agonists? I could as well use this example in a topic about phenylpiracetam.

Edited by medievil, 16 May 2010 - 09:56 AM.

[Guacamolium]

I apologize kind sir for your inquiry, but maybe MDMA low dose can get the "nootropic" juices flowing?

Working on a "nootropic" angle of Low dose PEA hallucinogens is difficult. What do you really want to achieve (LONG TERM) with a small dose hallucinogen? Empathy, perception, creativity?

Look, dude, PEA's are under the umbrella of the DEA - not my democratic choice, but explain clearer for us the CEing things you want. Explain thrice if you have to, but WTF?

[medievil]

Working on a "nootropic" angle of Low dose PEA hallucinogens is difficult. What do you really want to achieve (LONG TERM) with a small dose hallucinogen? Empathy, perception, creativity?

Just read the quotes in my openingspost. I dont want to achieve anything, i'm here to talk about what i DID achieve with low doses of 2CD, and talk about the experiences of the other ppl that tried those compounds.

What do you really want to achieve (LONG TERM)

Also thats in my OP:

Those compounds arent neurotoxic nor addictive and may be very usefull for an occasional boost.

I also posted a whole article with anecdotal experiences regarding 2CD as a smart drug.

but WTF?

Why wtf? From those experiences its clear that those compounds seem to have have nootropic potential in low doses, if there's any evidence that its dangerous to take them for such purposes id be glad to look at the references you provide, but a stupid comparison with mdma to get the "nootropic juices flowing" doesnt make any sense.

I know that the DEA doesnt like them, but discussions here should be based on science not on local legalities.

Edited by medievil, 16 May 2010 - 11:14 AM.

[medievil]

@Animal
Missed that you said likely. I wonder wheter anything is known about the causes of HPPD.

[Guacamolium]

Working on a "nootropic" angle of Low dose PEA hallucinogens is difficult. What do you really want to achieve (LONG TERM) with a small dose hallucinogen? Empathy, perception, creativity?

Just read the quotes in my openingspost. I dont want to achieve anything, i'm here to talk about what i DID achieve with low doses of 2CD, and talk about the experiences of the other ppl that tried those compounds.

What do you really want to achieve (LONG TERM)

Also thats in my OP:

Those compounds arent neurotoxic nor addictive and may be very usefull for an occasional boost.

but WTF?

Why wtf? From those experiences its clear that those compounds seem to have have nootropic potential in low doses, if there's any evidence that its dangerous to take them for such purposes id be glad to look at the references you provide, but a stupid comparison with mdma to get the "nootropic juices flowing" doesn't make any sense. (yeah empassion makes no sense at all in the nootropic world

If you have any contributions, id be glad to see them they're updated constantly

You are high. You are, you're on something alright, because you expect me to keep continuing to contribute to your ^ glance up Einstein, 2C-D experiments on yourself.[b] "I don't want to achieve anything."[b/] ~ those words came from you, and I was trying to help you.
GREAT talk here on the NOOTROPIC (hello) forum on imminst - so great it led nowhere, and thank you OP - despite my contributions of other suggestions to you[b]above[b/], which, weren't in hieroglyphics or anything. Hey on your way out, cite you sources for neurotoxicity and mammalian addictiveness and that low doses of 2C-XX may be beneficial to low dose cognitive enhancement in humans, since you claimed all three right above.

Damn, I was on your team until that last post of yours, but way to blow it, kid.

Don't EVER, bite the hand that feeds you. (oh, and go fuck yourself too)

Edited by somethingtoxic, 16 May 2010 - 11:52 AM.

[medievil]

Well, i started wondering wheter you were sarcastic because of your last post, if you werent well, naphyrone is probably carcinogenic (its discussed on bluelight). Besides, i dont know why you are mad because of my last post, i appreciate all contributions you can make. I apoligize if my last post was bit rude. Lets keep this discussion flowing .

The energy i got from 2CD likely only comes from serotogenic agonism and not dopamine release wich has some benefits compared to dopamine release induced by dopamine reuptake inhibitors and releasers, for example i can take a low dose of 2CD in the morning without feeling any sort of aftereffect when it wears off, so those compounds seem alot better as a occasional boost.

As for neurotixiticy i beleive a few DOx compounds have been screened, i'll see what i can find. Psychedelics arent known addictive drugs like cocaine, amphetamine etc. And i base the cognitive enhancing effects on the anecdotal reports ive seen.

Besides, this study may be off intrest:

Chronic phenethylamine hallucinogen treatment alters behavioral sensitivity to a metabotropic glutamate 2/3 receptor agonist.
Benneyworth MA, Smith RL, Sanders-Bush E.

Department of Pharmacology, Vanderbilt University School of Medicine, Nashville, TN 37232, USA.
Abstract
Recent clinical studies in schizophrenic patients show that a selective agonist of group II metabotropic glutamate (mGlu) receptors has robust efficacy in treating positive and negative symptoms. Group II mGlu receptor agonists also modulate the in vivo activity of psychotomimetic drugs, reducing the ability of psychotomimetic hallucinogens to increase glutamatergic transmission. The use of mouse models provides an opportunity to investigate the dynamic action that mGlu2/3 receptors play in regulating the behavioral effects of hallucinogen-induced glutamatergic neurotransmission using genetic as well as pharmacological strategies. The current study sought to characterize the use of the two-lever drug discrimination paradigm in ICR (CD-1) mice, using the hallucinogenic 5-HT2A/2C receptor agonist (-)-2,5-dimethoxy-4-bromoamphetamine [(-)-DOB)] as a stimulus-producing drug. The (-)-DOB discriminative stimulus was dose-dependent, generalized to the hallucinogen lysergic acid diethylamide, and was potently blocked by the 5-HT2A receptor antagonist M100907. However, contrary to our prediction, the hallucinogen-induced discriminative stimulus was not regulated by mGlu2/3 receptors. In a series of follow-up studies using hallucinogen-induced head twitch response and phencyclidine-induced hyperlocomotion, it was additionally discovered that the repeated dosing regimen required for discrimination training attenuated the behavioral effects of the mGlu2/3 receptor agonist LY379268. Furthermore chronic studies, using a 14 day (-)-DOB treatment, confirmed that repeated hallucinogen treatment causes a loss of behavioral activity of mGlu2/3 receptors, likely resulting from persistent activation of mGlu2/3 receptors by a hallucinogen-induced hyperglutamatergic state.

The positive effect of psychedelics on cognition likely comes for a big part from the increase in glutamate.

However, 2,5-dimethoxy-4-
iodophenethylamine (2C-I), 2,5-dimethoxy-4-ethylphenethylamine (2C-E), 2,5-dimethoxy-4-
chlorophenethylamine (2C-C), 2,4,5-trimethoxyamphetamine (TMA-2) and 2,4,6-
trimethoxyamphetamine (TMA-6), which are methoxylated phenethylamine derivatives,
slightly influenced the re-uptake and release of monoamines.

http://www.drugs-for...n...55&catid=18
It seems that these compound have a slight reuptake inhibition on monoamines.

Edited by medievil, 16 May 2010 - 12:27 PM.

[medievil]

Role of the serotonin 5-HT(2A) receptor in learning.
Harvey JA.

Department of Pharmacology and Physiology, Drexel University College of Medicine, Philadelphia, Pennsylvania 19118, USA. john.harvey@drexel.edu
Abstract
This study reviews the role of the serotonin 5-HT2A receptor in learning as measured by the acquisition of the rabbit's classically conditioning nictitating membrane response, a component of the eyeblink response. Agonists at the 5-HT2A receptor including LSD (d-lysergic acid diethylamide) enhanced associative learning at doses that produce cognitive effects in humans. Some antagonists such as BOL (d-bromolysergic acid diethylamide), LY53,857, and ketanserin acted as neutral antagonists in that they had no effect on learning, whereas others (MDL11,939, ritanserin, and mianserin) acted as inverse agonists in that they retarded learning through an action at the 5-HT2A receptor. These results were placed in the context of what is known concerning the anatomical distribution and electrophysiological effects of 5-HT2A receptor activation in frontal cortex and hippocampus, as well as the role of cortical 5-HT2A receptors in schizophrenia. It was concluded that the 5-HT2A receptor demonstrates constitutive activity, and that variations in this activity can produce profound alterations in cognitive states.

Psychopharmacology (Berl). 2006 Jan;184(2):173-81. Epub 2005 Dec 21.
Effect of serotonin depletion on 5-HT2A-mediated learning in the rabbit: evidence for constitutive activity of the 5-HT2A receptor in vivo.
Romano AG, Quinn JL, Liu R, Dave KD, Schwab D, Alexander G, Aloyo VJ, Harvey JA.

Department of Pharmacology and Physiology, Drexel University College of Medicine, Philadelphia, PA, 19102, USA. anthony.romano@drexel.edu
Abstract
RATIONALE: Associative learning during Pavlovian eyeblink conditioning has been shown to be regulated by 5-HT2A receptors. The existence of inverse agonists that retard learning through an action at the 5-HT2A receptor suggests the existence of constitutive activity at that receptor and that depletion of serotonin should have minimal effects on learning. OBJECTIVES: We examined whether depletion of serotonin would impair trace eyeblink conditioning or the enhancement of conditioning produced by the agonist lysergic acid diethylamide (LSD) and the retardation of conditioning produced by the inverse agonist MDL11,939. METHODS: Animals received bilateral intraventricular injections of 5,7-dihydroxytryptamine (5,7-DHT) at doses of 760 or 1,140 microg/side (1.88 or 2.82 micromol/side) and were later exposed to eight daily conditioning sessions. RESULTS: Serotonin depletion produced by the lower dose of 5,7-DHT was 71 and 72% in cortex and hippocampus, respectively, with no change in 5-HT2A receptor density, no effect on learning, and no effect on the ability of LSD to enhance and MDL11,939 to retard learning. The higher dose of 5,7-DHT produced serotonin decreases of 85 and 90% in cortex and hippocampus, respectively, accompanied by a 96% decrease in the density of the serotonin transporter, but no significant effect on learning. CONCLUSIONS: Pavlovian trace eyeblink conditioning is regulated predominantly by the constitutive activity of the 5-HT2A receptor rather than by serotonin release onto the receptor during learning. It was suggested that the 5-HT2A receptor regulates learning by modulating the release of dopamine, acetylcholine, and glutamate, transmitters known to affect eyeblink conditioning.

Modulating the release of dopamine, acetylcholine, and glutamate is VERY interesting when it comes to cogntive enhancement.

I wonder what lisuride would be like, wich combines agonism of 5HT1A, 5HT2A, 5HT2C and several dopamine receptors.

Lisuride is a dopamine and serotonin receptor partial agonist. It has a high affinity for the dopamine D2, D3 and D4 receptors, as well as serotonin 5-HT1A[1] and 5-HT2A/C receptors.[2]

Interesting is that despite its 5HT2A agonism it isnt a psychedelic.

Edited by medievil, 16 May 2010 - 12:41 PM.

[Animal]

Psychedelics arent known addictive drugs like cocaine, amphetamine etc. And i base the cognitive enhancing effects on the anecdotal reports ive seen.

That's not true, you're being far too general. There are many know cases of abuse with psychedelics, which include psychological dependence and physical withdrawal. I know of individuals who have continuously low dose on psylocybin mushrooms simply because they had convinced themselves that they are harmless, and they enjoyed being 'high' indefinitely. The only reason their addictive potential is lower then that of substances such as amphetamine and cocaine is because of the gradual onset and prolonged activity. They still modulate dopamine and stimulate the reward pathways. Euphoria, energy and massive mood enhancement are very psychologically addicting, and many of the PEA analog psychedelics have these effects.

I'm sorry but the anecdotal reports of 'cognitive enhancement' are bullshit, just because they are from the subjective perspective of an individual under the influence of a psychedelic. There are so many psychoactives out there that can make an individual utterly delusional in the belief that they are somehow 'enhanced' by the substance they are under the influence of, large increases in the availability of NE, DA and 5-HT in the synaptic cleft will cultivate these kinds of delusions regardless of whether they are based on any kind of evidence.

[medievil]

Several studies have shown that several serotonine receptors have a modulatory effect on cognition, therefor i wont dismiss all the reports as bullshit. I certainly dont see those compounds as harmless as daily use can definatly lead to heart valve damage (if they are potent 5HT2B agonists) but they do seem alot better for occasional use then amphetamines or other potent stimulants. For example because i can just take a dose for a boost in the morning, without feeling like crap when it wears off, wich would have been an issue with conventional stimulants.

But yeah, lets get to science! I'm very interested in the effects of serotogenic receptors on cognition. Most compounds we have as serotogenic agonists are psychedelics, while it would be interesting to try selective ligands, those arent easily available.

[medievil]

which include psychological dependence and physical withdrawal.

Interesting ive never heared of this before, while i do get a mood boost from 2CD it didnt seem addictive to me. (I'm not taking any 2CD at the moment tough as the glutamate increase my interfere with memantine's adaptation as i raised the dose).

"Addiction" is very complicated too, something that causes euphoria isnt automatically addictive, dopamine and glutamate need to play a key role, and interesting serotonine seems to curb self administration. (could be wrong, no ref at hand now).

Edited by medievil, 16 May 2010 - 01:48 PM.

[Animal]

which include psychological dependence and physical withdrawal.

Interesting ive never heared of this before, while i do get a mood boost from 2CD it didnt seem addictive to me. (I'm not taking any 2CD at the moment tough as the glutamate increase my interfere with memantine's adaptation as i raised the dose).

"Addiction" is very complicated too, something that causes euphoria isnt automatically addictive, dopamine and glutamate need to play a key role, and interesting serotonine seems to curb self administration. (could be wrong, no ref at hand now).

I would say any substance that causes such substantial mood enhancement has the potential for addiction, and certainly modulation of 5-HT activity is no indication of a substance lacking administration reinforcement. Cannabis and MDMA are examples of this. Don't try to tell me MDMA isn't addictive, because there are so many well publicised cases of abuse where ridiculous doses are consumed for extended periods. Psychologically it is definitely habit forming, with many individuals dosing once a week or more for years.

Really the only psychoactives which lack abuse potential are those that have subtle, or extremely gradual onset, and taper off in effect. I would say the epitome of this is a pharmaceutical that takes effect over multiple weeks of daily dosing, and which continues to have a sustained effect with no tolerance.

So 2CD got you high and gave you energy, does this make it a nootropic? Well the only way to tell would be to take a single blind placebo controlled trial of it, or at the very least take a before/after objective test of cognition. Even then I don't see it as a manageable and sustainable nootropic, as it's effects are immediate and not cumulative, therefore it's use is limited to a spontaneous basis.

What do you feel are it's effects on creativity? Apparently 5HT2A agonism or ligand mimicry is supposed to have a dramatic effect on creativity, at the expense of a loss of focus and difficulty concentrating.

[medievil]

What do you feel are it's effects on creativity? Apparently 5HT2A agonism or ligand mimicry is supposed to have a dramatic effect on creativity, at the expense of a loss of focus and difficulty concentrating.

2CD in particular seems to make my mind blank of background toughts, i think this is really usefull for studying and focus. I beleive that other compounds have a much better effect on creativity. I'l have to study on it to see how good it is for taking in information.

[Animal]

What do you feel are it's effects on creativity? Apparently 5HT2A agonism or ligand mimicry is supposed to have a dramatic effect on creativity, at the expense of a loss of focus and difficulty concentrating.

2CD in particular seems to make my mind blank of background toughts, i think this is really usefull for studying and focus. I beleive that other compounds have a much better effect on creativity. I'l have to study on it to see how good it is for taking in information.

That must be it's other agonism effects overwhelming the 5HT2A creative enhancement. The hallucinogenic effects (particularly environmental geometrization) of mescaline are primarily due to it's moderate to high affinity oscillation as a partial agonist of the 5HT2A receptor subtype. The frontal cortex and basal ganglia have an especially high presence of these receptors and this esoteric stimulation results in the random firing of neurons associated with mathematical abstraction and spacial awareness. As a secondary effect this massively increases the random association not only between these concepts but many other higher thought processes, since the random activation of neurons encompasses the entire frontal lobe.

Apparently there is also novel stimulation of the ventral tegmental area dopaminergic projection to the nucleus accumbens. While the frequency of neuronal depolarisation is reduced, the amplitude of each dopaminergic discharge is increased, resulting in a sensory state similar to severe schizophrenia, except because of the frequency modulation there is a serene calm instead of a agitated paranoia.

Personally I think manipulation of the VTA→NA dopaminergic interaction to have a lower activation threshold while maintaining frequency has the potential to be one of the most nootropic enhancements that exist. Simply because it is primarily subconscious in nature, yet it has an integral role in learning of all kinds. Imagine it as a way that your brain rewards itself for every positive synaptic reinforcement and engram encoding.

Edited by Animal, 16 May 2010 - 09:19 PM.

[medievil]

That must be it's other agonism effects overwhelming the 5HT2A creative enhancement.

I agree, if you look at this paper you can see that differend psychedelics have very differend effects on the serotogenic receptors, many of them are much stronger agonists at differend receptors then at 5HT2A itself.

Apparently there is also novel stimulation of the ventral tegmental area dopaminergic projection to the nucleus accumbens. While the frequency of neuronal depolarisation is reduced, the potency of each dopaminergic discharge is increased, resulting in a sensory state similar to severe schizophrenia, except because of the frequency modulation there is a serene calm instead of a agitated paranoia.

You mean this occurs with psychedelics?

Edited by medievil, 16 May 2010 - 09:24 PM.

[Animal]

Apparently there is also novel stimulation of the ventral tegmental area dopaminergic projection to the nucleus accumbens. While the frequency of neuronal depolarisation is reduced, the potency of each dopaminergic discharge is increased, resulting in a sensory state similar to severe schizophrenia, except because of the frequency modulation there is a serene calm instead of a agitated paranoia.

You mean this occurs with psychedelics?

No, just with mescaline.

Mescaline is actually unique in that the constituent ligand that has 5HT2A agonism has an oscillating conformation that changes it's binding affinity resulting in a very unique activation profile at this particular receptor. It's capacity to transduce this novel activation into randomised neuronal activity concentrated in the frontal cortex and basal ganglia is still not understood. I love mescaline!

Edited by Animal, 16 May 2010 - 09:40 PM.

[Guacamolium]

Well, i started wondering wheter you were sarcastic because of your last post, if you werent well, naphyrone is probably carcinogenic (its discussed on bluelight). Besides, i dont know why you are mad because of my last post, i appreciate all contributions you can make. I apoligize if my last post was bit rude. Lets keep this discussion flowing .

Well I apologize as well, for what I perceived as your rudeness towards me was not taken well by me who was genuinely trying to keep a "fencepost" bluelight topic on cognitive enhancers (not nootropics) from becoming a straight bluelight slanted topic, which provoked that response from me. I'll PM you to why there was misdirected anger, as it has nothing to do with this topic.

Like I said, LD naphyrone might be at least worth a try. As far as phenylethylamines of the hallucinogenic variety, honestly MDMA, 2cT7, or what you were going after, 2C-D, I believe could work. PEA RC's have limited evidence for safety long term and if you were to put a gun to my head on this topic, I'd actually go with LD ALD-52 or LSD from the ergot amide class. I unfortunately haven't tried all the PEA's, as due to being based around alterations to six different directions, they're vast, illegal, and when taken at their target potential, unfit for ingestion in the general public presence.

I also remember taking something from the tryptamine class long ago. I don't think it was AMT, but perhaps 5-meo-AMT, but I know it was an AMT anologue. I had a good time on it and felt that it helped with me being better socially, and maybe small doses of that could have potential.

Funny thing is, you can write Shulgin a letter and get his opinion. My boss actually showed me a letter that he wrote him in which Shulgin responded to regarding organization of useless, empathogenic, and negative PEAS that he's made, plus a synthesis question. To which he responded happily it seemed. I don't think LD/long term and toxicology is his forte, though, from reading through PIHKAL several times.

If you're interested I can call up my old boss and get you Shulgins info to ask the man himself - just let me know. Otherwise, I think I exhausted my brain trying to think of a hallucinogenic PEA that would be cognitively enhancing and somewhat safe at low dose.

[haha]

Well theres a real tiffy going on here, Both of you make good and bad points.
Firstly and most importantly I dont think that these drugs modulate there effects through the classical neurotransmitters system or only by part, these receptor systems are of more a conceptaul nature than a cause and effect singular object that we are taught to assign them.For all transmitters operate in the same system and hence all transmitters effect all systems, it is best to start with the binding target and work through the cause and effect pathways, furthermore PEA's usual binding target happens after it has been chemical alterated to a 3 domain(ring) structure, binding affinities studies are often compromised due to the use of test ligands that bind differently to how they are portrayed. Therefore if we dont know how they work how can we know with real certainity weather they are dangerous or not. I would go with some being more dangerous than others. From my understanding of 5ht-1a receptors are best antagonised and the positive effects of agonist are mediated through quick receptor down regulation, I might be wrong but its to do with its effects of glutamate hence working memory. LSD Mechanism Action is 5-ht-1a receptor antagonism, there are agonist effects later down the cascade....

Nice work animal bang on, assosiative learnings what its about.....5-ht-2a does this well but it prob also cause heavy stress on the brain. Instead of looking at it narrowly like biochemically its often good to look to individuals who used a similar substance heavily both famous and not so famous. There is real potential to endup a different person.

Just my opinions cant be bothered looking for the reasearch to support, but I have definitly had the best times of my life leading a normal life while high.

[medievil]

Interesting discussion going on, i have to admit tough that many things are really above my head but i'm very intrigued by the fact that ligands can have dramatically differend downstream effects, lisuride is a good example being a strong 5HT2A agonist and lacking psychedelic activity. Interesting facts about mescaline too.

I tried 2CD again today at 7mg but this dose is way to strong, its definatly more recreational and not nootropic as it induces some kind of brainfog wich feels nice but it isnt something productive. Lower doses induced a mind clarity wich i think do have potential to be cognitive enhancing.

That said, all psyhedelics seem to bind to 5HT2B wich would render them unable to be used in daily low doses, but lisuride could be the solution for this.

Lisuride seems to be a:
5HT1A agonist
5HT1B agonist
5HT2B antagonist
5HT2A agonist
5HT2C agonist
5HT5A didnt find yet
5HT6 agonist
5HT7 antagonist
D2 agonist
D4 agonist

And interacts with several adronergic receptors.

Now lets take a look at DMT:

DMT: 4.00 5ht7, 3.97 5ht1d, 3.91 5ht2b, 3.53 Alpha2B, 3.53 Alpha2C, 3.51 D1, 3.42 5ht2c, 3.28 5ht1e, 3.25 5ht6, 3.16 5ht5a, 3.13 Imidazoline1, 2.95 Alpha1B, 2.75 Alpha2A, 2.70 Alpha1A, 2.58 5ht2a, 2.37 SERT, 2.23 Sigma1;

(the higher the number the stronger its bind, under 2 is not significant)

DMT appears to bind strongly to D1, while lisuride binds strongly to D2 and D4, D1 and D4 are strongly implicated in learning and ADHD/ADD. 5HT2B agonism is a big issue with DMT but lisuride's extremely potent 5HT2B antagonism could counteract that.

Seems like a crazy idea to take lisuride+DMT daily in low doses, but interesting food for tought imo.

Edited by medievil, 17 May 2010 - 02:15 PM.

[medievil]

Well, i started wondering wheter you were sarcastic because of your last post, if you werent well, naphyrone is probably carcinogenic (its discussed on bluelight). Besides, i dont know why you are mad because of my last post, i appreciate all contributions you can make. I apoligize if my last post was bit rude. Lets keep this discussion flowing .

Well I apologize as well, for what I perceived as your rudeness towards me was not taken well by me who was genuinely trying to keep a "fencepost" bluelight topic on cognitive enhancers (not nootropics) from becoming a straight bluelight slanted topic, which provoked that response from me. I'll PM you to why there was misdirected anger, as it has nothing to do with this topic.

Like I said, LD naphyrone might be at least worth a try. As far as phenylethylamines of the hallucinogenic variety, honestly MDMA, 2cT7, or what you were going after, 2C-D, I believe could work. PEA RC's have limited evidence for safety long term and if you were to put a gun to my head on this topic, I'd actually go with LD ALD-52 or LSD from the ergot amide class. I unfortunately haven't tried all the PEA's, as due to being based around alterations to six different directions, they're vast, illegal, and when taken at their target potential, unfit for ingestion in the general public presence.

I also remember taking something from the tryptamine class long ago. I don't think it was AMT, but perhaps 5-meo-AMT, but I know it was an AMT anologue. I had a good time on it and felt that it helped with me being better socially, and maybe small doses of that could have potential.

Funny thing is, you can write Shulgin a letter and get his opinion. My boss actually showed me a letter that he wrote him in which Shulgin responded to regarding organization of useless, empathogenic, and negative PEAS that he's made, plus a synthesis question. To which he responded happily it seemed. I don't think LD/long term and toxicology is his forte, though, from reading through PIHKAL several times.

If you're interested I can call up my old boss and get you Shulgins info to ask the man himself - just let me know. Otherwise, I think I exhausted my brain trying to think of a hallucinogenic PEA that would be cognitively enhancing and somewhat safe at low dose.

Dont worry about it buddy

I have tried both AMT and MDAI in daily low doses.

MDAI: Boosted my mood and energy a little but it wasnt very powerfull, i took it in combination with memantine, 60mg twice daily.
AMT: Cured my ADD basicly and worked great for my mood, it definatly enhanced my cognition in the same manner as amphetamine would do, its both a powerfull serotonine and dopamine releaser, it was used as antidepressant in the sovjet union under the name indopan. It definatly made me more social.

Naphyrone may be interesting but it seems to be carcinogenic.

Also the dose seems magic, on 5 or 7mg AMT worked good, but higher it put me into a weird headspace wich seemed counterproductive.

I am very interested in exploring the potential of various things in low doses.

Edited by medievil, 17 May 2010 - 02:39 PM.

[Thorsten3]

@somethingtoxic

You've got some serious issues that you need help with. Your reaction was totally ridiculous actually. Read it all back right from the start and keep a rational impartial perspective. What do you see? I see a guy with a serious sensitivity problem. Medievil was simply partaking in a healthy debate on an internet forum and just because he wasn't licking your ass you get upset? I'm suprised medievil even showed the humility in forgiving you. Why take something to heart on an internet forum? I mean sounding like you're annoyed is one thing but you acted like he had just murdered your mother or something. What medications/supplements do you take? trust me you need to evaluate what you are taking because it isn't working for you with a reaction like that freind

Edited by HyperHydrosis, 20 May 2010 - 08:14 PM.

[Guacamolium]

Hey, I just had a suggestion from an old foxy friend that I hadn't been in contact with in years, and she suggested LD DOC. I've never taken it personally, but she has and she swears it makes her rational. Subjective, I know, but it's worth a try.

http://en.wikipedia....loroamphetamine

[medievil]

Hey, I just had a suggestion from an old foxy friend that I hadn't been in contact with in years, and she suggested LD DOC. I've never taken it personally, but she has and she swears it makes her rational. Subjective, I know, but it's worth a try.

http://en.wikipedia....loroamphetamine

Thx, yeah ive heared the DOx chemicals are good in treshold doses but i'm unable to get ahold of them at the moment.

Today i started my DMT experiment. I made a extract from mimosa hostilis rootbark but the dose i took this morning was too low, i think this one is better for cognitive enhacement as it binds to D1 with good affinity. I also notice a bit better motor coordination, but the dose is still too low, i will try a better dose in a few minutes.

I remember someone mentioning that DMT made he's brain "overclock" and noticed a big fluidity and enhanced motor coordination.

[Guacamolium]

My only reserve with DMT, is as it binds to the receptors (LD) it creates a very dreary depressant feeling(in me), until 4.5 hours comes along and all the natural serotonin built-up comes to swarm the receptors and then I'm super-happy, and plus, DMT has that switch that protects daily usage, right? That melatonergic or tryptaminergic switch or whatever it is that prevents daily dosing, can't remember the specifics, but know daily tryptaminergics usually don't work. Could be wrong, but, there's a stop-switch mechanism on DMT I know.