74 replies to this topic

[chris7900]

Methamphetamine induces autophagy as a pro-survival response against apoptotic endothelial cell death through the Kappa opioid receptor.

Our studies indicate that kappa opioid receptor can be therapeutically exploited for attenuating METH-induced Blood Brain Barrier dysfunction.

https://www.ncbi.nlm...pubmed/24603327

 

 

selegiline has l-methamphetamine as metabolite, is this the same substance ?

 

if so, is small dose selegiline effective for kor agonism or is its methamphetamine metabolite too weak ?

[Dichotohmy]

I have recently begun experimenting with low-dose salvia divinorum again. In the past, I had good sucess smoking 1x leaf or low doses of 5x extract to counteract the dysphoria and crash following (meth)amphetamine abuse and accompanying sleep deprivation. It would allow me to meditate and calm myself down so that I could get to sleep. When I would wake up, I would feel a sence of rejuventation that one gets following a good sleep. Also accompanying this rejuventation, stimulants drugs would suddenly work a lot better for me. This is important do me being on ADHD medication at this time, and that sence of rejuvenation when I wake up is incredibly well welcomed due to the chronic poor quality of my sleep. In my mind, the reported upregulation of dopamine/mu-opioid receptors, and thus reversal of tolerance, is there - although to be fair, it might be the effect of proper sleep rather than cascading effects of kappa-receptor agonism. 

 

Reading this thread, it might sound like the experience of salvia-d is unpleasant, esspecially in an amphetamine crash where the catecholamines are depleted - not to mention the strain on one's rewards center in such a state; but for me, the immediate salvia-d experience is completely neutral.  That is to say, it doesn't contribute to akathisia for other dysphoric states, nor does it create a pleasurable responce - hence why salvia is though to have limited (if any) abuse potential. Notably, I do not get a fear responce from much of anything, so even breathrough experiences with salvia-d are neutral in an "oh, wow" sort of way.

 

So, suffice it to say, I am quite interested in continuing my trial of daily low-dose salvia-d use. There seems to be a dearth of information out there about specific dosing regimens in regards to salvia as a treatment for depression. I'll put out for the record that the dosage I have sucess with is 2-3 "bowls" of 1x leaf tightly packed in a glass pipe or bong - smoked maybe 10-15 minutes apart. I feel like this is enough to get just a glimpse of a psychoactive dose of salvia, but has the benefits I described. Note that I've also had sucess with extracts and the full-blown hallucinatory trip you get from them, but I don't feel such an acute dose is at all necessary to enjoy the benefits of salvia-D. 

 

Also note that both the 1x leaf and extracts both remain stable after many years of proper storage. In my case, I kept my unused salvia stash in a sealed bag inside a lockbox at room temperature for 12+ years, and still managed to trip on the extract and get effects from the 1x leaf now that I have recently rediscovered.    

[VERITAS INCORRUPTUS]

This might be something of interest within the scope of related research:

http://teamtlr.com/o...jdtic-2hcl.html

[focus83]

This might be something of interest within the scope of related research:

http://teamtlr.com/o...jdtic-2hcl.html

 

How come this post hasn't received any attention? JDTic is now readily available through Tream TLR, yet nobody seems to care. Why?

[addx]

JDTic that has been tried by some members of the forum (not the same source) has not had good effects(a member claims to have serious effects for a few hours) and as the human study was also dropped because of some cardio issue or something and members experienced chest pain I think people are thinking twice about it now.

The company inventing JDTic also went on to research similar drugs and seemed to have abandoned JDTic.

It has been speculated that this is due to the long effect of JDTic on receptors(cca 30 days) making it difficult to dose and to ream profits from.
A less conspiracy-oriented interpretation might simply be that the cardio side-effects accidentally found in humans (there was no sign of it in animal testing IIRC) made it less of a potential than it was. I'd trust they figure this is something they can be designed out for humans by adapting the structure of the chemical while still retaining effects it had in animals.

Also, noone is really sure if they tried the real deal JDTic. The first two reports found on the net were neutral or very positive. But from people on this forum, not so much. Some reports only claim a mild nootropic effect so there's really nothing that can one do to prove to oneself that the ingestested substance is JDTic except paying for a costly verification procedure in a lab or something.

Proper dosing is also unknown and varies 10x between reports. It seems really low doses should be used which makes things even more difficult as measuring something like 200mcg isn't easy.

I'm still tempted to try it but also wary of the reports and seizing of research after that one human trial.

[chris7900]

first of all , thank you for the awesome information addx !!

 

i ve been researching and experimenting to find information on how to cure my complete anehdonia, almost a year has gone by, and after reading a lot, and trying tons of supplements, your theory makes total sence , it seems to realy be one important part to the issue. also your theory correlates 100% with all my personal experience.

 

Still one thing about kor antagonism concerns me. It may be that after antagonism kor doesn't get upregulated directly BUT what about it beeing upregulated indirectly ? wich is very likely, since the body always counteracts such actions.

I 've read a lot of papers wich show A FEW of the reactions the body has on kor antagosims. Of corse no one can make a prediction what the long term consecuenses due to kor antagonism can be, i think its just way too complex.

just out of curiosity, couldn'T it be that maybe after kor antagonism, the body has prepared in such way that the next time something happens that activates the kor system, this system responds to greater degree then previous to kor antagonism, reaching previous kor peak much faster and also expanding its degree.

i bet there are no studies on this, BUT "the absence of evidence is not the evidence of absence".

 

I'm concerned of whether kor agonism is the safer option.

 

Nevertheless i am going to give it a try since i dont have anything else left.

 

i wanted to try buprenorphine + naltrexone/subuxone. but since i cannot find bupre and naloxone on the pharmacies wich are recommended here in longecity, and also i dont realy like the agonism of the other opioids.

So think i will just go with naltrexone. in addition i will drink some cacao and take green tee extract, since the catechins may also have kor antagonism properties.

also my system does not produce any endorphins, not even during sports, quite the opossite, when i do joggin after 30 minutes where the endorphins are supposed to start getting produced my head starts getting energy drained, fatigued and i usualy start getting headaches, resulting later the day in complete mental fatigue. so even if naltrexone just helps with endorphines i would be realy happy.

 

so i have just one question about the naltrexone dosage, which is too specific i guess, since i want it for kor antagonism.

is low dose naltrexone effective for kor antagonism or should i just try to work my way up to standart dosage for good kor antagonism ?

i ve searched for this but there is no specific answer to kor antagonism dosage.

 

if someone knows a reliable pharmacy for buprenorphine, i would be very thankfull, combining it with naltrexone should be very effective, eventhough i have to rethink it if i use this combo due to opiod agonism.

 

i am going to post the results here if they are positive, or even negative ?.

 

 

 

 

 

Edited by chris7900, 30 June 2014 - 06:11 PM.

[addx]

Buprenoprhine is extremely addictive unfortunately :/

Currently I'm playing around with several ideas not really sticking to a regime though.

One of my very unadvocatable ideas is my low dose cocaine self-torment. It goes like this. I take a line of cocaine, get a little euphoric and then withdrawal starts, withdrawal is irritable and also has cravings. I would stick it out and then later after it passes I may take another line.

Soon enough the initial cocaine euphoria got so smaller and smaller than 1 line couldnt produce. Instead I got more and more anxious, scatter minded and sweaty(armpit profuse sweating). So tolerance grew. I actually started getting releif from the final parts of withdrawal now and I could feel it visceraly (I imagine visceral emotionality is definitely KOR related). So I continued to do it. The idea is, cocaine increases perception of control, most importanlty social control (meaning you have a notion that you control the opinion of others better) causing the usual cocaine sociability and talkativeness. This cocaine positive effects were pretty much abolished by the tolerance I developed. Acute tolerance to cocaine effects is created by KOR action. This is proven in countless studies, KOR is the single receptor that can abolish acute cocaine effects so profoundly and immediately and it is responsible for doing so. The whole idea of tolerance is in fact an increase in KOR tone so it can counteract cocaine better. So, my KORs should have been upregulated by chronic cocaine, but I beleive I also did something different to typical cocaine consuments. I used low doses and interrupted frequently in order to "induldge" in withdrawal. Withdrawal is characterized by loss of social control meaning irritability, impatience with people, avoidance of people. This is the part I forced to happen as the euphoria was eliminated by tolerance I was only getting the withdrawal effects - loss of control. My idea was, to get used to it, to losing control. So I tortured myself like that for months on and off.

Interestingly I used memantine on and off when I felt the cocaine regime needed a break. Memantine does something extremely weird with stimulants and so also cocaine, it antagonizes their effects in essence but it itself is a stimulant! If I have memantine in my system and take a line of cocaine I get pure KOR action! Memantine itself subdues cocaine(via NMDA antagonism) but it seems my tolerance still triggers causing KOR activation. Without cocaine to counter it, KOR (or rather dynorphin) causes sedation, some kind of nice visceral feeling, a rise in healthy appetite and no loss in erection function or any of such cardiovascular effects! Meaning exactly opposite than that from a line of cocaine!

So, currently I'm trying to make sense of this and today I actually found a study (posted a link on that cocaine reversal thread) that confirms that cocaine induces changes can be reversed by a D1 antagonist(I think) or a D2 agonist + NMDA antagonist. The study tested various combinations that fullfil that idea one of them actually used Memantine.

Memantine is proven to have very weird effects with cocaine intoxication and my introspective understanding is not far from what they've seen.

So, playing with this now, waiting for KOR research to become more inspiring again. Might order JDTic but I am wary now because of my extensive low dose cocaine I must have upregulated KORs and cocaine does take a toll on the heart and so I feel kinda vulnerable to this idea of JDTic causing heart issues.

It is very hard to make sense of these scientific studies. I presume presynaptic KORs and postsynaptic KORs have usually somewhat opposite effects as do most other neurotransmitters positioned like that. KOR activation can make you feel nice IMO, but it can make you dysphoric as well. Furthermore their ligands (dynorphin and endoprhins) have affinites for both receptors as well in fact, and the receptors also form heterdimers (a single KOR-MOR receptor requiring both ligands to activate).

Edited by addx, 30 June 2014 - 06:06 PM.

[Galaxyshock]

KOR activation can make you feel nice IMO, but it can make you dysphoric as well. Furthermore their ligands (dynorphin and endoprhins) have affinites for both receptors as well in fact, and the receptors also form heterdimers (a single KOR-MOR receptor requiring both ligands to activate).

 

Could it be also that endocannabinoids are released in response to KOR activation which can cause that somewhat pleasant feeling, for example CB1-antagonism seems to antagonize the 'rewarding' effect of Salvinorin A: http://www.ncbi.nlm....pubmed/17920565

[FeelsNumbMan]

Please keep us updated. Anyone else have any experiences with KOR?
 

I have my eyes on ALKS-5461, hopefully we'll hear more about it. I have little clue about it myself though.

[addx]

 

KOR activation can make you feel nice IMO, but it can make you dysphoric as well. Furthermore their ligands (dynorphin and endoprhins) have affinites for both receptors as well in fact, and the receptors also form heterdimers (a single KOR-MOR receptor requiring both ligands to activate).

 

Could it be also that endocannabinoids are released in response to KOR activation which can cause that somewhat pleasant feeling, for example CB1-antagonism seems to antagonize the 'rewarding' effect of Salvinorin A: http://www.ncbi.nlm....pubmed/17920565

 

 

 

I don't think I've ever had that feeling prior to my cocaine experiments and I've been using both cocaine and weed long before all this.

 

The only time I'd have similar feelings was comedown from cocaine and that was before when I could still process cocaine properly and binge. The "tummy sexual mellow" feeling, dunno how to explain it in other terms. 

 

I could be wrong of course... but it's a really distinct feeling :/

[FeelsNumbMan]

Salvia. Get an alcoholic extract in a dropper bottle. You can agonize your KOR without psychoactive effects besides some sedation. Must be taken subliminally because the active ingredient doesn't get absorbed by the stomach.

 

Unfortunately people are irrationally scared of salvia, because they watch people take massive doses on youtube and assume all doses are like that. You wouldn't compare a beer with half a bottle of vodka.

 

Your heartbeat increases after consumption, but is back to normal after 15 to 20 mins. In the short term (12 hours) it reduces dopamine. The positive effects are felt the next day.

I'm not scared of salvia, but my experiences with it were unpleasant. I did not enjoy it. It made me feel really weird, uncomfortable, and I got this magnetic pulling that made me feel like leaning towards one side. For the duration, I was also really sweaty... Overall, it made me feel uneasy.

 

If there's a way to make yourself get the KOR effects from salvia without needing to go through that "trip", then I'd be glad to try. But even so, things like .1 of salvinorum A costs quite a lot.

 

And my dose? 5x extract, about .1g smoked. Really little, I know, but it still made me feel like shit, so I'd prefer not to. :|

[Area-1255]

I agree with alpha 1 blockade to an extent, I do not agree with kappa agonism.....

 

NOT ONLY do KOR receptors inhibit dopamine, they also raise PDE-PHOSPHOSDIESTEARASE, leading to reduced nitric oxide, central energy production and reduced testosterone levels --------- which help to maintain dopamine receptor expression. 

 

J Pharmacol Exp Ther. 2002 May;301(2):599-604.

Inhibition of cAMP accumulation by kappa-receptor activation in isolated iris-ciliary bodies: role of phosphodiesterase and protein kinase C.

Dortch-Carnes J1, Potter DE.

Author information

 

Abstract

The present study was designed to examine the roles of protein kinase C (PKC) and phosphodiesterase (PDE) in modulating the action of kappa receptor stimulation on cAMP accumulation in isolated iris-ciliary bodies (ICBs) of New Zealand White rabbits. The kappa receptor agonist, (+/-)-1-(3,4-dichlorophenyl)acetyl-2-(1-pyrrolidinyl)methylpiperidine (BRL-52537) (BRL), and the PKC activator, phorbol 12,13-dibutyrate (PDBu), both caused a concentration-dependent inhibition of forskolin-stimulated cAMP production. The inhibitory effect of BRL on cAMP levels was significantly reduced in the presence of the selective kappa receptor antagonist, norbinaltorphimine (10(-6) M), but the effect of PDBu was not, thus supporting the involvement of kappa-opioid receptors in the response to BRL. In the presence of 3-isobutyl-1-methylxanthine or rolipram (10(-5) M), the inhibitory effect of BRL or PDBu (10(-6) M) on cyclic AMP accumulation was abolished. In the presence of the selective PKC antagonist, chelerythrine (10(-6) M), the inhibitory effect of PDBu or BRL (10(-6) M) was significantly reduced. Direct measurement of PDE activity demonstrated the ability of BRL and PDBu (10(-6) M) to augment the activity of these enzymes. Preincubation of ICBs with rolipram (10(-5) M) or chelerythrine (10(-6) M) caused significant reversal of both BRL- and PDBu-induced increases in PDE activity. These results indicate that stimulation of PKC and PDE4 activity is part of the complex mechanism whereby kappa-opioid receptor agonists reduce levels of cAMP in the rabbit ICB. This mechanism of action could contribute to the ability of kappa-opioid agonists to suppress aqueous flow rate and to lower intraocular pressure.

 

Biochem Pharmacol. 1993 Jan 7;45(1):207-16.

Relationship between kappa 1 opioid receptor binding and inhibition of adenylyl cyclase in guinea pig brain membranes.

Konkoy CS1, Childers SR.

Author information

 

Abstract

Previously, we showed that kappa-selective ligands inhibit adenylyl cyclase in guinea pig cerebellar membranes. The present studies explore the relationship between kappa 1 binding sites (as determined with [3H]U-69,593 binding) and kappa 1-inhibition of adenylyl cyclase (using U-50,488H) in guinea pig brain membranes. Various kappa opioids displaced [3H]U-69,593 binding at a single site with subnanomolar affinities. These agonists were several hundred-fold weaker in inhibiting adenylyl cyclase, but for most agonists the rank order of adenylyl cyclase inhibition paralleled the displacement of kappa 1 binding. The correlation of IC50 values for both adenylyl cyclase and binding was significant except for alpha-neo endorphin, which was relatively weak at inhibiting adenylyl cyclase despite a Ki value of 0.08 nM versus kappa 1 binding. Comparison between kappa 1 binding and kappa 1-inhibited adenylyl cyclase across eleven guinea pig brain regions revealed that kappa 1-inhibited adenylyl cyclase was highest in the cerebellum, absent in thalamus and superior colliculus, and moderate in other regions. In most regions, kappa 1 binding correlated with the efficacy of kappa 1-inhibited adenylyl cyclase. However, the hippocampus had high levels of kappa 1-inhibited adenylyl cyclase despite low levels of kappa 1 binding, while cortex exhibited a high density of kappa 1 sites but a relatively low level of kappa 1-inhibited adenylyl cyclase. Reaction of cerebellar kappa receptors with beta-chlornaltrexamine (beta-CNA) blocked both kappa 1 binding and kappa 1-inhibited adenylyl cyclase. The effect of beta-CNA on kappa 1-inhibited adenylyl cyclase was to inhibit efficacy with little decrease in agonist potency, thus suggesting no significant level of kappa receptor reserve for this effector system.

PMID:   8381004   [PubMed - indexed for MEDLINE]

 

 

J Pharmacol Exp Ther. 1993 Sep;266(3):1678-83.

The kappa opioid receptor expressed on the mouse R1.1 thymoma cell line is coupled to adenylyl cyclase through a pertussis toxin-sensitive guanine nucleotide-binding regulatory protein.

Lawrence DM1, Bidlack JM.

Author information

 

Abstract

The R1.1 mouse thymoma cell line expresses a high-affinity kappa opioid binding site. Opioid binding to this site is inhibited by guanine nucleotides, suggesting that the receptor is coupled to a guanine nucleotide-binding protein. Here, we present evidence that the kappa opioid binding site on R1.1 cell membranes is negatively coupled to adenylyl cyclase. The kappa-selective agonists (trans)-3,4-dichloro-N-methyl-N-[2-(1-pyrrolidinyl)- cyclohexyl]benzeneacetamide methane-sulfonate hydrate [(-)-U50,488], (5 alpha,7 alpha, 8 beta)-(-)-N-methyl-N-(7-(1-pyrrolidinyl)-1-oxas- piro(4,5)dec-8-yl)benzeneacetamide (U69,593) and several dynorphin peptides inhibited basal and forskolin-stimulated cyclic AMP production by up to 40% in R1.1 cell membranes. The order of potency for the inhibition of adenylyl cyclase activity by opioid agonists correlated with their Ki values for the inhibition of [3H]U69,593 binding. Opioid-mediated inhibition of adenylyl cyclase activity was stereoselective, as (-)-U50,488 was more potent than the (+) isomer, and the inhibition was blocked by the kappa-selective antagonist nor-binaltorphimine. The opioid-mediated inhibition of adenylyl cyclase activity was also completely blocked by incubating R1.1 cells with Bordetella pertussis toxin (PTX). Incubation of R1.1 cell membranes with PTX and [adenylate-32P]NAD+ resulted in the exclusive labeling of a 41-kDa protein, as determined by separating the membrane proteins under reducing conditions on a SDS polyacrylamide gel, followed by autoradiography. These results suggest that a PTX-sensitive inhibitory guanine nucleotide-binding protein mediates the link between the thymoma kappa opioid receptor and adenylyl cyclase.

PMID:   8103800   [PubMed - indexed for MEDLINE]

 

Eur J Pharmacol. 1988 Sep 13;154(2):169-78.

Mu-, delta- and kappa-opioid receptor-mediated inhibition of neurotransmitter release and adenylate cyclase activity in rat brain slices: studies with fentanyl isothiocyanate.

Schoffelmeer AN1, Rice KC, Jacobson AE, Van Gelderen JG, Hogenboom F, Heijna MH, Mulder AH.

Author information

 

Abstract

We investigated the effects of [D-Ala2,D-Leu5]enkephalin (DADLE). [D-Ala2,MePhe4,Gly-ol5]enkephalin (DAGO), [D-Pen2,D-Pen5]enkephalin (DPDPE) (0.01-1 microM) and bremazocine (0.001-0.3 microM) on the electrically evoked release of radiolabelled neurotransmitters and on the dopamine (DA)-stimulated cyclic AMP efflux from superfused rat brain slices. The differential inhibitory effects of these agonists on the evoked neurotransmitter release indicate that the opioid receptors mediating presynaptic inhibition of [3H]noradrenaline (NA, cortex), [14C]acetylcholine (ACh, striatum) and [3H]DA (striatum) release represent mu, delta and kappa receptors, respectively. In agreement with this classification, preincubation (60 min) of the slices with the delta-opioid receptor-selective irreversible ligand, fentanyl isothiocyanate (FIT, 0.01-1 microM), antagonized the inhibitory effects of DADLE and DPDPE on striatal [14C]ACh release only. On the other hand, the D-1 DA receptor-stimulated cyclic AMP efflux from striatal slices appeared to be inhibited by activation of mu as well as of delta receptors. In this case, the reversible mu antagonist, naloxone (0.1 microM), fully antagonized the inhibitory effect of the mu agonist, DAGO, without changing the effect of the delta agonist DPDPE but was ineffective as an antagonist in slices pretreated with FIT (1 microM). The inhibitory effect of DAGO on the electrically evoked [3H]NA release was antagonized by naloxone whether the receptors were irreversibly blocked by FIT or not. These data not only further support the existence of independent presynaptic mu-, delta- and kappa-opioid receptors in rat brain but also evidence strongly that mu and delta receptors mediating the inhibition of DA-sensitive adenylate cyclase could share a common binding site (for naloxone and FIT) and, therefore, may represent constituents of a functional opioid receptor complex.

PMID:   2906610   [PubMed - indexed for MEDLINE]

 

Edited by Area-1255, 12 December 2014 - 10:27 PM.

[vaarmen]

Today I had one my first experiences with Salvia.
I will be telling the experience soon and hope to get opinions about the following:

The KAPPA OPIOID SYSTEM, how it affects behavior and whether up or down-regulated state is more beneficial more a 21st century smart human.

First of all this is the first hallucinogen I have had an experience with and was not sure what to expect in general. I thought I would get something like virtual reality and I will be in the observer's point of view. What happened was quite fascinating, though.

 

The first time I did it was weird, it took me by surprise and I got into a dream like state where I could still think.

 

The third time I did salvia, after a few minutes of the dream like state I was back in the reality. I soon realized however, that my state of consciousness is alter. I felt like I am PURE CONSCIOUSNESS, other people have called this "death of ego". The feeling of SELF was not the entire body and mind but the PURE CONSCIOUSNESS only. 

 

Imagine you have a large human like robot, of a size of a large building, and you are sitting somewhere in the head of the robot. Visualize your world of at this point. How would you see the world ? What would you feel ? This is what I was feeling during the experience. The robot was my BODY and the driver was MY CONSCIOUSNESS sitting in my head, observing the world.

 

A lot of my subconscious processes, that work PARALLEL to the consciousness to produce behavior were barely present. Anxiety, fear, shame was basically nonexistence. There was only PURE CONSCIOUSNESS. I could do and say precisely ANYTHING I wanted to do. Have you experience social anxiety or discomfort in social situations, when it feels you don't have control ? When it feels your voice, your face expression or your behavior is partially out of your CONSCIOUS control, being governed my circuitry of fear, anxiety, social acceptance, anger or anything else ?
Salvia was the EXACT OPOSIT of that. All those were inexistent. Every part of the behavior was under complete control.

 

My BRAIN FOG and DEPRESSION was gone. My thought was CLEAR and CLEAN.

 

 

Now here is my hypothesis of the neuropsychiatry that was happening:
Salvia has a very clean action - KAPPA OPIOID AGONIST.
Kappa opioids and Mu opioids have somewhat opposite effects. Kappa Agonist are supposed to have no euphoria whatsoever.

One of recent Depression models is that it's a state of UPREGULATED KAPPA OPIOID SYSTEM.
Kappa Opioid System is hypothesized to represent the APPROACH / AVOID spectrum of the person towards challenges.

 

I read about the above and decided to give Salvia a try. I wanted to AGONIZE the receptors to achieve LONG term DOWNREGULATION of the system. I was expecting to feel fear and dysphasia after few minutes of administration, but was stunned to achieve the full control and pure consciousness I was talking about.

 

One explanation is the following. Kappa neurons are usually coupled with dopamine neurons. Dopamine in the anxiety and fear systems creates anxiety and fear. Kappa neurons have inhibitory action on dopamine neurons. Increased Kappa activity caused my Salvia my decrease the activity of the subconscious areas of the mind, leaving a feeling of PURE CONSCIOUSNESS.

 

Here is the DILEMMA, however ! 
Why is it then that previously, DOWNREGULATED KAPPA SYSTEM was considered preferable ? This is inconsistent with what I observed. 

 

Some people have experimented with JDTic which is a KAPPA ANTAGONIST. I would love to hear how they felt for the acute and withdrawal states. Any parallels ?

 

Anyone else has similar experiences with Salvia ?

 

P.S. I previously associated DOPAMINE with increased CONSCIOUS control. However being high on Salvia, I snorted some RITALIN which had NO EFFECT on the drive, motivation or thought process of my PURE CONSCIOUSNESS.

[peoplepleaser101]

Addx, why did you write this: "Perhaps low dose ketamine could do it, ketamine does agonize kappa and I fear that the known ketamine afterglow glow effect is due to KOR downregulation, just as is Salvias and Ibogaines."

 

Why do you fear it?

[gintrux]

Is anyone interested in this stepholidine group synthesis? It could help with amotivation, anhedonia, apathy. In one study it increased D1, D2 receptors by 40% https://www.longecit...ia-amotivation/