CCK-4, the "anxiety" inducing drug

[t_wrex]

Just on wiki the other day during an L trip, and found an article on "CCK-4". A phrase caught my eye:

CCK-4 reliably causes severe anxiety symptoms when administered to humans in a dose of as little as 50μg,[1] and is commonly used in scientific research to induce panic attacks for the purpose of testing new anxiolytic drugs.

Anyone have any more info about how this might work? I'm not a very "anxious" person and have never had a panic attack in my life. How would you think this substance would feel?

 

[polymath]

Pressure on the chest, shortness of breath, pounding heart, dizziness...

 

[Skorpio]

There are two types of cholecystokinin (cck) receptors. Cck1 is mainly in the gut and regulates motility. Cck2 is in the brain and can cause anxiety and decrease the effects of opioid signalling.

One possible mechanism for cck anxiety is pyramidal cells containing cck2 receptors causing cannabinoid release which retrograde signals to presynaptic basket cell GABA neurons with cb1 receptors. This causes a net decrease in GABA release (cb1 is an inhibitory receptor).

There is research on using cck2 antagonists to slow the development of tolerance to opioids and allow for analgesia at lower doses.

Proglumide, a cck1 and cck2 antagonist, apparently potentates the placebo effect, causing analgesia stronger than a placebo only when the patient knows they are being injected. It does not have painkilling abilities when injected surreptitiously. It is also a delta opioid agonist, though so drawing a clear conclusion is more difficult.

 

[t_wrex]

Proglumide, a cck1 and cck2 antagonist, apparently potentates the placebo effect, causing analgesia stronger than a placebo only when the patient knows they are being injected. It does not have painkilling abilities when injected surreptitiously. It is also a delta opioid agonist, though so drawing a clear conclusion is more difficult.

So it's like a "psychologically-induced" pain killer? That's interesting.

 

[Skorpio]

The placebo effect (in the context of analgesia) can be blocked by naloxone. This is probably potentiating the opioid signalling that is occurring.

 

[nuttynutskin]

Is it good for public speaking?

 

[Crowsonator2008]

Is it good for public speaking?

I would think definitely not.Anxiety fucking sucks and if you don't know what anxiety and if you don't know true anxiety is.Get tailed by the cops after staying up for 7 days on meth.Anxiety gives birth to paranoia.Paranoia is anxieties big brother.Paranoia leads to schizophrenia

 

[dopamimetic]

You are blessed if you never experienced pathological anxiety in your life ... for me it is a steady 'companion', only thing which really worked against it are the dissociatives which I can't use anymore thanks to prohibition and police catching up..

I think nuttynutskin probably refers to proglumide, for public speaking?

I'm interested in this substance, maybe it could help with "psychological" withdrawal.. Unfortunately it's hard to source and equally hard to guess what are just scam attempts..it's a shame that docs aren't allowed to prescribe experimental substances to people who willingly accept the risk (which is pretty low with many substances, or not higher than to try a random cocktail of high-dose approved meds) and maybe have to sign some disclaimer.. They do that with plastic surgery where I'd bet the statistical risk for lasting damage is much higher. Good old war on drugs. Argh.

Does a CCK-4-antagonist exist? Maybe even a herbal one?

 

[polymath]

Does a CCK-4-antagonist exist? Maybe even a herbal one?

Proglumide itself seems to have a simple enough structure that some natural compound may have the same required structural features to be able to bind to CCK-B receptors.

The benzodiazepine like compound L365-260 is a CCK-B antagonist, and in large doses also has "rewarding" effects in lab experiments:

Morphine place conditioning is differentially affected by CCKA and CCKB receptor antagonists - PubMed

In the present study we have examined the interaction between the selective cholecystokinin (CCK)A and CCKB receptor antagonists, devazepide and L365-260 on morphine conditioned place preference (CPP). Using an unbiased procedure, morphine (1.5 mg/kg) produced a reliable CPP which was observed...

www.ncbi.nlm.nih.gov

1-(1-methyl-2-oxo-5-phenyl-3H-1,4-benzodiazepin-3-yl)-3-(3-methylphenyl)urea

1-(1-methyl-2-oxo-5-phenyl-3H-1,4-benzodiazepin-3-yl)-3-(3-methylphenyl)urea | C24H22N4O2 | CID 104929 - structure, chemical names, physical and chemical properties, classification, patents, literature, biological activities, safety/hazards/toxicity information, supplier lists, and more.

pubchem.ncbi.nlm.nih.gov

Abstract
In the present study we have examined the interaction between the selective cholecystokinin (CCK)A and CCKB receptor antagonists, devazepide and L365-260 on morphine conditioned place preference (CPP). Using an unbiased procedure, morphine (1.5 mg/kg) produced a reliable CPP which was observed irrespective of the conditioning compartment type. Pretreatment with devazepide (0.001-0.01 mg/kg s.c.) produced a dose related attenuation of this response. At higher doses (0.1-1 mg/kg) this antagonism became variable and dependent on the training compartment with blockade only observed when conditioning was to the white/rough textured environment. This profile has also been reported for the serotonin (5-HT)3 receptor antagonist ondansetron. The CCKB antagonist L365-260 (0.000001-0.01 mg/kg) failed to antagonize the morphine CPP, if anything a mild potentiation was observed. To study this further we examined the interaction between L365-260 (0.01 mg/kg) and a subthreshold dose of morphine (0.3 mg/kg). At these doses neither drug elicited CPP, however when co-administered a significant CPP was recorded. Finally, L365-260 at 1 mg/kg induced a mild but significant CPP when administered alone. These results suggest a differential role of CCK receptor subtypes on reward-related behaviour and complement previous studies suggesting bimodal effects of CCK systems on mesolimbic dopamine function.

However, I'm not sure whether this apparent euphoric effect of L365-260 is based on the CCK-B blockage or some other mechanism (maybe affecting benzodiazepine receptors in large enough doses?).

 

[Rectify]

Amphetamines antagonize CCK.

 

[polymath]

Unfortunately. the Swiss Target Prediction app doesn't recognize the proglumide molecule, so that can't be used for designing new CCK-B ligands.

 

[Juniper Bruhmomentius]

Yooo, I have a problem.... I think my body produces this chemical on its own..... Any tests for that??