Oleamide?

[Drael]

Okay, im no pharmacology major, but i figured this would get a more educated response in here, and sorry if its a stupid question....

Is this compound psychoactive in humans? Anyone ever tried it, or found a report related to it? (at active doses obviously, being that its in food). Hazard a guess based on SAR?

Its used in industry as a lube, and found in food, as well as the human brain....it has measurable hypnotic type effects in rats, as well as some cannabimemitic (sp?) type effects....(memory loss for example)

Have been researching endocannibinoids, wondering if theres a way to use em to get high...I mean, all those good chemicals in my brain, must be some way to use em? (I find it interesting more importantly...)

Other interesting thing i heard of was jzl184, which inhibits breakdown of 2-ag ....and also creates some cannabinoid like behaviour in rats.... Could be interesting to increase natural levels of endocannabinoids, and have interesting medicinal applications..

Thoughts?

 

[Hammilton]

AFAIK, Oleamide's CB1 affinity is only speculation.

 

[Drael]

^ except that CB antagonists block some of the behavioural effects...And it causes some cannabimemetic behaviours in rats.

But im guessing no humans have tried it in active doses?

 

[JahRed24x]

So is this Oleamide stuff really in "Smoke" and "Smoke Plus" ? If its not active in humans then why would they put it in?

 

[Hammilton]

Because they think it might be? If they thought it would be effective, they wouldn't have bothered with JWH-018 and whatever that CP series chem was, since oleamide is so much cheaper.

 

[permastoned]

Then why would they bother putting both in.. pretty sure they would KNOW that it alters the high in some way, otherwise they wouldn't bother paying for the oleamide considering that the JWH's are very psychoactive in their own rights'

 

[JahRed24x]

I read an article from the journal of mass spectrometry that Oleamide was found in "Smoke" and "Skunk" Herbal incense blends.. and im about to try this "Smoke Plus" stuff, anyone else try the "Smoke" blend?

 

[Hammilton]

Then why would they bother putting both in.. pretty sure they would KNOW that it alters the high in some way, otherwise they wouldn't bother paying for the oleamide considering that the JWH's are very psychoactive in their own rights'

did you read? They thought it would. It's not like they were doing blind testing on the subject. Cannabinoids are notoriously difficult to judge. Just knowing that it was in the blend would make it extremely difficult to say whether it effected the high or not.

They were obviously at least somewhat familiar with the research, they knew that it might increase the effectiveness, and JWH-018 is extremely anxiogenic. They were probably looking for something that would smooth it out a bit.

Pretty impossible to say whether it did or not. It's incredibly cheap, so it matters little if it was active or not.

 

[MurphyClox]

Oleamides boiling point would make it quite difficult to apply this substance by smoking. Anybody already considered this?

- Murphy

 

[Hammilton]

More than 200C? That's 392F. How hot is the flame on a butane lighter?

 

[permastoned]

did you read? They thought it would. It's not like they were doing blind testing on the subject. Cannabinoids are notoriously difficult to judge. Just knowing that it was in the blend would make it extremely difficult to say whether it effected the high or not.

They were obviously at least somewhat familiar with the research, they knew that it might increase the effectiveness, and JWH-018 is extremely anxiogenic. They were probably looking for something that would smooth it out a bit.

Pretty impossible to say whether it did or not. It's incredibly cheap, so it matters little if it was active or not.

I figure if you hold the butane lighter over the substance it'd be fine, as long as u didn't take the lighter away. That's just a guess but I was pretty sure that butane burns above 200 C. Any cannnabinoid is anxiogenic, I don't necessarily think any is hugely more so than the others, its just that people use large amounts relative to its potency because it is so potent.

 

[MurphyClox]

The problem is not so much the (high) boiling point itself, but the stability of that compound at this temperature, too. I fear for the double-bond...

Murphy

 

[hamhurricane]

It's incredibly cheap, so it matters little if it was active or not.

i find that a bit hard to swallow...I'm not sure what the active dose of oleamide might be but apprently the analyzed samples had more oleamide than JWH-018.

besides JWH 018, a larger quantity of oleamide was found. Oleamide exhibits cannabinoid-like behavioural responses when ingested and may be an additional adulterant in these products.

With the amount of these blends being produced even an additional 1¢ per bag would add up very quickly. given that its cheep and unscheduled perhaps someone with access (i have never seen it offered) should pick some up, do a bioassay and solve the mystery.

 

[JahRed24x]

^ yeah for real, i just tried this Smoke (Vanilla) blend today. I smoked a bowl of it with a friend and we only got about half way threw and had to stop. It for sure has effects, but i dont really know what to make of them, it gave me a really strong body high. What was weird is that after like an hour or two i was completely back to normal again, no after-effect.

I prefer the real natural thing (dank) any day. I dunno if im going to even use the rest of this "Smoke" lol its a little wEiRd!

 

[Hammilton]

i find that a bit hard to swallow...I'm not sure what the active dose of oleamide might be but apprently the analyzed samples had more oleamide than JWH-018.

It's not that hard if you bother to do the math. It isn't as potent as JWH-018. And that ignores the really big concerns about it's vaporizability. Murphy has a good point, it will likely break down fast enough that you'll get very little.

With the amount of these blends being produced even an additional 1¢ per bag would add up very quickly. given that its cheep and unscheduled perhaps someone with access (i have never seen it offered) should pick some up, do a bioassay and solve the mystery.

They'd never, ever, ever reach one cent per bag. One of the more expensive vendors I've found (exluding sigma aldrich, of course, which is always insane for these things, offers it for 12.5 grams per Euro. That's about 8.76 grams per USD. That's 87.6mg per penny. I feel pretty safe saying that there's no way they had almost 90mg per bag. I doubt they had a quarter of that. In a 500mg bag, nearly 1/5th of it would be oleamide, with the obvious issues.

Any cannnabinoid is anxiogenic, I don't necessarily think any is hugely more so than the others, its just that people use large amounts relative to its potency because it is so potent.

But it's not any cannabinoid. Its pharmacology is quite different from the other known cannabinoids. I've used JWH-018 quite a bit, along with a few other synthetic cannabinoids, and JWH-018 is definitely a stronger anxiogenic drug compared to many of them. IMHO it's the worst of all I tried.

Oleamide is not exclusively cannabimimetic. It's a positive GABA-A allosteric modulator. It has some sort of activity on 5HT receptors too, but I forget which.

Edit: read below. references taken from sigma.

Verdon, B., et al., Stereoselective modulatory actions of oleamide on GABA(A) receptors and voltage-gated Na(+) channels in vitro: a putative endogenous ligand for depressant drug sites in CNS. Br. J. Pharmacol. 129, 283, (2000)
Lees, G., et al., Modulation of GABAA receptors and inhibitory synaptic currents by the endogenous CNS sleep regulator cis-9,10-octadecenoamide (cOA). Br. J. Pharmacol. 124, 873-882, (1998)
Boger, D.L., et al., Oleamide: an endogenous sleep-inducing lipid and prototypical member of a new class of biological signaling molecules. Curr. Pharm. Des. 4, 303-314, (1998)
Yost, C.S., et al., Oleamide potentiates benzodiazepine-sensitive gamma-aminobutyric acid receptor activity but does not alter minimum alveolar anesthetic concentration. Anesth. Analg. 86, 1294-1300, (1998)
Thomas, E.A., et al., The endogenous lipid oleamide activates serotonin 5-HT7 neurons in mouse thalamus and hypothalamus. J. Neurochem. 72, 2370-2378, (1999)
Leggett, J.D., et al. Br. J. Pharmacol. 141, 253-262, (2004)

 

[permastoned]

But it's not any cannabinoid. Its pharmacology is quite different from the other known cannabinoids. I've used JWH-018 quite a bit, along with a few other synthetic cannabinoids, and JWH-018 is definitely a stronger anxiogenic drug compared to many of them. IMHO it's the worst of all I tried.

Its pharmacology is quite different... I can't see any substantiation for this. As far as I know, CB1 (and also GPR55 and possibly other novel cb receptors, but not enough research has been done on those yet) is the only psychoactive cannabinoid receptor family, and as such, the selectivity of the cannabinoid is fairly irrelevant as long as it is active at CB1. Of course, it may activate CB2 in a different way than the other cannabinoids but I don't see any proof.

 

[permastoned]

*may activate CB1 in a different way (sorry, my edit isn't working)

 

[Hammilton]

Its pharmacology is quite different... I can't see any substantiation for this. As far as I know, CB1 (and also GPR55 and possibly other novel cb receptors, but not enough research has been done on those yet) is the only psychoactive cannabinoid receptor family, and as such, the selectivity of the cannabinoid is fairly irrelevant as long as it is active at CB1. Of course, it may activate CB2 in a different way than the other cannabinoids but I don't see any proof.

Are you talking about JWH-018 or Oleamide?

Either way, the whole statement is not grounded in reality. Cannabinoids vary widely in the degree of anxiogenic or anxiolytic effects. There is also scientific evidence for why this is (see quote below). Compare HU 210 to JWH-018. HU-210 doesn't produce much in the way of anxiety in humans. It's probably the most anxiolytic cannabinoid I've ever tried, actually.

When we're talking about partial agonists, there can be large differences between the efficacy at the receptor. I'd have to look up numbers, but JWH-018 has nowhere near the efficacy of HU-210, which is a full agonist. Partial agonists are way more psychedelic in nature.

Also, as I recall, it's fairly well established that CB1 has a pretty large active site, evidenced by the large range of novel structures that have high affinity. It's a GPCR, so it's possible, perhaps even likely, that different agonists may produce different signalling. Just speculation there, though.

Also, knockout mice still respond to THC, so CB1 is definitely not responsible for all central effects. Difficult to measure psychedelic effects, though, and I doubt we'll see knockout people any time soon...

I assume you were referring to JWH-018, though, because if you were talking about oleamide, it was doubly nonsensical.

Anxiogenic profile of AM-251, a selective cannabinoid CB1 receptor antagonist, in plus-maze-naïve and plus-maze-experienced mice.

Full Abstract
The notoriously inconsistent effects of cannabinoids on anxiety-like behaviour may be explained by recent research on CB1 receptor knockout (CB1-KO) mice suggesting that cannabinoids exert bidirectional effects via the CB1 receptor (anxiolysis) and a novel rimonabant-sensitive neuronal cannabinoid receptor (anxiogenesis). This hypothesis is supported by the anxiogenic-like profile of AM-251, an analogue of rimonabant that is a potent and selective CB1 receptor antagonist but which, unlike rimonabant, has no activity at the novel receptor. As we have previously shown that rimonabant reduces anxiety-like behaviour in test-experienced animals only, the current study assessed the effects of AM-251 (1.5-3.0 mg/kg) in male Swiss-Webster mice that were either plus-maze-naïve or had been exposed undrugged to the apparatus 24 h prior to testing. Results confirmed that prior maze experience per se significantly increases behavioural indices of anxiety without altering measures of general activity. In maze-naïve mice, the lower dose of AM-251 (1.5 mg/kg) significantly reduced % open-arm time and increased grooming while the higher dose (3.0 mg/kg) additionally reduced open-arm entries and total head-dipping, and increased closed-arm returns. These anxiogenic-like effects were observed in the absence of significant changes in general activity levels. Although AM-251 had a very similar profile in maze-experienced animals, significant drug effects on open-arm avoidance measures were precluded by experientially-induced changes in behavioural baselines (i.e. 'ceiling' effects). Nevertheless, AM-251 again significantly reduced total head-dipping and increased grooming (3.0 mg/kg) and, unlike effects in naïve animals, both doses markedly reduced time spent on the centre platform and increased time spent in the enclosed arms. Against a baseline of almost total open-arm avoidance, the pattern of behavioural change in maze-experienced mice would also be consistent with an anxiogenic-like action of AM-251. Data are discussed in relation to previous findings with rimonabant, the putative existence of a novel non-CB1 neuronal cannabinoid receptor and, more generally, the behavioural pharmacology of plus-maze 'trial 2'.

I don't think we have to resort to invoking poorly researched receptors to find a plausible answer to why JWH-018 is more anxiogenic than most cannabinoids. Like so many things, it most likely comes down to neuroanatomy

Neuropharmacology. 2008 Jan;54(1):151-60
Erratum in:
Neuropharmacology. 2008 Aug;55(2):247.
CB1 receptor stimulation in specific brain areas differently modulate anxiety-related behaviour.

Rubino T, Guidali C, Vigano D, Realini N, Valenti M, Massi P, Parolaro D.
DBSF, Pharmacology Section and Center of Neuroscience, University of Insubria, via A. da Giussano 10, 21052 Busto Arsizio (VA), Italy.
There is a general consensus that the effects of cannabinoid agonists on anxiety seem to be biphasic, with low doses being anxiolytic and high doses ineffective or possibly anxiogenic. Besides the behavioural effects of cannabinoids on anxiety, very few papers have dealt with the neuroanatomical sites of these effects. We investigated the effect on rat anxiety behavior of local administration of THC in the prefrontal cortex, basolateral amygdala and ventral hippocampus, brain regions belonging to the emotional circuit and containing high levels of CB1 receptors. THC microinjected at low doses in the prefrontal cortex (10 microg) and ventral hippocampus (5 microg) induced in rats an anxiolytic-like response tested in the elevated plus-maze, whilst higher doses lost the anxiolytic effect and even seemed to switch into an anxiogenic profile. Low THC doses (1 microg) in the basolateral amygdala produced an anxiogenic-like response whereas higher doses were ineffective. All these effects were CB1-dependent and closely linked to modulation of CREB activation. Specifically, THC anxiolytic activity in the prefrontal cortex and ventral hippocampus was paralleled by an increase in CREB activation, whilst THC anxiogenic response in the basolateral amygdala was paralleled by a decrease in CREB activation. Our results suggest that while a mild activation of CB1 receptors in the prefrontal cortex and ventral hippocampus attenuates anxiety, a slight CB1 receptor stimulation in the amygdala results in an anxiogenic-like response. The molecular underpinnings of these effects involve a direct stimulation of CB1 receptors ending in pCREB modulation and/or a possible alteration in the fine tuning of local neuromodulator release.

But then again, poorly researched receptors are likely relevant:

Proc Natl Acad Sci U S A. 1999 May 11;96(10):5780-5.

Comment in:
Proc Natl Acad Sci U S A. 1999 May 11;96(10):5338-9.
Increased mortality, hypoactivity, and hypoalgesia in cannabinoid CB1 receptor knockout mice.

Zimmer A, Zimmer AM, Hohmann AG, Herkenham M, Bonner TI.
Laboratory of Genetics, National Institute of Mental Health, Bethesda, MD 20892, USA. [email protected]
Delta9-Tetrahydrocannabinol (Delta9-THC), the major psychoactive ingredient in preparations of Cannabis sativa (marijuana, hashish), elicits central nervous system (CNS) responses, including cognitive alterations and euphoria. These responses account for the abuse potential of cannabis, while other effects such as analgesia suggest potential medicinal applications. To study the role of the major known target of cannabinoids in the CNS, the CB1 cannabinoid receptor, we have produced a mouse strain with a disrupted CB1 gene. CB1 knockout mice appeared healthy and fertile, but they had a significantly increased mortality rate. They also displayed reduced locomotor activity, increased ring catalepsy, and hypoalgesia in hotplate and formalin tests. Delta9-THC-induced ring-catalepsy, hypomobility, and hypothermia were completely absent in CB1 mutant mice. In contrast, we still found Delta9-THC-induced analgesia in the tail-flick test and other behavioral (licking of the abdomen) and physiological (diarrhea) responses after Delta9-THC administration. Thus, most, but not all, CNS effects of Delta9-THC are mediated by the CB1 receptor.
PMID: 10318961 PMCID: PMC21937

 

[ZzZzZ]

Have been researching endocannibinoids, wondering if theres a way to use em to get high...I mean, all those good chemicals in my brain, must be some way to use em? (I find it interesting more importantly...)

Only ways I could think of involve extraction. It would be easier to extract from non-human animals.

International potent legal herbal blends(i.e. Spice line, Organic Worx(smoke)) require potent actives(usually cannabinoids) to work. The potent actives required need to/should fit the general guidelines of:fairly stable in most temperatures, legal, pleasantly pot-like, active in small doses, relatively safe, and cheap and easy to mass manufacture. Substances that fit that description are few and far between. Oleamide is just a very cheap cannabanoid(speculated?) compared to the other ingredients that fits the guidelines. I guess organic worx decided it could help, it couldn't hurt and threw it in the cocktail of synthetic ingredients that make up smoke.

I have also heard it is used to potentiate other cannabanoid ingredients in smoke.

 

[vinylmesh]

More than 200C? That's 392F. How hot is the flame on a butane lighter?

Many people (including myself) have complained that these oleamide-containing blends cause irritation to the troath when smoked through a pipe or bong, but not through a joint.

Bearing in mind that wikipedia lists oleamide as a minor irritant I think all this information fits in together nicely.

If the stuff hardly reaches you when smoked in a joint (how most people smoke it) and otherwise causes noticeable irritation, what is the point of it?

The most reasonable explaination that i can think of is that it was thrown in as a red herring in case the product was tested. Unfortunately for them the jwh-018 was also found. It would be interesting to know if they've stopped adding oleamide to their blends.