Calystegines

[Gunter]

http://www.thenook.org/forum/index.php?showtopic=44595

The above thread is about I. carnea, I found out about calystegines though, these are nortropane alkaloids discovered in 1988 and found in numerous plants used as psychoactives. It is odd that Hoffman and Shultes never found them.

I think they may be active in some sense and was wondering what people thought.

The fact that these compounds are common in Datura species and relatives makes Torstens opinion on this very interesting to me.

[Torsten]

Hmmmm, I'd heard of tropanes in convolvulaceae before, but can't say that any of my experiences had any tropane like character to them. Ipomoea carnea is certainly a bit different than others in that it is weak, more sedating, and seems to have a longer residual effect, all of which are classic tropane symptoms rather than LSA effects.

[apothecary]

http://www.botanical.com/site/column_poudhia/150_jason.html

Blister beetle feeding on Jason flowers. These beetles also feed on flowers of common weed Beshram (Ipomoea carnea). The healers do not use the Blister beetle collected from Beshram flowers. This is unique information and has not been reported in reference literatures. The traditional healers of Sarguja region, use the flowers of Jason with this insect, in treatment of cancer.

http://www.botanical.com/site/column_poudh..._oodlabari.html

Near human habitat, as usual I have observed many weeds common in Chhattisgarh also. At first, I decided to ask few questions about these weeds and very soon I got one interesting observation. Ipomoea carnea is alien weed in India. It is commonly known as Beshram (means Shameless). In Oodlabari, Ipomoea is a common roadside weed. Although many uses of this weed have been reported and the natives of Chhattisgarh have developed many medicinal uses, but you will be surprised to know that many natives, particularly the poor people, use the leaves of Ipomoea carnea for edible purposes mostly as vegetable. The use of Ipomoea carnea leaves for this purpose has yet not been reported. They have informed me that they are using it since very long time and there is no harmful effects. I personally feel that there is a need to study the nutrient status of these leaves and to conduct detailed study on medicinal properties. The research on this waste land weed can open a new utility chapter in human history.

Ipomoea carnea leaf juice

S.K. Hore, Ram Ottalwar, K.M. Koley, A.K. Pathak, Possible involvement of cholinergic and adrenergic mechanisms in changing contractility of guinea pig ileum by Ipomoea carnea, Journal of Ethnopharmacology 71 (1-2) (2000) pp. 253 - 259.

Above paper would definitely be the place to start looking for more clues.

and dunno about this one Archaea but thought I'd throw it in since you mentioned mulberrys

Search for "Mulberry latex rich in antidiabetic sugar-mimic alkaloids" +carnea in google, can't get access to the article without paying though.

[apothecary]

Oop. Here's the abstract for that first paper.

The study aimed to elucidate the mechanism (s) of action of Ipomoea carnea leaf juice (ILJ) in changing contractility of guinea pig ileum. ILJ produced dose-dependent (10-10000 microg/ml) triphasic responses. The initial contractile phase was blocked by atropine (1 microg/ml) but had additive effect with acetylcholine (2 ng/ml) or carbachol (2 ng/ml). Neostigmine (30 ng/ml) or lignocaine (50 microg/ml) failed to alter the response. In cold-induced denervated preparations, this phase was augmented. The relaxatory phase of ILJ was not modified by phenoxybenzamine (35 microg/ml) but was reduced by propranolol (1 microg/ml) and abolished by lignocaine (50 microg/ml). The final contractile phase of ILJ was not affected by atropine (1 microg/ml). These results suggest that the triphasic response of ILJ is possibly mediated through cholinergic, adrenergic and non-cholinergic mechanisms, respectively.

Maybe someone who can speak "peer reviewed paper" can tell us exactly what that means, but to me it looks like if ILJ is passed through the cholinergic/adrenergic mechanism, then it must have a very similar psychoactivity to other tropanes.

[apothecary]

http://www.ncbi.nlm.nih.gov/entrez/query.f...8&dopt=Abstract

Toxic effects of prenatal Ipomoea carnea administration to rats.

Chronic exposure of livestock to Ipomoea carnea, a toxic plant, promotes toxicosis characterized by lysosomal vacuolization of different organs, and is clinically manifested by CNS signs, abnormal endocrine and gastrointestinal functions, alteration of the immune system, and abnormal embryogenesis. The present study evaluated the effects of different doses of the plant extract on pregnant rats and their offspring after oral administration to the dams from day 6 to day 20 of gestation. Histopathology of thyroid, pancreas, liver and kidneys of dams on gestational day 21 showed characteristic vacuolization promoted by I. carnea toxicosis in these organs; the same was observed in the organs of 7-d-old pups. On the other hand, no alteration was found in these same organs of dams the 7th d after parturition. Although the lesions were reversed in the dams, the same did not occur in their pups. I. carnea administration also promoted decreased body weight, thymus atrophy and spleen enlargement in pups. The toxic principle of I. carnea (swainsonine) seems to pass through the placenta.

Anti AIDS activity?

http://www.newsrx.com/newsletters/AIDS-Wee...00533354AW.html

"The water extracts of Ipomoea carnea subsp. fistulosa (aerial parts), Vitex glabrata (branch), Vitex trifolia (aerial part), Vitex negundo (aerial part), Canna indica (rhizome), and Justicia gendarussa (aerial part) showed HIV-1 RT inhibition ratio (%IR) higher than 90% at a 200 mcg/mL concentration."

http://www.ub.rug.nl/cgi-bin/htgrep.indian...=yes&style=none

(?)Abdelhadi, A.A., Y.M. el-Kheir and T. Hassan (1989) - A succinylcholine-like action of an Ipomoea carnea Jacq. subsp. fistulosa (Mart. ex Choisy) extract, Pharmacological Research 21, 431-437.

Succinylcholine is like...a muscle relaxant, it acts like acetylcholine in the brain but is metabolised along a slightly different pathway.

http://en.wikipedia.org/wiki/Succinylcholine

Its medical uses are limited to short-term muscle relaxation in anesthesia and intensive care, usually for facilitation of endotracheal intubation. Despite its many undesired effects on the circulatory system and skeletal muscles (including malignant hyperthermia, a rare but life-threatening disease), it is still much used because it arguably has the fastest onset of action of all muscle relaxants.

A single intravenous dose of 1.0 to 1.5 milligrams per kilogram of body weight will cause flaccid paralysis within a minute of injection. For intramuscular injection higher doses are used and the effects last somewhat longer. Suxamethonium is quickly degraded by plasma cholinesterase and the duration of effect is usually in the range of a few minutes. When plasma levels of cholinesterase are greatly diminished or an atypical form of cholinesterase is present (an otherwise harmless inherited disorder), paralysis may last much longer.

Side effects include fasciculations, muscle pains, acute rhabdomyolysis with hyperkalemia, transient ocular hypertension, and changes in cardiac rhythm including bradycardia, cardiac arrest, and ventricular dysrhythmias. In children with unrecognized neuromuscular diseases, a single injection of succinylcholine can lead to massive release of potassium from skeletal muscles with cardiac arrest.

Succinylcholine does not produce unconsciousness or anesthesia, and its effects may cause considerable psychological distress while simultaneously making it impossible for a patient to communicate. For these reasons, administration of the drug to a conscious patient is strongly contraindicated, except in necessary emergency situations.

And finally, a little more from Pankaj Oudhia

http://www.botanical.com/site/column_poudh...4_jatropha.html

Some farmers told me that the Sona keeda feeding on Ipomoea leaves are also toxic to cattle and wild animals.

(I am pretty sure when he says Ipomoea leaves here, he means I. carnea leaves)

[Gunter]

I am interested in the nortropane calystegines, they have been found in nearly every species of Solanaceaus plants used as a ritual hallucinogen. Hoffman and Shultes has no idea they existed when the majority of their chemical and field work on plant hallucinogens was done and their potential contribution to the activity of tropane alkaloids is unknown or so it seems.

Edited May 22, 2006 by Archaea

[apothecary]

Definitely agree there A, there is so much of the tropane experience that doesn't correspond directly to say, ingesting a sufficient amount of hyoscine butyl(or)hydrobromide or similar refined chemicals.

My guess is, a place to start as far as potential bioassay plants would be Calystegia sepium, as the plant that contains this class of chemicals as a major active constituent rather than a smaller fraction.

Perhaps leaves could be dried and smoked?

[Gunter]

I have a hunch the one to target initially is calystegine B2.

I also happen to think that LSAs may not be the actives in Ipomoea and Argyreia. I think Hoffman and Shultes got it wrong through little fault of their own and that people tend not to question them due to their status. I want to see some cold water ergot based bioassays that have results akin to the aqueous preparation of I violacea which is reported to have LSD like effects.

Wasson testifies in an Psychedelic Review article that the preparation was key to the activity and that the results were very much LSD like, he said he had taken the seeds in his home in New York and that the seeds were as potent when grown there as they were in Mexico.

Think about this: Wasson took the traditional prep of the seeds and reported LSD like effects, Hoffman who was familiar with LSA found it in the seeds and assumed that being similar to LSD chemically, it was responsible for the effects, however Hoffman's bioassay of LSA and Wasson's bioassay are extremely different.

Seeds of I. violacea cause LSA like effects when ingested in most cases. Extracts of the seeds likewise typically cause LSA like effects. The LSA related alkaloids in I. violacea do not cause symptoms like the aqueous extraction of the ground seeds. Hoffman's pronouncement that LSA was the active compound in the seeds seems to have been accepted due to the chemical relation of LSA and LSD, but no bioassay data exists which supports this conclusion and he would not have found calystegines as that they had not been discovered until 1988. I think the assertion that LSA is the culprit is premature.

Calystegines are used as chemotaxonomic markers for the Morning-Glory family and it is very likely that I violacea and Argyreia nervosa contain them. Also consider that calystegines are water-soluble and the active preparation of the morning glory seeds that results in auditory and visual hallucinations is performed by simply soaking the ground seeds in cold water for 20 minutes or so and then straining and drinking the solution, the seeds themselves are not ingested for ritual purposes and can cause some discomfort when eaten.

Here is what Wasson had to say about the preparation:

In recent years a number of experimenters have taken the Rives seeds with no effects, and this has led one of them to suggest that the reputation of ololiuhqui is due wholly to auto-suggestion? These negative results may be explained by inadequate preparation. The Indians grind the seeds on the rnetate (grinding stone) until they are reduced to flour. Then the flour is soaked in cold water, and after a short time the liquor is passed through a cloth strainer and drunk. If taken whole, the seeds give no result, or even if they are cracked. They must be ground to flour and then the flour soaked briefly in water. Perhaps those who took the seeds without results did not grind them, or did not grind them fine enough, and did not soak the resulting flour. The chemistry of the seeds seems not to vary from region to region, and seeds grown in the Antilles and in Europe are as potent as those grown in Oaxaca. I have taken the black seeds twice in my home in New York, and their potency is undeniable.

The black is widely regarded as the more potent. In some places the black seed is called macho, 'male', and the men take it; the Rives seed, known as hembra, 'female', is for the women. The dose is often seven or a multiple thereof-seven, or 14, or 21; or the seeds are measured in the cup of the hand; or, as one informant in the Sierra Mazateca told me, one takes a beer-cap full of Rivea seed.

Note that the black seed is said to be more potent, the black seed is I. violacea. More potent than Rivea and yet only a beercap full of Rivea is taken. I doubt that seeds, of I violacea which are more potent than Rivea, whose dosage is a beer cap full, require as much to work. I don't know how large the cap in question was but the number of them in the dose is enlightening.

I have read every single LSA and morning glory seed trip report at Erowid and nearly every person who ingested the seeds themselves reported LSA symptoms but no LSD like symptoms. The people who have the best results do not eat the seeds.

Wassons article also had this dosage information about the black seeds: the amount that fills the cup of the hand, or about a thimbleful. Note that a thimble and a beer cap are presumably not that distant in size.

Consider these excerpts from an Erowid experience report:

Having read someone's description of a cold water extraction, I decided to try it one day. I've tried this method several times and will describe my best trip to date following these notes…

I've found that the ideal dose for my body weight (5'9, 200 lb.) is 30 grams of seeds. I TRIPPED HARD AS HELL.

We saw geometric patterns in everything…

It ranked up there with the best trips of my life, and that includes Mescaline, LSD, and Mushrooms. The trip lasted for about 8 hours and seemed to peak at about 3 hours. Unlike an acid trip where I peak rapidly and then come down fast, this is more like I peak slowly, level off, and then come down slow. I am always in control of my faculties, and I could lay down and sleep anytime during the trip, I'm that relaxed.

Some of the success full trips I have read about used 10grams of the seeds and involved hallucinations that were very real looking as well as colors and patters. The word hallucination being far more apt for the experience than it is for LSD, which as Shulgin says causes visual phenomena. I read at Erowid that there are about "35 seeds per gram for rough estimates"

A bit more info: http://en.wikipedia.org/wiki/Ergine

, and LA-111, is an alkaloid of the ergoline family that occurs in various species of vines of the Convolvulaceae and some species of fungi. As the dominant alkaloid in the hallucinogenic seeds of Rivea corymbosa (ololiuhqui), Argyreia nervosa (Hawaiian baby woodrose) and Ipomoea violacea (tlitliltzin), it is often stated that ergine and/or isoergine (its epimer) is responsible for the hallucinogenic activity. In fact, the effects of synthetic ergine and isoergine, are not particularly hallucinogenic, see Mixing the Kykeon below for a summary of human trials, and Chapter 17 and entry #26 of TiHKAL for further discussion. Whether or not these compounds account for the hallucinogenic effects of the seeds remains unclear.

http://www.erowid.org/library/books_online.../tihkal26.shtml

LA-111, ergine, d-lysergamide. This is an active compound and has been established as a major component in morning glory seeds. It was assayed for human activity, by Albert Hofmann in self-trials back in 1947, well before this was known to be a natural compound. An i.m. administration of a 500 microgram dose led to a tired, dreamy state with an inability to maintain clear thoughts. After a short period of sleep, the effects were gone and normal baseline was recovered within five hours. Other observers have confirmed this clouding of consciousness leading to sleep. The epimer, inverted at C-8, is isoergine or d-isolysergamide, and is also a component of morning glory seeds. Hofmann tried a 2 milligram dose of this amide, and as with ergine, he experienced nothing but tiredness, apathy, and a feeling of emptiness. Both compounds are probably correctly dismissed as not being a contributor to the action of these seeds.

From personal communication I have learned that I. carnea seeds have been said to be between I. Violacea and A. nervosa in potency. Considering that I. carnea has a decent amount of calystegines and low to no LSA from what I have read, I believe that calystegines may be the active component of I violacea and A. nervosa.

I also have an interest in that the results of ingesting potato family hallucinogens seems inconstant with the effects of their tropane alkaloids alone, such as scopolamine I propose the nortropane calystegines are serious contributors.

http://www.erowid.org/psychoactives/faqs/n...highs_faq.shtml

Scopolamine was found to produce a state of excitement followed by a kind of narcosis in which, in the transition state between consciousness and sleep, hallucinations sometimes occur (Heimann, 1952). These effects explain the addition of belladonna and other solanaceous plants as ingredients of magic brews in medieval Europe and of sacred medicines by the Indians of Mexico and South America."

(Schultes and Hoffman, 1980)

I think Hoffman and Shultes were mistaken not only about the LSAs, I think they were wrong about scopolamine explaining the effects of the involved plants. Scopolamine must contribute, however I think that the calystegines contribute more to the action of these types of plants than is presently known. Of course I may be wrong.

[Gunter]

One more thing, calystegines are found in coca plants (Erythroxylum species.) Coca plants have been used as ayahuasca additives but the effects of cocaine tend to be short lived, it may be that coca is added for the calystegines themselves and it would be a source of them that lacks the more potentially dangerous alkaloids that Brugmansia species contain, such as scopolamine. Also please note I am not saying that scopolamine rich plants can't be used safely.

I also know that people often smoke scopolamine rich species and there is mention that I. carnea leaves are smoked for psychoactive effect. The scop rich species often contain calystegines so I wonder...

[Auxin]

One clue that has not been mentioned: the Ipomoea muelleri paradox in which some reports state that it is of comprable potency to species with 2 to 10 times the ergoline alkaloid concentration. Could just be some folks got abnormally strong I. muelleri or prepared it better but given this new evidence that might be a premature assumption.

[Gunter]

Nice info Auxin, I had no idea!

I am thinking that Morus alba may be a good choice for investigation. I picked some Morus material today but didn't have the guts to mash it up and take a cold water soak of it... maybe later.

It is worth noting that calystegines are not illegal in any nation despite being present in several psychoactive species. I also wonder if they can alter various experiences instead of being active on their own.

[teonanacatl]

nice work archaea. you show good suportive evidence, time to try a bioassay to clinch it i think.

[teonanacatl]

with LSA being so sensitive to light and heat and tropanes being stable you could leave in the light for a while an extract from HBWR or MG and see if it retains activity, Ehrlich's reagent could be used to test the degredation of LSA.

[MORG]

with LSA being so sensitive to light and heat and tropanes being stable you could leave in the light for a while an extract from HBWR or MG and see if it retains activity, Ehrlich's reagent could be used to test the degredation of LSA.

So perhaps failed attempts at tripping with old seeds are due to extraction methods too? i.e. LSA has broken down so crude extraction or seed ingestion yields no activity. And maybe it's still possible to get something from older seeds if your techniques are calystegine friendly?

Interesting thread...

[Rev]

i might add that Rivea seeds ARE active

15 fresh seeds are said to produce a mild intoxication similar to 1 to 2 fresh HBWR seeds

with Lysergic tendencies

They are bitter as Fck , like nasty blotter

or so i am told

[Torsten]

the problems with various researchers not being able to get effects from various potent Convolvulaceae can in most cases be tracked down to two issues:

1) seed was old

2) the extraction method allowed oxidation

Point one has been shown time and time again with Rivea seeds, which are simply no longer active after a few weeks/months. I have nibbled both fresh Rivea and Ipomoea seeds straight off the vine and got mild effects even from just a few seeds, however never had any decent effects from stored seed.

Point two is probably the greater variable. I had a friend in germany who spend literally hundreds of kilos of HBWR to try and work out a way to make a stable extract. He found out the hard way that any applications of heat or any exposure of the extract to air would render it useless (he was trying to make a dry powder extract for encapsulating). In the end he settled on an alcoholic extract as this was one of the few forms that stayed potent. Plain water extracts often lose the potency in a matter of hours to days. Saliva extracts almost universally fail.

One important aspect of extraction seems to be particle size. Fine powders are much more productive than chewed seeds. This is reinforced by the fact that swallowing the (5 minutes) chewed seeds will provide more than 50% of the potency.

Extracts have since been made in europe and marketed there, but they employ full extraction under the same conditions as listed in the literature for LSD production and the conversion to the tartrate before marketing. The tartrates of Lysergic compounds are well known to be stable while most other salts aren't. Surely this might apply to calystegines as well, but that would be another great coincidence.

I do not believe the calystegines are responsible for the main effect. They may well be responsible for the after effects or underlying effects, and also for the effects of really old seeds. All of these effects are very similar, while quite different from LSD. Then again, lysergic acid amide (singular!) effects are also more of the sedating nature rather than visionary. I think we will find the main active to be an amide of lysergic acid, but not lysergic acid amide itself.

Are the calystegines in Stipa robusta? cos I've had good effects from Stipa and they were very much like relatively fresh woodrose seeds.

[Torsten]

surely it can't be that hard to separate the LSA's from the calystegines?!? With all those hydroxyl on one and the fact the other is an amide there must be an easy preferential solvent based method we can all try.

Like, wouldn't the hydroxyls cause the calystegines to precipitate in an aqueous acetic acid solution?

anyone have solubility data for these buggers?

[apothecary]

Sigma only has nortropane (as far as I could find)

C155 (−)-2β-Carbomethoxy-3β-(4-iodophenyl)nortropane

Biochem/physiol Actions

5-HT serotonin transporter inhibitor; precursor of [123I]nor-β-CIT, a radioligand for SPECT imaging of the 5-HT transporter.

Properties

form

crystalline

optical activity

[α]25/D −67.4°, c = 1 in CHCl3(lit.)

drug control

USDEA Schedule II; Home Office Schedule 2

color

yellow

solubility

H2O: insoluble

dilute aqueous acid: soluble

dilute aqueous base: insoluble

ethanol: soluble

storage temp.

−20°C

[apothecary]

http://www.axxora.com/obesity__diabetes-AL...4.1637.4.1.html

(+)-Calystegine B2

SOLUBILITY: Very soluble in water.

(No google luck for b1,b3,b4)

[Torsten]

so, if calystegine freebase is very soluble in water, and LSA freebase is hardly soluble in water and very soluble in ether, then repeated washings of the polar solvent with water would remove the calystegines.

As most LSA purification steps would go via this route anyway, most crudely purified lysergic acid amides (eg the tartrate salts peddled in europe) would no longer contain the calystegines - yet these extracts are of the same activity as the starting material (except for less nausea and less sedation).

[Gunter]

I have not read any reports of extracts of LSA containing plants resulting in auditory or visual phenomena. I have neither read any reports of Stipa use. I would love to read both. Does Stipa cause OEV's?

I don't understand Hoffmans assertions myself, seeing as how his own bioassay conflicted with Wassons and he still said that LSA was the active.

It could all be a neat coincidence of course, but I wonder...

Edited May 24, 2006 by Archaea

[Conan Troutman]

very interesting posts..

With recent discussions of LSA like activity in certain cyperus species this would lead me to

wonder if there maybe calystegines present??

[Gunter]

Isoquinoline and or betcarbolines seem much more likely to be in cyperus species.