Sciencemadness Discussion Board - Psychoactive monoterpenes from natural oils

Psychoactive monoterpenes from natural oils

Ritter - 4-7-2008 at 08:19

Quote:

Z Naturforsch [C]. 2007 Jul-Aug;62(7-8):563-6

Sedative effect of monoterpene alcohols in mice: a preliminary screening.

de Sousa DP, Raphael E, Brocksom U, Brocksom TJ.

Departamento de Fisiologia, Universidade Federal de
Sergipe, CEP 49100-900 São Cristóvão-SE, Brazil. desousa@ufs.br

Many essential oils and monoterpenes are used therapeutically as relaxing drugs and tranquilizers. In this study, ten structurally related monoterpene alcohols, present in many essential oils, were evaluated in mice to investigate their pharmacological potential in the central nervous system. Isopulegol (1), neoisopulegol (2), (+/-)-isopinocampheol (3), (-)-myrtenol (4), (-)-cis-myrtanol (5), (+)-p-menth-1-en-9-ol (6) and (+/-)-neomenthol (8) exhibited a depressant effect in the pentobarbital-induced sleep test, indicating a sedative property. (-)-Menthol (7), (+)-dihydrocarveol (9), and (+/-)-isoborneol (10) were ineffective in this test. The results show that these psychoactive monoterpenes have the profile of sedative drugs, and this pharmacological effect is influenced by the structural characteristics of the molecules.

brew - 4-7-2008 at 23:04

Yes these are of interest. I cant find the document at present but a local group of scientists were exploring various traditional chinese medicines/herbs and discovered one that somehow lowered blood glucose without signiling insulin and its effect of glut-4 transporters. This is very good potentialy for those with diabetes. There really is so much too explore. I think this can also, to a degree, be initialy explored in a home lab set-up. Determining the structural characteristics of molecules might be difficult in my backyard and i'd imagine in most but there is things one can determine

Saerynide - 5-7-2008 at 03:27

Someone should do a study on thujone

There are people who swear absinthe is more than just alcohol, and then there are those who say nothing happens.

Nicodem - 5-7-2008 at 04:48

Thujone and pulegone are two examples of simple terpenes with rather unpleasant depressant CNS activity. Camphor is a CNS stimulant (just snort some and you will see what I mean). There are other simple terpenes with CNS activity that might account for the use of some herbs as old time medicines and there are many research papers dealing with this issues. So Ritter, do you mind explaining why you post that abstract without any commentary or question? What is the purpose of this thread?

Sauron - 5-7-2008 at 07:24

I know nothing about pulegone, but thujone (which is by the way pronounced two-yone) is a mild GABA antagonist, and temporarily increases brain electrical activity. I have never heard of any depressant effects.

Camphor and possibly thujone were formerly used as cemical convulsants in psychiatry as alternatives to electroshock. It took rather massive (like 500 mg-1 g) doses i.v. to have this effect. Fortunately AFAIK such barbarities are no longer standard practice.

A lot of the early toxicological research on thujone from the late 19th and early 20th centuries was seriously tainted by subsidies from organizations seeking to justify the banning of absinthe and other herbal liqueurs. As the EU has lifted all national bans on absinthe and merely imposes a very reasonable upper limit on thujone content in such liquors, obviously times have changed. A number of European countries never banned absinthe, including Spain and the UK. Even the Swiss have lifted their prohibition. Modern studies indicate that the high alcohol content rather than thujone was responsible for the effects of absinthe,

Absinthe made in the proper manner by maceration and distillation cannot contain more than the legal EU limit of thujone. Artemisia absinthium is not the principle herb employed in absinthe making. Those are anise, star anise sometimes, and fennel, all sources of anethole not thujone. Thujone comes from the absinthium. While there are many other essential oils that contain thujone, none of those herbs are used in absinthe making. These include the culinary spice sage and arbor vitae.

I used to make absinthe commercially. My former partner is the famous Ted Breaux, who manufactures Jade Absinthe in a century olf absinthe distillery using tradition copper alembics in France. His products are regarded as the finest modern absinthes, a far cry from the sheep dip produced in some eastern european nations.

Ritter - 5-7-2008 at 12:15

Quote:

Originally posted by Nicodem
So Ritter, do you mind explaining why you post that abstract without any commentary or question? What is the purpose of this thread?

This is the Biochemistry forum. I have always been interested in the psychoactive alicyclic natural products such as THC (a terpene-polyketide), nepetalactone, thujone, etc., and thought that posting this information might generate interest in this area as well as some experimentation with realtively easy-to-obtain materials. And it already has started a thread.

Quote:

Yes these are of interest.

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Someone should do a study on thujone

Quote:

thujone (which is by the way pronounced two-yone) is a mild GABA antagonist

If my posting this abstract of a recent research paper of general interest violates some unstated forum rule (the ones that aren't listed in the FAQ), perhaps you should post those rules for us all.

[Edited on 5-7-2008 by Ritter]

Nicodem - 7-7-2008 at 07:55

Quote:

Originally posted by Ritter
If my posting this abstract of a recent research paper of general interest violates some unstated forum rule (the ones that aren't listed in the FAQ), perhaps you should post those rules for us all.

Who said anything about rules? I only asked you if you could describe the purpose of this thread since you did nothing but post an abstract without any comment whatsoever. How is anybody supposed to know what is it that you want or need if you say nothing? Up to now, when one wanted to start a discussion on a topic he did so by literally starting it, while you seem to use a more orthodox approach which is not of my liking but breaks no rules - hence my question.

Ritter - 7-7-2008 at 11:27

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Originally posted by Nicodem

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I felt that that particular abstract spoke for itself. Many here are interested in naturally ocurring & legal psychoactive substances.

starman - 27-7-2008 at 23:48

We have some very interesting long chain resorcinol type compounds available from botanic sources in this part of the world.In searching for an optically active phytochemically derived partner for these I came across Trans p menthadien-(2,8) ol in Cymbopogon giganteus which has a range of reported effects vaying from cannibas like intoxication through to pschedelia/divinatory dreams etc.
Given that the analysis was preformed on steam volatiles I was wondering what else was left behind in the plant(Given the lack of steam volatility of either resorcinol type compounds or THC analogues.Hadn't considered that the humble terpene possessed this type of activity in its own right

kclo4 - 28-7-2008 at 01:49

Very interesting! Here are some other things...

"Conclusion-This study shows that S. nemorosa had both central and peripheral anti-nociceptive activities that may be mediated by opioid receptors." http://www.ams.ac.ir/AIM/0032/hosseinzadeh0032.html

http://research.ncl.ac.uk/medplant/about_mprc/My%20Webs/Sage... - some new chemicals in S. Nemorosa, which are in some ways very similiar to Salvinorin A, and Lactucine.

about Lactucopicrin and lactucine, It is foundin the Lacutca spp; the lettuce species, and occures highest in the wild varieties, such as Lactuca Verosa and Sierolla(sp)

From what i have read, Lactucopicrin is the most active, and can have Anti-nociceptive effects higher then, or equal to ibuprofen. It is an Enkephalinase Inhibitor.

I believe that the chemicals in salvia nemorosa are also enkaphalinase inhibitors.

Enkephalinase inhibitors elevate levels of endogenous opioids that act at multiple opioid receptors.

I would Imagine that the enkaphalinase inhibitors would only cause significantly notifiable effects if you were in pain, which might make this good to stop drug addiction/abuse. However, I don't know that much about the pharmacology of enkaphalinase inhibitors.. well, not yet anyways!

Ritter - 28-7-2008 at 09:37

Quote:

Originally posted by starman
We have some very interesting long chain resorcinol type compounds available from botanic sources in this part of the world.In searching for an optically active phytochemically derived partner for these I came across Trans p menthadien-(2,8) ol in Cymbopogon giganteus which has a range of reported effects vaying from cannibas like intoxication through to pschedelia/divinatory dreams etc.
Given that the analysis was preformed on steam volatiles I was wondering what else was left behind in the plant(Given the lack of steam volatility of either resorcinol type compounds or THC analogues.Hadn't considered that the humble terpene possessed this type of activity in its own right

That terpene occurs in that plant. Its most published use has been in its acid-catalyzed condensation with 5-alkylresorcinols such as olivetol to synthesize various isomers of tetrahydrocannabinol.

Quote:

Syntheses of THC and Analogs
L-(-)-delta-1(6)-THC HCA 52,1123(1969), cf. JACS 96,5860(1974).

Method I
This method gives about 50% yield for THC and about 90% for the 1',1'- dimethylpentyl analog. Olivetol 4.74 g (or equimolar amount of analog), 4.03 g (+) cis or trans p-methadien (2,8)-ol-1 (the racemic compound can be used but yield will be one-half), 0.8 g p-toluenesulfonic acid in 250 ml benzene; reflux two hours (or use 0.004 Moles trifluoracetic acid and reflux five hours). Cool, add ether, wash with NaHCO3 and dry, evaporate in vacuum to get about 9 g of mixture (can chromatograph on 350 g silica gel - benzene elutes the THC; benzene:ether 98:2 elutes an inactive product; then benzene:ether 1:1 elutes unreacted olivetol; evaporate in vacuum to recover olivetol).

Source: http://designer-drugs.com/pte/12.162.180.114/dcd/chemistry/p...

Do you have any references on CNS activity in that terpene? It is of interest as being possibly another example of a psychoactive tertiary allylic carbinol.

[Edited on 28-7-2008 by Ritter]

(+)-trans-Mentha-2,8-dien-1-ol.gif - 5kB

(+)-trans-Mentha-2,8-dien-1-ol.gif - 5kB

starman - 28-7-2008 at 17:53

Yes Ritter,have both those papers in full.Also a great many others all the way back to the Adams /Todd era of the 1940's.The first ,racemic,low yeild condensations for delta 9 had citral(also derived from a lemongrass member) as the terpene.Inthe cannabis plant one sees no longer condensable p cymene as the terpene component.I suupose my interest is whether a p mentha type compound could possibly account for the reported activity or there are moe interesting non-volatiles yet within,with the p mentha compound uncombined giving us a clue to what they might be.Any thoughts?

Ritter - 28-7-2008 at 18:39

I did not find any references to any biological activity of that terpene, which is my main interest.

Cannabanoid synthesis is very difficult & involves multi-step chemistry to just get to the 5-alkylresorcinols. The tetrahydrocannabinols are resinous products that are hard to work with. In summary, not a likely field to find amateur experimentalists.

starman - 29-7-2008 at 03:12

We have some very interesting long chain resorcinol type compounds available from botanic sources in this part of the world.
Chromatographic separation of these substances is a relatively easy affair.Fast type dyes(literature always say blue but I have used green sucessfully)are essential to view.
They can be resolved both by chain length and degree of saturation(silicic acid impregnated with silver nitrate)
If you review latter research you will see a degree of unsaturation of the alkyl lower carbons furnishes a compound fo equivalent og greater potency to the much vaunted branched side chain such a the dimethylheptyl compound.
Yes even ultra pure thc from state of the art laboratories is always an oil.Many have used the sideways step through the 11 hexhydro crystalline compound as an aid to purification.
Yes synthesis of an alkylresorcinol is well beyond my humble synthetic abilities.Like I said

lucky to live where I do.....

If you would do me the courtesy of carefully reading the post and asuume that I know at least as much as you it would be much appreciated.

Ritter - 29-7-2008 at 04:21

Quote:

Originally posted by starman
We have some very interesting long chain resorcinol type compounds available from botanic sources in this part of the world.
.

Can you supply references or structures? I have fairly extensive files in this area, collected over the years. Biological activity in the tetrahydrocannabanoids falls off below alkyl chain C5 & above C7. There are many naturally-occurring 5-alkylresorcinols that have either chains too short (as in orcinol) or too long to result in biologically active derivatives.

starman - 31-7-2008 at 03:17

Quote:

Biological activity in the tetrahydrocannabanoids falls off below alkyl chain C5 & above C7.

Not quite sure what you are talking about there.Though it is difficult to view the alkyl chain in isolaton all sources agree that peak potency of straight,branched and unsaturated chains occur at C9 and activity at the C10-11 region is still well above the range of natural cannabinoids.
See for instance Martin et al..... Journal of Pharmeceutical and experimental therpeutics....Vol 290 /pgs 1065-1079.
(can down load free at PubMed.)
If you have looked into sources of phenolic lipids you will see this opens up some possibilities,particularly where the double bond is positioned furthe back than C4 allowing for possibly active compounds in the C13 region.A fuul appreciation of the relationship of long chain endocannabinoids such as 2AG si required to select possibly active candidates.
A final word is all these tests(Dog ataxia,mouse tetrad,calcium channel etc are not human testing

Quote:

Cannabanoid synthesis is very difficult & involves multi-step chemistry to just get to the 5-alkylresorcinols. The tetrahydrocannabinols are resinous products that are hard to work with. In summary, not a likely field to find amateur experimentalists

The is no assay like bioassay

starman - 1-8-2008 at 04:23

Dug this out of hardcopy.Is from 'Medical Cannabis' by Lowe and illustrtates a few things to whih I have been refering.
M,N,E,F,Q and G represent straight and various branched chains for delta 9 series.
The lower series of lines are various delta 3 series.
As you can see peak activity in the side chain relates to the position of(or absence of) the double bond in the terpene ring.This relationship became much clearer with the discovery of substances like anadamide and 2AG.
Hope is a useful addition to your extensive files in this area.

Ritter - 1-8-2008 at 10:17

Quote:

Originally posted by starman

Hope is a useful addition to your extensive files in this area.

Yes, thanks.

IIRC, 1,2-dimethylheptyl was found to be the optimal resorcinol substituent. If that's what they are referring to as 'C-9,' then they are technically correct but it's still C-7 to me. I'm focused on chain length, not the total number of carbon atoms in it.

Since you haven't forwarded any references on the supposed psychoactivity of that terpene, I can only assume that your interest in it relates to homebrewing your own THC starting from it & some local 5-alkylresorcinols. Good luck with that.

[Edited on 1-8-2008 by Ritter]

starman - 1-8-2008 at 17:50

No they both these references are referring to a C9 chain either unsaturated(which was the critical dicovery)or branched at the C1 -C3 position with additional methyl or other groups.If you have information stating the 1,2 dimethylheptyl compound as the most active it is about 20 years out of date.
I put my 2 cents worth in on this thread primarily for my interset in biosynthetic pathways.Cannabis ,to my knowledge is unique in the regard of combining a monoterpene with a phenolic lipid to furnish a pharmacologically active compound.I had wondered abou the presence of the ideal relatively unusual monoterpene in the presence of an essential oil of a reportaedly psychoactive plant.

You may note I preface a statement "to the best of my knowledge"in areas of my uncertain knowledge.Something you might wish to consider where your knowledge is facile at best.

Ritter - 2-8-2008 at 06:12

Quote:

Trans p menthadien-(2,8) ol in Cymbopogon giganteus which has a range of reported effects vaying from cannibas like intoxication through to pschedelia/divinatory dreams etc.

Since you have been unable to provide the requested references supporting this claim, I can only assume that it is bogus. Your real interest in this terpene appears to be, as I have posted earlier in this thread, as the terpene synthon in a well-known synthesis of THC & analogs of it. I would greatly appreciate getting this thread back on topic for psychoactive molecules from natural oils, primarily terpenes but including also molecules such as thujone & nepetalactone. If you want to discuss THC chemistry, I suggest you start a thread on that topic.

starman - 2-8-2008 at 17:01

Yes ,rereading that post I see I havce written in ambiguity.It is lemongrass plant Cymbopogon giganteus which has reported psychoactive affects.Not specifically the terpene isolated in the essential oil.That lead to speculation on non-volatile phenolic lipids and the whole THC sidetrack.
Most of my files are boxes of photocopy but can dig this reference up(I make a lousy secretary)From memory, a group of African tribes were smoking the dried plant in ritualistic fashion,seeking knowledge of the future.