2,5-dimethoxy-3,4-methylenedioxy-amphetamine discussion

[entheogenic-gnosis]

2,5-dimethoxy-3,4-methylenedioxy-amphetamine (DMMDA) has fascinated me ever since I first gazed upon its structure, it has the CH3O (methoxy) groupings at positions 2 and 5 of the benzene ring identical the 2C-X and DOx series, and it possess a methylenedioxy ring attached to carbons 3 and 4, identical to MDMA, MDA, MDE, MDEA, etc...

This is why this molecule caught my attention, at 45:15 minutes into THIS David E. Nichols he goes into a quick SAR activity where he will display a molecule and ask "Is this a stimulant, an entactogen, or a psychedelic?"

he explains that the psychedelics will tend to have methoxy substitutions at 2 and 5, and explains that when furan rings are placed in this same position it also has psychedelic effect, as the methoxy groups are essentially still there, only only they have become cyclized into a 5 membered ring structure with an additional carbon atom, you will notice how the oxygen atoms are in the same location on "the furan ring substituted /amphetamines/phenethylamines" as they would be on the "2,5-dimethoxy substituted amphetamines/phenethylamines", (if the furan rings contain double bonds it creates a new compound (these are the "Dragon-fly" compounds) ) resulting in similar pharmacology, both these series of compounds will have a halogen, an alkyl chain, or something else, at position 4, meaning that if you have something hydrophobic or lipid like at position 4, and methoxy groupings or furan rings covering 2 and 5, it's likely psychedelic.

He then outlines the 3,4-methylenedioxy-substituted compounds, and the 3 and/or 4 carbon substituted amphetamines and explains how this substitution results in an entactogenic or psychostimulant pharmacology depending on serotonin agonism...3,4-methylenedioxy substitutions are generally entactogenic, substitutions at 3 and/or 4 or are generally psychostimulant.

With DMMDA This structural combination between psychedelic and entactogenic substitutions caught my eye. Though in reality there doesn't appear to be anything entactogenic here. The effects are actually very light until the high end of the dose spectrum is reached, even at 50mgs effects were described as "light", though abstract thinking was apparently induced:

with 50 mg) In the middle of this all, I found myself getting into abstract thinking, and maybe some imagery as well. The effects were disappointingly light

Shulgin states:

DMMDA was the first of the tetraoxygenated amphetamine derivatives that was ever explored in man, back in 1962. -PIHKAL; shulgin

So it's a wonder it's not a more well known compound...

Not much is said in PIHKAL, some brief history and some information on the compounds structure and the structure of related compounds dominates the "extensions and commentary" section for this compounds entry, one qualitative report did catch my attention:

(with 75 mg) This was equal to somewhere between 75 and 100 micrograms of LSD. I was caught up with the imagery, and there was an overriding religious aspect to the day. The experience had an esthetic value. I liked it. -PIHKAL; shulgin

In Jared ledgards "a laboratory history of narcotics volume one amphetamines and derivatives" he mentions the compound as having LSD like effects, and PIHKAL vaguely corroborated this assertion, which again, caught my attention.

The final qualitative entry in PIHKAL hints at Entheogenic properties as well, stating that "there was an overriding religious aspect to the day"

Shulgin also gives this detailed report:

Date: Nov. 15 1962
Subject: Alexander Shulgin
Observer: A.O.

Dose 24.7mg (<0.3 mg/kg) 7:17 AM. All times corrected to this. I shall transcribe my notes taken throughout the experiment, as far as they are legible.

Comments are added in [].

1:15 Intoxication hit - very very like LSD eyes 30% dilated [there was absolutely no preliminary warning in the form of nausea]

1:45 Shaky - leg problem [knees a little weak] not much more intoxicated - eyes 50% dilated.

1:55 Into head - mild depersonalization (as w/ LSD) - took crap, wiped - sans really caring - eyes closed - slight early - mescaline clouds - no color [this was last urination in nearly 4 hrs - cannot recall amount voided]

2:00 Time seems slightly slowed - warm feeling in genitals - may yet be nauseated [handwriting deteriorating]. Tried to proof-read a couple of papers - wow [actually did an excellent job]

2:05 teeth rubby - legs w/ ataxia (very mild) still feel a little urpy.

2:10 talk a little garbled - taste in throat of something eaten a couple of hours ago (nothing) - slight nausea

2:10 arm ataxia now too [handwriting quite bad]

2:15 good & drunk now - no motion, no color.

2:20 time subjectively slowed - feel that several people have become aware - AO assures me not so. pulse 92 [felt guilty being in back of lab looking at clock for such a long 15 seconds - felt certain I was conspicuous]

2:30 I am certainly as intoxicated as under 80 (micrograms) LSD.

2:35 subject AQ knows [he didn't, when I confided in him later] AO says no - must remember molasses joke [which undoubtedly seemed much more funny then it was - I laughed uproariously]

3:00 must be paranoid [I sure was] - I am sure Uma knows but how can I ever find out - paradox of observation - reflexes are excellent though coordination pretty grim [handwriting pretty grim too]

3:15 into dark room - interesting 3D effect from nude on door - must check [actually it was a photograph of the cushion she was resting on that had the 3D effect - had to feel to make sure button and cushion weren't attached in reality to the door] afraid of discovery - coming out - seen by both Val and Wind -
they both looked at me strangely - verified that they couldn't have seen me come out of dark room Janitors closet [true] druggedness of lots LSD - but seem to be able to cope w/ people

3:25 teeth still rubby - no nausea

4:05 mental stuff going fast - I am hyperthyroid - but luckily w/ pretty good coordination - intoxicated still - going full blast. I may recover [at this time I sailed into stockroom to wrap a gram bottle of methylenedioxy amphetamine for Gladys - swept in did the job - swept out quickly & efficiently]

4:25 lucid - clear

4:45 eat lunch - mouth doesn't quite work right yet [the apple was almost too much][and seemed incredibly noisy]

5:15 seem to be out of the drug OK [handwriting normal]

5:45 occurs to me to urinate. Hadn't all morning. Small pass - strong color [no odor] right eye still dilated, left almost normal [It seems to be difficult to function the muscles necessary to urinate - could there be a little paralysis?]

6:05 teeth still disturbingly rubby. I'm going to load up on coffee.

7:15 (2:30 real time) passed another 50 cc urine - color O.K. all will be O.K. - write all this up now [which I just did, at this time].

End of concurrent notes. time 3:00 PM (7:45 of experiment)

At 8hrs - urinate again - but muscles still don't seem to be right - also still some tremor in hand - tingle in legs. apparently really have some ache shock.

Eye dilation gone at 8:00 PM (13 hrs) and urination apparatus worked normally. slept well - AM - excellent spirits.
DMMDA - Erowid Exp - 'Subjective Response'

After first discovering the compound many years ago, I set the information aside and did not resume research until reviewing its synthesis in Jared ledgard's "amphetamines and derivatives" last week, where research resumed.

this compound is interesting in every way, LSD like action, structure which relates to the 3,4-methylenedioxy entactogens as well as the 2,5-dimethoxy psuchedelics, and a great synthesis procedures which are actually fairly simple, but still retain enough challenge to keep it interesting.

At this point I'm interested in anything related to this compound, anecdotes, research papers, publications, thoughts, ideas, opinions, anything...

-eg

 

[entheogenic-gnosis]

2,5-dimethoxy-3,4-methylenedioxy-amphetamine (DMMDA) molecule.

-eg

 

[entheogenic-gnosis]

I have been looking for information on the N-methyl homologue of DMMDA (2,5-Dimethoxy-N-methyl-3,4-methylenedioxy-amphetamine ) and have come up with very little...

Any information would be appreciated.

-eg

 

[downwardsfromzero]

The Shulgin Index states that there is nothing known of DMMDMA save for the synthesis mentioned in PIHKaL. The lower homologue 2C-DMMDMA has a reference regarding its synthesis (Dallacker et al., 1971), also including 2C-DMMDA which has a further reference (Supniewski, 1932) stating: "2C-DMMDA in the mouse causes respiratory paralysis, in the cat causes a drop in blood pressure and heart dilation, in the frog causes irregular heartbeat and acceleration of respiratory movements; responses are similar to those produced by mescaline." [emphasis added] Such an activity is, I feel, unsurprising although these crude animal tests in no way suggest central activity in humans - but it is, indeed, a tantalising hint...

*Supniewski, J.V. (1932) Pharmacodynamic properties of β-apioleethylamine. Acta Biol. Exptl. (Warsaw) 7: 49-60.

Also worth considering might be the 2,3-dimethoxy-4,5-methylenedioxy isomer,

which is to dillapiole as the "original" DMMDA is to apiole (parsley apiole) itself. And the N-methyl of that, of course.

In benzodioxole-style nomenclature, these would be 4,5-dimethoxy-6-(2-aminopropyl)-1,3-benzodioxole and 4,5-dimethoxy-6-(2-(methylamino)propyl)-1,3-benzodioxole, or thereabouts. And the "original" would be 4,7-dimethoxy-5-(2-aminopropyl)-1,3-benzodioxole, etc.

 

[entheogenic-gnosis]

Thank you for responding to this! I greatly appreciate the information.

I've been incredibly busy today, and I'm exhausted, but I returned to the nexus just to write a short response to this post, even though I need rest.

I'm going to go into great detail in this area first thing tomorrow morning when I'm rested enough to produce an adequate response.

DMMDA and DMMDA-2 are both part of shulgins essential amphetamines:

The spice cabinet is a rich source of chemical treasures, each source plant containing a host of com-pounds, some of which are true essential oils. And the next spice from the next plant has some of the same components and some new ones. Does one organize by plant (spice or herb) or by essential oil (amphetamine)? Let's do it by the ring substitution pattern of the amphetamine, and gather the spices and oils as a secondary collection.

(8 ) The 2,5-dimethoxy-3,4-methylenedioxy pattern. The parent allyl benzene is apiole (with a final "e" ) or parsley camphor, and it is the major component of parsley seed oil. Its conjugated isomer is called isoapiole, and they are valuable as the chemical precurors to the amination product, DMMDA. Whereas both of these essential oils are white solids, there is a green oily liquid that had been broadly used years ago in medicine, called green, or liquid apiol (without the final "e" ) . It comes from the seeds of parsley by ether extraction, and when the chlorophyll has been removed, it is known as yellow apiol. With the fats removed by saponification and distillation, the old term for the medicine was apiolin. I would assume that any of these would give rise to white, crystalline apiole on careful distillation, but I have never tried to do it. The commercial Oil of Parsley is so readily available.

(9) The 2,3-dimethoxy-4,5-methylenedioxy pattern. The second of the three tetraoxygenated essential oils is 1-allyl-2,3-dimethoxy-4,5-methylenedioxybenzene, commonly called dillapiole and it comes, not surprisingly, from the oils of any of the several dill plants around the world. It is a thick, almost colorless liquid, but its isomerization product, isodillapiole, is a white crystalline product which melts sharply. This, by the theoretical addition of ammonia, gives DMMDA-2.
Shulgin;PIHKAL;TMA entry: essential amphetamines list

I actually have quite a bit to say about DMMDA, I can't go into synthesis details here, but there's quite a bit of other research research which I have been conducting that I can discuss, and, there is plenty of research that still needs to be done:

EXTENSIONS AND COMMENTARY: DMMDA was the first of the tetraoxygenated amphetamine derivatives that was ever explored in man, back in 1962. And it is not easy to find an acceptable single phrase to describe its action or an acceptable number to describe its potency. I have put the value of 10 mescaline units (M.U.) into the literature and this would imply that maybe 30 milligrams was an active dose. This is probably too low, and some day I would like to run an experiment with the entire research group with this compound to see just what it really does.
Shulgin;PIHKAL;DMMDA entry

I'm half asleep, and wrote the tangent beneath the bold line in regards to independent research that has been conducted in the past, it was quite long, but I did not want to delete it, so.I moved it to.the bottom beneath the bold line.

Any way, I've been doing tons of research regarding 2,5-dimethoxy-3,4-methylenedioxy-amphetamine, 2,5-Dimethoxy-N-methyl-3,4-methylenedioxy-amphetamine, as well as the closely related 2,5-dimethoxy-3,4-dimethyl-amphetamine and 2,5-dimethoxy-3,4-dimethyl-phenethylamine, which are amazing compounds as well.

With 2,5-dimethoxy-3,4-dimethyl-amphetamine and 2,5-dimethoxy-3,4-dimethyl-phenethylamine it is pretty much the only case where the amphetamine homologue is nearly the same potency as the corresponding phenethylamine, generally alpha methylation of a phenethylamine compound will drastically increase its potency...

Any way, this remark from PIHKAL was very intriguing:

(with 32 mg) Superb material, to be classified as a 'true psychedelic' unless one is publishing, in which case it could be best described as an 'insight-enhancer' and obviously of potential value in psychotherapy (if one would wish to spend 30 hours in a therapy session!). I suppose it would be best to simply stick with the insight-enhancing and skip the psychotherapy. Just too, too long. There was not any particular visual impact, at least for me. The non-sexual and the anorexic aspects might indeed change, with increasing familiarity. Remains to be seen. The length of the experience is against its frequent use, of course, which is a pity, since this one is well worth investigating as often as possible.
Shulgin;PIHKAL;2,5-dimethoxy-3,4-dimethyl-phenethylamine entry)

I have to be awake really early tomorrow, I was awake incredibly early today and have done a ton of work today as well, so I need rest, but I'm going to get back to this topic as soon possible.



-eg

-------

Should have been deleted:

Casey hardison preformed an independent survey involving a large group who had bioassayed 2C-t-7, this research caught the attention of, and was published by MAPS. This type of research was right in line with the type of research which Darrell Lemaire and Alexander shulgin would be quite familiar with, and seeing that Casey had a chemistry degree was capable preforming research of this type, it's no surprise that Darrell Lemaire reached out to Casey.

Darrell Lemaire was an alchemist and his "lazy lizard school of hedonism" was his research group, (Darrell Lemaire also provided phenethylamines to the psychotherapy community) shulgin was also an alchemist with a trusted research group attached to him, and clearly it appeared that Casey could be an alchemist capable of brilliant research as well, at least this is why I think Darrell Lemaire reached put to Casey, well, that, and it's clear that Casey had the proper energy, philosophy, intelligence, out-look, and enthusiasm. His defense in court after his troubles in the UK was a true inspiration, he made a reasonable and eloquent case for these beautiful molecules and for every humans God given right to consume them. Casey made the case which I would imagine myself making in that situation, and it's clear that he was genuine.

These molecules and the magic of the chemistry related to them will open up opportunities for receptive individuals, they will set you in line with a beautiful "Tao" (for lack of a better word) where the universe will provide everything for you almost effortlessly, and the universe, and the power of these molecules will seemngly "look out" for you, it's a type of indescribable magic that must enter the life of every Entheogenic chemist...

Casey Hardison, a graduate student at the University of Idaho, conducted an informal survey of 2C-T-7 users at the Entheobotany conference in Palenque, Mexico in February 2000.

-eg

 

[entheogenic-gnosis]

So far, 2,5-dimethoxy-3,4-methylendioxy-amphetamine and it's N-methyl homologue, 2,5-dimethoxy-3,4-dimethyl-phenethylamine/amphetamine, 2,5-dimethoxy-4-methyl-phenethylamine, and 4-methyl-2,5,beta-trimethoxy-amphetamine have dominated my research.

Any information regarding any of these molecules would be much appreciated.

-----

Speaking of novel methylenedioxy substituted molecules, I have also had much interest in 4,5-methylenedioxy-N,N-diisopropyl-tryptamine and 4,5-methylenedioxy-N,N-dimethyltryptamine. The methylenedioxy substitution pattern had much success in the phenethylamine world, but has not been seen much use in the active tryptamine world. Positions 4 and 5 are you substitution "hot-spots" on tryptamine molecules, so it's a wonder that this pattern with so much success in the phenethylamine world was not further explored when applied to the "substitution hot spots" of tryptamine molecules.

4,5-methylenedioxy-N,N-diisopropyl-tryptamine
(25 mg, orally) Nothing much happened for about 3 hours, and then I suddenly shot up. I was at the plateau for a fair time, the recovery was difficult to define chronologically. This was in daylight; I was reminded very much of LSD -shulgin; TIHKAL

This was the only qualitative comment given by shulgin for either molecule. In my mind it shows promise and warrants further research, however I've been quite occupied with the phenethylamines mentioned above, and may not have the time to dedicate to researching these molecules for quite sometime.

-eg

 

[entheogenic-gnosis]

Jared ledgard' s 2,5-dimethoxy-3,4-methylenedioxy-amphetamine entry
Though this sample of the book cuts off page 242 and forward.

I've been working on a modification of the technical work-up for the synthesis of DMMDA found in the above link with great sucess...

... but I still have some lingering interests regarding the pharmacology of this compound as well as the subjective phenomena produced by consumption of this novel alpha-methyl-phenethylamine...

I think the majority of the published reports are already found in this thread...even erowid was limited to 2 entries, both authored by shulgin.

Again:

DMMDA was the first of the tetraoxygenated amphetamine derivatives that was ever explored in man, back in 1962. -PIHKAL; shulgin

This compound is far from new, being explored in humans as early as 1962, and being known as a psychoactive for just as long (if not longer) so I'm curious as to why information is so limited in this regard.

I've seen some other forums discussing this compound, and was fairly disappointed, a good deal of misunderstandings, factual errors, and misinformation, I can say that I'm not missing much by not participating in other forums, honestly I generally won't even read other forums unless it's a topic on which information is sparse, and in this case it was a fruitless venture, yielding nothing of value...thank God for the DMT-nexus, which is the only forum I will ever use.

I'll keep doing research. I wish I could discuss synthesis, but there's still a good deal here to discuss otherwise...

I feel the extensions and commentary excerpt from PIHKAL for DMMDA was quite fitting for this thread, as it covers many of the points previously mentioned here:

EXTENSIONS AND COMMENTARY: DMMDA was the first of the tetraoxygenated amphetamine derivatives that was ever explored in man, back in 1962. And it is not easy to find an acceptable single phrase to describe its action or an acceptable number to describe its potency. I have put the value of 10 mescaline units (M.U.) into the literature and this would imply that maybe 30 milligrams was an active dose. This is probably too low, and some day I would like to run an experiment with the entire research group with this compound to see just what it really does.

The essential oil that corresponds to DMMDA is, of course, apiole from the Oil of Parsley, which again ties together the spice world and the amphetamine world. And there is isoapiole, also a natural thing. This pair represents the ring-substitution pattern of one of the ten essential oils and DMMDA is one of the ten essential amphetamines.

Several people have asked me what I thought about the potential activity of a compound with a methyl group added to DMMDA. One of these possibilities would be the N-methylated derivative, 2,5-dimethoxy-N-methyl-3,4-methylenedioxyamphetamine, or METHYL-DMMDA (or DMMDMA for the dimethoxy-methylenedioxy-methamphetamine nomenclature). It is a MDMA analogue, and is described in the recipe for METHYL-MMDA-2.

The placement of an added methyl group onto the beta-position of DMMDA, rather than on the nitrogen atom, produces a pair of stereoisomeric homologues. These are the threo- (or-trans-) and erythro- (or cis)-2,5-dimethoxy-beta-methyl-3,4-methylenedioxyamphetamines. They have never been assigned trivial names (my original codes for them were S-1495 and S-1496 which is not too intuitively informative). Their chemically proper names would have the 2-amino-3-substituted phenylbutane form. The synthesis of these DMMDA homologues started with the reduction of the nitrosyrene to the ketone (see under METHYL-MMDA-2 for this preparation), followed by methylation with fresh sodium isopropoxide and methyl iodide, to give the beta-methyl product. This formed the two possible oximes, one with a mp of 120 °C, and the other from MeOH with a mp of 146 °C. The 120 °C oxime, with fresh sodium ethoxide gave threo-2-amino-3-(2,5-dimethoxy-3,4-methylenedioxyphenyl)butane hydrochloride. This salt had a mp of 247-249 °C. The 146 °C oxime gave erythro-2-amino-3-(2,5-dimethoxy-3,4-methylenedioxyphenyl)butane hydrochloride with a mp of 188-189 °C. The threo-isomer showed a possible threshold effect at 80 milligrams, with hyperventilation and perhaps some mental muddiness. The erythro-isomer showed no effects, but it had been taken up only to 10 milligrams.

The only other beta-methyl homologue of an active material that was explored chemically, was related to MDA. The ketone (3,4-piperonylacetone, see under MDMA) was methylated with sodium isopropoxide and methyl iodide, and a crystalline oxime was obtained. Reduction with Zn dust gave what appeared to be 2-amino-3-(3,4-methylenedioxyphenyl)butane hydrochloride, but there were sufficient uncertainties (possible dimethylation, only one oxime isolated, the need of strong reducing conditions) that the entire project was placed in, and still is in, an indefinite holding pattern. The similar analogues for DOM are the two Classic Ladies, DAPHNE and ELVIRA, and they, too, are for some time in the future. -shulgin ; PIHKAL

-eg

 

[Mindlusion]

All of the essential amphetamines have been well explored, if not by Shulgin, then by home enthusiasts.

These two especially, DMMDA and DMMDA-2 have been well explored, due to the abundance of apiole and dillapiole, and the pleasant effects of the amphetamine. (compared to not so pleasant ones, like antheole, and the less abundant elemicin and mystricin) DMMDA is much like MMDA and 2-MMDA, a nice drug. The N-methyl analogues suck, following the expected pattern.

DMMDA from apiole is the most common, since apiole is relatively abundant, easier to purify compared to it's isomer dillapiole, which is also more difficult to purify by distillation due to very high bp fraction. Conversely, dill oil can contain almost solely dillapiole, where apiole dominant oils usually contain mystricin as well as dillapiole, which can be frustrating to separate effectively, requiring multiple distillations. So, others will swear by DMMDA-2! Each to his own.

David E. Nichols he goes into a quick SAR activity where he will display a molecule and ask "Is this a stimulant, an entactogen, or a psychedelic?"

I felt the same way about MMDA-2. Very interesting molecule... It first drew my interest when I heard it had very little to no dopamine action.. Strange for an amphetamine, but some of the psychedelic amphetamines do indeed behave this way.

I was looking for a non-stimulating entactogen, MMDA-2 was not very euphoric actually, did not feel much like a stimulant, but it will keep you up at night. It felt more like very mild DOx analogue. A milder MDA perhaps. Had no desire to try it again. MBDB interests me for the same reasons, im sure it will be a better fit than MMDA-2

 

[entheogenic-gnosis]

Thank you for your input mindlusion. It is much appreciated.

·2,5-dimethoxy-3,4-methylenedioxy-amphetamine
·2,5-dimethoxy-3,4-methylenedioxy-N-methyl-amphetamine
·2,5-dimethoxy-3,4-dimethyl-phenethylamine
·2,5-dimethoxy-3,4-dimethyl-amphetamine
·2,5-dimethoxy-4-methyl-phenethylamine (as well the "tweetios" the 2-eto's, -the 2-ethoxy homologues of 2C-D and related molecules, and the 5-ethoxy homologue of 2C-d, and the 2,5-diethoxy homolugue of 2C-D, as well as these same ethoxy substitutions applied to some of the 2C-T-X series, as well as DOM)
Have all been the focus of my recent research, and I have been utterly fascinated by this work, from the relation of these psychedelic alpha-methyl-phenethylamines to the essential oils, and the chemistry which can begin with these essential oils, or even starting from an innocuous item like store bought vanilla extract and ending with 3,4,5-trimethoxybenzaldehyde, to the chemical procedures involved with the synthesis of rest of these molecules, to the novel chemical structures of these compounds (some of which combine moieties of well known psychedelics), down to the most interesting aspect, these compounds effects when ingested, all of it is amazing research and work.

Do you remember Casey hardison's 2C-T-7 survey conducted at the Entheobotany conference in Palenque, Mexico, which was later published by MAPS? This is the type of information I would love to see regarding some of these novel phenethylamines, particularly DMMDA.

DMMDA seems to produce some very novel psychedelic effects, some actually quite similar to LSD, and boarding the entheogenic, as mentioned in PIHKAL:

(with 75 mg) This was equal to somewhere between 75 and 100 micrograms of LSD. I was caught up with the imagery, and there was an overriding religious aspect to the day. The experience had an esthetic value. I liked it
Shulgin;PIHKAL

This is what first drew me to the compound, and what an adventure it has been, in this case this work and research actually turned out to be far more interesting than anticipated, and all of this is still in the very early stages, I intended to continue researching the above molecules as I feel I have just scratched the surface, and there is no shortage of work left to be done.

(Not just with the molecules mentioned, but with many of these novel psychedelic molecules, in PIHKAL/TIHKAL shulgin leaves tons of open ends, leads, and hints towards research which remains incomplete or unconducted all altogether, in Darrell lemaire's publications the situation is the same, anytime you research the work of these big names in psychedelic chemistry, you will also find that there was more work than these individuals could handle, and that they were never shy in regards to putting out there what still needed to be done. )


... I should probably stop smoking cannabis extract before I write these things, as I feel it's starting to affect the content of the posts.

I'm aware that my enthusiasm for psychedelics and their chemistry leads some of my speech to be fairly grandiose or hyperbolic, and that at times my writing can probably be perceived as being fairly eccentric, which I don't necessarily think is a bad thing, but I can understand how it "rubs some people the wrong way", any way I've noticed that ingesting cannabis tends to exacerbate these tendencies in my writing, which would be great if I were writing fiction, but which tends to hinder the efficacy of my posts regarding scientific issues such as chemistry or pharmacology...though I'm probably not going to stop smoking cannabis before I write.

-eg

 

[entheogenic-gnosis]

It is an interesting fact that most of the known psychotropic phenylisopropylamines (amphetamines) possess ring-substitution patterns identical to those of natural essential oils. (The single exception is the active 2-methoxy-4,5-methylenedioxyamphetamine (MMDA-2, IId1); neither the allyl nor the propenyl counterpart has been observed in plant extracts.) Thus 3,4-methylenedioxyamphetamine (MDA, IIa) is related to safrole (Ia)2 (Table 1), 3,4,5-trimethoxyamphetamine (TMA) to elemicin3, 3-methoxy-4,5-methylenedioxyamphetamine (MMDA, IIc) to myristicin (Ic)4 (Table 1), 2,4,5-trimethoxyamphetamine to asarone, and 2-methoxy-3,4- methylenedioxyamphetamine (MMDA-3a, IIb) to croweacin (Ib) (Table 1). C. F. Barfknecht, of Idaho University, tells us that there is preliminary evidence that these olefins may be aminated in the living organism, and this reaction can be readily performed in vitro. There are two additional essential oils known that contain the methylenedioxy ring. These are apiole (Ie) and dillapiole (If) (Table 1). the two naturally occurring aromatic ethers are the two possible ring-methoxylated analogues of myristicin. We have synthesized the two amphetamines which correspond in structure to these essential oils, that is, 2,5-dimethoxy-3,4-methylenedioxyamphetamine DMMDA, IIe) and 2,3-dimethoxy-4,5-methylenedioxyamphetamine (DMMDA-2, IIf).

DMMDA was synthesized directly from apiole (obtained from oil of parsley) using the same sequence of steps (isomerization, beta-nitration, and hydrogenation) that was successful in the conversion of myristicin to MMDA4 It was not possible to isolate useful quantities of dillapiole, so it was obtained synthetically5 and converted through the above steps to DMMDA-2.
A threshold intoxication with DMMDA in human volunteers was consistently recognized at about 200 ug/kg (calculated as the free base and administered orally the hydrochloride). With most subjects* concentrations within the range 250-300 ug/kg produced a psychotropic episode with the following chronology. The initial 1.5 h, preceding the first indications of mental change, were quite free of the signs of the autonomic distress that have frequently been observed with both mescaline and TMA, but only occasionally within the MMDA series. Mild incoordination marked the start of the intoxication period which lasted 2-4 h. During this interval there only mild perceptual distortions and, in common with MDA, there were increased generalizations of the thought processes, increased emotional affect and empathy, as well as euphoria and a lack of anxiety. The colour exaggerations of mescaline and the eyes-closed images characteristic of MMDA were absent. The gradual disappearance of this syndrome was complete in 8-12 h the subjects' recall of these events and interpretations was unimpaired, as has been consistently true with the amphetamines. The syndrome of DMMDA-2 intoxication was qualitatively similar in nature; the threshold was first observed at 400 ug/kg and an effective range was established as lying between 600-1000 ug/kg. DMMDA-2 has therefore an activity intermediate between DMMDA and MMDA, the latter being active in the vicinity of 2-2.5 mg/kg.
Two arguments must be considered in any explanation of the activity of compounds such as these. First, it has been suggested that beta-phenethylamines may participate in central nervous system metabolism through ring closure with the formation of an indole intermediate.
This cyclization has been argued as involving an electrophilic attack by the protonated amine on the aromatic ring. In this manner both epinephrine6 and the demethylation products of mescaline7 have been oxidatively cyclized in vitro, although no evidence has appeared to support such reactions in vivo. At first appearance this argument is supported by the observation that the addition of a methoxyl group to either of the ortho- positions of MMDA (to produce DMMDA or DMMDA-2) increases the potency of the product in vivo. Such substitutions would certainly enhance electrophilic ring closure. Specifically, the dose levels of DMMDA and DMMDA-2 reported here allow assignments of potencies of 12 and 5 mescaline units (MU)1 respectively, whereas the trisubstituted counterpart MMDA has a rating of about 3 MU.
An alternate indole synthesis route must also be considered. It will be noted that if the meta-methoxyl group were removed from either of these tetrasubstituted amphetamines (so actually reducing its theoretical ease of cyclization) MMDA-3a (IIb) would be obtained from DMMDA, and MMDA-2 (Id) from DMMDA-2, yet both of these simpler bases are of still higher potencies (MU of 18 and 21, respectively). Thus it may not be the presence, but rather the position, of the additional group that leads to an enhanced activity. This latter route would then suggest an interaction of the amino-groups with a quinonic intermediate in which the oxygen atom of the ortho-methoxyl group participates.
A second argument is that several phenolic amines are known to act as neurotransmitters. Methylated and methoxylated analogues might function directly (without chemical modification) either as inhibitors or as false transmitters in the specific neural networks served. On the basis of this hypothesis a psychotomimetic molecule should be resistant to chemical attack, rather than sensitive to it, as would be required for conversion to an indole.
Any attempts to understand the mechanisms of action of these materials must still consider the qualitative distinctions that have been noted, however. The two new psychotropic agents reported here, as is true with the two-oxygen methylenedioxy analogue MDA, exhibit changes in affect and empathy and in general are intoxicants, but they should not be classified as psychotomimetics. It seems that this property occurs, at least among the phenylisopropylamines only in those which are trisubstituted.
Note
* All subjects were familiar with the other materials mentioned in the comparisons; MDA, MMDA, MMDA-3a.

Shulgin: Psychotropic Phenylisopropylamines derived from Apiole and Dillapiole - [www.rhodium.ws]

-eg

 

[downwardsfromzero]

It is an interesting fact that most of the known psychotropic phenylisopropylamines (amphetamines) possess ring-substitution patterns identical to those of natural essential oils. (The single exception is the active 2-methoxy-4,5-methylenedioxyamphetamine (MMDA-2, IId1); neither the allyl nor the propenyl counterpart has been observed in plant extracts.)

It has now: Asaricin, the Main Component of Ocotea opifera Mart. Essential Oil

This compound, an isomer of myristicin, was first reported in 1970 in an oil from leaves of Beilschmiedia miersii (J. Kumamoto, R.W. Scora (1970) j. Agric. Food Chem., 18, 544-545.)

Asaricin = 2-methoxy-4,5-methylenedioxyallylbenzene.

 

[entheogenic-gnosis]

It is an interesting fact that most of the known psychotropic phenylisopropylamines (amphetamines) possess ring-substitution patterns identical to those of natural essential oils. (The single exception is the active 2-methoxy-4,5-methylenedioxyamphetamine (MMDA-2, IId1); neither the allyl nor the propenyl counterpart has been observed in plant extracts.)

It has now: Asaricin, the Main Component of Ocotea opifera Mart. Essential Oil

This compound, an isomer of myristicin, was first reported in 1970 in an oil from leaves of Beilschmiedia miersii (J. Kumamoto, R.W. Scora (1970) j. Agric. Food Chem., 18, 544-545.)

Asaricin = 2-methoxy-4,5-methylenedioxyallylbenzene.

Thank you. Your input is always appreciated.

These novel phenethylamines have still been the focus of the majority of my recent research, and have actually turned out to be far more fascinating than I had initially anticipated, this is such a rich field of study, of coarse my focus is always regarding synthesis and chemistry, but that's only "half of the story" here as it were...

I have modified synthesis procedures for many of these compounds, and have been making amazing progress, there's definantly no lack of inspiration when doing this type of work...I have also expanded my general research beyond chemistry and pharmacology and have found myself fully immersed in everything related to these molecules, from their chemistry, to their history, to their consumption...

-eg

 

[entheogenic-gnosis]

A Laboratory History of Narcotics, Vol. 1 Amphetamines and Derivatives

A Laboratory History of Narcotics Vol 1 is a revolutionary book that covers the pharmaceutical preparation of amphetamines and amphetamine derivatives. This latest book by Jared Ledgard has reached another plateau of detail, and excellence in the area of laboratory science. The book contains a...

books.google.com

DMMDA from lab history of narcotics

-eg