Posted by: Lines_of_Thought
July 23, 2015
MDMA is one of the most popular drugs of the past few decades. It began in 1912 when a Merck chemist named Anton Kollisch. The discovery of the compound was a freak occurrence in the search for a substance that could prevent internal bleeding. The compound was only an intermediate in the synthesis to Methylhydrastinine and as such it’s effects were never seen. However a patent was filed and in it was the synthesis.
It was then promptly forgotten about until 1927 when a chemist named Max Oberlin studied it’s pharmacological effects on smooth muscles and related it’s effects to ephedrine. However again it was lost to the sands of time until the ’50s.
During the 1950’s Merck began to study it again and the CIA used it as one of the numerous drugs used in MKUltra.. However it wasn’t until the 1976 that it was used as a recreational drug, by Alexander Shulgin, the “Father of MDMA”.
After initial usage and spreading it to his colleagues at Berkely, word began to spread of it’s unique empathogenic properties and for a long time it was used as tool for psychotherapy and for a select few, recreation. Soon enough, it was being manufactured to sell to the public in clandestine laboratories. It’s use started to become involved with the gay scene in the US, which then moved to a more public level with nightclubs around the country being introduced to this new compound.
Then in the late 80’s it hit the UK. The British took it’s use to a whole new level, creating all kinds of music to fit the compound’s personality and the parties held would be rich in colour, social inhibition and loud repetitive music. This movement was a major part of how society is structured today and was a significant catalyst for electronic music of all kinds.
MDMA’s pharmacology is quite unique in comparison to other phenethylamines. This is due to it’s methyl bond at the amine (the nitrogen). Usually adding an N-methyl bond would eliminate it’s activity as with Methyl-DOB and even Methyl-MMDA-2 (another methylenedioxy compound). MDMA is a serotonin, norepinephrine and dopamine releasing agent and also acts as a weak 5-HT1 & 2 agonist. Activation of the serotonergic system also releases large amounts of Oxytocin (a compound that enables the user to free their inhibitions and trust more often), due to it’s 5-HT1a agonist capacity.
It’s parent compound, MDA, however, while being similar in it’s releasing agent properties has a higher affinity to the 5-HT2a receptor (responsible for visuals). It may even have reuptake inhibition properties like the analogues of it 5 & 6-APB. This 5-HT2a agonism however becomes a lot more apparent once you start to add substitutions on the other positions of the molecule. For instance MMDA-3a is primarily a visual distortion agent, with much milder empathogenic properties.
Once you start to play with the MDA basic compound, the effects get more and more interesting. For instance MMDA (5-Methoxy-MDA) is famous for it’s ‘brain movie’ properties which is quite unique in the world of psychedelics (that we know about of course!). Further alteration of the main compound increases visual aspect and can increase the euphoric aspects to the compound.
Such compounds as 5-APDI (MDA with a simple pyrollidine ring instead of the usual methylenedioxy ring) are twice as potent and have a far longer duration but in addiction to this it is a selective serotonin releasing agent. This causes a lighter amount of euphoria but it retains serotonin receptor agonism causing more visuals and due to the 5-HT1a agonism, release of dopamine (which causes even more euphoria).
So as we can see with these examples of MDA analogues there is much to be done. There are literally hundreds of analogues that could be much more effective empathogens and/or hallucinogens. Various positions on the main molecule give various different effects. So the 2 position next to the alpha-methyl, if a methoxy bond is added it increases potency around 4x. The 3 position (or 5 as stated in most modern guides) while it does produce increased visuals, lowers the potency slightly and you’d be unable to add the 2-MeO bond as it would become too bulky. The 5 position however (or 3 as stated by Shulgin/modern literature) both increases potency and increases visual affect.
The main additions one could add to these positions are numerous however if they become too heavy they will lose out on potency or even activity. The 2 position must hold a methoxy bond, however the other two can be played with in many different ways. Basic alkyl bonds up to perhaps the molecular mass of an ethoxy bond (for instance: Ally, Vinyl, Ethanyl). Then Thiosulphate and Oxygen bonds with similar alkyl bonds attached. Or halogens, used in various different ways (such as methylfluoro, Chloro, Thiomethylfluoro etc.). These can all be used in different ways but should be limited to only on positional substitution, except if following DMMDA, then the bonds should be kept quite light.
Other positions include; at the 3,4 position where the Methylenedioxy ring is held (this can be substituted for benzofuran rings, Methylene-6-thio-5-oxy, Methylenedithio, Ethylenedioxy, Cyclopropyl (with each end at the 3 & 4 positions) etc.), each opposite position of a benzofuran ring (i.e. 5-fluoro-6-APDB, 5, 6 dimethyl-IAP, or even deuterium bonds at each position on the ring), the alpha position (not much can be done here as anything much larger than an ethyl bond turns it into an antidepressant with SSRI effects, however there could be some leniency for a methyl, vinyl or methoxy bond), the beta position (where cathinones traditionally have a ketone bond, however vinyl, methoxy, methyl or even fluorine bonds could sit here) and finally at the amine where MDMA holds it’s methyl bond (again not much can be done here, apart from perhaps a methoxy or fluorine bond. However with the use of that 2-MeO bond, one could potentially have allyl, isopropyl, butyl or even a cyclopropyl bond).
So as you can see there is a huge amount of analogues that could be produced. Each one untested but waiting for that one guinea pig to find the right combinations to produce some gems. In my opinion this one; [2-amino-1-(1-fluoro-4-hydroxy-1H-inden-5-yl)-1-hydrogeniyliumprop-2-en-1-yl]hydrogenylium (or FHDV-API) would be wonderful.
The deoxygenated ring would make it more similar to 5-APDI however with a double bond along one side (lightening psychedelic and empathogenic effects as too much could be dangerous). The fluorine could decrease potency however it could enhance either euphoric or psychedelic effects. The hydroxy at 5, being fairly lightweight would increase potency and psychedelic effects, the dideuterium bond at the beta position should smoothen the compound out so that any bodyload that could occur would be eliminated and the alpha-vinyl bond could decrease potency and reduce stimulant effects or it could do the complete opposite. We’ve not seen either the Fluorine or the Vinyl at these positions before in pharmacology so their effects are somewhat unknown, except via SAR (Structure Activity Relationship) study. Use of an NMDA antagonist, such as Memantine or Huperzine A may be needed for protection from neurotoxicity when first being tested.
The future is now and as we enter new realms of being we should adapt to this new environment. This means change from the old ways. Nothing was ever accomplished by living in the past so let’s live in a new world. A world that’s bright, euphoric and with a few more fluorines!