------------------------------------------------------------------------------- Notes on the pharmacology of 4-Methoxymethamphetamine (4-MMA or PMMA) ------------------------------------------------------------------------------- Initial characterization of PMMA as a discriminative stimulus. Abstract The phenylisopropylamine PMMA or N-methyl-1-(4-methoxyphenyl)-2- aminopropane, a structural hybrid of paramethoxyamphetamine (PMA) and methamphetamine, has been previously shown to unexpectedly lack amphetamine-like or hallucinogen-like stimulus properties in animals. For example, in tests of stimulus generalization, neither a (+)amphetamine stimulus nor a DOM stimulus generalized to PMMA. It has also been shown, however, that stimulus generalization does occur in animals trained to discriminate the designer drug MDMA ("Ecstasy" or N-methyl-1-(3,4-methylenedioxyphenyl)-2-aminopropane) from vehicle. In order to further characterize this unique agent, we trained a group of six Sprague-Dawley rats to discriminate 1.25 mg/kg of PMMA (ED50 = 0.44 mg/kg) from saline vehicle. The PMMA stimulus failed to generalize to the phenylisopropylamine stimulant (+)amphetamine, or to the phenylisopropylamine hallucinogen DOM. Stimulus generalization occurred to (+/-)MDMA (ED50 = 1.32 mg/kg) and S(+)MDMA (ED50 = 0.48 mg/kg). Partial generalization occurred with R(+)MDMA, PMA, 3.4-DMA, and fenfluramine. The PMMA stimulus also generalized to the alpha-ethyl homolog of PMMA (EH/PMMA, ED50 = 1.29 mg/kg). Taken together, the results of these studies suggest that PMMA is an MDMA-like agent that lacks the amphetamine-like stimulant character of MDMA. These findings support our previous suggestion that PMMA be considered the structural parent of the MDMA-like family of designer drugs. Ref: Pharmacol Biochem Behav, 1997 May, 57:1-2, 151-8 ------------------------------------------------------------------------------- Beagle Boy: I guess that this must be another paper from Glennon, since discriminative stimulus paradigm is really his bag. It really is the best animal model we have now for evaluating hallucinogens/stimulants, but certainly not as good a way to evaluate a cpd. as shulgins method. Thats the price you pay for govt. funding. Does anyone need an explanation of how discriminative stimulus test works? I guess that these 3 abstracts don't mean much if you don't, so just ask. I view the fact that partial generalization occured to alpha-ethyl homolog of PMA as encouraging, but partial generalization to fenfluramine and 3,4-DMA is confusing. Good thing that we have data on PMMA in humans (thanx dpHarma). Glennon = Richard A. Glennon, chemist/researcher in all things psychedelic or stimulating. Based at Virginia Medical College. Publishes many articles a year on drugs and drug abuse but curiously he seldom references or is referenced by Nichols or Shulgin, the other big names in this area. His papers have shown a softer slant over the years towards drug use. In the paper mentioned in this thread he even says that MDMA has potential to enhance communication. This is very different from previous papers where the evils of drug use are (over)emphasized. I appreciate all his efforts, but have heard that he can be hard to work with. Top-notch scientists can be like that. I once met a former disgruntled employee of his who had some interesting storys to tell. I don't suppose that he stops by here, but if he does: Hey Richard, missing anything? ------------------------------------------------------------------------------- dpHarma: Human trials of 4-MMA! So THAT's what dpHarma will be remembered for! Needless to say folks, dpHarma ain't no dumb ol' guinea pig. no siree! dpHarma's got a dee-ploma! Not dumb at all! guinea pig... well ok! Actually, since Oct. 28, 1998 2am, 4-MMA ain't held a LOT of interest for dpHarma but it is definitly an curious animal. There are clear commonalities w/ MDMA and some obvious ones w/ MDA. Whether it's the parent compound remains to be proven, BUT, the limited research w/ MDMA and the observation of side effects, especially from large extended dosing (up to 280 mg/day for 5 days) of MDMA, produced many transient yet salient effects of bodily sensation and mental aberration, some of which had been very evident w/ 4-MMA. These side effects were very long lasting, some lingering mood elevation, transient chills, and increased tinitus, up to 5 or 6 days after large, prolonged doses of MDMA. The tests, however were not conducted with any degree of control as the MDMA tests followed the 4-MMA tests by only a few days. dpHarma is chagrined that no other private researcher reports human trials of this obvious easily prepared substance! Surely someone prepared (theoretically) 4-MP2P? Surely someone attempted Al/Hg reductive amination using MeNh2? Could someone prepare it and NOT test it? The excellent article posted by Lone Deranger (thanks Lone),does not mention human trials. 4-MMA is a subtle critter with a loud bark. Starts out rough w/ lotsa yawning and jawing, then settles down and disappears. BUT it aint gone, just quietly waiting for some external stimulus (sex works wonders) to present a stimulus response. It's more like a mirror that only shows movement when something is directly in the reflective path. Cannabis also accentuates it's effects and of course alcohol, especially beer and wine w/ their MAOI qualities change the the quality and duration of the effect. dpHrama is mostly concerned about the longer term side effects. So far, all seems well. A 'viral' type digestive tract affliction affecting overall 'wellness' makes observation of subtle factors difficult for now. Whether these are in any way related will have to be determined at such time as they go away, and stay away. Anxiety can also cause digestive upset or IBS so even worrying about possible side effects can cause them! Cholinergic (temp control)factors seems the greatest concern. This is true for MDMA as well and though it's been lotsa years, dpHarma remembers MDA having similar effects. ------------------------------------------------------------------------------- dpHarma: 4-MMA **WARNING** side -effects!!!!! In sharp contrast to previous posts concerning 4-MMA, this once carries a message of caution. recent 'binges' of 4-MMA exceeding 300mg and approaching 500mg. daily over 5 days have produced a 'delayed' onset side-effect. The effect from the the ever-increasing doses was an ever-flattening mental and emotional state until the main effect was curl up and nod. after 48 hrs. cessation, an extremely uncomfortable 'mental' and obviuosly 'brain chemistry' condition arose (presently). A normally bearable tinitus 'shreiks' and explosive 'expansion' bursts in the hearing center causes sudden loud sounds or 'gating' of external sounds. The overall effect is like one of a deadly 'flu' infection. The second feature of this phenomena is acute emotional rawness. anything at all, triggers an outburst of crying uncontrollably.(even typing these words brings tears). The state so far has lasted over 36 hrs, and has lessened only slightly. sleep is nearly impossible due to vivid and relentless mental imagery shifting continuosly around some 'schema' which on evaluation is meaningless. an extreme 'mental' thumb twiddling. These effects and the disturbance caused on general living are not worth enduring for the sake of some 'fun'. whether these or similar effects result from low dosage , occasional use of 4-MMA is unknown. Someone else can check it out, this one is done . Please be careful with this material.. ------------------------------------------------------------------------------- dpHarma: The 'grande' effects so disturbing initially have subsided, but some lingering after effects are going more slowly. Pot exacerbates the 'head noise' causing a loss of enjoyment of this fundamental and essential entheogen. Sleep is still shallow after nearly 10 days. Ocassional moments of feeling 'really high' as if some amount of stored drug was being released from an inactive form. These are short lived and not unlike LSD flashback. These began after the experiment and were an unusual event. A bloated feeling with pressure in the solar plexus persisted until day 6. As regards your comments Randolph, again I never assayed the MA material, but shulgin's commentary suggest so. The tendancy to tweak is to some extent, personal, but the state of mind produced by the drug, tends to re-inforce dosing to maintain the peak. There is pronounced physical depression about 12 to 18 hours after taking the drug. ready availablity, and no notion of the withdrawl symptoms to come, make it easy to ignore common sense. A predisposition, in a pair of experimenters to use any euphoriant to excess doesn't help either. Unfortuneately, the bad effects don't start until 48 hours after stopping the drug. so if you tweak daily, you have no idea what's ahead. A real analysis of the effects was clouded by the cessation of a year long VERY heavy alcohol binge, only a few days before. It's conceivable, some of the physical & mental aberrations were influnced by the chemical changes resulting from the lack of alcohol. Maybe even awakening awareness to degraded neuropathy. Well, I'll report on any new developments, but It's fair to say I'm 90% 'myself', whatever the fuck that means. Ain't that what good clandestine chemistry is about? The right to make yourself sick as hell! I have to draw the line at passing such sickness to others though. dpHarma's friend and lab partner Alice Cramden didn't suffer as severe a reaction even though on a mg/kg basis got higher doses. She did however suffer the insomnia, 'head noise' and cholinergic (temp control) problems. Pioneers! hhhmpf! my ass! dpHarma ------------------------------------------------------------------------------- wonder_boy: i have found that the symptoms you describe are actually caused by the malnutrition and dehydration that one puts their bodies through during these extended periods of heavy use and not so much the drug. i'm not saying that the drug or the lack of sleep doesn't cause any of it, just that i have been able to keep these things from happening by just making sure i do a couple of things. i always make sure i eat at least two nice sized meals a day plus vitamins. your brain as well as your other organs requires certain nutrients to function, if you don't give them the nutrients they start to malfunction. i also have found that i really need to eat the food, no shortcutting and just taking the vitamins. i guess my stomach starts to shrinking and causing me pain, which just starts the snowball effect. also your body needs to digest the food so it can break down the vitamins also. the other thing is to make sure you drink alot of fluid. this is probably the most important. if the average person should drink a gallon of water a day, how much do you think the average person using thes drugs, which dehydrate you, should drink? dehydration causes your brain as well as your other organs to start to draw up and that causes all sorts of problems. they use dehydration in some foreign countries as a torture treatment and it has been proven that it will make you crazy. i have found that if i follow these two basic things that i don't get any of the nasty side effects. one other thing if you start noticing some of the edginess or any of the jumpiness, pop a xanax, not alot, about .25 - .50 usually does the trick. within twenty minute everything is just fine. hope this helps. wonder_boy ------------------------------------------------------------------------------- Guinea Pig: Guinea Pig seemed bored and listless from his usual testing of cosmetics and OTC eyedrops, so good ole' Doc decided to dose him up with some p-MMA and observe. @ 50mg initial dose: - 15minutes to 45 min. mildly speedy onrush, Guinea Pig displayed the similar giddyness experienced when dosed with LSD mildly. - 1h-1.5h some rolling of the eyes, mild. stimulated and yet relaxed to the point of not really wanting to do much but chill. - at 2 hours, dosed 50mg more - eye rolling increased and the desire to remain inactive increased to the point of not really wanting to open the eyes. - 4h-close. still awake, but not too jacked anymore, sleep occured automatically leaving Guinea Pig to awaken wondering how and when he got into bed. Trial 2 Needing social interaction for added data, Guinea Pig was dosed with 90mg at his workplace with the other Labrats around for stimulation. Guinea Pig immediatly noticed a strange audio stimulation occuring at the peak. It would seem like sounds were all emanating from within his own head. Other's voices were heard as one hears one's own voice, somewhat muffled and within one's own scull. Other sounds seemed to echo from within a cave. When others spoke to Guinea Pig he felt as if it were he that utter the words, call it empathy. Intent behind the words seemed more clear. Having to conceal this state from the other rats was no problem for GP, but he did grow tired of idle insignificant conversations rather quickly, longing for his own cage away from the silly rats and closer to his little Guinea Hooka. Again, sleep came very easily; awakening refreshed and somewhat still mentally blurry(PROZAK monotone).. Trial 3 110 mg Dosed GP on a day he was scheduled to do a bit of house work at the homecage to analyze his performance. Initial stimulation sent GP into a mad cleaning spree which only lasted about 1 hour, leading into a 'who needs to work' attitude which was fairly persistant. All Guinea pig wanted to do was sit with his hooka and enjoy the A/C. He did notice that his skin crawled with strange cold tingling sensations which GP thought were rather pleasant (he thinks higher dosage would accentuate this effect). Mentally, the wheels turn very slowly. No anxiety whatsoever, almost too calm. GP's girlfriend can't even tell when he's on it cause it's so mellow (at these low doses).. and believe me, GP's girlfriend don't like it when he volunteers for testing...not one bit.. subsequent testing was also done with smaller amounts. at the <50mg level it serves as a nice general stimulant, no balls to the wall meth'd up or nothing.. just awake and happy, similar to ginseng or other mild stimulants. It also seems to blurr out emotional turmoil, IE worrying and dwelling on issues (PROZAK EFFECT!) Motivation seems a bit diminished though, as it's just as fine to do nothing as it is to work. In comparison th MDMA, GP would say that pMMA seems to lack the super RUSH of MDMA in the initial onset. The overwhelming feeling was not there, but this could be due to dosage. The experience was much more controllable, GP could keep his eyes focused if needed.. MDMA just plain FUCKS his eye control to hell. The feeling of being out of control and at the mercy of the drug was not present either. Also, The down time is nowhere near that of MDMA. The next day GP felt good, not slammed in the head and sick as with MDMA. He was able to eat only 4h after dosing (with an APETITE!), where MDMA almost always sent GP into a fit of anerexia for 3 days. Personally, GP thinks this is way cooler than MDMA.. maybe he's just burnt on that shit, but he likes it better...No illin and he can eat... that's enough for him. ------------------------------------------------------------------------------- Spiceboy: Hey all. This is the story of a guy with nothing to do, so he tried this: anethole-->4-MDP2p--->4-MMA Saturday night: Went to club, saw friend, ate one commercial bean called a 'euro'.... they arent bad at all.... went home after about 4 hours and was coming down, and looked at the small vial of 4mma sitting on the table. On the spur of the moment, I measured out 215 mg, and did it. Of the oil, not a salt. After 45 minutes I returned to rolling, HARD. My jaw went into total lockdown and my eyes began to cross. The eye thing was weird as hell. I had a little trouble focusing. But the euphoria was there, the feeling in your chest was there. There was the awareness of the nature of the experience being very similar to mdma. 6 hours later, and Im in a stupor. Didnt sleep much, but that night, I did it again, w/ the same amount, and POW! back in the space I was at the night before. Today, I am a little disoriented, but its not bad. Some people would like this. I think its closer to MDA in its nature. - - - - - This is a few days later.(3, exactly) I must agree with the assesment of dpharma, at least in part, as I have found myself much more introspective and emotional than usual for these past post-dosage days. Crying for very little reason has occurred twice, and as I was playing a video game to check out my responses, etc, I noticed a certain 'surging' or jumpiness of a reflex-type nature, where I did a mini-twitch or something, I dunno, but it was a little irritating. Knowing what i know about psychedelics, though, I would have to say it most definitely IS active, in a psychedelic way, at these dosages. Amphetamine component was not really there, now that you mention it, but hte other stuff was... Very difficult on the body, as recovery has been very slow. Slight disorientation over the past few days, improving slowly. This was a HARD HEAVY EXPERIENCE. I have never, till now, experienced my eyes crossing horizontally AND vertically, but they did on this stuff, and the physical parts of a roll were present in excess. The inside of my mouth is torn up. Ala Shulgin; "I am not inclined to repeat the experience anytime soon, given the body-load". But it was very powerful. Mentally, yes, but not in an LSD way, not in an X way. I realize that the interpretations are subjective, but this package is probably a little rough for a lot of people. I reccommend it for the hardcore, as this challenge; Take it as a co-dose, as I reported, w/ MDMA, and check out the synergistic effects. They are mighty. ------------------------------------------------------------------------------- Methaco(s)mic: Warning bees, the dose/response curve for pMMA can in some subjects be very steep. Very mild, relaxing, euphoric and physically pleasant effects at 100mg. But at 150mg some weeks later severe physical ill effects. I am usually rather sensitive; very strong and intense effects from 100mg MDMA, no control at all over hallucinogenic activity with 20mg 2c-b, can't recognise or understand (due to hallucinations) people/friends on 250u LSD, three times more sensitive to shrooms then most friends, 150mg codeine makes me almost immobile for several hours, and so on. My response to nonalkaloide drugs is much more normal for my 170lb body. Let's have a closer look: 100mg on empty stomach is noticed at 0.30, the onset is slow and gradual. Tickling electric feelings in the back of my head spreading to my arms and upper torso. I felt relaxed and there was no speedy part at all. More like GHB then MDMA to me. This lasted to the 2 hour point, now the effects were almost identical to how 10mg meth feels for me after 2 hours. But as reported by others I was much lazier then on meth and it was nice just to lie down hugging my girlfriend (115lb), who was also on 100mg, but much drowsier then me. The stimulant effects only last for about an hour and a half and sleep was possible at 4.00. Physical symptoms: Real but not extreme mydriasis, no nystagmus, and no tremor, hyperthermia I guess. My heart also felt fine. 150mg on empty stomach is felt at 0.20, the onset is faster and there is a real push (rather then a rush). At 0.30 my hands were wet from transpiration, tremor made it hard to make notes. Soon I also experienced severe nystagmus; this was different then with MDMA, very high frequency but not much amplitude, so to speak. My body became very stiff. My back hurt, my head hurt bad and my stomach hurt very, very bad. I felt very sick and distracted my mind with loud noisy music. Mentally it was hard to think but no anxiety at all. My pulse didn't rise much but I guess my bloodpressure did (my head hurt bad, my face and neck turned really RED). My jaw felt locked (no clenching as with MDMA) and I got this great pressure over my chest making it hard to breathe, placing my hands on the back of my head helped respiration. I also experienced nausea. At some point I believed I would pass out. The eyes were very much useless so I had them shut most of the time. Eventually I reached the 2 hour point, the physical terror had begun to decline at 1.30 but the stomach pains lasted until 2.0. Now I was nicely stimulated with full-grown mydriasis and sat down reading in a book for the next hour. Sleep was possible at 4.0, (I can't sleep on stimulants, not until 12.00 on LSD and 7.00 on meth, BzP) so the effects were over at this point. Had this been a psychedelic all the effects could be illusions, but its not, so I guess it can be rather toxic even in small amounts. Take care, if you try this stuff, go up slowly to find your optimal dose. -------------------------------------------------------------------------------