• Neuroscience & Pharmacology Discussion Welcome Guest
    Posting Rules Bluelight Rules
    Recent Journal Articles Chemistry Mega-Thread
    FREE Chemistry Databases! Self-Education Guide

  • N&PD Moderators: Skorpio

Psychedelic Amphetamines (DOx, etc.) + Methoxetamine: Any safety concerns?

Saucy

Saucy

Bluelighter
Joined
Aug 20, 2009
Messages
324
Due to a recent spike in available variety from two of my favorite vendors, I now have DOC, DOI, 3,4-DMA, and TMA-2 in my drug stockpile, and I am wondering if anybody has experience with combining any of these with methoxetamine, or if there are any known or speculated concerns with such combinations.

I have tried 2C-I and 2C-C in combination with methoxetamine several times without issues (although I found them both less profoundly synergistic than most simple and substituted tryptamines). I am less experienced with the DOx series, but with their only significant differences in MoA when compared with the 2C's being increased selectivity to 5-HT2 subtypes over 5-HT1 subtypes, the existence of agonism at 5-HT2b, and significantly stronger agonism at 5-HT2a relative to 5-HT2c vs. the 2C series, I don't see much possibility for a direct contraindication with MXE from either of their pharmacological profiles.

Does anyone know if any of the substituted amphetamines mentioned above is known (or speculated) to act as a monoamine releasing agent in addition to possessing agonistic action on the serotonin-2 receptor subtypes? Also, are any of these chemicals postulated to compete with dopamine reuptake directly in the neuronal synaptic cleft? (judging from its structure it is a virtual certainty that 3,4-DMA would do this, likely giving it mild to moderate efficacy as a dopamine reuptake inhibitor). These would be my main concerns with these combinations, but I am also wondering if the stimulant effects possessed by all substituted amphetamines (to varying degrees, of course) could cause cardiovascular complications such as a dangerous rise in systolic blood pressure, arrhythmia, etc. when taken in combination with Methoxetamine.

TMA-2 hasn't been pharmacologically profiled as formally as the DOx series, so I am reluctant to combine it with a substance that has demonstrated the possibility for adverse reactions with an odd and largely unpredicted selection of amphetamines (notably including bk-MDMA, MDAI, and 5-APB to name a few).

If anyone has experiences with combining psychedelic substituted amphetamines with methoxetamine, please share. I am very curious to hear your thoughts on the matter, especially given my recently acquired fondness for DOC and DOB (which I am now out of... probably for a long time, it looks like). If methoxetamine combines as well with DOC as it does with 2C-C, I think I'm probably going to be exploring the combination very throughly. You can take a lot of MXE bumps in the 24 hours it takes to complete a DOC trip haha.

Thanks in advance for the responses,

-Saucy
 
Some of the DOx, including I believe DOC and DOM, have some SERT affinity, but it's very low at ordinary doses such that monoamine reuptake inhibition and/or release is considered to play a very small part in their action.

In particular, though, (S)-N-methyl-DOM could be one to look at for potentially entactogenic qualities, since (S)- isomers tend to be more transporter-y and (R)- isomers the opposite. The 4C- compounds have also demonstrated such; this category includes ARIADNE and 4C-B.

From my own experience, combining MXE with 25C-NBOMe resulted in significant potentiation and visual enhancement, and it seems not unlikely that MXE would significantly potentiate other psychedelics. It was noticeably stronger than I expected, so I was glad to have "shot low" as it were -- approach with caution.
 
MXE is a dopamine reuptake inhibitor, I also heard rumblings that ketamine (and maybe mxe too) interact with 5-ht2 receptors somehow. The end result is a potentiated experience all round.
 
atara- Interesting about the SERT affinity. I would have thought that the methoxy subunits would prevent it from binding. It is the higher polarity of DOC relative to the other 4th position halide-substituted amphetamines that gives it this property (I'm assuming from your post, perhaps incorrectly, that DOB and DOI are expected to lack it)?

sekio- I have also heard such rumblings, but am not inclined to believe that they are true, at least in any sort of direct sense. Just look at the structures of every known 5-HT2 agonist, antagonist, and inverse agonist and compare them to arylcyclohexylamine. Ketamine and its analogs simply do not possess a suitable structure to interact with serotonergic receptors.

Note to others- I have combined methoxetamine with a very wide range of psychedelics (four simple tryptamines, five 4-substituted tryptamines, one 5-substituted tryptamine, and four phenethylamines). I know that serotonergic psychedelics combine well with arylcyclohexylamines and that these two classes of substances copotentiate each other's effects. I knew this a long time before the name "methoxetamine" had ever been uttered.

The only things I am looking for in this thread are a fairly advanced discussion of specific pharmacological properties that are relevant to the combinations in question, and reports from people who have already attempted any of the aforementioned combinations.

Thanks!
 
The relationship between this profile (Saucy) and my AFK self was discovered by another user last night, and although I'm trusting him to keep his mouth shut, this will be my last post under the name Saucy. I will not be posting back in this thread with my new profile, but I will follow it eagerly, so if you have more info, please share.

Fondest farewells, bluelight. I will be back soon.
 
dean stark said:
URL="http://www.ncbi.nlm.nih.gov/pubmed/11191649"]"Potentiation of DOM-induced stimulus control by non-competitive NMDA antagonists: a link between the glutamatergic and serotonergic hypotheses of schizophrenia"[/URL]
Which would suggest fun.
Click to expand...

Very interesiting! I had not come across this study before, but it certainly suggests some interesting findings.

Saucy said:
The relationship between this profile (Saucy) and my AFK self was discovered by another user last night, and although I'm trusting him to keep his mouth shut, this will be my last post under the name Saucy. I will not be posting back in this thread with my new profile, but I will follow it eagerly, so if you have more info, please share.

Fondest farewells, bluelight. I will be back soon.
Click to expand...

Saucy-- If you are still following this thread, I have to say that I am sorry to see you go. I have read several of your reports regarding methoxetamine combinations and found them both entertaining and informative. If you are willing, I would appreciate it if you could PM me through your new username so I can follow your future posts on this topic.
 
I would really like to know about combining a DOx with Methoxetamine.

One subjective concern about strong 5HT2 agonists is the affinity to the 5HT2c subtyte because that one has negative cardiovascular effects. LSD is an exception here btw.. I often notice that by having to dry-cough in an unpleasant manner which could be a sign of pulmonary hypertension. This most often happens on come-up. On the other side, the release of Dopamine induced by a cascade of presynaptic 5HT receptor activation seems to counter the negative effects of 5HT2c. So the coadministration of a DRI such as Methoxetamine could actually be in favour of Dox safety.

On the other hand, Ketamine and co. are also known to further increase blood pressure by inhibiting the parasymphatic system.

The good thing is, that while on DOx, you can very slowly titrate the addition of Methoxetamine. My guess therefore is rather in favour of the combo.

BTW. I recently posted this in the 3-Meo-PCE tread:

Frogster said:
Hmm, sounds fxxxing interesting!

until now, i had two TOTALLY DIFFERENT +4 (shulgin scale) experiences with psychotropic comounds.

1. 5mg DOI: Full-blown ego-dissolution followed by an 18 hour evolutionary reconstructive-associative trip back to sobriety.

2. 100mg MXE: Full blown ego-connection followed by a one hour episode of redestructive-dissociative schizomania back to sobriety.

I wonder WTF would happen if one combines a good Dose of DOI with a good dose of MXE's longer lasting cousin 3-Meo-PCE??

Anyone?
Click to expand...
 
sekio said:
MXE is a dopamine reuptake inhibitor, I also heard rumblings that ketamine (and maybe mxe too) interact with 5-ht2 receptors somehow. The end result is a potentiated experience all round.
Click to expand...

Not exactly action at 5HTR, but related to sekio's suggestion:


"The role of serotonin in the NMDA receptor antagonist models of psychosis and cognitive impairment."
Psychopharmacology (Heidelberg, Germany) (2011), 213(2-3): 289-305.
Abstract
Objective: To review the evidence that agents which preferentially affect serotonin (5-HT) attenuate the ability of N-methyl-D-aspartate (NMDA) receptor non-competitive antagonists (NMDA-RA), e.g., phencyclidine (PCP), dizocilpine (MK-801), and ketamine, to stimulate locomotor activity (LA), and to impair novel object recognition (NOR).
Rationale: NMDA-RA-induced increased LA and impairment of NOR are widely used models of the pathophysiol. of schizophrenia, the mechanism of action of antipsychotic drugs (APDs), and the identification of novel treatments. Serotonin (5-HT) plays an important role in attenuating these effects of NMDA-RA.
Results: Selective 5-HT2A inverse agonists, e.g., M100907 and ACP-103, and atypical APDs, which are more potent 5-HT2A than D2 antagonists, e.g., clozapine and lurasidone, are more effective than selective D2 receptor antagonists to attenuate NMDA-RA-induced increased LA. 5-HT2A inverse agonists alone are not effective to improve NMDA-RA-impaired NOR, but augment the effects of atypical, but not typical APDs, to improve NOR. The 5-HT1A receptor partial agonist tandospirone alone and the 5-HT1A agonist effects of atypical APDs may substitute for, or contribute to, the effects of D2 and 5-HT2A receptor antagonism to reverse the NMDA-RA impairment in NOR. 5-HT6 and 5-HT7 receptor antagonists may also attenuate these NMDA-RA-induced behaviors. 5-HT2C receptor inverse agonist, but not neutral antagonists, block NOR in naive rats and the effects of atypical APDs to restore NOR in PCP-treated rats, suggesting the importance of the constitutive activity of 5-HT2C receptors in NOR.
Conclusions: Multiple 5-HT receptors contribute to effective treatments to reverse adverse effects of NMDA-RA which model psychosis and cognitive impairment.​


Well, and the confirmation of sekio's suggestion:

"NMDA receptor antagonists ketamine and PCP have direct effects on the dopamine D2 and serotonin 5-HT2 receptors-implications for models of schizophrenia."
Molecular Psychiatry (2002), 7(8): 837-844.
Abstract
Ketamine and PCP are commonly used as selective NMDA receptor antagonists to model the putative hypoglutamate state of schizophrenia and to test new antipsychotics. Recent findings question the NMDA receptor selectivity of these agents. To examine this further, we measured the affinity of ketamine and PCP for the high-affinity states of the dopamine D2 and serotonin 5-HT2 receptor and found that ketamine shows very similar affinity at the NMDA receptor and D2 sites with a slightly lower affinity for 5-HT2 (0.5 µM, 0.5 µM and 15 µM resp.), while PCP shows similar affinity for the NMDA and 5-HT2 sites, with a slightly lower affinity for the D2 site (2 µM, 5 µM and 37 µM resp.). Further, ketamine and PCP in clin. relevant doses caused a significant increase in the incorporation of [35S]GTP-γ-S binding in CHO-cells expressing D2 receptors, which was prevented by raclopride, suggesting a partial agonist effect at the D2 receptor. Thus, ketamine and PCP may not produce a selective hypoglutamate state, but more likely produce a non-selective multi-system neurochem. perturbation via direct and indirect effects. These findings confound the inferences one can draw from the ketamine/PCP models of schizophrenia.​
 
I had one of the best experiences of my life tripping 3.5mg DOC + repeated dosing of methoxetamine with my girlfriend (who took 2.5mg + MXE) last weekend. It brought us so much closer together and helped me shed some emotional baggage that I had been suppressing for quite a while. The combination did not appear to produce any adverse effects, and provided profound enhancement of music and sexual activity.

I'm guess I'm going to have to recommend the combination. It definitely felt more synergistic than either of the halogenated phenethylamines I have combined with methoxetamine. Perhaps not quite as synergystic as the combination of simple tryptamines and methoxetamine, but then again, few things are.

The only negative aspects I could report from the experience was that we both felt a little strung out past the 12h mark, although this was probably due to the extended periods of, um... physical activity as much as anything else. Heartrate was very high while engaging in sexual activity too (185 for me, measured immediately afterwords, but I am tachycardic).
 
I have also combined DOC and methoxetamine. Don't know the dosage of MXE (redosed multiple times). Don't know the dose of DOC either (My DOC is impure I think, was technically 8mg). It made the DOC feel more warm and fuzzy, more like mescaline IMO. I redosed at least 5 times with MXE. I was without my scale so I was using very small bits of MXE to get where I wanted to be, which I regret because it led me to a very manic state in the end. But it was very enjoyable for a while and I certainly didn't die nor suffer any problems. I am looking forward to trying it again with a measured dose of MXE.
 
Might take some MXE at the tail end of a DOC trip tonight, we'll see!
 
There does seem to be similar downstream modulation of glutamate & AMPA systems consequent to usage of both serotonergic psychedelics & NMDA antagonists. Here's the citation if any of you who have journal access haven't read it yet ;) I'd link it but its paywalled

Nature Reviews Neuroscience 11, 642-651 (September 2010)
The neurobiology of psychedelic drugs: implications for the treatment of mood disorders
Franz X. Vollenweider & Michael Kometer
doi:10.1038/nrn2884
 
I downed 20mg MXE and 2mg DOC simultaneously and did not like the combination, the only MXE combo I haven't liked so far. It felt like the anasthesia from the MXE and the body high/energy from the DOC were conflicting. Great visuals though, reminded me of DMT when you are done breaking through and everything is all round and shiny and more colourful.

No plans to mix DOx with MXE again.
 
I was given DOx (DOi or DOc, not sure) once on a blotter, someone sold it to me as acid. I had taken a bump of MXE earlier in the day, and then took two tabs of the DOx. I tripped for well over 24 hours. The MXE seemed to conflict with the DOx, I felt like I was being torn apart and like my skin was made of paper that could rip at any moment. I remember it causing serious vasoconstriction, my limbs were cold and I felt extremely lightheaded. I puked a few times (never puked on MXE before) and kept downing more and more water, feeling so dehydrated but nothing would help. The MXE also caused the trip to turn very introspective, and the weird body load and contradictory feelings of the two drugs caused a very terrifying thought loop where I freaked out about my health and thought I was going to die. I was also unable to sleep at all because I was too overstimulated, but benzos helped with that.

As the above poster, not a combination I will ever do again.
 
I would have expected more comments on the dopaminergic action of DOX compounds being potentiated by the DARI effects of MXE, wouldn't that make the experience much more stimmy? Although I am not sure the nasty vasoconstriction would be stronger as well, that is alpha adrenoceptor mediated right?

Let me remind you that amphetamines are put in the "neutral / suspect / be careful & dose lower if you must at all" category in the MXE combinations subthread. That should be based on actual reactions from people who tried it, and had some time for 'peer review' right? Neutral might not be the appropriate term, that makes it sound OK even though that is not sure at all.
Apparently it doesn't kill you on the spot but I would definitely avoid. I bet it lowers the overdose threshold for the DOX.

And just like without combining... DOB, DOI and BDFly are probably more tricky even than DOC and DOM.
 
From personal experience I know mxe can be a very intense experience on the body both physically and mentally.

I noticed elevated heart rate, decrease of motor functions and vision amongst other neutral to negative effects.

I would take initial dosage carefully and then re dose accordingly.

The dosage I took was 200 mg over a period of 24 hours and the experience was very interesting. I enjoyed it thoroughly.
 
You must log in or register to reply here.
Top