cocaine/mdma while on SNRI & anticonvulsant

[Inso]

I haven't touched coke or MDMA in almost seven years. Lately I can't stop thinking about them (especially coke),and have almost convinced myself to give them another go.

Aside from the problem of me being a massive addict, I am on Duloxetine (Cymbalta) 120mg & Lamotrigine (Lamictal) 600mg for my headache conditions.

I've researched online and people warn of serotonin syndrome if MDMa or coke are combined with Duloxetine. Yet there are also plenty of reports of people doing them and just having reduced effects from the coke/MD at worst.

So, can you scientific peolpe do your best to give me an honest answer about the risks & what to watch out for if combining my prescribed meds with coke or MDMA? Also if I wasn't on Duloxetine does Lamotrigine interact with these drugs on its own at all?

I know I'm a bit of an idiot even considering it but I have a history of terrible decision making and just in case I end up making the wrong choice here (i.e. someone is chopping out lines in front of me) I'd like to know what I'm in for. Also I am interested from an academic perspective on how the brain chemistry works with SNRI/SSRIs combined with these drugs.

Hope this is the right forum for this. Not been on in a while and couldn't find Advanced Drug Discussion that used to be a subforum.

 

[Weltmeister]

Just because they dont feel it doesnt mean the damage is there and more importantly that doesnt mean its safe for everyone.

 

[aced126]

SNRIs will attenuate a lot of MDMA's physiological effects, and some of cocaine's effects as well.

 

[Inso]

Just because they dont feel it doesnt mean the damage is there and more importantly that doesnt mean its safe for everyone.

Yep very true. Just I'm wondering exactly what the real risks are, like what happens in the brain, what I should watch out for, etc. Since I could end up doing it. Bluelight usually gives a better answer than anywhere else.

 

[sekio]

Given that duloxetine is basically just another SNRI (stronger binding for serotonin transporters than for norepinephrine transporters) you will likely have better luck with cocaine than MDMA.

Cocaine and duloxetine will also synergize somewhat as they are both transporter blockers (rather than monoamine releasers like MDxx), and as duloxetine is already blocking some of your serotonin and norepinephrine transporters, I would expect the cocaine to be potentiated. How much I can't say.

With that in mind try not to take too much cocaine. It's bad for your heart & nose, especially in excess. And if it's at all possible, see if you can get it tested for dewormer (levamisole)...

 

[Jabberwocky]

) I'd like to know what I'm in for. Also I am interested from an academic perspective on how the brain chemistry works with SNRI/SSRIs combined with these drugs.

A WASTE of time, money and drugs

 

[WSH]

Cocaine and duloxetine will also synergize somewhat as they are both transporter blockers (rather than monoamine releasers like MDxx), .

Cocaine actually has more in common with classical releasers than with classical reuptake inhibitors:

Dopamine reuptake transporter (DAT) "inverse agonism"--a novel hypothesis to explain the enigmatic pharmacology of cocaine

Although there is the difference that cocaine's dopamine release is firing dependent.

So therefore cocaine doesn't fit in any category (well, maybe "firing dependent monoamine releaser" ).

 

[serotonin2A]

Cocaine actually has more in common with classical releasers than with classical reuptake inhibitors:

Dopamine reuptake transporter (DAT) "inverse agonism"--a novel hypothesis to explain the enigmatic pharmacology of cocaine

Although there is the difference that cocaine's dopamine release is firing dependent.

So therefore cocaine doesn't fit in any category (well, maybe "firing dependent monoamine releaser" ).

If cocaine acts a DAT "inverse agonist" then its action would be firing-independent. Cocaine tends to inhibit dopaminergic neurons indirectly via autoreceptor activation.

 

[aced126]

If cocaine acts a DAT "inverse agonist" then its action would be firing-independent. Cocaine tends to inhibit dopaminergic neurons indirectly via autoreceptor activation.

How does it produce reinforcing behaviour if it inhibits dopaminergic neurons?

 

[neurotic]

The duloxetine will certainly block the effects of MDMA - having antidepressants bound to your serotonin receptors, probably with high affinity, will prevent MDMA from interacting with them and doing its thing. The reports from people who have tried such combos confirm that, I believe - personally I have taken ecstasy once when just off of some SSRI and barely rolled, if at all. The ones who were claiming you would have serotonin syndrome were probably just conjecturing it, probably based on the fact that combinations of antidepressants with say tramadol or DXM can cause it, but that's a different case - tramadol and DXM are reuptake inhibitors, not releasers like MDMA.

 

[WSH]

If cocaine acts a DAT "inverse agonist" then its action would be firing-independent. Cocaine tends to inhibit dopaminergic neurons indirectly via autoreceptor activation.

Yeah, I also don't know exactly how that works, but they proved that cocaine is a releaser rather than a reuptake inhibitor and that TTX blocks cocaine's dopamine release, which makes it firing-dependent.

 

[MeDieViL]

Tramadol is a serotonin releasing agent not a reuptake inhibitor, the effects of cymbalta and cocaine will be individual, it would dysrubt the synergetic elevation of monamines with coke for example.

 

[MeDieViL]

Lamotrigine shouldnt interfere much, its reduces glutamate, memantine potentiates coke euphoria, i dont know how lamotrigine will affect it.

 

[Nagelfar]

Cocaine actually has more in common with classical releasers than with classical reuptake inhibitors:

Dopamine reuptake transporter (DAT) "inverse agonism"--a novel hypothesis to explain the enigmatic pharmacology of cocaine

It still is a re-uptake pump ligand and not a substrate; so I'd venture to say it still has more in common with re-uptake inhibitors (esp. since, being the proto-typical example; cocaine *is* the "classical" reuptake inhibitor by definition)

 

[WSH]

It still is a re-uptake pump ligand and not a substrate; so I'd venture to say it still has more in common with re-uptake inhibitors (esp. since, being the proto-typical example; cocaine *is* the "classical" reuptake inhibitor by definition)

Cocaine and releasers are addictive, whereas classical reuptake inhibitors are not.
Classical reuptake inhibitors increases dopamine to less than 500%, whereas both cocaine and releasers increase it to 1500%.
Classical reuptake inhibitors just block the transporter, whereas cocaine makes it work in reverse (kinda like releasers, but still different).

Cocaine is definitely more of an classical releaser than a classical reuptake inhibitor (while still being different).
Yes, it was thought for a long time that cocaine was a classical reuptake inhibitor, but people also thought for a long time that the earth was flat

 

[Nagelfar]

Cocaine and releasers are addictive, whereas classical reuptake inhibitors are not.
Classical reuptake inhibitors increases dopamine to less than 500%, whereas both cocaine and releasers increase it to 1500%.
Classical reuptake inhibitors just block the transporter, whereas cocaine makes it work in reverse (kinda like releasers, but still different).

Cocaine is definitely more of an classical releaser than a classical reuptake inhibitor (while still being different).
Yes, it was thought for a long time that cocaine was a classical reuptake inhibitor, but people also thought for a long time that the earth was flat

I don't know where you're getting your info. I was the individual to put the inverse agonist hypothesis on the cocaine article of WP years ago. Cocaine *is* considered "typical", so is methylphenidate whereas mazindol, benztropine etc are considered "atypical" and non-reinforcing (save in non-humans, Beagel dogs show preferred placement with mazindol, etc., it depends on the type of DAT)

Typical = reinforcing, that's the definition according to the academic publishing everywhere to now, before and since the "inverse" hypothesis.

It's a lot more complex than closed-to-out, open-to-out, there are C1 position analogues which are open-to-out but do not seem to be reinforcing in animal models like the closed-to-out DAT binding ligands, it has to do with every portion of how it rests in the cocaine receptor ligand site just outside the substrate area:

 

[WSH]

I don't know where you're getting your info. I was the individual to put the inverse agonist hypothesis on the cocaine article of WP years ago. Cocaine *is* considered "typical", so is methylphenidate whereas mazindol, benztropine etc are considered "atypical" and non-reinforcing (save in non-humans, Beagel dogs show preferred placement with mazindol, etc., it depends on the type of DAT)

I got my info from this study which considers mazindol to be typical and cocaine to be atypical of a "classical reuptake inhibitor":

Dopamine reuptake transporter (DAT) “inverse agonism” – A novel hypothesis to explain the enigmatic pharmacology of cocaine

However, drugs with rapid brain penetration like sibutramine, bupropion, mazindol and tesofensine, which are equal to or more potent than cocaine as dopamine reuptake inhibitors, produce no discernable subjective effects such as drug “highs” or euphoria in drug-experienced human volunteers. Moreover they are dysphoric and aversive when given at high doses. In vivo experiments in animals demonstrate that cocaine's monoaminergic pharmacology is profoundly different from that of other prescribed monoamine reuptake inhibitors, with the exception of methylphenidate.

 

[Nagelfar]

I got my info from this study which considers mazindol to be typical and cocaine to be atypical of a "classical reuptake inhibitor":

Saying "profoundly different from that of others" and literally saying 'typical' or 'atypical' or one or the other are different assignations, if not intuitively so, most papers class cocaine & MPH with the name "typical"

 

[Inso]

Forgot about this thread. I ended up doing 0.5g of supposedly decent quality coke last night. I hadn't done it in seven years but I certainly felt less of an effect than I should, probably due to the Cymbalta.

It was still enjoyable, my heart rate was barely elevated, proper chilled rather than stimulating. I reckon my meds are altering the buzz a bit too, makes sense since the meds are all designed to calm down excessive brain activity. It's funy someone mentioned Glutamate, from my research Cannabis is suspected to also calm down neurotransmitters like this, which Lamotrigine and Duloxetine do also. My condition is hypothesized to be attributed in some way to excessive activity of Glutamate and the like. Smoking a fair amount of medical grade weed reduces my pain hugely. It's very interesting stuff, perhaps I'll make a thread about it some time.

No negative side effects that I noticed, just took a while to get to sleep which is pretty normal! It was free too so even if it did nothing I wouldn't have been bothered lol

 

[Dresden]

Cocaine And MDMA Don't Mix, Like Two Dicks And No Chicks, Find Yourself In Some Serious Shit. Pharmacological Destructive Interference.