Tips on interpreting pharmacodynamic/pharmacokinetic studies on mephedrone?

[candidsurprise]

Recently I have been interested in whether mephedrone carries the same risks on the serotonergic system as MDMA. The studies are largely on rodents, and I am having trouble working out whether the doses used for rodents in these studies are comparable to recreational doses used for humans. I know that a formula for converting mouse doses is mg/k multiplied by the Km factor of mice divided by the Km factor of humans. I have found that the studies use doses similar to the doses used in humans using this conversion calculation, but I am unsure on issues of bioavailability. The studies use subcutaneous administration, and I have no idea what the subcutaneous or oral bio availability of mephedrone is. Does anyone have any tips on how to find these values, or how to apply a best estimate approach?

An interesting point about the studies is that rodent doses of over 10 mg/kg produced deficits in serotonergic and dopaminergic indicators for a period of at least weeks after dosing, but doses of 3-10 mg/kg did not. This is a crucial point, because it may indicate that mephedrone lacks these risks of MDMA just like 4-FA does, so the required safe wait times may be significant lower for mephedrone compared to MDMA.

 

[candidsurprise]

Recently I have been interested in whether mephedrone carries the same risks on the serotonergic system as MDMA. The studies are largely on rodents, and I am having trouble working out whether the doses used for rodents in these studies are comparable to recreational doses used for humans. I know that a formula for converting mouse doses is mg/k multiplied by the Km factor of mice divided by the Km factor of humans. I have found that the studies use doses similar to the doses used in humans using this conversion calculation, but I am unsure on issues of bioavailability. The studies use subcutaneous administration, and I have no idea what the subcutaneous or oral bio availability of mephedrone is. Does anyone have any tips on how to find these values, or how to apply a best estimate approach?

An interesting point about the studies is that rodent doses of over 10 mg/kg produced deficits in serotonergic and dopaminergic indicators for a period of at least weeks after dosing, but doses of 3-10 mg/kg did not. This is a crucial point, because it may indicate that mephedrone lacks these risks of MDMA just like 4-FA does, so the required safe wait times may be significant lower for mephedrone compared to MDMA.

Update on this, it was found that intranasal administration leads to 4.5x the peak blood concentrations of mephedrone compared to oral administration. Subcutaneous is more closely analogous to intranasal administration, so the peak effects of mephedrone in these studies are far higher than the blood levels of mephedrone in sensible human users of oral mephedrone. The lower dosing schedules of 10mg/kg in mice (which still translate to doses higher than medium human doses) did not show deleterious effects on serotonin or dopamine 7 days later. Therefore, the available evidence tentatively suggests that in rodents, mephedrone does not cause neurotoxic effects, at doses comparable to the doses used by humans. This variable may be strongly influenced by ambient temperature, so maintaining a cool environment is absolutely essential if you want to be reasonably confident in actually avoiding neurotoxicity, which some evidence (not all though) suggests occurs at higher doses.

 

[F.U.B.A.R.]

So if you bosh your meow meow in a cold shower you won't end up retarded?

Sounds good to me...

 

[candidsurprise]

So if you bosh your meow meow in a cold shower you won't end up retarded?

Sounds good to me...

Haha, that is not entirely clear though. The studies that used the high temperature parameter stupidly used excessive doses for humans. We can't reason by analogy from the studies demonstrating hyperthermic neurotoxicity from MDMA, because the research is clear that mephedrone is less toxic than MDMA overall. My guess is that clubbing temperatures might switch on the neurotoxicity to a mild degree, but I think that can be overcome by supplementation and just getting a bit cold water on your body every so often. There research is clear that cannabis prevents some of the hyperthermia from MDMA, so smoking weed whilst on mephedrone might be enough to be in the clear, since hyperthermia from mephedrone is less problematic than hyperthermia from molly. Carvedilol too shows potential for mitigating hyperthermia by preventing vasoconstriction .