What do the sigma opioid receptors do when agonized?

[G_Chem]

Isn't DMT (mainly) just a 5-HT receptor (mainly 5-HT2a and 5-HT1a) agonist like most other psychedelics? According to wikipedia, it was hypothesized that DMT was the endogenous sigma opioid agonist, but "Under these conditions, notions of receptor selectivity are moot, and it seems probable that most of the receptors identified as targets for DMT (see above) participate in producing its psychedelic effects.".

This interests me as I read Sigma 1 agonists are supposed to be cancer promoting agents. As much as I love DMT I worry it may cause cancer via this mechanism based on reports I’ve heard here and there as well as my own anecdotal experience.

Out of classic psychedelics and empathogens, which ones have strongest Ki values for Sigma 1 and 2?

-GC

 

[sekio]

There is certainly evidence that there is increased expression of sigma1 in tumors, and antagonism causes tumor cell death. But I don't think there is definitive evidence that sigma1 agonists are actually carcinogenic or mutagenic. [ref][ref]
After all, sigma1 lkigands have been used in pharmacy for quite some time, and there are many drugs that act as agonists that are used daily, in large populations. The endogenous ligand is thought to be dimethyltryptamine, and other notable drugs include amitryptiline, citalopram, fluvoxamine, dextromethorphan, memantine, and methamphetamine. When you multiply the number of prescriptions for these drugs, with the number of doses taken every year, the amount of sigma1 agonism that happens worldwide make me positive that we would know by now if sigma1 agonism was carcinogenic.

 

[G_Chem]

There is certainly evidence that there is increased expression of sigma1 in tumors, and antagonism causes tumor cell death. But I don't think there is definitive evidence that sigma1 agonists are actually carcinogenic or mutagenic. [ref][ref]
After all, sigma1 lkigands have been used in pharmacy for quite some time, and there are many drugs that act as agonists that are used daily, in large populations. The endogenous ligand is thought to be dimethyltryptamine, and other notable drugs include amitryptiline, citalopram, fluvoxamine, dextromethorphan, memantine, and methamphetamine. When you multiply the number of prescriptions for these drugs, with the number of doses taken every year, the amount of sigma1 agonism that happens worldwide make me positive that we would know by now if sigma1 agonism was carcinogenic.

This makes me feel a tad bit better, I suppose there would be a high correlation between general drug use and cancer if this were true as well with how many drugs hit Sigma receptors..

-GC

 

[allone]

This interests me as I read Sigma 1 agonists are supposed to be cancer promoting agents. As much as I love DMT I worry it may cause cancer via this mechanism based on reports I’ve heard here and there as well as my own anecdotal experience.

Out of classic psychedelics and empathogens, which ones have strongest Ki values for Sigma 1 and 2?

-GC

even if those do cause cancer, lets assume they do, isnt it still much better to help someone with a mental disorder and severe suicidal ideation and depression which might kill them much sooner than cancer ever will, also likely to prevent the killing of others because of such a person being extremely emotionally and mentally unbalanced??

 

[G_Chem]

even if those do cause cancer, lets assume they do, isnt it still much better to help someone with a mental disorder and severe suicidal ideation and depression which might kill them much sooner than cancer ever will, also likely to prevent the killing of others because of such a person being extremely emotionally and mentally unbalanced??

I agree 100%. But it’s still good to know all the risks to weigh the options. In fact right now I’m someone battling cancer who still uses psychedelics so your preaching to the choir here.

-GC

 

[Nagelfar]

↑There is an interesting series of σ receptor ligands that are 8-aminopentacyclo trishomocubane analogs.

Sigma agonists limit cocaine's cardiotoxicity

↑The above study seems to indicate sigma agonism can be protective, namely for cocaine's toxicity.