Promethazine

[Pontius Pilate]

You might say I'm in the wrong neighborhood, but just hear me out first.

Usually promethazine is discussed in the context of combination with codeine, but if you check out the pharmacology, you'll notice that it also acts on the 5ht2a and 5ht2c sites.

Does that mean that promethazine alone could cause hallucinations or psychedelia?

 

[Hodor]

Usually promethazine is discussed in the context of combination with codeine, but if you check out the pharmacology, you'll notice that it also acts on the 5ht2a and 5ht2c sites.

Does that mean that promethazine alone could cause hallucinations or psychedelia?

It's an antagonist at these sites, so it will suppress, and not cause, serotonergic hallucinations. It even used to see limited use as an antipsychotic.

The only way I could see promethazine causing "hallucinations" is as an anticholinergic deliriant à la diphenhydramine, but these are generally neither safe nor pleasant.

 

[Pontius Pilate]

Good catch, someone also pointed that out to me on another forum. I couldn't sleep, so I drank some GHB, and I guess I was a bit out of it when I was reading, lol.

So do you think that using promethazine in combination with dissociatives would tame the hallucinations? They're different mechanisms of action, right?

 

[Hodor]

Good catch, someone also pointed that out to me on another forum. I couldn't sleep, so I drank some GHB, and I guess I was a bit out of it when I was reading, lol.

So do you think that using promethazine in combination with dissociatives would tame the hallucinations? They're different mechanisms of action, right?

Dissociatives work mostly by blocking the so-called NMDA receptor, so an antipsychotic might not directly neutralize their effects like it would with a classical psychedelic (i.e. 5HT2a agonist).

*However*, consider that there are a lot of interactions between different neural signaling pathways downstream. So (random examples) drug X activates serotonin receptors in brain region A which causes increased dopamine release in brain region B which eventually results increased glutaminergic neurotransmission in brain region C.
In clinical research, they often use MK-801 - a very powerful and long-lasting NMDA antagonist - to simulate psychosis in lab animals in order to test antipsychotics for their efficacy. This suggests that yes, dissociative effects can to some extent be controlled using antipsychotics, even though they do not seem to act on the NMDA receptors directly.

With drugs like promethazine blocking a lot of receptors across the board (ex. 5HT2a, 5HT2c, a1 adrenergic, D2 dopaminergic...), a strong enough dose is probably going to rein in all sorts of agitated and psychedelic thinking. However, promethazine is not particularly active at blocking these sites (at least when compared to its antihistaminergic effect), so any dose strong enough to completely abort a trip might also cause unpleasant anticholinergic side effects.

 

[heatlessbbq]

You might say I'm in the wrong neighborhood, but just hear me out first.

Usually promethazine is discussed in the context of combination with codeine, but if you check out the pharmacology, you'll notice that it also acts on the 5ht2a and 5ht2c sites.

Does that mean that promethazine alone could cause hallucinations or psychedelia?

Yes.