Eh, thinking about it the pharmacology of pretty much all psychedelics is too messy anyway to be able to say anything. I found this:
http://www.nature.com/npp/journal/v28/n2/full/1300057a.html
Activation of 5-HT2A and 5-HT2C receptors also leads to opposing effects on sexual function in rodents (Berendsen et al, 1990), in a manner suggesting that activation of 5-HT2A receptors could be responsible for the sexual side effects of SSRIs.
But that
reference isn't very convincing. Basically they found that mCPP induced erections were antagonised by 8-OH-DPAT (1A agonist, ED50 0.03mg/kg), 5-MeO-DMT (supposed to be their 5-HT2 agonist, but also has high 1A affinity, ED50 0.4mg/kg) and DOI (more 5-HT2 selective, ED? >1mg/kg). And do mCPP/TFMPP even 'induce' erections in humans? Antagonism of induced erections doesn't necessarily mean suppression of regular erections, and besides, that doesn't seem to be the effect of SSRI's. IME, and I
think this is the most common, they just make achieving orgasm harder.
I'm still skeptical that 2A antagonism along with SSRI's is going to have any benefit. The nature paper says
The central thesis argued above is that 5-HT2A receptors actually oppose the therapeutic effects of activating non-5-HT2A receptors in diverse neuropsychiatric syndromes such as depression, OCD, and PDDs. This broad range of clinical effects may be caused by localization of 5-HT2A receptors at critical sites in the prefrontal cortex regulating cortico-striatal-pallidal-thalamic loops. The target receptor(s) that actually mediate the therapeutic effects of increased synaptic 5-HT caused by SSRIs is far from clear and may be different for these and other psychiatric syndromes.
But there's very little to be found about trials of really selective antagonists. They reference one with
ritanserin, which seems quite well tolerated, so why is there nothing in the following 22 years? It doesn't really work, or not patentable? So instead we get
this
Mean change in Montgomery-Asberg Depression Rating Scale total score was significantly greater with adjunctive aripiprazole than placebo (-8.5 vs -5.7; P = 0.001). Remission rates were significantly greater with adjunctive aripiprazole than placebo (25.4% vs 15.2%; P = 0.016) as were response rates (32.4% vs 17.4%; P < 0.001). Adverse events occurring in 10% of patients or more with adjunctive placebo or aripiprazole were akathisia (4.2% vs 25.9%), headache (10.5% vs 9.0%), and fatigue (3.7% vs 10.1%). Incidence of adverse events leading to discontinuation was low (adjunctive placebo [1.1%] vs adjunctive aripiprazole [3.7%]). Aripiprazole is an effective and safe adjunctive therapy as demonstrated in this short-term study for patients who are nonresponsive to standard ADT.
More criticism of that paper
here. There is a
trial registered for use of MDL-100,907 alongside escitalopram in depression, but it was last updated 5 years ago and hasn't been published so I guess it doesn't work.
