The research on LSD and 5-HT2A antagonists from the video:
Psychedelics produce fast and persistent antidepressant effects and induce neuroplasticity resembling the effects of clinically approved antidepressants. We recently reported that pharmacologically diverse antidepressants, including fluoxetine and ketamine, act by binding to TrkB, the receptor for BDNF. Here we show that lysergic acid diethylamide (LSD) and psilocin directly bind to TrkB with affinities 1,000-fold higher than those for other antidepressants, and that psychedelics and antidepressants bind to distinct but partially overlapping sites within the transmembrane domain of TrkB dimers. The effects of psychedelics on neurotrophic signaling, plasticity and antidepressant-like behavior in mice depend on TrkB binding and promotion of endogenous BDNF signaling but are independent of serotonin 2A receptor (5-HT2A) activation, whereas LSD-induced head twitching is dependent on 5-HT2A and independent of TrkB binding. Our data confirm TrkB as a common primary target for antidepressants and suggest that high-affinity TrkB positive allosteric modulators lacking 5-HT2A activity may retain the antidepressant potential of psychedelics without hallucinogenic effects.
If anyone tries this they should prepare for their 5-HT2A antagonist not working, have benzos at hand, and be ready for a trip, in case it didn’t work.
In my experience, phenibut largely prevents both anxiety and discomforting physical effects from developing on psychedelics, while also preserving the subjective effects. It’s a great combination, and I rarely take psychedelics without it.
It hits more targets than 5 HT2A though, I think the point of this therapy is to only block 5HT2a if possible as the therapeutic effects might be lost if others are blocked. Makes also Seroquel not so good.
I’m going to rephrase that after taking 4gm of cubensis extracted with lemon juice over the weekend. It was not what I would call enjoyable and I can see it knocking the cheese off of someone’s cracker. But I do find it incredibly therapeutic. And not my first rodeo.