Personally, smoking weed my whole life was making me obsess over drugs and I was becoming delusional, thinking it was doing good for my spirituality. The weed alone was enough to make me antisocial, anxious, very aggressive, and depressed, which led me to do Mdma back in 2010 a whole lot in order to have a great time going out. If he's using Mdma that much, I'm surprised that he hasn't lost interest in it, but in my experience smoking way too much pot altered my personality way more than using a lot of Mdma and psychedelics, so I propose this is where the negative changes are coming from and also the tendency to abuse those other drugs stems from his pot addiction. Long term potheads can end up in deep, dark places with insane attachments to the drug.
If he stops smoking weed for even just a few days he'll become a different person and hopefully gain a new perspective on his life. He'll totally become more normal after the short (but possibly torturous) withdrawal. Unfortunately, it is extremely tough to get a pothead to stop smoking weed. Depressed potheads can alienate themselves from society, I would never listen to my friends who told me it was making me stupid... in one ear out the other, and it took me many years before I snapped out of it and realized just how awful it had become.
I'd start by confronting him about his pot use next time he's really stoned. Just say something like, "You know, you're addicted to that shit and you're not the same person when you're on it. I miss the old you and it's sad what you have become. You're stupid when you're stoned." Don't mention the other drugs initially, see if you can help him stop smoking so much of that shit because it really can make people dumb and abusive.
Good luck
edit - this all depends on how much weed he's smoking, and for how long he has been doing so. I would smoke all day from morning til night, and once other drugs got involved the weed made me snap. It got bad after a few steady years of doing this. Once I stopped blazing I was totally sane, my old self. I would use other drugs because of what a burnout I had become from the pot and I wanted to change but couldn't stop smoking. If it's a long term thing that has gotten completely out of hand, then this is most likely his problem.