Hi Tyge!
Mail issues can have a multitude of causes. It might be that your mail server doesn't allow connections from the server where Naviserver is running. A firewall might need to allow the port etc. Office 365 needs extra configuration I believe.
I think as a starting point, you don't need to look at nssmtpd. Basic mail should work out of the box once configured correctly. If I recall correctly, ACS Mail Lite needs to have the BounceDomain parameter configured, apart from the obvious SMTPHost and SMTPPort. Assuming you have checked all your config, I would start debugginb by calling some of the ACS Mail Lite APIs directly.
If you have the Developer Shell configured, you can try something like this (replacing YOUREMAILADDRESS with an email address):
acs_mail_lite::send_immediately -to_addr YOUREMAILADDRESS -from_addr YOUREMAILADDRESS -subject Subject -body Body -mime_type "text/html"
You should then check your error log to see if it's an error with your config, or a timeout etc.
For more advanced debugging, if you are comfortable with the command line, you can do some more direct calls to the mail server using SMTP calls like this https://mailtrap.io/blog/smtp-commands-and-responses/#Example-of-an-SMTP-session
Happy to help further if you need more input.
Brian