Sanchez Watt played for more than an hour and Dan Holman and Macauley Bonne also featured for the U's youngsters, in their first home game of the new Porfessional Development League Two season.
It is likely to be Richard Hall's final game in charge of the under-21s, following his elevation to first-team coach alongside new boss Humes.
Wayne Brown and John McGreal, who are currently in charge of Colchester's under-18 side, are expected to take charge of the under-21 side.
Colchester went in trailing at half-time, after goals from Josh Rees and Oliver Burke put Forest in command.
The closest the U's came to scoring in the first half was when Jack Curtis's low effort struck a post.
Forest threatened to add to their lead in the second half, with Tyler Walker smashing a powerful shot against the crossbar for the visitors.
But Colchester pulled a goal back just after the hour when Tyler Brampton fired a fine low shot through a crowd of bodies to reduce the deficit.
The U's did their best to find an equaliser after that but it was not forthcoming.
And Louis Laing rifled in Forest's third goal near the end to condemn Colchester's youngsters to their first defeat of the new development league season.
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