In my experience: yes, but I would draw them on the computer.
Prototypes that look hand-drawn have the following advantages:
- They look discardable. Stakeholders will not be afraid to tell you there's something wrong with them. Even if you spent three days drawing them, people will be happy to discuss changes, because it doesn't look like you poured your heart and soul into it.
- They communicate the level of detail that should be discussed. If you draw straight lines and use a nice typeface, people will be distracted by the details, when you need them to look at the big picture.
- They are a two-way language. If you're doing co-design, and you show a user a wireframe to give a suggestion of a feature, they can respond by drawing another, which you can then interpret to get at their wishes for the product. If you show them a clean, Photoshopped design, they can only describe what they think is wrong with it.
The drawback is that drawing wireframes by hand takes ages, and if you're iterating fast, you have to redraw the whole thing after each test. The solution is to move to computer-drawn wireframes, that look hand-drawn. Much like the wireframes here on the UX stackexchange:

download bmml source – Wireframes created with Balsamiq Mockups
These allow you to draw elaborate designs consisting of dozens of pages, with many copied elements, without any re-drawing. After testing, you can quickly change your design.
If you want a nice, informal user test, you then print them out as needed. For a slightly more formal test, you can make them clickable, and present them on a computer.