Nepenthe was published at MIT and focused on poetry. The first issue appeared in December 1940 and carries a dedication that reads: "This / the first issue of Nepenthe / is for Trudy— / who / if we are not / mistaken / was at the Chicon." "Trudy" was Trudy Kuslan, co-editor of The Nucleus, who attended the Chicon along with Singleton and with whom she had a brief romantic relationship.
Contributors to the first issue included Louis Russell Chauvenet, Del Cross, Ian Davies, Corinne Ellsworth, E. Everett Evans, Larry B. Farsaci, John Francis, Paul Freehafer, "Curl Gradient", B.M. Hendrick, Jr., Richard Kraft, Arthur Lambert, Allan Lang, Grady L. McMurtry, A. Merritt, Jack Chapman Miske, "P. Tex Sigma", Charles R. Tanner, Dale Tarr, Harry Warner, Jr., and Stanley G. Weinbaum. Cover art by Marie Johnson and illustrations by Grady L. McMurtry.
The second hektographed issue appeared in Spring 1941. Contributors included Spencer Bailey, Louis Russell Chauvenet, Del Cross, Arthur Cusp, E. Everett Evans, Dale Harding Exum, Larry B. Farsaci, "Curl Gradient", Dale Hart, Arthur Lambert, Robert A. W. Lowndes, Grady L. McMurtry, A. Merritt, John B. Michel, Jack Chapman Miske, Edgar Salute, Oliver King Smith, Bob Tucker as 'Hoy Floy Doy', Donald A. Wollheim, and Christopher Samuel Youd (John Christopher). Cover art by Leslie Perri (Doris Baumgardt), and was silkscreened by John B. Michel.