In addition to its being a superlative gothic horror tale, the story can also be read as a fine example of the effects of the use of the drug opium on a highly imaginative writer. During the Romantic period, many writers experimented with the hallucinogenic effects of various drugs. (Among the famous English Romantics who experimented with drugs, there were Thomas De Quincey and Samuel Taylor Coleridge; De Quincey wrote The Confessions of an English Opium Eater, and Coleridge often wrote under the influence of opium. Opium, likewise, was also considered to be an essential part of life for many French Romanticists.) Since the narrator is an opium addict, then, the entire story can be read as a visual and mental result of hallucinogenic drugs, the result of opium on the mind of the addict. From this point of view, all of the effects described in the story could exist only in the mind of the narrator — that is, the opium simply caused him to see and hear all the supernatural, phantasmagorical events that took place; they never really happened. Such an explanation is possible; we know, for example, from many written accounts, that drugs can cause the addict to vividly sense things of seemingly otherworldly natures that the non-addict is incapable of feeling or sensing. Therefore, the reincarnation of the Lady Ligeia could be, first of all, a direct result of the strong love, attachment, and need for the lost Lady Ligeia, combined with the fact that the narrator feels a repulsion toward the Lady Rowena, who is the complete physical and sensual opposite to the Lady Ligeia. These strong, subconscious desires are freed under the influence of opium and make the narrator feel that they are real. As Poe handles the story, such an interpretation is possible; certainly the story lends itself to the possibility that it is the visualization of the hallucinatory effects caused by opium. As such, it is certainly a brilliant example in its surrealistic depiction of the supernatural.
The Lady Ligeia can also be viewed as the typical Romantic woman of mystery, a variation of the "femme fatale." As is typical of this type of woman, she is pale and wan, yet she has a fierce dark beauty, with rich luxuriant hair and dark raven eyes. Significantly, there is "some strangeness in the proportion." This, for the Romantic, was absolutely essential; some irregular aspect of one's mien individualized one's beauty and gave a certain "peculiar" flaw to perfect beauty. (See, for example, Hawthorne's story "The Birthmark," a short story which Poe admired very much — so much so that he even modeled the room of the narrator's English abbey, in this story, after the description of the house in Hawthorne's story.)
