By the time of contact with Europe, tobacco smoking was widespread in North America. Although the habit of consuming hallucinogenic, DMT-containing snuffs also prevailed in the Caribbean cultural area, so far there have been no confirmed reports of any other smoking materials besides tobacco.

The high culture of the Mayan Indians, which flourished in Mesoamerica until the mid-800s, had a long and complex relationship with tobacco and its habit of smoking. The classic Mayan tobacco was the tobacco Nicotiana rustica, which is still in use among the indigenous populations of South America to this day. This species is much stronger, potentially chemically hallucinogenic in contrast to the commercial varieties available today, Nicotiana tabacum. The difference between this tobacco and cigarette is very large. Wild tobacco was dried and rolled up into cigars, which were then smoked. The trance-like state that followed as a result of smoking, in part because of synergy with the compounds present, including MAO inhibitors, was central to Mayan shamanism. Recently introduced antidepressants, MAO inhibitors are distant synthetic relatives of these natural compounds. Francis Robishek wrote a lot about the fascination of the Maya people with tobacco and its chemically complex composition.

It should also be recognized that nicotine is in no way the only bioactive substance in a tobacco leaf. Recently, the harmala group alkaloids — garman and norgarman — were isolated from commercially produced tobacco and their smoke. They make up the chemical group of beta-carbolines, which include harmine, harmaline, tetrahydroharmine, and six-methoxygarmine, all with hallucinogenic properties. Although so far none of the natural varieties of tobacco have been tested for the presence of these substances, it is reasonable to assume that their content can vary widely depending on the type and development of tobacco and that some of the local types of tobacco may contain relatively high concentrations.

Tobacco was and is always an appendage of more powerful plants and visual hallucinogens, wherever they are consumed in both Americas in the traditional and shamanic form.

And one of the traditional ways of using tobacco includes an enema invented in the New World. Peter Furst studied the role of enemas and klysters in Mesoamerican medicine and shamanism.

Only today it turned out that the ancient Maya, like the ancient Peruvians, used enemas. Syringes, or narcotic enemas, and even enema rituals, reflected in the art of Maya, are found. An outstanding example is a large painted vase, dated to 600–800 AD. O., which depicts a man inserting an enema, and a woman who helps him. As a result of this newly discovered image, archaeologist M.-D. Coe was able to identify a strange object that holds the jaguar deity on another painted Mayan vessel, like a syringe. If the enemas of the ancient Maya consisted, like those of the Peruvian Indians, of intoxicating or hallucinogenic substances, then they may have consisted of fermented balche, a honey drink. Balche – a sacred drink that was made stronger with the help of an admixture of tobacco or bindweed seeds. Thus, it was possible that they took dope extracts and even hallucinogenic mushrooms. Of course, they could use and just tobacco impurities.