Very little other than alcohol in widespread use in 1500. By the mid-17th century, you've got tobacco and coffee.

Psilocybin-containing and other "magic mushrooms" were always present, and there's some suggestion of use as far back as 6000 years ago in Europe. Psilocybes and amanita muscaria grow wild, and were presumably eaten by accident and perhaps on purpose, but evidence of intentional ingestion is very rare. If you were in 1550 Prague and asked the equivalent of "how can I get high" -- perhaps some herbalist would have known which mushrooms to pick, but they weren't "available" in the sense of being sold for that purpose, nor do you find commentary suggesting their use for this purpose.

Fungus infecting grains -- notably ergot -- could have psychoactive properties, and there are disputed suggestions that ergotism from rye was responsible for hallucinations and the Scottish witch hunts of the early 16th century, these suggestions are similar to those for the 17th century Salem witch trials. This remains an interesting and controversial historical argument; what we can say for certain is that while perhaps may have happened, it was not widespread, and there was no hallucinogen "available" to be purchased.

Laudanum -- tincture of opium- - is sometimes attributed to Paracelsus, though his laudanum was apparently substantially different in its ingredients from the later drug of the same name that flourished after the mid 17th century. Whatever Paracelsus' recipe was, it does appear that he's the first European to begin to explore the powers of opium and its derivatives. That said, this was not anything that would have been known or "available" to the average European in 1500.

So if you're thinking of 16th century Europe, alcohol is the premier psychoactive substance. Its also a time when drink is getting much stronger. In 1500, Hieronymous Brunschwig publishes his Liber de arte destillandi (The Book of the Art of Distillation), the first book on the subject, although knowledge of distilling had existed since about the 13th century. Up until that time, the strongest drink available would be beer and wine.

There's the possibility of some mild psychoactive effects from spices-- notably nutmeg, which was an expensive and rare luxury good in the 16th century. Parkinson's Theatrum Botanicum of 1640 mentions nutmeg as a cure for various ailments, but doesn't mention psychoactive properties.

With respect to cultural reception, in 1500 alcohol is the only "recreational drug" in widespread use in Europe, and the full range of sentiments with respect to alcohol are present, from celebration to denunciation, although outside the Muslim world prohibition is rare. Christians typically celebrate alcohol as a gift from God in this period, neither side in the Reformation is anti-alcohol, though Calvin and Zwingli both attack drunkenness. Later, there are condemnations of both coffee and tobacco, which are largely ignored.

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Sources

A Prehistoric Mural in Spain Depicting Neurotropic Psilocybe Mushrooms?

SIGERIST, HENRY E. “LAUDANUM IN THE WORKS OF PARACELSUS.” Bulletin of the History of Medicine, vol. 9, no. 5, 1941, pp. 530–544. JSTOR, www.jstor.org/stable/44440627.

Duncan, Kirsty. “Was Ergotism Responsible for the Scottish Witch-Hunts?” Area, vol. 25, no. 1, 1993, pp. 30–36. JSTOR, www.jstor.org/stable/20003209.

Weil, Andrew T. “Nutmeg as a Narcotic.” Economic Botany, vol. 19, no. 3, 1965, pp. 194–217. JSTOR, www.jstor.org/stable/4252602.

Bowers, John M. “‘Dronkenesse Is Ful of Stryvyng’: Alcoholism and Ritual Violence in Chaucer's Pardoner's Tale.” ELH, vol. 57, no. 4, 1990, pp. 757–784. JSTOR, www.jstor.org/stable/2873084. [Earlier than your date, but Chaucer gives a good picture of attitudes towards drunkenness in the late medieval period, his family were in the wine and tavern business, so he's a very good first person view from someone familiar with the subject]

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