A dose of LSD can weigh one two-hundredth of a sand grain
LSD is among the most potent mind-altering substances known: 20 micrograms, about a two-hundredth of a grain of sand, is enough to notice. Discovered by accident in 1943, banned worldwide by 1971, it was named a breakthrough therapy for generalized anxiety by the US drug regulator in 2024.
Lysergic acid diethylamide is a semisynthetic psychedelic derived from ergot. The Swiss chemist Albert Hofmann first made it in 1938 and found its effects five years later after swallowing some by mistake. Psychiatrists explored it in the 1950s and 1960s for alcoholism and schizophrenia. By the mid-1960s it was woven into the counterculture of San Francisco and London, shaping art and music, and in 1966 Timothy Leary founded a League for Spiritual Discovery with the drug as its sacrament.
Its potency helped it spread: it is about 200 times stronger than psilocybin and 5,000 times stronger than mescaline, which made it cheap to produce. Typical psychedelic doses run from 20 to 200 micrograms. Street strength has fallen over time; the underground chemist Owsley Stanley made 270 microgram doses in the mid-1960s, while 1990s samples held 20 to 80. Taken by mouth it starts within an hour and usually lasts 7 to 12 hours. In one trial, the drug ketanserin cut a trip from 8.5 hours to 3.5.
The drug works mainly by binding tightly to serotonin receptors, especially the 5-HT2A type. Brain imaging suggests it weakens the thalamus's filtering of sensory input and flattens the usual hierarchy of brain activity. Unusually, it seems to have two phases: a psychedelic stage, then, around 4 to 6 hours in, a more suspicious, paranoid stage linked to dopamine activity of a metabolite. Visual changes are typically pseudo-hallucinations, patterns the user does not place in real space around them.
No fatal human overdose has been documented, and a 2010 ranking by David Nutt placed it near the bottom of 20 drugs for harm, well below alcohol. The dangers are psychological: bad trips, psychosis in people with or predisposed to conditions such as schizophrenia, and lingering visual disturbances called HPPD. The United States made it Schedule I in 1970, and the CIA secretly dosed unwitting people during MKUltra. Research, stalled for decades, has resurged since 2009.
Source: LSD
