"LSD" is an initialism formed from the German chemical name of the compound, Lysergsäure-diethylamid.
It was first synthesized in 1938 by Swiss chemist Dr. Albert Hofmann at the Sandoz Laboratories in Basel as part of a large research program searching for medically useful ergot alkaloid derivatives. Its psychedelic properties were unknown until 5 years later,
when Hofmann, acting on a hunch, returned to work on the chemical. He attributed the discovery of the compound's psychoactive
effects to the accidental absorption of a tiny amount through his skin on April 16, which led to him testing a larger amount on himself for psychoactivity. [1]
Until 1966, LSD and psilocybin were provided by Sandoz Laboratories free of charge to interested scientists.
The use of these compounds by psychiatrists to gain a better subjective understanding of the schizophrenic experience was an accepted practice. Many clinical trials were conducted on the potential use of LSD in psychedelic psychotherapy, generally with very positive results.
Cold War era intelligence services were keenly interested in the possibilities of
using LSD for interrogation and mind control, and also for large-scale social engineering. The CIA conducted extensive research on LSD, which was mostly destroyed.
[2] Project MKULTRA (also known as MK-ULTRA) was the code name for a CIA mind-control
research program begun in the 1950s and continued until the late 1960s. There is much published evidence that the project
involved not only the use of drugs to manipulate persons, but also the use of electronic signals to alter brain functioning;
for details, see the MKULTRA article proper.
The British government also indulged in LSD testing; in 1953 and 1954, scientists working
for MI6 dosed servicemen in an effort to find a "truth drug". (In all probability,
MI6 was motivated by rumors that the Soviet Union had developed brainwashing drugs.) The test subjects were not informed that they were being given
LSD, and had in fact been told that they were participating in a medical project to find a cure for the common cold. One subject,
aged 19 at the time, reported seeing "walls melting, cracks appearing in people's faces ... eyes would run down cheeks, Salvador Dali-type faces ... a flower would turn into a slug". After keeping
the trials secret for many years, MI6 agreed in 2006 to pay the former test subjects financial compensation. Like the CIA,
MI6 decided that LSD was not a practical drug for brainwashing purposes. [3]
LSD first became popular recreationally among a small group of mental health professionals such as psychiatrists
and psychologists during the 1950s, as well as by socially prominent and politically powerful individuals such as Henry and Clare Boothe Luce to whom the early LSD researchers were connected socially.
Several mental health professionals involved in LSD research, most notably Harvard psychology professors Drs. Timothy Leary and Richard Alpert (later known as Ram Dass), became convinced of LSD's potential as a tool for spiritual growth. In
1961, Dr. Timothy Leary received grant money from the Harvard University to study the effects of LSD on test subjects. 3,500
doses were given to over 400 people. Of those
tested, 90% said they would like to repeat the experience, 83% said they had "learned something or had insight," and 62% said
it had changed their life for the better. [jk’s observations support this conclusion.]
Their research became more esoteric and controversial, alleging links between the LSD experience and
the state of enlightenment sought after in many mystical traditions. They were dismissed from the traditional academic psychology
community, and as such cut off from legal scientific acquisition of the drug. The experiments lost their scientific pretence,
and the pair evolved into countercultural spiritual gurus, encouraging people to question authority and challenge the
status quo, a concept summarized in their catchprase, "Turn on, tune in, and drop out". Predictably, the drug was banned in
the United States in 1967, with scientific therapeutic research as well as individual research also becoming prohibitively
difficult. Many other countries, under pressure from the U.S., quickly followed suit.
Since 1967, underground recreational and therapeutic LSD use has continued in many countries, supported
by a black market and popular demand for the drug. Legal, academic research experiments on the effects and mechanisms of LSD
are also conducted on occasion, but rarely involve human subjects
Dosage
LSD is, by weight, one of the most potent drugs yet discovered. Both subjective reports and pharmacological
methods such as receptor binding assays determine LSD to be, per mole, around 100 times more potent than psilocybin and psilocin and around 4000 times more potent than mescaline. Dosages of LSD are measured in micrograms (µg), or millionths of a gram. By comparison, dosages of almost all other drugs, both recreational and
medical, are measured in milligrams.
The dosage level that will produce a threshold hallucinogenic effect in humans is generally considered
to be 25 micrograms, with the drug's effects becoming markedly more evident at higher dosages. In the late 1990s, LSD obtained
during drug law enforcement operations in the United States has usually ranged between 20 and 80 micrograms per dose. During
the 1960s, dosages were commonly 300 micrograms or more. Dosages by frequent users can be as high as 1200 micrograms, although
such a high dosage may precipitate unpleasant physical and psychological reactions.
Estimates for the lethal dosage ( LD50) of LSD range from 200 micrograms per kilogram to more than
1000 micrograms per kilogram of human body-weight, though most sources report that there are no known human cases of such
an overdose. Other sources note one report of a suspected fatal overdose of LSD in which there were indications that ~1/3
of a gram (320 mg or 320,000 µg) had been injected intravenously, i.e., over 3,000 more typical oral doses of ~100 µg had
been injected. [4]
LSD is not considered addictive, in that its users do not exhibit the medical community's commonly accepted
definitions of addiction and physical dependence. Rapid
tolerance build-up prevents regular use, and there is cross-tolerance shown between LSD, mescaline and psilocybin. This tolerance diminishes after a few days' abstention from use.
[LSD
has a half life given variously as 2 or 4 hours. During peak experience the amount
is under ½ that of what had been absorbed. This is possible because its effect
is through an alteration in the level of serotonin (one of the neurotransmitters), rather than through direct action. Thus LSD produces a natural high: the
change in the level of a neurotransmitter rather than the drug is producing the high.
This is explain why it is active in a dosage of 1/100th that of the most potent psychoactive drugs—jk.]
Pharmacological
LSD affects an enormous number of receptors, including all dopamine receptor subtypes, all adrenoreceptor subtypes as well as many others. LSD binds to most serotonin receptor subtypes except for 5-HT3 and 5-HT4.
However, most of these receptors are affected at too low affinity to be activated by the approximate 10-20 nM of LSD which
penetrates the brain. [8] Recreational doses of LSD can affect 5-HT1A, 5-HT2A, 5-HT2C,
5-HT5A, 5-HT5 B and 5-HT6 The hallucinogenic effects of LSD are attributed to its strong
partial agonist effects at 5-HT2A receptors as specific 5-HT2A receptor agonists are hallucinogenic
and largely 5-HT2A specific antagonists block the hallucinogenic activity of LSD.
