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PSYCHEDELIC 101
While what occurred in 1951 can hardly be considered “news” – 50 years after
the “cursed bread of Pont-Saint-Esprit” was newsworthy in France, the real
story behind it is now out. The Central Intelligence Agency of the United
States dabbled in many versions of mind-control drugs during the “cold war”.
LSD was considered a candidate for this type of chemical intrusion. Thus the
CIA spiked its own agents (5700 of them!) with LSD in order to experiment with
the plan and also ran an illicit test on the residents of a sleepy French town.
After consuming LSD-spiked bread, residents suffered mass hallucinations that
resulted in at least 5 deaths. One man believed he was a plane and tried to fly
from a second story window. After breaking both legs he “got up” and
continued some 50 yards from where he landed. Another man drowned himself
to escape the snakes that were eating his belly. Many more residents were
committed to psychiatric asylums. Recently-released documents clearly
document that this mass hysteria was indeed part of a CIA “secret cold war
experiment”.1
As mentioned in the preceding lesson, psychedelic or hallucinogenic drugs are numerous and
most of the ones we have talked about could be or ARE often categorized hallucinogenic by
experts. Our psychedelics are LSD, psilocybin (mushrooms), and salvia. LSD and psilocybin
(lysergamides) could well be considered stimulants, as you will see, and salvia could well be
considered a depressant. Keep this in mind as you study the psychedelics. LSD and psilocybin
have so very much in common, it doesn’t make sense to study them separately. So in
psychedelic 101, we first touch on this classification of drugs and their uses, the history of
psychedelics, and begin to dissect LSD and psilocybin – two prime examples of lysergamides.
In psychedelic 102, we’ll consider how lysergamides work, how they influence the neuron and
the brain. In the last lesson, psychedelic 103, we’ll describe salvia and set the stage for the endof-quarter movie and review.
Objectives
After successfully completing this lesson you will be able to:
understand the history behind psychedelic drugs
1
Henry Samuel in The Telegraph, April 29, 2011
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PSYCHEDELIC 101
recognize several reasons why these drugs are used
compare LSD (synthetic) and psilocybin (from an organism) in terms of effect and side effect
associate common side effects with these drugs
recognize and dispel common myths about these drugs
Before you begin!
Your ideas
What is the difference between good trips and bad trips (using psychedelics)
Who are Timothy Leary and Albert Hofman?
What do psilocybin (magic mushrooms) and LSD have in common?
Previously learned material
What kinds of symptoms can be expected when serotonin works better than usual?
What do sympathomimetic drugs have in common?
Lesson 26: Psychedelic 101 – Lysergamides
Guiding Questions
1.
2.
3.
4.
5.
6.
7.
How are “natural” psychedelic drugs used by ancient peoples?
What makes a drug psychedelic or hallucinogenic (as opposed to a stimulant or depressant)?
How have psychedelics been involved in mass hysterias such as the Salem Witch Trials?
What kinds of experiences are common with lysergamides?
How potent is LSD?
For what clinical applications are lysergamides being tested?
Are lysergamides addictive?
Key Terms





Hallucinogen/ hallucination
Lysergic acid diethylamide, lysergamide
Psilocin, psilocybin, psilocybe
Entheogen
Empathogen
Activity One: Web Site Review
1) Please review the history of hallucinogenic drugs at the Medscape site given below.
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PSYCHEDELIC 101
Guiding questions
What is a hallucination? Do hallucinogenic drugs always cause hallucination?
What are a few hallucinogenic substances found in nature and how have they been used?
What is the first synthetic hallucinogen?
Which hallucinogens are lysergamides?
What do they have in common?
How do LSD’s therapeutic and lethal doses compare?
What is a “bad trip” and what is thought to trigger this response?
What are the effects of LSD on the circulatory system?
http://emedicine.medscape.com/article/293752-overview
http://emedicine.medscape.com/article/293752-overview#a0104 (second page – read about lysergamides)
2) The next piece is a National Geographic short piece on ancient, spiritual use of mood altering drugs.
This is one of a five part series, and you should join in this video at 2 minutes with the presentation of
“yopo” and its use as a spiritual aide.
Guiding questions:
Why did ancient peoples use drugs?
How were these drugs used (under what situations and conditions)?
What is the role of training in spiritual use of psychedelics?
http://www.youtube.com/watch?v=GDyPpwNFlEw&feature=related
3) in this last video, discover how psychedelic drugs are being used as medicine – in psychotherapy
Guiding questions:
What types of conditions are psychedelics being tested as treatment for?
What is the explanation the proposed beneficial effects of psychotherapy involving
psychedelics?
http://www.youtube.com/watch?v=r3CbfMuR2YA&feature=related
Activity Two: Psychedelics: Modern Experimentation vs. Ancient Spirituality
Arguably the most ancient of drug categories, hallucinogens or psychedelic drugs have been used for
millennia. In most indigenous cultures, regular people could not use these mystical drugs: they were
reserved for the practiced spiritual guides of the community, the Shamen. The drugs served as
“lubricants” that enabled the spiritual leader to contact other worlds, speak with deities, and divine what
the best course of action was for his/her community. These drugs were held in high regard, treated with
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enormous respect and deference. They were not drugs to be taken for fun. Even spiritual peoples used
them with some reluctance and enormous respect. As the course closes, we will ask you to watch
“Ancient Drugs“, a program made by the History Channel. Of course, this will encompass other drugs,
such as ethanol and cannabis as well as cocaine. But it helps put in context why our current use of drugs
often gets us into more trouble even for drugs that have been around for a very long time.
The use of entheogens (drugs used to enhance spirituality) was highly ritualized. Often the rituals
involved deprivation; from food, sleep, rest, and companionship. The added meaning that ritual
afforded the drug-using Shamen influenced their own perception of the drug experience as well as the
perception of others who were around these Shamen.
Some propose that the removal of the ancient and spiritual context of drug use results in frivolous and
unmanageable, untempered drug use. Continue to consider this proposal for the remaining lessons.
In 1938, a Swiss chemist invented lysergic acid (LSD) in an attempt to
isolate active components of the ergot fungus that had medicinal
properties, such as stimulating respiration and circulation (but ergot is
also hallucinogenic and probably accounts for the supposition that
witches were bringing on the delirious behavior of citizens during the
Salem Witch Trial period). Albert Hofman returned to this project 5
years later and accidentally absorbed some of his product through his
hands. What followed was the first, and only objective (not framed by
expectations) LSD trip. Please read the excerpts from Hofman’s journal - reproduced in Liska (pages
299-300 in 8th edition). Image citation – Phillip H. Bailey from
http://commons.wikimedia.org/wiki/File:Albert_Hofmann_Oct_1993.jpg
An interpretive reading of Albert Hofman’s journal entries describing the first LSD experiences –
http://www.youtube.com/watch?v=WRs5h4BGZOk&feature=related.
Keep track of the adjectives Hofman uses to describe his experience.
Consider how Hofman’s ability to engage in normal daily activities was impacted
What did Hofman do in preparation for his journey home after his second dose?
Thus, we entered into a new era of psychedelic drugs with synthetic LSD. Its properties were
remarkable with respect to potency (see activity seven) and many activists and
academics in the 1960-1970s became advocates for the drug. One particularly notable
advocate was Harvard professor, Dr. Timothy Leary. In 1963 his appointment with
Harvard was terminated. Although the board responsible for his dismissal cited
“failure to keep appointments” among other lessor charges, many scientists believe
the real harm done by Leary was to negate the role of scientist as objective observer. Leary believed that
unless he and his fellow researchers were also taking LSD, they could not fully understand what their
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test subjects were experiencing. Image citation – Phillip H. Bailey from
http://commons.wikimedia.org/wiki/File:Timothy-Leary-Los-Angeles-1989.jpg .
TEST OF CONTENT
What did Hofman have to suggest about the phenomenon of “flashback”?
What does Hofman’s accidental dosing and subsequent second dose suggest about
LSD’s potency?
Leary and his research assistants took LSD along with their subjects. How does this relate to
the idea of a double blind experiment?
Activity Three: Why do people use LSD or Psilocybin?
Among the reasons people use lysergamides LSD and psilocybin, are three main categories:
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To obtain spiritual and contextual meaning of one’s own self
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To promote creativity and artistic inspiration
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To promote healing and cleansing of the spirit and psyche
Activity two touched on the first reason in the list above. The second reason requires a little clarification.
In favor of the notion that lysergamides promote creativity, a number of famous individuals credit LSD
(among other things) for their out-of-the-box inventions.
Even Biologist, Kary Mullis, who invented polymerase
chain reaction (PCR) to amplify DNA outside of a cell,
credits LSD for the idea of PCR.
In 1989, a psychologist named Oscar Janiger performed
an experiment on LSD and creativity. All 70 test subjects
said they felt more creative while using LSD and
continued to feel more creative after use.2 What would
outside viewers think about the work these LSDinfluenced artists produced? The pieces produced in the
Janiger study (some 250 pieces of art) have been analyzed
and the LSD-influenced art has not been characterized as
more creative, but was brighter, more abstract, with less
un-filled space. This raises the point of who art is for and who has the right to judge its creativity. A nonbiological point you are free to muse about! As you do, consider the series of drawings of a cat, made by
schizophrenic-artist Louis Wain. The first cat (top left) was drawn early on – prior to schizophrenia
symptoms. Later cats were drawn as the disease progressed. Image citation – public domain
http://commons.wikimedia.org/wiki/File:Wain_cats_6.jpg
The last point is something we will turn to in activity six.
2
www.ncbi.nlm.nih.gov/pubmed/2723891
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Activity Four: What are Some Common Side Effects of Lysergamides?
Lysergamides have many common side effects, let’s start with those.
Lysergamides are sympathomimetic. You might remember this from units 1 and 4. Sympathomimetic
drugs stimulate the sympathetic nervous system which causes an elevation of body functions that
prepare us for potential danger. The bombardment of the sensory systems that psychedelic drugs bring
about can be interpreted by the brain as potential danger. Thus norepinepherin levels rise, followed by a
rise in blood pressure (due to vasoconstriction), pulse, and alertness. Psilocybin is only one alkaloid in
the “magic” mushroom. Another is phenylethylamine. If you don’t remember this molecule, look back
at the amphetamine lesson. Thus psilocybin is particularly good as a sympathomimetic.
Lysergamides, indeed many psychedelic drugs, cause some degree of paranoia. In fact, paranoia is
noted as a side effect of many drugs, such as cannabis. But the paranoia experienced by a person who
does not know they have been exposed to a drug, when that drug is associated with very strong
alterations of perception, is particularly troubling. The opening story about the “Cursed Bread”
indicates that many lives were lost during this attack – lives lost not due to drug toxicity, but instead to
people responding to their altered state in life-threatening ways. If you were interested enough to
follow the cursed-bread story further, you would have happened upon a CIA program referred to as
MK-Ultra. In this program, CIA operatives were dosed with LSD without their knowledge. Whether the
purpose was experimental (to see how people would respond and how easily they could be “controlled”
by intelligence officers) or, even more sinister, the purpose was to unravel personnel that the agency
thought to be a threat to their operations, these individuals had a rather predictable response. Thinking
that they were going crazy and that this state was not drug induced but permanent, at least ONE
operative took his own life. The paranoia experienced by people who KNOW they have used the drug is
much less frightening, generally.
One common side effect many believe to be caused by lysergamides deserves some attention. Most
people believe that they will experience flash backs at some time after the drug experience has passed.
They imagine that days or weeks after using one of these drugs they will slip into a drug-induced state
of confusion. While there is certainly some truth to this notion, the common beliefs about WHY this is
are unfounded. The half-life of LSD is about 2-3 hours, the half-life of psilocybin is about 1-2 hours.
Neither is stored in fat or anywhere in the body, so it cannot “lurk” and then reappear later in the blood.
But because the sensory experience while using lysergamides is so intense, many people have a “deja
vu” experience – one equated with post traumatic stress disorder (PTSD). Like PTSD, it is believed that
small triggers might stimulate the sympathetic nervous system and make a person anxious in the least.
Many claim that psychedelic drugs can lead to prolonged psychoses. The evidence here is lacking, but
this does not make it a false claim. The incidence of psychosis following LSD use is very low (0.05 – 1%)
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but this not notably higher than the incidence in the population (estimates vary, but frequently reported
incidence is 1%). We cannot know if the now-psychotic, past LSD user was not just presymptomatic.
We also cannot know if LSD use is not elevated in people who are presymptomatic for some form of
psychosis. The number of people willing to confess to LSD use is low enough that this will be a very
hard question to answer empirically.
Mushroom users have a few other side effects to be mindful of. Both the Psilocybe (pronounced sil-AHso-bee) mushroom is a more typical find, but Amanita mushrooms are also used. Both have an increased
risk of systemic effects such as severe GI irritation, vomiting, and, in the case of Amanita – toxicity that
can lead to death. The reason mushrooms differ from LSD in this way is that mushrooms are organisms,
and organisms have more “ingredients” than synthesized drugs.
A couple of side-effects have been associated with LSD that are NOT true. In the 1960’s the drug
authorities told people that LSD caused chromosomal breakage. This is not true. Several people believe
that LSD toxicity is a concern. While it is extremely potent – no overdose victims have died. Aldous
Huxley (English author who wrote “Brave New World”) did die after his wife “medicated” him with
LSD (per his request). But he was death did not result from LSD, rather from cancer.
TEST OF CONTENT
Which side effects are expected for someone using LSD? Check all that apply.
Chromosome breakage
Death
High pulse and blood pressure
Anxiety
Nausea
Activity Five: Are LSD and Psilocybin Addictive?
There is no evidence that these drugs are addictive in any way. There is no evidence that these drugs
stimulate the reward pathway. Similarly, they do not cause a user to become dependent. Tolerance
DOES happen. With LSD, tolerance is fairly steep and is accounted for by a thinning of the receptor to
which it binds. 3 Many scientists believe that the extremely unsettling effects of lysergamides, while
sometimes sought after, are very profound and therefore a user is not likely to use the drug with even
moderate frequency.
Activity Six: Do LSD or PSILOCYBIN do ANY Good?
3
PMID 1969270
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PSYCHEDELIC 101
1) Please read the Scientific American article “Hallucinogens as Medicine” – December 2010 – Griffiths
and Grob. Page 77-79.
http://offcampus.lib.washington.edu/login?url=http://search.ebscohost.com/login.aspx?direct=true&db=hxh&AN
=55151889&site=ehost-live
Guiding questions:

What kinds of patients, with what types of symptoms are being tested for therapeutic
uses of psychedelic drugs?
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What is the setting provided to or recommended for people trying psychedelic drugs
in the laboratory?

Who are the test subjects – are they drug-seekers?

In what ways were the 1960’s and Timothy Leary influential in the field of psychedelic
medicine?

We said previously that psychedelics are not addictive. What does this article claim
about the role of psychedelics in addiction treatment?
2) Next read the cover story from November 2010s Village Voice found at
http://www.villagevoice.com/2010-11-17/news/ibogaine-hallucingen-heroin/ . The drug being discussed
here is ibogaine – which is another lysergamide. Note, this article was authored by a student who
previously took Biology 100! It’s a long article, so skim looking for the following guiding question
answers (feel free to read it in its entirety!). Note also that there is some objectionable language in this
article.
Guiding questions:

What is ibogaine?

What addictions is it being used to treat?

If you wanted ibogaine treatment for an addiction – where would you have to go (name 1
– 2 places)?

What is 18-MC and how effective is it?
Activity Seven: Relevant Statistics (TI and half life) of LSD and Psilocybin
The half-life of LSD is about 3 hours. The half-life of psilocybin is about 1 hour. The metabolic enzymes
for these drugs are not known.
A typical dose of LSD is currently 50 micrograms. Hofman used 250 micrograms in his second and
intentional trip. Huxley’s wife injected him with 100 micrograms when he was dying (and repeated the
injection after several hours). LSD is a very potent drug. Nearly all of it is blocked from passing through
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the blood brain barrier. It is estimated that no more than 10% of LSD arrives at receptors in the brain
that mediate its hallucinogenic impact (see Psychedelics 102). For modern doses, that means that only
about 4 micrograms arrives to the brain. There is no known lethal dose of LSD.
Psilocybin is a bit harder to quantify for a number of reasons. Because people usually consume the
mushroom, it is quite variable how much psychoactive alkaloid one will find in a given fungus.
Alkaloid concentrations vary by the season, the humidity, and even the time of harvesting. LSD is
estimated to be about 50 – 100 times more potent than psilocybin. The therapeutic index of psilocybin is
about 600.
We intentionally did not give you the effective and lethal doses of psilocybin. Can you calculate them?
The metabolism of psilocybin is an interesting story. Psilocybin is the form of the alkaloid found in the
mushroom, but our bodies convert it into psilocin. It is thought that this psilocin is the active form of the
alkaloid. The enzymes responsible for the metabolism of psilocybin and psilocin are not known.
TEST OF CONTENT:
We previously learned about two drugs that get altered into a psychoactive form by the
body’s metabolic machinery. Which were these?
Heroin into morphine
D9-THC into D8-THC
Nicotine into cotineine
Ethanol into acetyl aldehyde
Activity Eight: Individual Experience May Vary
Psychedelics, generally, are among the most subjective mood-altering drugs. A user’s experience can
vary greatly. Generally the experience is intense, but the variation in how that intensity manifests is well
known (“good trips” vs. “bad trips”). The influences upon the quality of experience are largely based on
set, setting, and expectations. A person who is in a bad mood and is looking for a drug to self-medicate
that bad mood is much more likely to have a negative experience on the drug. Refer back to the guiding
questions from the Scientific American article. How were the subjects “prepared” for their psychedelic
treatment?
A second, important factor in determining how a person will experience a lysergamide drug is what
other serotonin-influencing drugs that person uses. Serotonin syndrome is a potentially life-threatening
adverse reaction to drug combinations when the individual drugs influence serotonin (to learn more,
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visit http://www.ncbi.nlm.nih.gov/pubmedhealth/PMH0004531/ ). Incidentally, when past-LSD users
were placed on therapeutic anti-depressants, many of them experienced flash backs! 4
Activity Nine: Reading
Required Reading
Liska chapter 12: 12.1 – 12. 5, 12.6.6, 12.15, chapter 2 – section on psilocybin
Lay literature
Scientific American, December 2010
Village Voice, November 2010
Internet
http://emedicine.medscape.com/article/293752-overview
http://emedicine.medscape.com/article/293752-overview#a0104
Supplemental Reading
Internet
http://www.ncbi.nlm.nih.gov/pubmedhealth/PMH0004531/
4
PMID:7965440
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