Hallucinogens of the Serotonergic Type (5-HT)

Question 1

Albert Hoffman

Answer 1

• Lysergic acid diethylamide (LSD) was synthesized in 1983
• he was studying the derivatives of ergot fungus for their vasoconstrictive action and ability to give muscle tone to the uterus
• Lysergic acid amine is an alkaloid obtained from ergot - parasitic fungus found on a variety of grains

Question 2

Ergot derivatives

Answer 2

• of interest bc it was known that ergot caused contraction of the uterus and had been used speed up childbirth (used since 1582)

Question 3

was Hoffman attempting to create a hallucinogen?

Answer 3

• he created LSD by accident but on the 25th derivative that he produced it had strong hallucinogen properties (ie. LSD-25)

Question 4

what other compounds was Hoffman able to produce?

Answer 4

• produced compounds with therapeutic usefulness (ie. Methergine)

Question 5

Methergine

Answer 5

• leading drugs used to control uterine bleeding and muscle tone and a variety of ergot derivatives used to treat migraines

Question 6

when did the hallucinogen effects of LSD get discovered?

Answer 6

• 1943 when Hoffman accidentally dosed himself with some LSD by getting a sample on his hands
• he ingested 250 micrograms orally to study the effect (he chose a dose that is 5x larger than the minimal psychoactive dose) - the minimal psychoactive dose is about the size and weight of a grain of salt

Question 7

why did government agencies want to use LSD?

Answer 7

• they believed that it would be useful when interrogating people

Question 8

Dr. Timothy Leary and Richard Alpert

Answer 8

• began their research on psilocybin

- they started distributing the drug to students on campus and told young people to “turn on” acid

Question 9

what were the uses of LSD?

Answer 9

• The 1950s and 60s LSD was used in the psychotherapy bc they believe that people who were under the influence would be more open to communicating about their inner feelings and be more open to therapeutic suggestions

Question 10

what times were LSD popular?

Answer 10

• from 1967-1971 the % of college students reported at least one use of LSD in their lifetime rose from 1%-18%
• use has generally declined since then

Question 11

when did LSD become a schedule I drug?

Answer 11

1966

Question 12

what are the charcterisitics of LSD?

Answer 12

• colourless, ordorless, readily absorbed from the gastrointestinal tract and easily crosses the blood-brain and placenta barrier
• can be taken orally as a tablet or as absorbant paper
• the street dose of LSD is generally 50 micrograms (which is one quater the size of the typical dose in the period of peak use (200 micrograms)
• oral ingestion: effects in at most 60mins, peak concentration at 90mins and duration for 5-12hrs
• the hallucinogen effects dont start until 1-2 hours after ingestion and primarily when the eyes are closed - the first effect is SNS which is the undesired effects (dilated pupils, analgesia)

Question 13

Effects of LSD: wave-like and rhythmic movements in objects

Answer 13

• trees appear to be swaying or walls pulsate

Question 14

Effects of LSD: object trials

Answer 14

• perceptual residue of an object moving acress the visual area

Question 15

Effects of LSD: form constant

Answer 15

• eyes are closed, images of gratings, latticework, honey combs etc. appear
• this is very common to users

Question 16

Effects of LSD: Synaesthesia

Answer 16

• perception of one sense in another modality

- most users report seeing sounds (seeing vivid colours while listening to music with their eyes closed)

Question 17

Effects of LSD: distortions in time perception

Answer 17

• often report small periods of time seeming to be very long
• this can be a problem if the user is experiencing a bad trip and the minutes feel like hours

Question 18

Effects of LSD: ego disimtegration

Answer 18

• users may feel the melted/meshed into the bed or sofa on which they are resting and feel like they’ve become part of the atmosphere
• this effect is primarily due to the analgesic effects of the drug

Question 19

Effects of LSD: default mode network

Answer 19

• a group of brain regions that show lower activity when we are engaged in a particular task but show higher activity when we are awake and not involved in any specific mental exercise
• basically an ego mechanism that keeps us in control of ourselves, centers our experience by filtering perceptions and keeping everything normal
• with LSD users the default mode network lost synchronization and that was correlated with volunteers reporting a disintegration of their sense of self or ego

Question 20

Effects of LSD: Bad Trips/ Panic attacks

Answer 20

• potential adverse effects
• bad trips are most common in novice users with a preexisting psychological disturbance or in people who have unknowingly been given
• users with a bad experience feel that the trip might be permanent
• these people are able to be consoled
• incidence of a bad trip is less than 5%

Question 21

Effects of LSD: flashbacks

Answer 21

• unexpected psychedelic experiences long after the most recent use of LSD
• short-lived, self-terminating and often not distressing
• occurs in 1 in 3 users
• cause of flashbacks is unknown - the general explanation is something responding to cue related to a previous drug experience that evokes a particularly vivid memory

Question 22

Effects of LSD: Hallucinogen Persisting Perception Disorder (HPPD)

Answer 22

• diagnosable in the DSM 5
• long-lasting, distressing, recurrent and only slowly (if at all) reversible psychedelic experiencing occurring long after
• prevalence is 4% and it’s mostly identified with LSD but also occurs in other drugs

Question 23

Effects of LSD: fatal

Answer 23

• can be fatal

- LD/50 is 14,000 micrograms which is about 300x greater than the minimal psychoactive dose estimated at 50 micrograms

Question 24

Effects of LSD: tolernace

Answer 24

• occurs to most hallucinogenic effects of LSD
• happens in as little as 3 to 4 days of once-daily exposure
• occurs rapidly to other serotonergic and nonadrenergic hallucinogens
• cross-tolerance occurs meaning that if there is tolerance in LSD there is also tolerance in psilocybin or mescaline
• there’s also evidence of Pavlovian conditioning which contributes to the tolerance of LSD

Question 25

Effects of LSD: withdrawal?

Answer 25

• no evidence of physical dependence so there is no withdrawal symptoms

Question 26

Effects of LSD: teratological effects

Answer 26

• LSD does not cause teratological effects

Question 27

Neurochemical action of LSD and other 5-HT hallucinogens

Answer 27

• produce hallucinogens effects by action on serotonergic neurons
• the consensus that LSD produces its effects mainly via an agonistic action at the postsynaptic 5-HT receptors
• evidence for this hypothesis is the findings that the magnitude of the drug hallucinogenic effects correlates strongly to the drug’s potency for 5-HT binding and blocking at the 5-HT receptor antagonizes the effects of LSD
• LSD also acts to some extent on the dopaminergic agonist

Question 28

Lysergic Acid Amide

Answer 28

• aka ‘cockspur’
• less potent but naturally occurring form of hallucinogen related to LSD
• found on ergot (fungus present on mouldy grains)
• these effects have been found in the narrative relating to “Holy fire” or “St. Anthony’s fire” - may have resulted from the string vasoconstrictive action of lysergic acid amide found in bread from the infected grains (restriction of blood flow to the limbs gave off a tingling warm sensation) so when people with “Holy Fire” made a journey to the sacred St. Anthony’s shrine they may have been cured bc they removed themselves from the area with infected grains
• lysergic acid amide is one-tenth the potency of LSD
• ergotism: afflicted behaviour caused by ingestion of ergot - there was an outbreak of ergotism in a small French town

Question 29

Psilocybin

Answer 29

• naturally occurring substance in a variety of mushrooms native to Mexico and Central America
• isolated in 1958 by Hoffman and is called “flesh of the gods” by Mayan and Aztec people and have been used dating back to 1000BC
• typically eaten or drank
• 4 to 8 mg of psilocybin is needed to produce psychoactive effects and greater than 15mg is needed to produce hallucinogen effect
• onset is in 30mins and duration is 2-6 hours
• in the body, it’s converted to psilocin which is a more lipid-soluble and is thought to be the active ingredient
• tolerance and cross-tolerance occurs
• users of street dosed LSD and psilocybin say that the latter is more strongly visual, less emotionally intense, more euphoric and less likely to produce a panic reaction (but in the lab, there seems to be no difference)
• street name: “shrooms”
• it has similar neurochemical action as LSD and that it affects the DMN in a similar matter
• it has also been studied to the pharmacological addition in the treatment of other drugs (opiates, nicotine) and various psychiatric conditions (depression and end of life anxiety) - been compared to the use of mindfulness in the treatment of these disorders

Question 30

Dimethyltryptamine (DMT)

Answer 30

• several plant genus (Virola and Piptadenia peregrina) which is native to South and Central America
• Entheogens: naturally occurring plant substances that produce mystical or religious experiences
• can be taken as a drink but also has to be ingested with a monoamine oxidase inhibitor (something with harmaline alkaloid) bc without it the monoamine oxidase will metabolize the DMT into an inactive form
• Ayahuasca: is one of the most common drinks used by indigenous people – the effects of the drink are excitability and otherworldly experience”
• although it’s not medically recognized as a treatment it ayahuasca has been used to help people suffering from PTSD, addictions and other psychiatric conditions
• it also serotonergic effects similar to LSD and psilocybin

Question 31

Bufotenine (5-hydroxy-DMT)

Answer 31

• found in varients of plants, fish and toads in Haiti and Venezuela
• the toads have something to do with witches brew
• hallucinogen that’s used by indigenous in the form of ‘snuff’
• people have tried to ingest it by licking toads, or by drying the secretions and smoking it
• it produces stronger sympathetic arousal than other drugs which limits its attractiveness
• cyanosis: skin turns purple/blueish