4 - Hallucinogens Flashcards
Why is alcohol considered to some to be the most harmful hallucinogen?
Because it has a very high risk for doing risk to others
What did Albert Hofmann synthesize LSD from?
ergotamine, which is an alkaloid produced by fungus that grows on grain
Many hallucinogens share a similar structure to what neurotransmitter?
5-HT
5-HT2A can induce psychadelic effects by acting on ____ cells in the _____ (part of the brain)
Pyramidal neurons in the prefrontal cortex
LSD is involved in the activation of what two G protein-coupled receptors?
- All dopamine receptor subtypes
- All Adrenoreceptor subtypes
- Serotonin 52a receptor activates phospholipase A2 (instead of PLC)
- And other serotonergic receptors
How can hallucinogens be used to treat alcoholism?
The delirium effects of these drugs may be enough to develop an aversion to alcohol. However, clinical trials yield unclear results.
How harmful are hallucinogens?
According to criteria set by a team of UK experts, the hallucinogenic drugs (Mushrooms, LSD, Ketamine) belong to a group of low harm risk whereas alcohol, heroin and crack are on the other, high risk, end of the scale.
List some common hallucinogens and the systems they work on
- 5-HT agonism
- cannabinoid agonism (i.e., D9- tetrahydro-cannabinol),
- NMDA antagonism (i.e., phencyclidine, ketamine),
- muscarinic receptor antagonism (i.e., scopolamine),
- k opioid agonism (i.e., salvinorin A),
- mixed action monoamine release (i.e., 3,4-methylenedioxmethamphe- tamine [MDMA]), and more.
Describe the effects of LSD, which are similar to other hallucinogens.
LSD’s effects typically begin within 30 to 90 minutes of ingestion and may last as long as 12 hours. Users refer to LSD and other hallucinogenic experiences as “trips” and to the acute adverse experiences as “bad trips.” Although most LSD trips include both pleasant and unpleasant aspects, the drug’s effects are unpredictable and may vary with the amount ingested and the user’s personality, mood, expectations, and surroundings. LSD also has dramatic effects on the senses. Colors, smells, sounds, and other sensations seem highly intensified. In some cases, sensory perceptions may blend in a phenomenon known as synesthesia, in which a person seems to hear or feel colors and see sounds etc.
Describe (broadly) the chemical structure of hallucinogens
- Many hallucinogens share structural similarity with neurotransmitter 5-HT.
What are two main categories of hallucinogens that act via serotonergic receptors?
Hallucinogens that act via serotonergic receptors activation can be classified into two main categories: tryptamines (eg. psylocibin, LSD) and phenethylamines (eg. mescaline). All are agonists of the 5-HT2A receptors.
What has to happen to psilocybin for it to be active?
Psilocybin is inactive; it has to be metabolized in the user body by alkaline phosphatases that cleave phosporyl esther, to hydroxy compound – psilocin.
Psilocybin is orally active, with effective doses in the range of 6–20 mg. The onset of action is typically 20–30 min, with the effects completely gone within about 4–6 hr.
Describe the biosynthesis of mescaline in peyote cactus.
How potent is mescaline?
Mescaline is synthesized from L-tyrosine in peyote cactus (Lophophora williamsii) and also in some other cacti species.
Peyote cactus is harvested by “peyoteros” for sale to the Native American Church.
Mescaline is about 1,000–3,000 times less potent than LSD and about 30 times less potent than psilocybin.
How is the effect of hallucinogens unpredictable? How does this create issues in conducting research?
- The effects are usually unpredictable and depend on the expectations of the user (‘‘set’’) and the environment (‘‘setting’’) in which the use takes place. Volunteers given LSD in a clinical settings and warned that they might experience schizophrenia-like symptoms indeed often did suffer panic, anxiety, negative effects, and feelings of insanity. The effect is highly dependent on the personality of the drug taker.
- The unpredictability of an effect makes clinical research with LSD and other hallucinogens a real challenge. The bad “trips” make also difficult to find volunteers for clinical studies.
True or false? The use of hallucinogens is declining
The use of hallucinogens was popular among high-school students however in the last years this behavior has been constantly declining.
The motivation for taking hallucinogens is usually not connected with reward but rather with curiosity and “self-discovery”
What is psilocybin a precursor of? How does its effects compare to ketamine?
Psylocybin (precursor of psilocin an 5-HT2A agonist and ketamine (an NMDA receptor antagonist) dose-dependently induce an overlapping altered states of consciousness. Psilocybin effects are stronger within the perceptual alterations whereas ketamine more affects the control and cognition.
How must DMT and MDMT administered for their hallucinogenic properties?
The simple tryptamines DMT and 5-MeO-DMT are not active orally but are typically smoked or nasally insufflated. The duration of action for these simple tryptamines is very short, with the effects typically dissipated in less than 1 hr for DMT and 20–30 min for 5-MeO-DMT. The dose of DMT is typically 60– 100 mg of the free base and 6–20 mg for 5-MeO-DMT.
What is the most active and least active hallucinogens?
- LSD (tartrate) is “per os” active and is the most potent of all the hallucinogens, with doses ranging from 0.05 to 0.20 mg. LSD is also very long acting, with effects that can last as long as 10–12 hr.
- Mescaline is orally active but is the least potent of all the classical hallucinogens. Mescaline is also a long-acting compound, with effects that can last up to 10–12 hr. Effective doses of the sulfate salt are in the 200–400 mg range.
Describe hallucinogen toxicity and addiction
- Hallucinogens produce altered states of consciousness, but at doses that are not toxic to mammalian organ systems.
- In contrast to many other abused drugs, hallucinogens do not induce drug dependence or addiction and are not considered to be reinforcing substances.
- There is no literature report of successful training animals to self-administer classical hallucinogens, indicating that these substances do not possess the necessary pharmacology to either initiate or maintain dependence.
Why are hallucinogens not usually addicting?
Nearly all hallucinogens lack affinity either for DA receptors or for the DA uptake transporter and therefore do not directly affect DA neurotransmission.
What are three pathologies associated with hallucinogens?
- Flashbacks (can persist for months after use)
- Accidents (eg. staring at the sun, retina damage)
- Psychosis (can lead to depression, suicide)
What receptors do hallucinogens activate ‘to cause their effects?’
5-HT2a receptors
They also activate 5-HT2c receptors, but effects were blocked with 5-HT2a antagonists
How do people accumulate tolerance to hallucinogens?
It was observed development of rapid tolerance to hallucinogens, which correlated with down-regulation of the 5-HT2A receptor.
Where is the highest density of 5-HT2a receptors found in the brain?
Cortical pyramidal neurons
