75
5
Non-synthetic hallucinogens include psilocin, which is metabolized from psilocybin.
This can be found in certain mushrooms (e.g. Psilocybe semilanceata, liberty cap or
“magic mushroom”). Psilocin induces somatic (dizziness, nausea, blurred vision), perceptual (altered shapes and colours, sharpened hearing) and psychic effects (hallucinations, distorted sense of time, dreamlike feeling, visual hallucinations and an altered
concept of reality). The latter are so-called positive effects of schizophrenia (see 7 Box 5.3)
and the drug is also used to induce a “schizophrenic” condition in animal models. Similar
effects are caused by the synthetic drug LSD. Mescaline is found in the San Pedro or
Peyote cactus Echinopsis pachanoi which is growing in Peru and Ecuador. DMT (dimethyltryptamine) is one of the chemicals from Psychotria viridis, known as Ayahuasca. These
compounds all have structural similarity with the neurotransmitter serotonin, and their
effects are caused in large parts by their binding to the 5HT 2A subtype of the serotonin
receptor, whereby mescaline only partially agonizes the receptor. It has been known for
a very long time that the symptoms seen in people after mescaline uptake are almost
identical with symptoms of patients suffering from schizophrenia (Osmond and Smythies
1952). With mescaline, in contrast to psilocybin, therefore also the negative effects of
schizophrenia, like social withdrawal and apathy, are induced. Further hallucinogens
include ketamine, a neurotoxic NMDA-channel blocker (see 7 Sect. 6.5) (Nickalls and
Nickalls 1988).
5-hydroxytryptamine (5HT) or serotonin receptors have seven families, (5HT 1–7 ).
They are all GPCRs with the exception of 5HT 3 , which is a ligand-gated Na + and
K + channel. Many pharmacological and animal studies have indicated that LSD and
the plant- derived psychedelic drugs mentioned above target 5HT 2A (Nichols 2004).
This receptor is coupled to Gq. Thus, it mediates activation of phospholipase C leading to production of IP3 and DAG and as a result to opening of IP3 Ca 2+ -channels
in the ER and activation of PKC. In addition it is suggested that 5HT 2A also mediates activation of phospholipase A, thus stimulating the arachidonic acid pathway,
and phospholipase D, releasing second messengers choline and phosphatidic acid
(Nichols 2004).
Localization studies have revealed that 5HT 2A receptors are predominantly postsynaptic. They are mainly found in the neocortex and the thalamus of the brain. They have also
been identified at locations further away from synapses and therefore function in neuromodulation. Receptor agonists cause a robust increase in the activity of pyramidal neurons. These are multipolar neurons with large apical dendrites, multiple basal dendrites
and a large number of dendritic spines involved in neuroplasticity and cognition. They are
excited by glutamate and inhibited by GABA. Because of their dendritic complexity, a
Box 5.3 Schizophrenia
Schizophrenia describes “any of a group of severe mental disorder that have in common such
symptoms as hallucinations, delusions, blunted emotions, disordered thinking and withdrawal
from reality” (The New Encyclopedia Britannica, 15th edition); positive symptoms of schizophrenia then refer to conditions of excess or distortion of normal function and include hallucinations,
delusions and thought disorder; negative symptoms refer to a loss of normal function such as
lack of emotion, social withdrawal, loss of motivation and others.
5.6 · 5HT2 A Receptors: Psilocybin, Mescaline and Dimethyltryptamine
5
Non-synthetic hallucinogens include psilocin, which is metabolized from psilocybin.
This can be found in certain mushrooms (e.g. Psilocybe semilanceata, liberty cap or
“magic mushroom”). Psilocin induces somatic (dizziness, nausea, blurred vision), perceptual (altered shapes and colours, sharpened hearing) and psychic effects (hallucinations, distorted sense of time, dreamlike feeling, visual hallucinations and an altered
concept of reality). The latter are so-called positive effects of schizophrenia (see 7 Box 5.3)
and the drug is also used to induce a “schizophrenic” condition in animal models. Similar
effects are caused by the synthetic drug LSD. Mescaline is found in the San Pedro or
Peyote cactus Echinopsis pachanoi which is growing in Peru and Ecuador. DMT (dimethyltryptamine) is one of the chemicals from Psychotria viridis, known as Ayahuasca. These
compounds all have structural similarity with the neurotransmitter serotonin, and their
effects are caused in large parts by their binding to the 5HT 2A subtype of the serotonin
receptor, whereby mescaline only partially agonizes the receptor. It has been known for
a very long time that the symptoms seen in people after mescaline uptake are almost
identical with symptoms of patients suffering from schizophrenia (Osmond and Smythies
1952). With mescaline, in contrast to psilocybin, therefore also the negative effects of
schizophrenia, like social withdrawal and apathy, are induced. Further hallucinogens
include ketamine, a neurotoxic NMDA-channel blocker (see 7 Sect. 6.5) (Nickalls and
Nickalls 1988).
5-hydroxytryptamine (5HT) or serotonin receptors have seven families, (5HT 1–7 ).
They are all GPCRs with the exception of 5HT 3 , which is a ligand-gated Na + and
K + channel. Many pharmacological and animal studies have indicated that LSD and
the plant- derived psychedelic drugs mentioned above target 5HT 2A (Nichols 2004).
This receptor is coupled to Gq. Thus, it mediates activation of phospholipase C leading to production of IP3 and DAG and as a result to opening of IP3 Ca 2+ -channels
in the ER and activation of PKC. In addition it is suggested that 5HT 2A also mediates activation of phospholipase A, thus stimulating the arachidonic acid pathway,
and phospholipase D, releasing second messengers choline and phosphatidic acid
(Nichols 2004).
Localization studies have revealed that 5HT 2A receptors are predominantly postsynaptic. They are mainly found in the neocortex and the thalamus of the brain. They have also
been identified at locations further away from synapses and therefore function in neuromodulation. Receptor agonists cause a robust increase in the activity of pyramidal neurons. These are multipolar neurons with large apical dendrites, multiple basal dendrites
and a large number of dendritic spines involved in neuroplasticity and cognition. They are
excited by glutamate and inhibited by GABA. Because of their dendritic complexity, a
Box 5.3 Schizophrenia
Schizophrenia describes “any of a group of severe mental disorder that have in common such
symptoms as hallucinations, delusions, blunted emotions, disordered thinking and withdrawal
from reality” (The New Encyclopedia Britannica, 15th edition); positive symptoms of schizophrenia then refer to conditions of excess or distortion of normal function and include hallucinations,
delusions and thought disorder; negative symptoms refer to a loss of normal function such as
lack of emotion, social withdrawal, loss of motivation and others.
5.6 · 5HT2 A Receptors: Psilocybin, Mescaline and Dimethyltryptamine