Saved from url http://sulcus.berkeley.edu/mcb/165_001/papers/manuscripts/_471.html .
Every two years the Student Drug Use Survey, sponsored by the Addiction Research
Foundation of Ontario, conducts surveys of students enrolled in grades seven
through thirteen to obtain statistics on the prevalence of drug use. In the
previous years the prevalence of drug use increased for all drugs; however,
the surveys from 1995 to 1997 showed only one significant increase-the use of
the hallucinogen psilocybin (Adlaf 1998).
According to the survey there was an approximate 10.1 percent increase in
the use of psilocybin while the trend for all other drugs was a significant
drop (Adlaf 1998). Educators or administrators, who are developing drug education,
prevention or intervention programs for youth, should incorporate information
on hallucinogenic drugs. Because of the increased popularity of psilocybin among
recreational drug users, knowledge and understanding of this hallucinogen is
critical. The chemical psilocybin occurs naturally in many mushrooms but it
is best known from Psilocybe mushrooms commonly called "magic" or sacred mushrooms.
In this paper, I will present a historical, clinical and psychological analysis
of psilocybin by presenting recent research, information, and reports concerning
the study of this hallucinogen.
Psilocybe mushrooms or hallucinogenic mushrooms have probably existed longer
than humanity. Throughout history, ancient pictures of mushroom-like humans
have been prevalently reported. In Central and Southern America, use of psilocybian
mushrooms was a common religious practice until the arrival of Spaniards who
spread the Catholic faith with sword and fire and forbade the use. For Indians
the mushroom is known as a sacred mushroom and historically, it is considered
a religious path to the spirit world (Wasson 1980).
Mushroom art and sculptures that depicted motifs under the cap of a mushroom
were found even from an earlier era of 1000-500 BC. The purpose of these sculptures
and artifacts was not certain, but it is speculated that the stones had religious
meaning (Allegro 1970). The Codex Vienna Mixtec manuscript that dated back to
thirteen century depicted the ritual use of the sacred mushrooms by the Mixtec
Gods. The God known as Seven Flowers was the Mixtec God for hallucinatory plants,
especially the secret mushroom, and he was depicted carrying a pair of mushrooms
in his hands (Wasson 1898). In addition, the Aztecs believed that they were
capable of moving back and forth between the earthly and supernatural realms
(Schwartz 1988). This travel between realms was often associated with hallucinatory
trances guided by their god for the entheogens-the Prince of Flowers. The Aztecs
called this ritual "the flowery dream;" this was induced by sacred mushrooms
The appeal of mushrooms in the "modern world" originated when Gordon Wasson
came to the Mazatec village of Huatla de Jimenez, and experienced a session
of "velada" held by curandera Maria Sabina. Velada included a religious ritual
under a heavy influence of Psilocybe mushrooms (Wasson 1898). Information about
the mushrooms spread and experimentation began. In 1958 the active ingredients
of the mushroom, Psilocybin and psilocin, were found and their analogues were
synthesized by Dr. Albert Hoffman, who also discovered lysergic acid diethylamide
(LSD) (Schwartz 1988). Experimentation with the mushrooms historically increased,
leading to their significant influence in the part of the "60's psychedelic
movement" (WWW 1). And even these days, psilocybin mushrooms are one of the
most common hallucinogenic substances for recreational use (Adlaf 1998).
Hallucinogenic mushrooms grow naturally in fields and in cow pastures mainly
in northwest and southeast of the United States. The most common psilocybin
mushroom in the United States is Psilocybe cubenis (Schwartz 1988). The primary
active ingredients of Psilocybe mushrooms are psilocybin and psilocin. Individual
mushrooms contain approximately up to two percent of the psychoactive ingredient
psilocybin, while psilocin is only found in trace amounts (Pedersen-Bjergaard
1998). Between 4 to 10 mgs of psilocybin is considered to be an average content
for psilocybin per grams of mushroom, and that is also the usual dose ingested
The primary difference between psilocybin and psilocin is that psilocin is
unstable, and it breaks down when the mushroom is dried (Pedersen-Bjergaard
1998). Psilocybin is highly stable, and it has been reported that psilocybin
can last for an extremely long amount time and was even detected in a hundred
fifteen year old mushroom sample (WWW 1).
Both of the two compounds are equally psychoactive, since one molecule of psilocybin
(O-phosphoryl-4-hydroxy-N) can be broken down into one molecule of psilocin
(4-hydroxy-N,N-dimethyl-tryptamine). The breakdown occurs when the mushroom
is orally ingested. In the digestive track, psilocybin dephosphorylates to psilocin;
the dephosphorlytaion process is accomplished by a readily present digestive
track enzyme, alkaline phosphatase (Vollenweider 1998).
Psilocybin and psilocin belong to the tryptamine (indoleamine) family of psychedelics.
They occur naturally in many mushrooms. The species of Psilocybe mushrooms have
high a capacity to transform fed tryptamine into a psychoactive ingredient psilocybin
by a methylation and hydroxylation reaction. Studies of psilocybin biosynthesis
in mushrooms show that the amino acid tryptophan and tryptamine are precursors
to the indole alkaloids (Gartz 1989). Although psilocybin can also be chemically
synthesized, it is very difficult and expensive. (Cuomo 1994).
Psilocybin and psilocin are closely related to the neurotransmitter serotonin.
Psilocin, especially, is structurally related to a neurotransmitter serotonin
(5-hydroxytryptamine or 5-HT) (Vollenweider 1998). The structural resemblance
to serotonin also parallels with psilocybin's activity. The primary effect of
psilocybin seems to be the inhibition of the neurotransmitter serotonin, because
the indole binds to 5-HT receptors. More specifically, the effect of psilocybin
is to act as an agonist to the 5-HT2 receptor. The potency of the hallucinogens
in humans is related to the binding affinity for the 5-HT2 receptor in animals.
In addition, animal studies have demonstrated that the action of the hallucinogenic
drug can be blocked by 5-HT2 antagonists, thus supporting psilocybin as a 5-HT
analog (Vollenweider 1998).
Although animal studies conclusively prove the involvement of 5-HT2 receptor
systems in hallucinogenic drug action, animal hallucinogenic drug action might
not be reliable when applied to the human model. For instance, many scientists
question if psilocybin has an effect on the dopamine receptors in humans because
of psychotic-like symptoms of the drug. Psychosis is correlated with over-stimulation
of the dopamine pathways in the central nervous system, thus leading to the
hypothesis that the dopamine system is not modulated through interactions of
serotonin and dopamine in humans (Vollenweider 1998).
In order to prove lack of involvement of the dopamine system in humans for
the psilocybin mechanism, the Psychiatric University Hospital in Zurich, Switzerland,
conducted psychological research on human subjects. They investigated the current
animal hypothesis of the psilocybin mechanism to test weather 5-HT2 and/or dopamine
receptors are effected through psilocybin. Their results support that the effects
induced by psilocybin results from the activation of a 5-HT2 subtype of serotonin
receptor in human subjects as well as in animals. The conclusions were drawn
from the study of influence to pretreatment with 5-HT2 antagonist (ketanserin),
dopamine receptor D2 antagonist (haloperidol) and mixed 5-HT2/D2 antagonists
(risperidone) on psychological effects of psilocybin on healthy human subjects
(Vollenweider 1998). The study concluded that "psilocybin-induced psychosis
could be completely prevented by either the atypical neuroleptic and mixed 5-HT2/D2
antagonist risperidone or by the 5-HT2 antagonist ketanserin, but not by the
typical neuroleptic and D2 antagonist haloperdol" (Vollenweider 1998). This
study added substantial evidence to the hypothesis of the 5-HT2 agonist is responsible
for the psychological effects of psilocybin. The 5-HT2 post-synaptic agonist
appears to mimics the effects to 5-HT and cause psychological changes in the
central nervous system (Vollenweider 1998).
The hallucinogenic psilocybin and psilocin found in mushrooms have low toxicity.
Studies in mice showed that doses up to 200 mg of psilocybin/kg of body can
injected without lethal effects. That implies that an average human with body
weight of 65 kg can be injected 13 grams of the psychoactive mushroom ingredient
without experiencing any lethal effects (WWW 1).
The most traditional measurement of toxicity of a drug is a therapeutic index
that is a ratio of the lethal dose (LD50) to the effective dose (ED50) (Gable
1993). According to the Registry of Toxic Effects, the therapeutic index for
psilocybin is 641. In comparison to other substances it is relative non-toxic.
For example the therapeutic index for vitamin A is 9637, 4816 for LSD, 199 for
aspirin and 21 for nicotine, thus psilocybin appears to have a relatively low
toxicity (WWW 1). In addition, literature states that the oral intake of psilocybin
appears to be the lowest risk out of all other drugs for both acute lethality
and dependence (Gable 1993).
Although much of the literature supports psilocybin as having relatively low
toxicity, dependence and lethality, in the last two years, cases of serious
physiological intoxication by natural hallucinogenic substances have surfaces
around the world. A frequent use of hallucinogenic mushrooms have demonstrated
to have effects not previously classified by the use of psilocybin. Currently,
clinical case and overdose studies of patients showed that psilocybin use results
from arrhythmia and myocardial infarction. The indole concentrations of hallucinogenic
mushrooms do not present risks of adverse central nervous system effects but
also cardiac toxicity (Borowiak 1998).
The myocardial infarction in the frequent users and in cases of sever intoxication
suggest the possibility of cardiac damage related to psilocybin. According to
recent studies, indole alkaloids are agonists at the 5-HT receptor in the central
nervous system. However, peripherally they induce a sympathomimetic stimulation
that leads to tachycardia and hypertension. In the past, the use of 5-HT agonists
in migraine headaches was linked to myocardial infarction due to coronary vasoconstriction.
In addition, serotonin receptor agonists can cause platelet hyperaggregation
and occlusion of small coronary arteries. Because psilocybin is also an agonist
of 5-HT receptors, it is conclusive from these observations that the use of
this drug can lead to cardiac toxicity (Borowiak 1998).
The historical mind-altering effects of psilocybin are described as a voyage
to the spirit world. These hallucinogenic effects are similar to those of LSD;
however, psilocybin is two hundred times less potent and also has a shorter
duration time (Schwartz 1988). Common physiological reactions include muscular
relaxation, coldness of the limbs and abdomen, and dilation of the pupils. A
stronger dose includes vision and mental hallucinations and other sensory distortions.
Use of the mushroom causes a feeling of disconnection from reality and an altered
state of consciousness (Cumno 1994).
As with all major hallucinogens, psilocybin can precipitate psychotic episodes
and bring up previous mental illnesses. Therefor, individuals that are prompt
to being stressed, depressed, or have schizophrenia in their history should
not take mushrooms or other psychedelics. Mushrooms, similar to LSD, can significantly
change a person's perception and cause a "bad trip" or an experience that can
have a significant impact on someone's life. For this reason they are more then
a purely recreational drug; they can be extremely psychologically impacting
(Schwartz 1988; WWW 1).
The physiological and psychological effects of mushrooms are influenced by
the dose and the individual's sensitivity to psilocybin. For some people, as
small amount as 0.25 grams of Psilocybe mushroom can be enough for a full visionary
experience, unpleasant stomach cramps or gas, and other effects usually present
at high doses. In other users, the same amount might not cause any noticeable
effects. Thus, it is very critical that a user understands his individual reaction,
and to be safe during the first use. It is "recommended" to start with only
a small amount of psilocybin. The minimal dose for any notable effect is often
referred to as the threshold effect. This effect can be induced by amounts ranging
from 0.25 grams to 0.75 grams of Psilocybe mushroom (Schwartz 1988; WWW 1).
A more profound effect can be induced with an amount that ranges from 0.75
grams to 2.5 grams of mushroom. Similarly to a small dose, the feeling of reduced
temperature, gas and/or stomach discomfort, nausea occurs, but they might be
more profound. However, this dose might induce powerful distortion of space,
increased ability to visualize creatively, spontaneous detailed images, feelings
of time distortion. These effects of psilocybin are often more pronounced in
users who have used mushrooms before. Emotional sensitivity and an increased
ability to focus on emotional problems can raise the probability of thinking
or dwelling on a single feeling that usually has a negative content--a content
that can lead to psychological crises come out (Schwartz 1988; WWW 1).
At a dose ranging from 2.5 grams to 10 grams, all of the effects of the medium
dose should be expected, usually with significantly more uncomfortable side
effects. These side effects include pronounced nausea that can result in vomiting
and significant mental discomfort associated with feelings of fear and often
times accompanying a "what have I done to myself." These effects usually lessen
as the experience becomes familiar to the person and knowledge about the characteristics
and side effects of mushrooms becomes more apparent. The effects of high doses
can lead to acute adverse effects and intoxication that might lead to extreme
fears, panic and even intense psychosis. These psychological effects are almost
indistinguishable from true schizophrenia. After acute intoxication, the user
is usually extremely exhausted and mentally depressed (Schwartz 1988).
The behavioral effects induced by psilocybin are often complicated by the fact
that users mix different substances. For example, the effects of psilocybin
can be made stronger by taking them with a monoamine oxidase inhibitor (MAOI).
The best known MAOIs are harmine and harmaline from the plant Peganum harmala.
Combining MAOIs and other substances with tryptamines is an unsafe activity
because it increases amounts of monoamides in the body (WWW 1). This might cause
a hypertensive crisis that is due to elevated tyramines in the body.
The field of psychedelic research extends beyond the investigation of biochemistry
and recreational use. There have been great promises for medical use of psychedelics.
Studies focused on the role of psychedelics in religious experience and behavior
change. Psilocybin experiments were conducted in the early 1960's under the
direction of Timothy Leary, Ph.D. Dr. Leary had obtained permission from the
Massachusetts Department of Corrections to administer psilocybin to volunteers
in Concord Prison (WWW 2). The hope for the experiment was to test if psilocybin
experiences can change the prisoner's cycle of antisocial behavior and reduce
their recidivism. The action of psilocybin was used to help the prisoners recognize
the impact of their past behavior. Such realization was hoped to connect them
to their spirit and consciousness, leading to resistance of desire to commit
future crimes. The final results showed that psilocybin experience alone were
not sufficient to reduce recidivism. However, the failure of the research originated
from the lack of group support meetings for the prisoners. However, similar
studies disclosed that psilocybin could cause a behavioral change in people
with strong religiously conviction. People who took psilocybin with a religious
context experienced deeper spiritual connection (WWW 2).
In conclusion, the prevalence of psilocybin throughout history and its current
use has lead to intensive studies and research. The studies on human and animal
models both demonstrated that psilocybin produces psychosis-like symptoms primarily
through serotonin-2 receptor stimulation. Although many of the psilocybin effects
are understood and well documented, we keep learning more about this substance
as more data is collected through research of psilocybin users. As the understanding
continues, the field of psychedelic research will likely extend beyond its current
use because of the great promise for medical use in the treatment of various
Adlaf, Edward M. et al. Recent findings from Ontario Student Drug Use Survey.
Canadian Medical Association 5. 451-455 (1998).
Borowiak, Krzysztof S. et al. Psilocybin Mushroom Intoxication with Myocardial
Infarction. Clinical Toxicology 36. 47-49 (1998).
Vollenwieder, Franz X. et al. Psilocybin induces schizophrenia-like psychosis
in humans via a serotonis-2 agonist action. NeuroReport 9. 3897-3902 (1998).
Pedersen-Bjergaard, Stig. et al. Strategies for capillary electrophoretic separation
of indole alkaloids in Psilocybe semilanceata. Electrophoresis 19. 27-30 (1998).
Cuomo, Micheal J. et al. Increasing Use of "Ecstasy" (MDMA) and Other Hallucinogens
on College Campus. College Health 42. 271-274 (1994).
Gable, Robert S. Toward a Comparative Overview of Dependence Potential and Acute
Toxicity of Psychoactive Substance Used Nonmedically. Drug Alcohol Abuse 19.
Gratz, Jochen. Extraction and analysis of indole derivatives from fungal biomass
Basic Microbiology 29. 347-352 (1988).
Schwartz, Richart H. and Smith, Deborah. Hallucinogenic Mushrooms.
Clinical Pediatrics 27. 70-73 (1988).
Wasson, Robert G. The Wondrous Mushroom. Library of Congress Cataloging in Publication
Wasson, Robert G. Maria Sabina and her Mazetec Mushroom Velada. Library of Congress
Cataloging in Publication Data (1974).
Allegro, John M. The Sacred Mushroom & The Cross. National General Company
WWW 1. The Vault of Erowid: Sacred mushrooms.
WWW 2. Psilocybin: Concord Prison Follow-up from the Newsletter of the Multidisciplinary
Association for Psychedelic Studies MAPS-
Volume 6 Number 2 Winter 1995-96