Psilocybin with psychological support for treatment-resistant depression: an open-label feasibility study
Overview of attention for article published in "The Lancet Psychiatry", May 2016
Psilocin is an indoleamine that is structurally related to the neurotransmitter
of the central nervous system serotonin (5-hydroxytryptamine;
5-HT) and the drug lysergide (LSD-25). The psychotomimetic effects
observed after exposure to psilocybin/psilocin result from stimulation of 5-hydroxytryptamine receptors, especially the 5-HT2a receptor (Strassman,
1992; Vollenweider et al., 1998). It is discussed in the scientific
community whether also other receptors are influenced by psilocybin/psilocin.
In contrast to LSD, psilocybin has no affinity for dopamine
receptors (Creese et al., 1975).
Using PET methodology to study brain metabolism of psilocybin,
Gouzoulis et al. (1999b) found no increase of global brain metabolism
after per oral exposure to 0.2 mg/kg psilocybin, whereas Vollenweider et
al. (1997) found a general increase of cortical metabolism in various parts
of the brain after slightly higher exposure levels (0.26 mg/kg).
6.2 Pharmacological effects in humans
Psilocybin and psilocin are stoichiometrically equivalent in potency.
Therefore, the symptoms induced by psilocybin-containing mushrooms,
psilocybin or psilocin are more or less equivalent. It is believed that the
former is dephosphorylated to psilocin in vivo. Psilocybin is an inhibitor
of serotonin, the major indolic neurotransmitter of the central nervous
system. It is also an autonomic stimulant, leading to characteristic mydriasis,
piloerection and hyperthermia. The mono- and demethylated analogues
baeocystin and norbaeocystin are much less explored pharmacologically.
Already in the first publication reporting the isolation of psilocybin
from hallucinogenic mushrooms, it was stated that per oral application of
the compound in man produce similar psychotropic effects to the mushroom
Psilocybe mexicana (Hofmann et al., 1958a). Depending on the
individual, an intake of 4–10 mg psilocybin/psilocin, or 1–2 g of the dried
Psilocybe mushroom, results in effects searched for. These psychic effects
include stimulation, enhanced ability for introspection and altered
psychological functioning in the direction of Freudian primary processes,
also known as hypnagogic experience and dreams (Passie et al., 2002).
Especially noteworthy are generally pleasant sensation of intellectual and
bodily relaxation and detachment from the environment (perceptual
changes such as illusions, synaestesias, affective activation, and alterations
of thought and time sense), without producing a setback. The central
effects obtained become apparent in about 20–30 minutes and develop
with a startling rapidity over the following 20 minutes. Higher doses, at
least 6 mg, produce more profound changes associated with altered temporal
and spatial perception, an introspective state, and a variety of visual
effects. Illusions and hallucinations may be experienced (Cerletti and
A difficulty with the hallucinogenic compounds is that the subjective
experiences produced vary considerably from person to person and within
the same person on different occasions. These experiences are markedly influenced by the expectations of the user and the setting in which the
drugs are taken, as well as by the personality structure and mental status
of the user (Franz et al., 1996). There is frequently time distortion (subjective
slowing) under influence of psilocybin/psilocin. The activity plateau
rarely lasts much more than an hour and is characterized by alterations
in spatial and temporal perception, often with distortions in awareness
of body image. Positive expectations usually lead to pleasant
experiences and, conversely, larger doses in users with anxiety or uncertainty
may allow adverse experince. In the absence of visual and auditory
input (as with night-time isolation) the experience can be largely fantasy
and rich with hypnogogic imagery. Gradual recovery requires an additional
two to three hours and there is a good recall of the phenomena
experienced (Shulgin, 1980).
There are a number of general features which are characteristic of the
psychedelic reaction. Perceptual changes include illusions, pseudohallucinations,
and hallucinations. Vision seems most affected. Most
common are illusions. Objects, pictures, or patterns seem to come alive,
shift, ripple, or become wavy. Depth relationships are altered so that twodimensional
objects appear three-dimensional.
More common than true hallucinations, are pseudo-hallucinations in
which the user has a visual experience without any appropriate sensory
cue, but he knows his visions are subjective, a result of the influence of
the drug. He may se geometric figures, kaleidoscopic shapes, or flashes
of light. He may see dream-like sequences of panoramic visions related to
previous life experiences, tranquil scenes, or imagined horrors. True hallucinations
are rare but may assume almost any form.
Colours appear more brilliant and intense. Nuances of colours are often
experienced as emotionally meaningful and exceptionally beautiful.
Changed perception in the other senses is not as dramtic, but taste, touch,
smell, and hearing all seem to become more acute.
A remarkable feature of the hallucinogenic drug reaction concerns the
translation of one type of sensory experience into another, or synesthesia.
Sounds or music may be experienced visually or as bodily vibrations. The
user may think he can feel or taste colours and images. Perception and
mood become interwoven. Colour may come to represent a particular
emotion and induce it.
When psilocybin was given to healthy volunteers, psychological
symptoms reported were emotional alterations (100%), disorders/alterations
of consciousness (91%), depersonalisation (84%), perceptual
alterations (75%), disorders/alteration of volition and psychomotor
behaviour (34%), body image distortions (25%), disorders/alteration of
attention (22%), disturbances in thought processes (22%), and disorders
of memory (19%) (Parashos, 1976–1977; Spitzer et al., 1996; Vollenweider
et al., 1999). Similar symptom picture was noted in schizophrenic
patients consuming psilocybin, as illustrated by two case reports by Nielen et al. (2004). The cases illustrate that in schizophrenic patients
hallucinogenic mushrooms may induce an acute psychotic state that necessitate
hospitalisation (Nielen et al., 2004). The psychotic symptoms in
volunteers appeared within 20 to 30 minutes after oral ingestion, lasted
for about two hours and subsided completely within six hours. There are
no epidemiological on long-lasting psychiatric complications (Supprian
et al., 2001).
However, psilocybin is also an autonomic stimulant, leading to characteristic
mydriasis, piloerection, irregularities in heart and breathing rate,
and hyperthermia. Similar pharmacological effects have been documented
in mice, rats, rabbits, cats, dogs and rhesus monkeys (Cerletti,
1958; Horibe, 1974). The mono- and demethylated analogues baeocystin
and norbaeocystin are much less explored pharmacologically.
Emotional lability, extreme mood swings, and spontaneous emotional
discharges are common. The user may become profoundly depressed,
anxious, fearful, giggly, euphoric, serene, or ecstatic during a single drug
experience. Occasionally, blunting of affect, suspiciousness, hostility, or
suicidal urges may be felt. The user can usually converse rationally when
pressed to do so and can subsequently recall much of his drug experince.
Importantly, it has not been established whether the potential benefits
of the use of psychedelic drugs justify the risk of adverse reactions. From
the users point of view, out of all mushroom users in a study 73% reported
some positive effects of the use and approximately 45% reported
only positive effects. Only 5% reported predominantly negative effects
(Thompson et al., 1985). In a double-blind study on hallucinogen-naïve
subjects, Griffiths et al. (2006) recently showed that psilocybin under
supportive conditions give rise to experiences similar to spontaneously
occurring mystical experiences that were rated very positively by the
volunteers. Negative effects were rare. Higher rates of adverse reactions
have been reported in habitual drug users (Schwartz and Smith, 1988).
6.3. Hallucinogenic experience and potential toxicity
The magic mushrooms are inconspicuous and are not likely to attract the
interest of anyone looking for food mushrooms. However, intoxications
due to ingestion of hallucinogenic mushrooms thought to be edible mushrooms
have been reported. Ancient or historic evidence of cerebral mycetisms
induced by accidental ingestion of psychoactive mushrooms in
various parts of the world has been reviewed by Allen et al. (1991). The
authors of this review article points out that outside of a few intoxications
caused by Psilocybe cubensis and Psilocybe semilanceata (Cullinan and
Henry, 1945; Charters, 1957; Stein, 1958; Wasson, 1959; Stocks, 1963;
Heim, 1971; Harries and Evans, 1981), the majority of all intoxications
that occurred before the deliberate recreational use of hallucinogenic mushroom species was caused by various species of Panaeolus, with the
exception of Japan where some of the inebriations were the result of ingesting
Gymnopilus species and some that were attributed to the ingestion
of Stropharia caerulescens. Because of some similarities with the edible
mushroom Marasmius oreades (Bolt.:Fr.) Fr., Inocybe aeruginascens has
subsequently caused accidental hallucinogenic poisonings in previous
East-Germany and Hungary (Drewitz, 1983; Gartz and Drewitz, 1985,
1986; Gartz, 1986, 1989). Other cases of miss-identification of food
mushrooms have been described by Bigwood and Beug (1982), Rold
(1986), Raff et al. (1992) and Calvino et al. (1998).
Magic mushrooms are usually collected by persons solely interested in
mushrooms containing hallucinogens. These mushroom collectors frequently
rely on only two identifying characteristics: a habitat on or near
dung in pastures, and stems that stain blue on handling. Since even professional
mycologists have difficulties identifying many of these small
brown mushrooms, it is no wonder that the uninformed mushroom hunter
makes mistakes. Some of these mistakes may be of low risk, others may
lead to poisoning, which sometimes may be severe.
Other risks to become intoxicated by hallucinogenic mushrooms are
usually related to natural variation in psilocybin content of the mushrooms
(see, Table 4; differences between flushes, differences between
wild and cultivated mushrooms, etc.), miss-quantification of dose (mushroom
weight and number) or exaggerated intake (e.g., Harries and Evans,
1981), and differences in individual tolerance to hallucinogenic mushrooms
(Beug and Bigwood, 1982; Bigwood and Beug, 1982). Stamets
(1996) has calculated the threshold for intoxication to approximately 40
g psilocybin/kg body weight, which typically would correspond to about
1–2 g of dried mushroom, or approximately 4 to 20 mg psilocybin. Allen
et al. (1991) have drawn similar conclusions, whereas others have indicated
that clinical doses usually require larger amounts (Stein, 1958; Lincoff
and Mitchell, 1977; Weil, 1980).
It should be noted that several of the mushrooms mentioned in Table 4
and 5 contain other bioactive constituents in addition to the hallucinogenic
compounds. These constituents can of course influence the intoxication
syndromes described. For example, the most common hallucinogenic
mushroom in the Nordic countries, Psilocybe semilanceata, contains
the biogenic amine phenylethylamine (Beck et al., 1998).
In Mexico, where hallucinogenic mushrooms has a natural niche in
everyday life, there are persons who have consumed hallucinogenic
mushrooms since their youth until they die over 70 years of age, without
apparent physical illness (Allen et al., 1991). The acute toxicity of psilocybin/psilocin
is very low (Cerletti, 1959; Hofmann, 1960; Auert et al.,
1980; Leuner, 1981; Flammer and Horak, 1983; Gartz and Drewitz, 1986;
Holm et al., 1997). In a recent double-blind, placebo-controlled doseeffect
study with psilocybin in healthy subjects, the investigators found no cause for concern that psilocybin is hazardous with respect to somatic
health (Hasler et al., 2004). Damage to the body may, however, occur
when the perception of reality of an individual is influenced in such a
way by the hallucinogenic mushrooms that he or she behaves in a risky
way. For instance, Asselborn et al. (2000) describe an incident where two
girls ingested a handful of Psilocybe mushrooms (species undefined)
together with soft drinks. One of the girls tried to fly from a window on
the second floor, fell to the ground and fatally fractured the scull. Chemical
analysis of the mushroom revealed around 11 000 mg psilocybin and
5 000 mg psilocin/kg mushroom. Post-mortem studies of heart blood
revealed 0.09 mg psilocin/mL, one third of which was free psilocin. The
compound was also quantified in femoral venous blood, urine, bile, liver,
kidney and lung. No psilocin, or other drugs, was found in the hair, indicating
that the girl had no history of drug use. It should be mentioned,
however, that there are two reports on severe toxicity, although the role
of the hallucinogenic mushrooms for these cases is not totally clear. In
one case rhabdomyolysis was reported in a hepatitis C-infected man with
a history of heroin, opiate and cannabis abuse (Bickel et al., 2005). In the
other case (Gerault and Picart, 1996), a 22-year old man used to alcohol
consumption and cannabis smoking died after first having consumed 30–
50 raw mushrooms (most likely Psilocybe semilanceata) when picking
them, another 10 raw mushrooms three hours later, and a cup of tea prepared
on mushrooms another two hours later, although he at this time did
not feel well. When he got unconscious and was taken to hospital, there
was no care to get. Having been transported back to his home he died. A
standard forensic analysis on body fluids and tissues were performed
without identification of any drugs and foreign substances except psilocin.
The level of psilocin in the blood was 4 μg/mL. Four friends who
joined the victim drinking tea prepared on the mushrooms collected by
the victim showed different symptoms from only feeling drunk to having
colour vision or getting cramp.
The minimum amount of mushrooms required to promote “therapeutic”
doses is somewhere between two and six, assuming mushrooms of
high content of psilocybin or psilocin. Agitation and hallucinations may
be seen with 10 mushrooms in one case, whereas 200 may produce only
gastritis in another. Prolonged sympathomimetic effects and psychosis
have been seen with 50 to 60 mushrooms (Hyde et al., 1978). Hollister
and co-workers have described both the time sequence of onset of clinical
effects from psilocybin among 16 subjects exposed orally to doses between
60 and 209 g/kg, and the frequency of response among 19 subjects
given an oral dose of 150 g/kg (Hollister, 1961; Hollister and
Hartman, 1962; Hollister et al., 1960). The following clinical effects were
mentioned for psilocybin intoxication in humans: 0–30 min Slight nausea, giddiness (light headed), abdominal discomfort,
weakness, muscle aches and twitches, shivering,
anxiety, restlessness, and a numbness of lips.
30–60 min Visual effects (blurring, brighter colour, sharper outlines,
longer after-images, visual patterns with closed eyes). Increased
hearing, yawning, sweating, facial flushing. Decreased
concentration and attention, slow thinking, feelings
of unreality, depersonalisation, dreamy state. Incoordination,
60–120 min Increased visual effects (coloured patterns and shapes,
mostly with eyes closed). Wave-motion of viewed surfaces.
Impaired distant perception. Euphoria, increased
perception, and slowed passage of time.
120–240 min Waning and nearly complete resolution of above effects.
Returning to normal within 4–12 hours. Other effects often
included decreased salivation and appetite; uncontrollable
laughter, transient sexual feelings and synethesis.
Similar symptoms and absence of adverse toxic effects in humans have
been observed by others (Isbell, 1959; Gouzoulis-Mayfrank et al., 1999b)
In cases of intoxication, it might be useful to distinguish between the
primary toxic effects and the secondary effects resulting due to the exposed
persons emotional reactions to the primary symptoms of intoxication.
The primary toxicological actions of psilocybin and related compounds
are sympaticomimetic adrenergic symptoms and mental effects.
Sympaticomimetic adrenergic symptoms include mydriasis, flushing and
hyperreflexia, and elevated blood preassure, heart rate, frequency of respiration
and body temperature; also tremor, dizziness, nausea, dryness of
the mouth and tiredness may occur. The mental effects include euphoria,
experiences of unreality, altered conception of time, feeling of happiness
and clearness of mind. As a consequence of the previous reactions, illusions,
pseudohallucinations or real hallucinations may occur. Table 6
summarizes most of the case reports on acute psychiatric symptoms after
consumption of psilocybin-containing mushrooms. It should be stressed
that most cases described in Tables 6 and 7 themselfes chose to consume
the hallucinogenic mushrooms, that is, it is a recreational activity. The
five reported cases from Japan (Musha et al., 1986), where Psilocybe
argentipes were consumed, were, however, accidental cases. None of
these consumers expected to have the type of experience they had.
Although primarily psychological effects are associated with consumption
of psilocybin-containing mushrooms, depressive or paranoid reactions,
mood changes, disorientation, and an inability to distinguish between real-ity and fantasy may sometimes occur (Leary et al., 1963; Mills et al., 1979;
Weil, 1980; Grinspoon and Bakalar, 1981). Understandably, other routes of
exposure might be significantly more dangerous. There are case reports on
persons that have extracted Psilocybe mushrooms and experienced severe
toxic symptoms after having injected the extract intravenously (Sivyer and
Dorrington, 1984; Curry and Rose, 1985).
Fatal intoxications from the exposure to hallucinogenic mushrooms
are rare (McCawley et al., 1962; Gonmori and Yoshioka, 2003). The first
case was a 6-year-old child who developed hyperthermia and status epilepticus
following ingestion of Psilocybe baeocystis (McCawley et al.,
1962). In the latter case a 27-year-old man was found in an irrigation
canal. Cultivations of Psilocybe subcubensis was found in his home and
psilocybin/psilocin were detected both in the mushroom, and in body
fluids of the diseased man. It was suggested that the case had been influenced
by the hallucinogenic substances and died of cold temperature in
A death of an 18-year-old male living in Hawaii, was in commercial
media declared to have died due to consumption of ten hallucinogenic
mushrooms. Later investigations into his death, however, showed that the
youngster died of an overdose of heroine. Psilocybin or psilocin were not
detected in the stomach content, nor was amatoxins (Allen, 1988).
An unexpected risk was highlighted by two young mushroom hunters
being shot in Florida when looking for their afterthought treasure (Lincoff
and Mitchel, 1977). In summarising the 150 known cases of intoxication from psychoactive
mushrooms in Australia and New Zealand between 1934 and 1989, Allen
et al. (1991) pointed out that only one case required hospital care, and
that was because he had fallen and cut his head. However, three of 150
persons (2%) had suffered prolonged psychological difficulties following
their mushroom experience, two of which were flashbacks. In these cases
a predisposition was acknowledged for two of the people. Therefore, it
could be argued that certain people are psychologically at serious risk
from these substances and must be urged to avoid them (Allen et al.,
There has been continuing concern as to the long-term effects of psilocybin
and other hallucinogenic compounds on the human body. The
most notable concerns have been the possibility or recurrent flashbacks.
Flashbacks are spontaneous recurrences of a previous psilocybin experience
after the immediate effect of the drug has worn off and without renewed
intake of the compound. Table 7 summarizes cases of persistent
psychiatric symptoms described in the literature. Espiard et al. (2005)
described a 18-year old student that appeared at the clinic with perceptual
impairments. These were lasting for 8 months. The patient had a history
of social anxiety and a troubled family situation. He smoked moderate
amounts of cannabis regularly. Perceptual distortions initially appeared
after unique psilocybin consumption (40 mushrooms of the species Psilocybe
semilanceata in infusion). During later use of cannabis he reexperienced
the symptoms (objects’ distortions, relief’s modifications,
auditory disturbances with resonance feeling, depersonalisation, derealization,
body lightness or weightiness feeling, spatiotemporal disturbances,
and inability to distinguish illusion from reality). The flashbacks
started to weaken when the student stopped using cannabis. No somatic
lesions were identified. The flashbacks disappeared six month later after
several months on chemotherapeutica. The prevalence of flashbacks, and
its requirement for expression is difficult to estimate.
Other long-term effects investigated include potential reproductive
toxicity, teratogenicity and mutagenicity. The result of none of these has
given rise to concern. Already in 1967 Rolsten evaluated the effect of oral
administration of 25 mg psilocin per kg body weight on pregnant
C57BL/10 mice and their offspring. The psilocin treatment had no influence
on fertility as determined by pregnancy rate, pregnancy length, and
weight gain. It also did not influence maternal brain weight, liver glycogen,
and serum cholesterol, and brain, liver, and heart organ to body
weight ratios, or mean litter weight. Neither were any influences on serum
and organ biochemistry of the offspring at birth found (Rolsten,
1967). An American population-based case-control study performed
1989–1991 found no increased risk for neural tube defects due to maternal
and paternal periconceptional use of psilocybin/mushrooms/peyote or
other recreational drugs (Shaw et al., 1996). No micronuclei were induced in mice exposed to 4, 8 or 16 mg psilocybin
per kg body weight (Van Went, 1978). Tolerance to psilocybin (or
cross-tolerance with LSD) might develop, but physical dependence does
not occur (Abramson et al., 1956; Isbel et al., 1961; Abramson and Rolo,
1965; Balestrieri, 1967).
6.4. Hallucinogenic mushroom use in the Nordic
In Norway the first report on the use of Psilocybe semilanceata as delivering
a recreational drug appeared in 1977, and several others have appeared
thereafter (Nordbø, 1979, Kvambe and Edenberg, 1979). These
reports described hallucinogenic intoxications of consuming the mushroom
and stimulated investigations into the content of psilocybin and
psilocin in Norwegain mushrooms (Høiland, 1978; Høiland et al., 1984;
Christiansen et al., 1984; also see Table 4). It was concluded that Psilocybe
semilanceata is rich in hallucinogenic compounds, and that there is
a marked difference in psilocybin content between samples (Christiansen
et al., 1982). It was also concluded that it is a risk that mushroom pickers
looking for P. semilanceata might by mistake collect several different
toxic mushrooms with a similar structure.
Beck and his colleagues (1998) have discussed the clinical data that
had been collected from hospital case records and sent to the Swedish
Poison Information Centre concerning Psilocybe mushroom poisoning
during the period 1980–1995. The total number of patients was 25, of
which 21 were between 19 and 27 years of age. Five of the cases occurred
in 1995. The recorded symptoms in these hospitalized patients
included mydriasis (68%), visual hallucinations (52%), tachycardia
(44%), anxiety (40%), euphoria (24%), agitation (16%), hypertention
(16%), , hyperflexia (12%), flushing (12%), nausea (12%) and flashbacks
(8%). Thus, the symptoms in Swedish patients were the same as those
observed in patients from other countries (Malitz et al., 1960; Peden et
al., 1981, 1982).
Beck and colleagues (1998) also verified the presence of 1000–3 500
mg/kg wet weight psilocybin in Psilocybe semilanceata mushrooms that
had resulted in intoxications at three different locations in Sweden. However,
these investigators also noted that these mushrooms contained the
biogenic amine phenylethylamine (1–146 mg/kg wet weight). The sample
with the highest level of phenylethylamine came from the clinical case of
hospitalization after the ingestion of magic mushrooms. The pharmacological
mode of action of phenylethylamine is not fully elucidated, but it
has been reported to exert amphetamine-like activity and to have peripheral
sympathomimetic effects (Schwarts and Smith, 1988; Shulgin, 1980;
Mantegazza and Riva, 1963; Sabelli and Giardina, 1972). The neurophysiological effects have been related to the enhancement of catecholaminergic
activity (Sabelli and Javaid, 1995). Systemic administration of
phenylethylamine produces behavioral effects in rats and mice (Saavedra
et al., 1970). The serotonergic system is thought to mediate the neurophysiological
responses to hallucinogens (Glennon et al., 1984; Strassman,
1992). It is therefore interesting to note that serotonin receptor
blockade can potentiate the behavioral effect of phenylethylamine
(Goudie and Buckland, 1982). The high amount of phenylethylamine in
the case of mushroom intoxication mentioned above suggests that
phenylethylamine may contribute to the adverese reactions. The much
higher variability in phenylethylamine content as compared with psilocybin
is intriguing because it could explain why adverse reactions occur
only in certain cases.
Lassen and co-workers (Lassen et al., 1990, 1992, 1993b) and Holm et
al. (1997) have summarised available information on Danish mushrooms
containing psilocybin, and the use of these mushrooms in society. Up to
1996, the Danish Poison Information center had registered 22 contacts
due to hallucinogenic mushrooms of the species P. semilanceata (Holm
et al., 1997). The reason for contacting the Poison Information center was
mainly negative secondary psychic reactions on the psychomimetic effects
of psilocybin. In seven of these cases the patients experienced hallucinations,
showed tremendously anxiety and could not stay calm. The
other 15 cases were milder – dysfori and some anxiety – sometimes followed
by moderate sympatomimetic or gastrointestinal symptoms. One of
the cases was a young man that experienced flashback phenomena during
three months in the form of diffuse anxiety after ingestion of “magic
mushrooms” in Thailand (Holmgaard Kristensen and Harding Sørensen,
1988. In none of the cases severe somatic complications were registered.
Psilocybe semilanceata is also occacionally used as hallucinogenic
mushroom in Finland, where is grows more or less over the whole country.
Jokiranta et al. (1984) reported that the psilocybin content can be
failry high, up to 23 700 mg/kg dry weight.
6.5. Treatment of psilocybin-intoxication
The major dangers associated with psilocybin are primarily psychological
in nature. Anxiety or panic states (bad trips), depressive or paranoid reactions,
mood changes, disorientation, and inability to distinguish between
reality and fantasy may occur (Allen et al., 1991). Recommended treatment
for these types of adverse reactions to hallucinogenic mushrooms is
mainly supportive and consists mostly of calming the patient’s fears and
preventing him from harming himself or others (Mitchel and Rumack,
1978), but may, when indicated by symptomatic. This report does not aim
to cover the management of poisoning of psilocybin-containing mush-rooms. The readers interested in this area are referred to reviews available
(e.g., Leikin et al., 1989; Köppel, 1993).
In severe poisoning, restraints must be used. Diazepam (Valium), up
to 10 mg in adults, will control seizures. Chlorpromazine (Thorazine)
or equivalent phenothiazines can be used to control hallucinations (DiPalma,
1981). Mostly it is enough to follow the patients carefully during
the progressive decline in psychic experience. If the patient arrives at the
hospital within two hours after ingestion of the mushroom, active charcoal
may be given to the patient. Ventricular aspiration would not be the
preferred method of removing the toxins, since in this case the treatment
could be a higher risk than the exposure to the toxin. However, measures
could be taken to reduce the absorption of the toxins involved, either by
gastric lavage or emesis when it is suspected that a very poisonous mushroom
has been mistaken for a hallucinogenic mushroom (Francis and
Murray, 1983; Allen et al., 1991).
6.6. Medical uses of psilocybin and psilocin
In April 1966, Sandoz decided to withdraw its sponsorship of investgations
on hallucinogenic drugs such as psilocybin and LSD. The firm
transferred all of its remaining stock of these compounds to the National
Institute of Mental Health in the USA. Because the compounds are legally
handled in Schedule I of the Controlled Substances Act in the
United States, studies on their usefulness for society, for example, in
relation to treatment of various mental illnesses, is severly restricted.
Nontheless, psilocybin has been tested as a treatment for anxiety and
post-traumatic stress disorder, and mediator of mystical experiences.
Thus, Francisco Moreno of the University of Arizona at Tucson has
treated patients to test anecdotal reports that the drug can help patients to
manage symptoms of obsessive-compulsive disorder, and Charles Grub at
the University of California, Los Angeles, treated patients to investigate
whether psilocybin is able to relieve anxiety in terminally ill cancer patients
(Check, 2004). Doctor Griffiths at John Hopkins University School
of Medicine, Baltimore, have evaluated the acute and longer-term psychological
effects of a high dose of psilocybin in hallucinogen-naïve
adults regularly participating in religious or spiritual activities, and reported
positive changes in attitudes and behaviour.
24-year-old man Two weeks before symptoms he had eaten 25
psilocybin mushrooms together with two pints
Three month history of daily attacks of tension, anxiety, fear that
something was about to befall him, depersonalisation, palpitations,
bounding pulses, dryness of the mouth, and “butterflies in
the stomach”. Attacks sometimes accompanied by disturbed vision.
25-year-old man A frequent user of cannabis, LSD and ‘magic
mushrooms’. He had not used LSD for several
days when he tried 200 mushrooms together
with whisky and smoked cannabis.
He felt euphoric, colours appeared more vivid, and he experienced
a loss of time sence. A paranoid and aggressive reaction
developed. He described his reaction as disturbed sleep rhythm,
irritability, spathy and lack of concentration. The patient followed
instructions for treatment badly. Two days later he experienced a
‘flashback’ accompanied by visual distortions and he became panicky
and aggressive. As there was no improvement after 14 days,
he was given four ECT’s with beneficial results.
22-year-old man Sine puberty the man had used alcohol and
marijuana. He had also tried amphetamine but
stopped using it since he lost weight. Half a
year later i tried magic mushrooms.
Shortly after having consumed 15 Psilocybe semilanceata the
man became unconsious, experienced spasms and a bad trip. Two
months later he went to the doctor for suspected epilepsy. During
the period since the bad trip with magic mushrooms, he had revived
som of the experiences from the bad trip. Symptoms included
heavy heart beat, blurred sight, uncontrolled muscles,
Holmgaard Kristensen and
Garding Sørensen, 1988
Two cases Conditions of mushroom use not identified. Two of 150 cases of intoxication on New Zealand involved the
precipitation of a severe prolonged paranoid psychosis, eventually
requiring psychiatric treatment for a long period. In both cases
predisposing features were observed but there were clearly no
Allen et al., 1991
2 individuals The patients ingested an undetermined quantity of Gymnopilus
validipes which they mistook for the an edible mushroom
The patients quickly developed dysphoria, dizziness, and abnormal colour vision shortly
after consumption of the mushroom. Within an hour the individuals experienced difficulty in
expressing their thoughts, anxiety, time distortion, and vivid visual hallucinations.
Hatfield et al., 1978
3 Japanese men After dinner, two patients consumed 5 or 6 cooked Psilocybe
subaerulipes, respectively, whereas the third patient consumed
4 cooked fruitbodies and three raw. They all had the intention to
consume the selected species.
The patients experienced nausea, , became warm and sweaty, and experienced paralysis
of the limbs (maximum at 3 h after intake). Paralysis of the feet disappeared within another
1½ h but the fingers were affected for another few hours. Two of the patients had hallucinations
and one of them felt depressed. A fourth person who ingested only one mushroom
experienced on effects. All recovered within 24 hours, but one patient was taken to hospital
were a stomach wash was performed after emesis.
A 56-year-old man The man consumed 2–3 fried Pholiota spectabilis (Gymnophilis
spectabilis) in the belief it was Armillaria mellea, an edible
Fifteen minutes efter mushroom consumption he felt disconnected and woozy. His head
felt numb, and his vision was blurred. The size of the room changed, things became
shimmery, and appeared yellow with dark centers. The intellect was sharp, but memory
during the hallucination poor. He was unsteady on his feet and felt slight nausea and
abdominal distress. His wife who tried a small portion of mushrooms felt giggly, and
vomited. Both recovered within a few hours.
A 58-year-old woman A neighbor to the man above consumed a tablespoon of fried
Pholiota spectabilis (Gymnophilis spectabilis) in the belief it was
Armillaria mellea, an edible species.
Fifteen minutes efter mushroom consumption she felt dissy, was unable to move her joints
freely, felt chilly and then hot, and when she closed her eyes things seemd far away. She
experienced no colour sensation. She was unable to co-ordinate. On hearing her
neighbors experience she vomited. Recovery within a few hours.
4 men (16–29 years
Wheras three of the men had intentionally ingested 40–60
cooked or uncooked Psilocybe mushrooms, one had consumed
around 60 fruit bodies of Inocybe patouillardii.
The patients contacted the hospital because of nausea and being afraid of collaps. Symptoms
appeared 0.3–5 hours after mushroom consumption and included increased blood
preassure, dilated pupils, blurred vision, auditory hallucinations, disorientation and anxiety.
No pathological changes were found, and patients could leave the hospital 3–6 hours
later, in some cases after given activated charcoal, laxative and fluid.
Satora et al., 2005
20-year-old man Although the patient had not used drugs for 6 months, he was
not new to drugs. He once tried 20 mushrooms with friends and
experienced pleasant effects for 6-8 hours. He continoued to
take similar doses several times during over the ensuing week,
and at the same time depriving himself of sleep and food intake.
He then took a final major dose of 50–-60 mushrooms.
He was brought into the hospital within 24 hours after the consumption in a dreamy
euphoric state. His speech was restricted. Sympatomimetic signs were present, marked
mydriasis, brisk hyperfeflexia, hypotonia, a tachycardia of 104 per minute and facial
flushing. In another 24 hourshe became fareful and aggressive. At 48 hours he showed
spasmodic stupor and excitation, and at 72 hours he showed cataleptic phenomena and
began to display episodes of agitation and fear.
Hyde et al., 1978
Young male student The patient consumed 15–25 P. semilanceata. One hour after consumption of the mushroom he first became giggly, well disposed and
talkative.This was followed by a period when he felt threathened, and later on time began
to go wrong, and colourfull hallucinations occurred.
Hyde et al., 1978
7 males (17–23 years
All patients were regular users of Psilocybin mushrooms. One of
the patients used also other drugs. Two patients had consumed
20–30 raw mushrooms, the rest around 100 mushrooms.
Six of the patients presented within four hours of taking the mushrooms, the remainng
patient after 2 days. The patients in general reported pleasant stimulatory effects that were
accompanied by frequent visual, auditory and tactile hallucinations. One patient was
disorientated, unco-operative and ran around naked. The presented complains were mild
and were of nausea, cramping abdominal pain, feeling of stiffness and the unpleasant
sensation of swelling in the limbs, dry mouth and tachycardia. The effects were over in 10
Mills et al., 1979
36 year-old man The man consumed 6–7 Psilocybe argentipes with soup to
The man was initially dizzy, and he felt unreal. He became unable to stand up and later
experienced hallucinations. Later on the patient was impossible to contact, allthough he
was awake all the time.
Musha et al., 1986
35 year-old woman The woman consumed 3 Psilocybe argentipes with soup to
The woman became dizzy, experienced mild hallucinations, and later became sleepy. Musha et al., 1986
70 year-old woman The man consumed Psilocybe argentipes with soup to supper. The women became dizzy, experienced mild hallucinations and got scared that she was
Musha et al., 1986
62 year-old man The man consumed 3 Psilocybe argentipes with soup to breakfast.
The patient experienced hallucinations and had unsteady walk. The experience was unpleasant and he was frightened of becoming insane and of death. Musha et al., 1986
55 year-old woman The man consumed 2 Psilocybe argentipes to supper. The patient first felt dizzy and giddy, and euphoric, and later experienced hallucinations.
She felt anxiety and fear of death.
Musha et al., 1986
9 women and 35 men
with a mean age of
17.6 years (11–33 y.o.)
Of 35 patients able to quantify the consumption of P. semilanceata,
a mean of 87 mushrooms per person were ingested
(8–300). Ten patients brewed the raw mushrooms up in boiling
water and drank the resulting tea while the remainder consumed
the raw mushrooms (in 4 cases after drying). Eight patients had
also ingested alcohol (in 1 case in large quantities) while 1 hand
Eleven patients had vomited prior to appearing at hospital on average 3.8 h (range 1–8 h)
after mushroom consumption, while 12 others had experienced nausea and 9 patients
experienced upper abdominal pain. Eight patients exhibited flushing of the face and neck,
10 patients had tachycardia (>100 bpm), 17 patients were hypertensive (diastolic blood
preassure >100 mm Hg), and 16 patients showed hyperreflexia. Seven patients were
aggressive, 5 patients were restless and hyperkinetic, 2 patients were disoriented, 6
patients were drowsy but easily roused, 4 patients were euphoric, 4 patients appeared
fully conscious but were withdrawn, 26 patients described their experience as frighening.
Abnormalities of perception was registered by the majority of the patients, sometimes full
blown hallucinations occurred
Peden et al., 1982
21-year-old man The patient had consumed around 30 psilocybin-containing
The patient was excited and anxious; he vomited on arrival at the hospital. He had hallucinations
connected to previous bad experiences, he became restless and could not be
addressed. His skin got varm and dry, blood pressure (diacystolic) was high, heart rate
was high and the body temperature high.
van Poorten et al., 1982
44 men and 5 women
of an average age of
17.5 years (12–28 y.o.)
The patients were presented to the hospital at various times
after consumption of different quantities of P. semilanceata. Four
of the patients had also ingested alcohol.
Fortyone (83.7%) of the patients had evidence of sympatomimetic stimulation including
mydriasis and tachycardia, while 47 (95.9%) had experienced or were experiencing
euphoria and/or visual hallucinations.
Young et al., 1982
20-year-old woman The patient had smoked hasch during the last two years. She
had also injected amfetamin, tried LSD and experimented with
other drugs. As the only exposure, she had consumed 15 mushrooms
(probably a Psilocybe sp.) a few days before the symptoms.
The first two to three days after the mushroom consumption the woman had a normal
behaviour. After that the got confused and tore of her clothes. She came into a deliriumlike
state and could not be reached until when given electroconvulsive therapy.
Bergman and Karlsson, 1995
One women and one
man – self-test
2 500 mg dried P. semilanceata (12 mg psilocybin), 7 500 mg
dried P. mairei (150 mushrooms) (12 mg psilocybin, or 15 mg
The first symptoms of intoxication appeared already 30 min after mushroom consumption
and were a pricking sensation in the hand. The symptoms developed into intense tiredness,
apathy, and lack of attention. After another 30 min an euphoric stage was reached,
including the experience of being easily mobile, like in a dream. During this period the
tested persons seemed to be in very good mood but started to focus on theirself and
became hungry. After another 30 min the test objects had difficulties to concentrate. Then
the persons entered a dream-like stage where optical artefacts were common – colours
became more intense and were sensitised by musik. This stage continoud until around 5–
6 hours after the intake of the test samples.
Auert et al., 1980
18-year-old man The person had consumed hallucinogenic mushrooms (Psilocybe
semilanceata) frequently during the last month. The patient was hospitalised efter seizures followed by cardiopulmonary arrest. Despite resuscitation and intubation, he remained unconscious, with periodic hyperkinetic activation,
dilated pupils, and massive, repeated vomiting in the first three hours. An ECG after 3
hours showed regular sinus rhythm 100/min, Wolff-Perkinson-White syndrome, early
anterolateral myocardial infarction, and hypokinesis of the para-apical segment of ventricular
Borowiak et al., 1998
26-year-old man The patient had recently become a religious ‘back-to-nature’
freak. He had heared inner voices that gave him a mission. He
had experimented with various drugs, but during the last two
years only with pot and occasional amphetamine tablets – but
neither of them during the last six months. At that time he had
started using dried P. semilanceata.
The mushroom intake resulted in heightened awareness, perceptual distortion, and visual
21-year-old man The patient had tried marihuana/hasch a few times. One year
appart he consumed a pizza with 75 small hallucinogenic mushrooms
collected in Rogaland, Norway, a pizza with 75 large
A feeling of happiness but without hallusinogenic parts appeared after consumption ov the
first pizza dish.
After the second dish, he shortly felt being moved into un unrealistic world, and time
perception dissappered. He experienced that his house was on fire and was terribly afraid.
After some hours the body started to skjelva and fradga started to flow from his mouth.
16-year-old woman The patient had been offered unknown amounts of raw P.
semilanceate at a party.
Two hours later she experienced unpleasant hallucinations. Later on she became “desorienterad”,
and her mood oscillated between apathy andhyperactivity. Pupills were dilated. Kvambe and Edenberg, 1979
35-year-old man The patient had consumed an unknown amount of raw P. semilanceata
together with alcohol. The patient experienced colourfull hallucinations, were unable to sit still and showed severe signs of anxiety. He also had thoughts of suicide. Kvambe and Edenberg, 1979
27-year-old man The patient had tried LSD years earlier, but was brought into the
hospital 2½ h after consuming the cocking water of P. semilanceata.
The patient was afraid and agitated, and had visual hallucinations – colours being extremly
Hyde et al., 1978
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