Psilocybin with psychological support for treatment-resistant depression: an open-label feasibility study
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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

Hofmann, 1963).

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,

tremulous speech.

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

winter time.

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.,

1991).

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

countries

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

of beer

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.
Benjamin, 1979

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.

Dewhurst, 1980

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,

deafened ears.

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

preexisting psychosis.

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.

Yokoyama, 1973

A 56-year-old man The man consumed 2–3 fried Pholiota spectabilis (Gymnophilis

spectabilis) in the belief it was Armillaria mellea, an edible

species.

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.

Buck, 1967

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.

Buck, 1967

4 men (16–29 years

old)

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

old)

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

hours.

Mills et al., 1979

36 year-old man The man consumed 6–7 Psilocybe argentipes with soup to

supper.

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

supper.

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

just dying.

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

smoked marijuana.

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

mushrooms.

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

pure psilocybin

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

septum

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

hallucinosis.

Davies, 1979

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

mushrooms, respectively.

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.

Gundersen, 1979

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

vivid.

Hyde et al., 1978

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