The compounds responsible for the psychological effects of the Psilocybes are known as tryptamines.
Tryptamines are those compounds that contain an indole ring. These compounds resemble the neurotransmitter serotonin. They are thought to be competitive agonists of 5-HT2 receptors (a particular subtype of the serotonin receptor.) Psilocybin is the most abundant tryptamine in Psilocybe mushrooms and has been present in concentrations ranging from 0.36% in P. stuntzii to 0.98% in P. semilanceata . However, after ingestion it is rapidly dephosphorylated by the enzyme alkaline phosphatase in the intestine. Thus, it is the metabolite psilocin which is thought to be responsible for hallucinations and psychological effects.
Psilocin is the next most abundant compound, ranging from 0.12% in P. stuntzii to .60% in Psilocybe cubensis. Its bioavailability (the amount that is absorbed in the bloodstream from the intestines) was found to be around 50% in mice. Psilocin distributes uniformly in most body tissues, except for higher concentrations in the liver and adrenals. In rats, psilocin concentrates in specific areas of the brain: the neocortex, the hippocampus (involved in learning and memory), and thalamus (sensory processing). In rats, about 20% of psilocin is excreted unaltered in the urine, with the remainder excreted as polar conjugate metabolites such as glucoronides. It has been estimated that less than 4% of psilocin is degraded by monoamine oxidase, the enzyme that degrades endogenous monoamines like serotonin.
Baeocystin is usually present in concentrations of less than 0.1%. However, a few species, such as P. semilanceata (Liberty Caps) may have a content as high as 0.36%. Because few pharmacologic studies have been done with baeocystin, its potency relative to psilocin is unknown.
Some mushrooms of genera other than Psilocybe also contain psychoactive tryptamines, including Paneolus, Gymnopilus, and Inocybe.
Short Term Toxicity
Psilocybin does not qualify as a highly toxic substance when one uses traditional measures of acute toxicity such as the LD 50 (the dose required to kill 50% of experimental animals, usually rats.) Psilocybin has an LD 50 of 280mg/kg. In comparison, the LD 50s of LSD, THC (the active compound in marijuana), and mescaline are 30mg/kg, 42mg/kg, and 370 mg/kg. Thus, when death is considered as the toxic endpoint, psilocybin is one of the least toxic of the hallucinogens. Also, the potential for dependence (physical addiction) of psilocybin and hallucinogens in general is minimal to non-existent, which also tends to support the contention of the relative safety of psilocybin in comparison to other narcotics. However, fatalities and injuries have resulted from falling or car accidents caused by short-term behavioral and perceptual impairment. In a survey of adolescent Psilocybe users, 13% reported serious injury such as head trauma and loss of consciousness.
The most important aspect of psilocybin intoxication in the short-term is the unpredictable time-course and intensity of the symptoms. Psilocybin mushroom ingestion results in hallucinatory symptoms which begin as early as ten minutes post ingestion and typically last anywhere from four to twelve hours, although cases of much longer duration have been reported in the literature. While personal accounts of intoxication share some common themes, both the intensity and length of the hallucinogenic effects of Psilocybes are highly variable. This variability has been attributed to many factors, including the psychological characteristics of the user, the cultural background of the user, the mood or expectations of the user prior to ingestion (the "set"), the environment of the user (the setting), the psilocybin content (which can vary ten-fold between individual species and may change as a result of preparation or handling), previous use of hallucinogens, and concurrent use of other drugs or alcohol. Also, it is possible that individual sensitivities may result from inherited differences in metabolic capability.
The following are common symptoms reported during a typical
- Onset: dizziness, giddiness, nausea, weakness, muscle aches, shivering, anxiety, restlessness, abdominal pain.
- Hallucinogenic and Physiologic Effects: visual effects which include brightening and distortion of colors, after-images, visual patterns, and wave-like motion of surfaces, altered faces; increased body temperature, facial flushing, tachycardia (increased heart rate), dilation of pupils, sweating; feelings of unreality and depersonalization, dreaminess, panic feelings; impaired judgment of distances, incoordination; impaired judgment of time; also, a schizophrenoid state of double-conception of both slightly altered real world events and hallucinatory effects has been described.
- Recovery: gradual waning of above effects; headache; extreme fatigue, resulting in 10-15 hours of sleep; profound mental depression; decreased appetite.
There are cases reported in the literature of more serious acute effects when extracts of these mushrooms were used intravenously. Persistent vomiting, muscle aches, fever, low blood oxygen, elevated liver enzymes (used as a measure of liver toxicity) and methemoglobinemia (a blood condition resulting in reduced oxygen carrying capacity) have been reported.
Children are apparently more susceptible to poisoning from Psilocybe mushrooms, and this has had lethal consequences as in the case below:
A six year old girl ate mushrooms, identified later as P. baeocystis, growing near a conifer stand near her home in Kelso, Washington. She was found by her parents in an ataxic and incoherent state. She was admitted to a local hospital in a convulsive state, with fixed, dilated pupils and warm skin. Her temperature was 106 degrees. She died three days later after developing pulmonary edema.
Many poisonings and deaths have resulted from mistaken identification of common, similar-looking but poisonous species. A case of acute renal failure in a 20 year old female due to ingestion of Cortinarius mushrooms has been reported. The patient admitted that she had bought what she thought were magic mushrooms from a drug dealer. Some deadly North American Cortinarius species may look similar to other mushrooms such as Psilocybes, even for professional mycologists.
Long Term Toxicity
While lethal overdoses with hallucinogens in general and psilocybin in particular are rare, there are a number of case reports of long-term psychiatric and neurologic disturbances attributed to the abuse of hallucinogens which seem to indicate that these substances exert a more long-lasting neurotoxicity, at least in a subset of individuals. LSD, which has a similar structure to psilocybin, has caused persistent palinopsia (visual after images) in some individuals for as long as five years after they ceased taking it. Apparently this phenomena (previously termed 'flashbacks') is a frequent enough occurrence that it has been given its own medical term: Hallucinogen Persisting Perceptual Disorder (HPPD). HPPD is thought to be caused by permanent alterations of visual centers in the brain by LSD. It is not yet clear whether psilocybin also causes HPPD.
Ecstasy/XTC (MDMA), a hallucinogen/amphetamine which also interferes with serotonin, has been shown to be neurotoxic to serotonergic nerve fibers in experimental administrations to rats and non-human primates at dosages which could be considered high recreational doses in humans.
**THE ABOVE IS FALSE INFORMATION. THE GEORGE RICAURTE STUDY WAS RETRACTED.**
All three of these hallucinogens, including mushrooms of the genus Psilocybe, have been implicated in cases of prolonged drug-induced psychosis following brief recreational use. The following studies and case reports describe prolonged psychiatric disturbances after ingestion of Psilocybe mushrooms:
- In Britain, a 24 year old man presented to a psychiatric outpatient department with a three month history of daily panic attacks, complaining of tension, anxiety, depersonalisation, palpitations, dry mouth, and bounding pulses. He also admitted to feeling suicidal several times since the onset of his illness. Two weeks prior to the onset of these symptoms, he had ingested 25 Psilocybe mushrooms with two pints of beer, after which he became emotionally unstable and experienced pronounced visual disturbances three hours afterward. The patient had no other history of psychiatric problems.
- A 25 year old with no history of psychiatric illness but a history of hallucinogen abuse consumed, by his own estimate, approximately 200 mushrooms over the course of a day. He also drank alcohol and smoked marijuana. After experiencing the typical symptoms of psilocybin intoxication, he suddenly became extremely paranoid and aggressive, threatening three detectives who arrested him. The next day he complained of disturbed sleep, irritability, and lack of concentration. Several days later his condition worsened, despite treatment with tranquilizers and anti-depressants for his anxiety and depression, and eventually he was admitted to a hospital. He admitted to consuming 50 mushrooms on two additional occasions prior to his admission. He experienced a flashback episode two days later, along with visual disturbances and panic attacks, and he became aggressive and violent towards the hospital staff. These symptoms continued for fourteen days and did not resolve until four electro-shock therapy sessions. He was finally discharged after ten weeks in the hospital.
- A case is reported in the Scandinavian medical journal Ugeskrift For Laeger of a 24 year old Norwegian man who sought psychiatric help for persistent psychological symptoms nine months after consuming Psilocybe mushrooms.
- In a study of confirmed cases of P. semilanceata ingestion, a prolonged psychiatric illness occurred in 26 out of 318 cases (over 8%). Of these 26 cases, 21 patients experienced flashback-type episodes lasting up to four months after the initial ingestion of mushrooms. In only five of these 26 cases could the prolonged psychiatric illness be attributed to other possible causes such as prior mental illness. Of the 160 cases in which a follow-up questionnaire was returned, 82 patients were hospitalized. Of these 82 cases, 8 were hospitalized for two or more days because of prolonged hallucinations. Interestingly, in the 16 cases in which these mushrooms were abused with other drugs or alcohol, none had serious or prolonged symptoms of intoxication.
- In a study of 27 cases of P. semilanceata ingestion recorded at a British hospital, two patients complained of episodes of panic attacks after ingestion of alcohol, one seven days after the initial ingestion of mushrooms, the other nine days after. In another case, a terrified patient required admission to a psychiatric unit because he believed both God and the Devil were speaking to him. These hallucinations continued for three consecutive nights, despite treatment with anti-psychotics.
The number of cases similar to those described above that do not seek medical attention due to fear of legal consequences cannot be determined. The biological basis for these types of adverse reactions is not known. Some of these cases (1 and 2) seem to involve large quantities of mushrooms and/or concurrent alcohol consumption, while other studies (4 and 5) could not find any correlation between quantity ingested and length or severity of symptoms, or any influence of drug interaction. As the tryptamine content within and between individual mushroom species can vary greatly, it is difficult to get more than a rough estimate of intake of these compounds.
Perhaps the biggest confounding factor in the assessment of adverse reactions to these mushrooms is the large percentage of sham Psilocybe mushrooms sold on the black market which are laced with adulterants. In a 1985 analysis of 886 illegally sold mushrooms claimed to be Psilocybe, only 28% were actually Psilocybes while 31% were common store mushrooms or other varieties laced with LSD or PCP, and 37% were inert. However, individual sensitivity to psilocybin and related compounds could result from inherited deficits in enzymes important for the metabolism of these compounds, which is a well known phenomena for alcohol and prescription drugs, or differences in brain chemistry which result in different vulnerabilities to psychiatric diseases such as schizophrenia or depression. Also, as these mushrooms may naturally contain many different types of compounds other than tryptamines, perhaps a high concentration of an unidentified compound in certain species or strains may be responsible. Because the abuse of these mushrooms is increasing in prevalence among young people, more research in this area is needed.
There is no specific antidote to Psilocybe intoxication, although a clinical report of reversal of confirmed psilocybin intoxication with physostigmine is interesting and deserves further follow up study. Management of psilocybe intoxication consists mostly of emotional support and reassurance during panic episodes, and monitoring of vital signs. However, in cases of long-term adverse reactions, tranquilizers such as Valium and anti-psychotics such as Thorazine have been used. Also, in cases where the exact species of mushroom cannot be confirmed, gastric lavage or treatment with activated charcoal has been recommended.
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