'Magic mushrooms' could treat depression - new research shows [Archive]

vapor

03-26-2007, 07:45 PM

http://www.24dash.com/content/news/viewNews.php?navID=47&newsID=7986

Scientists are to investigate a hallucinogenic chemical in "magic mushrooms" as a possible new treatment for depression, anxiety and drug dependence.

The move follows an unusual study which showed that the compound, psilocybin, can prompt long lasting positive changes in mood and behaviour.

Researchers also found that people who took the chemical experienced genuine mystical experiences, as defined by psychologists.

A third of the 36 study participants described their psilocybin experience as the "most spiritually significant" of their lives.

Some likened it to the importance of the birth of their first child or the death of a parent.

Magic mushrooms, or "shrooms", come in several varieties, all of which contain psilocybin.

Until last year a loophole in the law meant they were not illegal in their natural state in the UK.

Under the Drugs Act 2005 they are now classified as a Class A drug, like heroin or cocaine. Possession may be punishable by several years in jail, while supplying the mushrooms could result in a life sentence.

Professor Roland Griffiths, from Johns Hopkins Medical Institutions in Baltimore, Maryland, USA, led the study, the first rigorous investigation of the effects of "tripping" on a drug for decades.

The volunteers were all healthy, well-educated, mostly middle-aged and with no family history of psychotic illness.

Each attended two separate eight hour drug sessions at two month intervals. On one occasion they received psilocybin, on the other the drug Ritalin which was used as a placebo.

Medical professionals were on hand to act as "monitors" and observe what happened. Neither the participants nor the monitors knew when the test drug was being taken.

The trials took place in a room fitted out as a comfortable lounge, with soft music and indirect lighting.

Heart rate and blood pressure were measured, and questionnaires used to assess volunteers' experiences.

During the study, more than 60% of those taking part described the effects of psilocybin in ways that met the recognised criteria of a "full mystical experience".

Two months later, 79% reported moderately or greatly increased well being or levels of life-satisfaction.

Most said their mood, attitudes and behaviour had changed for the better. This was confirmed by interviews with family members, friends and work colleagues.

The findings were published today in the journal Psychopharmacology.

Prof Griffiths said: "Under very defined conditions, with careful preparation, you can safely and fairly reliably occasion what's called a primary mystical experience that may lead to positive changes in a person. It's an early step in what we hope will be a large body of scientific work that will ultimately help people."

The scientists said scrupulous care was taken to minimise adverse side effects and warned of the dangers of taking psilocybin unsupervised.

Even under the controlled conditions of the study, a third of participants reported significant fear, and some experienced temporary feelings of paranoia.

"Under unmonitored conditions, it's not hard to imagine those emotions escalating to panic and dangerous behaviour," said Prof Griffiths.

His team now intends to look into the therapeutic potential of the magic mushroom chemical.

Trials are planned involving patients suffering from cancer-related depression or anxiety. Other studies will test a role for psilocybin in the treatment of drug dependence.

Prof Griffiths said human research into the potential positive effects of hallucinogen drugs had been "frozen in time" for 40 years due to the excesses of the 1960s.

A number of promising leads were left "dangling" as a result.

"Our study is among the first to re-open this field," said Prof Griffiths.

Another expert commentating on the work in the same journal said he did not think the research would spark off a wave of experimentation with magic mushrooms.

Dr Herbert Kleber, Professor of Psychiatry at Columbia University in New York wrote: "The positive findings of the study cannot help but raise concern in some that it will lead to increased experimenting with these substances by youth in the kind of uncontrolled and unmonitored fashion that produced casualties over the past three decades.

"Any study reporting a positive or useful effect of a drug of abuse raises these same concerns. In this internet age, however, where youth are deluged with glowing personal reports in chat rooms and web sites as well as detailed information about the various agents and how to use them, it is less likely that a scientific study would move the needle much."

Magic mushrooms produce "trips" lasting between four and eight hours.

Users see hallucinogenic visions, lose track of time, and may experience laughing fits. Colours and lights are intensified.

Among the known adverse effects are vomiting, anxiety and paranoia. "Shrooms" are especially risky for anyone with mental problems.

The fungi have a long history in human culture, and have been taken for their drug effects for several thousand years.

Magic mushrooms are linked to ancient religious ceremonies, such as those practised by the Aztecs, who called them "Teonanacati", or "God's flesh".

In European folklore, tales of flying witches and fairy rings, and depictions of elves sitting on toadstools, have all been ascribed to magic mushroom "trips".

The first documented magic mushroom experience in Britain occurred in London's Green Park in 1799. A man who had been picking mushrooms for breakfast accidentally sent his whole family on a trip.

The doctor who treated them described in the Medical and Physical Journal how the youngest child was "attacked with fits of immoderate laughter".

It has been suggested that magic mushrooms influenced Lewis Carroll, author of Alice in Wonderland.

A hookah-smoking caterpillar urges Alice to eat pieces of mushroom which has the effect of making her grow and shrink.

c-ray

03-27-2007, 07:17 AM

from http://sulcus.berkeley.edu/mcb/165_001/papers/manuscripts/_471.html

PSILOCYBIN AWARENESS

Category: Neurochemistry
Term Paper Code: 471

Every two years the Student Drug Use Survey, sponsored by the Addiction Research Foundation of Ontario, conducts surveys of students enrolled in grades seven through thirteen to obtain statistics on the prevalence of drug use. In the previous years the prevalence of drug use increased for all drugs; however, the surveys from 1995 to 1997 showed only one significant increase-the use of the hallucinogen psilocybin (Adlaf 1998).

According to the survey there was an approximate 10.1 percent increase in the use of psilocybin while the trend for all other drugs was a significant drop (Adlaf 1998). Educators or administrators, who are developing drug education, prevention or intervention programs for youth, should incorporate information on hallucinogenic drugs. Because of the increased popularity of psilocybin among recreational drug users, knowledge and understanding of this hallucinogen is critical. The chemical psilocybin occurs naturally in many mushrooms but it is best known from Psilocybe mushrooms commonly called "magic" or sacred mushrooms. In this paper, I will present a historical, clinical and psychological analysis of psilocybin by presenting recent research, information, and reports concerning the study of this hallucinogen.

History:

Psilocybe mushrooms or hallucinogenic mushrooms have probably existed longer than humanity. Throughout history, ancient pictures of mushroom-like humans have been prevalently reported. In Central and Southern America, use of psilocybian mushrooms was a common religious practice until the arrival of Spaniards who spread the Catholic faith with sword and fire and forbade the use. For Indians the mushroom is known as a sacred mushroom and historically, it is considered a religious path to the spirit world (Wasson 1980).

Mushroom art and sculptures that depicted motifs under the cap of a mushroom were found even from an earlier era of 1000-500 BC. The purpose of these sculptures and artifacts was not certain, but it is speculated that the stones had religious meaning (Allegro 1970). The Codex Vienna Mixtec manuscript that dated back to thirteen century depicted the ritual use of the sacred mushrooms by the Mixtec Gods. The God known as Seven Flowers was the Mixtec God for hallucinatory plants, especially the secret mushroom, and he was depicted carrying a pair of mushrooms in his hands (Wasson 1898). In addition, the Aztecs believed that they were capable of moving back and forth between the earthly and supernatural realms (Schwartz 1988). This travel between realms was often associated with hallucinatory trances guided by their god for the entheogens-the Prince of Flowers. The Aztecs called this ritual "the flowery dream;" this was induced by sacred mushrooms (WWW 1).

The appeal of mushrooms in the "modern world" originated when Gordon Wasson came to the Mazatec village of Huatla de Jimenez, and experienced a session of "velada" held by curandera Maria Sabina. Velada included a religious ritual under a heavy influence of Psilocybe mushrooms (Wasson 1898). Information about the mushrooms spread and experimentation began. In 1958 the active ingredients of the mushroom, Psilocybin and psilocin, were found and their analogues were synthesized by Dr. Albert Hoffman, who also discovered lysergic acid diethylamide (LSD) (Schwartz 1988). Experimentation with the mushrooms historically increased, leading to their significant influence in the part of the "60's psychedelic movement" (WWW 1). And even these days, psilocybin mushrooms are one of the most common hallucinogenic substances for recreational use (Adlaf 1998).

Biochemistry

Hallucinogenic mushrooms grow naturally in fields and in cow pastures mainly in northwest and southeast of the United States. The most common psilocybin mushroom in the United States is Psilocybe cubenis (Schwartz 1988). The primary active ingredients of Psilocybe mushrooms are psilocybin and psilocin. Individual mushrooms contain approximately up to two percent of the psychoactive ingredient psilocybin, while psilocin is only found in trace amounts (Pedersen-Bjergaard 1998). Between 4 to 10 mgs of psilocybin is considered to be an average content for psilocybin per grams of mushroom, and that is also the usual dose ingested (Schwartz 1988).

The primary difference between psilocybin and psilocin is that psilocin is unstable, and it breaks down when the mushroom is dried (Pedersen-Bjergaard 1998). Psilocybin is highly stable, and it has been reported that psilocybin can last for an extremely long amount time and was even detected in a hundred fifteen year old mushroom sample (WWW 1).

Both of the two compounds are equally psychoactive, since one molecule of psilocybin (O-phosphoryl-4-hydroxy-N) can be broken down into one molecule of psilocin (4-hydroxy-N,N-dimethyl-tryptamine). The breakdown occurs when the mushroom is orally ingested. In the digestive track, psilocybin dephosphorylates to psilocin; the dephosphorlytaion process is accomplished by a readily present digestive track enzyme, alkaline phosphatase (Vollenweider 1998).

Psilocybin and psilocin belong to the tryptamine (indoleamine) family of psychedelics. They occur naturally in many mushrooms. The species of Psilocybe mushrooms have high a capacity to transform fed tryptamine into a psychoactive ingredient psilocybin by a methylation and hydroxylation reaction. Studies of psilocybin biosynthesis in mushrooms show that the amino acid tryptophan and tryptamine are precursors to the indole alkaloids (Gartz 1989). Although psilocybin can also be chemically synthesized, it is very difficult and expensive. (Cuomo 1994).

Psilocybin and psilocin are closely related to the neurotransmitter serotonin. Psilocin, especially, is structurally related to a neurotransmitter serotonin (5-hydroxytryptamine or 5-HT) (Vollenweider 1998). The structural resemblance to serotonin also parallels with psilocybin's activity. The primary effect of psilocybin seems to be the inhibition of the neurotransmitter serotonin, because the indole binds to 5-HT receptors. More specifically, the effect of psilocybin is to act as an agonist to the 5-HT2 receptor. The potency of the hallucinogens in humans is related to the binding affinity for the 5-HT2 receptor in animals. In addition, animal studies have demonstrated that the action of the hallucinogenic drug can be blocked by 5-HT2 antagonists, thus supporting psilocybin as a 5-HT analog (Vollenweider 1998).

Although animal studies conclusively prove the involvement of 5-HT2 receptor systems in hallucinogenic drug action, animal hallucinogenic drug action might not be reliable when applied to the human model. For instance, many scientists question if psilocybin has an effect on the dopamine receptors in humans because of psychotic-like symptoms of the drug. Psychosis is correlated with over-stimulation of the dopamine pathways in the central nervous system, thus leading to the hypothesis that the dopamine system is not modulated through interactions of serotonin and dopamine in humans (Vollenweider 1998).

In order to prove lack of involvement of the dopamine system in humans for the psilocybin mechanism, the Psychiatric University Hospital in Zurich, Switzerland, conducted psychological research on human subjects. They investigated the current animal hypothesis of the psilocybin mechanism to test weather 5-HT2 and/or dopamine receptors are effected through psilocybin. Their results support that the effects induced by psilocybin results from the activation of a 5-HT2 subtype of serotonin receptor in human subjects as well as in animals. The conclusions were drawn from the study of influence to pretreatment with 5-HT2 antagonist (ketanserin), dopamine receptor D2 antagonist (haloperidol) and mixed 5-HT2/D2 antagonists (risperidone) on psychological effects of psilocybin on healthy human subjects (Vollenweider 1998). The study concluded that "psilocybin-induced psychosis could be completely prevented by either the atypical neuroleptic and mixed 5-HT2/D2 antagonist risperidone or by the 5-HT2 antagonist ketanserin, but not by the typical neuroleptic and D2 antagonist haloperdol" (Vollenweider 1998). This study added substantial evidence to the hypothesis of the 5-HT2 agonist is responsible for the psychological effects of psilocybin. The 5-HT2 post-synaptic agonist appears to mimics the effects to 5-HT and cause psychological changes in the central nervous system (Vollenweider 1998).

The hallucinogenic psilocybin and psilocin found in mushrooms have low toxicity. Studies in mice showed that doses up to 200 mg of psilocybin/kg of body can injected without lethal effects. That implies that an average human with body weight of 65 kg can be injected 13 grams of the psychoactive mushroom ingredient without experiencing any lethal effects (WWW 1).

The most traditional measurement of toxicity of a drug is a therapeutic index that is a ratio of the lethal dose (LD50) to the effective dose (ED50) (Gable 1993). According to the Registry of Toxic Effects, the therapeutic index for psilocybin is 641. In comparison to other substances it is relative non-toxic. For example the therapeutic index for vitamin A is 9637, 4816 for LSD, 199 for aspirin and 21 for nicotine, thus psilocybin appears to have a relatively low toxicity (WWW 1). In addition, literature states that the oral intake of psilocybin appears to be the lowest risk out of all other drugs for both acute lethality and dependence (Gable 1993).

Although much of the literature supports psilocybin as having relatively low toxicity, dependence and lethality, in the last two years, cases of serious physiological intoxication by natural hallucinogenic substances have surfaces around the world. A frequent use of hallucinogenic mushrooms have demonstrated to have effects not previously classified by the use of psilocybin. Currently, clinical case and overdose studies of patients showed that psilocybin use results from arrhythmia and myocardial infarction. The indole concentrations of hallucinogenic mushrooms do not present risks of adverse central nervous system effects but also cardiac toxicity (Borowiak 1998).

The myocardial infarction in the frequent users and in cases of sever intoxication suggest the possibility of cardiac damage related to psilocybin. According to recent studies, indole alkaloids are agonists at the 5-HT receptor in the central nervous system. However, peripherally they induce a sympathomimetic stimulation that leads to tachycardia and hypertension. In the past, the use of 5-HT agonists in migraine headaches was linked to myocardial infarction due to coronary vasoconstriction. In addition, serotonin receptor agonists can cause platelet hyperaggregation and occlusion of small coronary arteries. Because psilocybin is also an agonist of 5-HT receptors, it is conclusive from these observations that the use of this drug can lead to cardiac toxicity (Borowiak 1998).

Psychological effects:

The historical mind-altering effects of psilocybin are described as a voyage to the spirit world. These hallucinogenic effects are similar to those of LSD; however, psilocybin is two hundred times less potent and also has a shorter duration time (Schwartz 1988). Common physiological reactions include muscular relaxation, coldness of the limbs and abdomen, and dilation of the pupils. A stronger dose includes vision and mental hallucinations and other sensory distortions. Use of the mushroom causes a feeling of disconnection from reality and an altered state of consciousness (Cumno 1994).

As with all major hallucinogens, psilocybin can precipitate psychotic episodes and bring up previous mental illnesses. Therefor, individuals that are prompt to being stressed, depressed, or have schizophrenia in their history should not take mushrooms or other psychedelics. Mushrooms, similar to LSD, can significantly change a person's perception and cause a "bad trip" or an experience that can have a significant impact on someone's life. For this reason they are more then a purely recreational drug; they can be extremely psychologically impacting (Schwartz 1988; WWW 1).

The physiological and psychological effects of mushrooms are influenced by the dose and the individual's sensitivity to psilocybin. For some people, as small amount as 0.25 grams of Psilocybe mushroom can be enough for a full visionary experience, unpleasant stomach cramps or gas, and other effects usually present at high doses. In other users, the same amount might not cause any noticeable effects. Thus, it is very critical that a user understands his individual reaction, and to be safe during the first use. It is "recommended" to start with only a small amount of psilocybin. The minimal dose for any notable effect is often referred to as the threshold effect. This effect can be induced by amounts ranging from 0.25 grams to 0.75 grams of Psilocybe mushroom (Schwartz 1988; WWW 1).

A more profound effect can be induced with an amount that ranges from 0.75 grams to 2.5 grams of mushroom. Similarly to a small dose, the feeling of reduced temperature, gas and/or stomach discomfort, nausea occurs, but they might be more profound. However, this dose might induce powerful distortion of space, increased ability to visualize creatively, spontaneous detailed images, feelings of time distortion. These effects of psilocybin are often more pronounced in users who have used mushrooms before. Emotional sensitivity and an increased ability to focus on emotional problems can raise the probability of thinking or dwelling on a single feeling that usually has a negative content--a content that can lead to psychological crises come out (Schwartz 1988; WWW 1).

At a dose ranging from 2.5 grams to 10 grams, all of the effects of the medium dose should be expected, usually with significantly more uncomfortable side effects. These side effects include pronounced nausea that can result in vomiting and significant mental discomfort associated with feelings of fear and often times accompanying a "what have I done to myself." These effects usually lessen as the experience becomes familiar to the person and knowledge about the characteristics and side effects of mushrooms becomes more apparent. The effects of high doses can lead to acute adverse effects and intoxication that might lead to extreme fears, panic and even intense psychosis. These psychological effects are almost indistinguishable from true schizophrenia. After acute intoxication, the user is usually extremely exhausted and mentally depressed (Schwartz 1988).

The behavioral effects induced by psilocybin are often complicated by the fact that users mix different substances. For example, the effects of psilocybin can be made stronger by taking them with a monoamine oxidase inhibitor (MAOI). The best known MAOIs are harmine and harmaline from the plant Peganum harmala. Combining MAOIs and other substances with tryptamines is an unsafe activity because it increases amounts of monoamides in the body (WWW 1). This might cause a hypertensive crisis that is due to elevated tyramines in the body.

Clinical Implication:

The field of psychedelic research extends beyond the investigation of biochemistry and recreational use. There have been great promises for medical use of psychedelics. Studies focused on the role of psychedelics in religious experience and behavior change. Psilocybin experiments were conducted in the early 1960's under the direction of Timothy Leary, Ph.D. Dr. Leary had obtained permission from the Massachusetts Department of Corrections to administer psilocybin to volunteers in Concord Prison (WWW 2). The hope for the experiment was to test if psilocybin experiences can change the prisoner's cycle of antisocial behavior and reduce their recidivism. The action of psilocybin was used to help the prisoners recognize the impact of their past behavior. Such realization was hoped to connect them to their spirit and consciousness, leading to resistance of desire to commit future crimes. The final results showed that psilocybin experience alone were not sufficient to reduce recidivism. However, the failure of the research originated from the lack of group support meetings for the prisoners. However, similar studies disclosed that psilocybin could cause a behavioral change in people with strong religiously conviction. People who took psilocybin with a religious context experienced deeper spiritual connection (WWW 2).

In conclusion, the prevalence of psilocybin throughout history and its current use has lead to intensive studies and research. The studies on human and animal models both demonstrated that psilocybin produces psychosis-like symptoms primarily through serotonin-2 receptor stimulation. Although many of the psilocybin effects are understood and well documented, we keep learning more about this substance as more data is collected through research of psilocybin users. As the understanding continues, the field of psychedelic research will likely extend beyond its current use because of the great promise for medical use in the treatment of various psychological conditions.

References

Adlaf, Edward M. et al. Recent findings from Ontario Student Drug Use Survey. Canadian Medical Association 5. 451-455 (1998).

Borowiak, Krzysztof S. et al. Psilocybin Mushroom Intoxication with Myocardial Infarction. Clinical Toxicology 36. 47-49 (1998).

Vollenwieder, Franz X. et al. Psilocybin induces schizophrenia-like psychosis in humans via a serotonis-2 agonist action. NeuroReport 9. 3897-3902 (1998).

Pedersen-Bjergaard, Stig. et al. Strategies for capillary electrophoretic separation of indole alkaloids in Psilocybe semilanceata. Electrophoresis 19. 27-30 (1998).

Cuomo, Micheal J. et al. Increasing Use of "Ecstasy" (MDMA) and Other Hallucinogens on College Campus. College Health 42. 271-274 (1994).

Gable, Robert S. Toward a Comparative Overview of Dependence Potential and Acute Toxicity of Psychoactive Substance Used Nonmedically. Drug Alcohol Abuse 19. 263-281 (1993).

Gratz, Jochen. Extraction and analysis of indole derivatives from

fungal biomass Basic Microbiology 29. 347-352 (1988).

Schwartz, Richart H. and Smith, Deborah. Hallucinogenic Mushrooms.

Clinical Pediatrics 27. 70-73 (1988).

Wasson, Robert G. The Wondrous Mushroom. Library of Congress Cataloging in Publication Data (1898).

Wasson, Robert G. Maria Sabina and her Mazetec Mushroom Velada. Library of Congress Cataloging in Publication Data (1974).

Allegro, John M. The Sacred Mushroom & The Cross. National General Company (1970).

WWW 1. The Vault of Erowid: Sacred mushrooms.

WWW 2. Psilocybin: Concord Prison Follow-up from the Newsletter of the Multidisciplinary Association for Psychedelic Studies MAPS-

Volume 6 Number 2 Winter 1995-96