Review the less potent and abused drugs but

  Review The History, Effects and Mechanism On The Hallucinogen PeyoteLara VinsonAthabasca UniversitySubmitted on the 17th of January 2018Abnormal Psychology PSY435Dr. Trevor Gilbert« Our desire to alter our sate of consciousness may be as fundamental as our desire for food, water and sex. » (Nadelmman, 2015) Introduction Hallucinogenics are some of the less potent and abused drugs but their psychological and behavioral experiences are some of the most intensely felt in kingdom of natural drugs. They are substances whose primary effects are perceptual and cognitive disturbances but without causing toxic delirium. Peyote is one of the earlier hallucinogenics to be used, dating back to 5,700 years ago, as was determined by anthropological studies through radio-carbon dating (Kapadia, 1970). The cactus is part of the pale kingdom and is called lophophore williamsii. It contains the phenethylamine alkaloid mescaline, which is a potent hallucinogen. It offers you deep introspection and insight as well as spiritual guidance. Up until today, peyote is know to be called the « divine messenger », which is translated from the Aztec word «peyote», it is believed that you are able to receive god’s message when under its effects, or so Meyer et al. (2013) state. The field examination study of the use of peyote in the Native American rituals (15 tribes) was first led by ethnographer Weston LaBarre in 1938 and the first modern field research on drug use; ‘The peyote cult’ (LaBarre, 1938).  The peyote cactus is native to the NorthWest region of Mexico and southwest region of Texas and can usually be found near settlements of limestone. The seeds require hot and humid conditions to fully germinate. It will take them about 3 years to reach their adult phase where they can then be harvested for their psychoactive and anesthetic properties (Stork, 2014). The plant can reach heights from 2 to 7 centimeters and its diameter can be in between 4 to 12 cm. The plant in itself may be blue, green, yellow, or red/green, and flowers March through May, the flowers are pink with thigmotactic anthers. The flowers open up during the day. It is a spineless cactus and therefore can be consumed because of that feature. On the top of the cactus are buttons that possess mescaline, these buttons are harvested that will be ingested. To ingest the drug you must eat or boil the dried peyote buttons (tops) on the crown of the cactus to get the desired psychoactive effects (Kulma, 2007). Analysis Mescaline is the active ingredient in peyote; it is a naturally occurring phenethylamine alkaloid. Its chemical compound is called 3,4,5 – trimethoxyphenethylamine. It is an entheogen and a stimulant and is part of the catecholarminergic family of drugs. The biosynthesis of mescaline has 4 steps to it (Anderson, 1996). The first is the oxidation of tyrosine to dopa, the second the decarboxylation of dopa into dopamine, the third the oxidation of dopamine into 3,4,5-trihydroxy-?phenyethylamine and the fourth is the methylation of 3,4,5-trihydroxy-?phenyethylamine into mescaline (Anderson, 1996). Mescaline which is structurally related to norepinephrine and epinephrine, are thought to exert their psychedelic actions by altering the transmission of nerve impulses at norepinephrine and serotonin synapses in the brain. As an alternative to chewing the buttons or boiling them, the mescaline can be extracted from the cactus and consumed as a relatively pure powder if it properly synthesis (Anderson, 1996).  Derived in 1956 from the Greek root of the word for “mind revealing,” the term psychedelic substance coins a broad range of drugs that can include peyote, LSD, and psilocybin, the primary active ingredient in so-called magic mushrooms. Around 40 years, ago the United States federal government shut down most research on psychedelics. To justify themselves they inferred that in its publications, the Journal of the American Medical Association had written that psychedelics can cause permanent personality deterioration, even in previously healthy users.  sort of nervous breakdown in other terms. These publication are enough to alarm the general public, however alarmist it might there are documented dangers associated with the recreational use of the drugs and this risks should be taken seriously.  Mescaline is classified as a Schedule I hallucinogen in the U.S and as Schedule III controlled substance in Canada, due its high cognitive and perceptual disturbances. The possession and distribution of peyote is legal because of its classification as a controlled drug for religious use. The Indian Religious Freedom Act of 1978 gave legal protection for the Church’s use of peyote. As such it is illegal for anyone that does not posses a Native Amercian Church card to be found in possession of distribution of it. It is also allowed for scientific and medical research. Interestingly, in the U.K, dried mescaline containing cacti can be bought and soled legally (Kovacic, 2009). The cactus has been abusively over harvested in the recent decades and the plant is today classified as an endangered specie with a G3 risk, a federal law in the U.S was passed protecting and limiting the harvesting and cultivation of peyote. The hallucinogen belongs to the class of 2AR agonists which regulate pathways in cortical neurons. Ironically it is the least potent of all classified hallucinogens (Meyer, 2014).  A typical dose of mescaline has been calculated to be between 200 and 500 mg in which case the « trip » that you will experience will last in between 6 to 12 hours, depending on your metabolism. A higher dose of mescaline (500 mg or above) will cause an abnormally increased blood flow which is associated with the physiological effects of  hallucinogens. The on set time mescaline is of maximum 2 hours, after which the drug’s side effects will be at their peaks. It also served as the lead molecule in structure-activity relationship studies of the phenethylamine. The drug is used as an entheogen and as such is used for meditation, psychonautics, psychedelic psychotherapy and medical uses (Anderson, 1996). Peyote has been used for the last 5,700 years mainly by Native Americans in their religious ceremonies. The drug is used for social revitalization. Since its foundation in 1918, peyote is used by members of the Native American Church. Any normal chronological event can be used for their ceremonies; birthdays, graduations, deaths, births, etc. The traditional way of taking the peyote is to cut of the head from the roots, using the latter to regrow another head, and then grind the buttons into powder to then capsulate them to avoid the bitter taste of the cactus that may cause some negative side effects to raise in the on set of the drug. The ritual is scened in a tipi with an elder or priest performing it. It involves scripting, dancing, reading, praying, singing and drumming. The ceremonies usually last from sundown on Saturday night to sunup on Sunday morning. It is a tradition to then have a breakfast after the ceremony that encompasses the ‘seven sacramental food’ to counterbalance the after effects of the peyote (Kapadia, 1970).  When it is ingested recklessly and in large doses, mescaline can generate distressing short-term experiences. If the subject has a mental illness or more than one, it is possible that the aforementioned experiences can cause long-term psychopathology. Nevertheless, more than 20 million people in North America have tried a psychedelic at least once in their life time, and 1 million are regular users of the drugs, by far the most popular of which is now MDMA, or Ecstasy which are religiously used in social gatherings such as partie for concerts. It shown, that those that regularly use psychedelics and especially hallucinogens run a higher risk of suffering from brain damage.  Medically, peyote was commonly used (before modern antibiotics) to relieve pain. It was used as an anesthetic for tooth pains, labor pains or child birth, fevers, skin diseases and blindness. Interestingly enough, mescaline has no long term effects on cognitive abilities, it does not damage or alter them (Halpern, 2005). Due to this feature the use of peyote, during the Native American Church meeting has been reported to be an effective treatment for alcoholism. While it is not the most beneficial or accepted method of treatment its has been proven to alleviate the symptoms of alcohol dependence (Stork, 2014). Halpern’s conviction that psychedelics might help towards the treatments of alcoholics and addicts is based both on research by others and on his personal observations of members of the Native American Church. All of the subjects in Halpern’s research are from a tribe referred to as Navajo, who account for roughly 10 percent of the church’s membership and hold key leadership positions in them. Even though for many years tribal leaders have tried to ban alcohol from their reservation, alcoholism is still a main problem. Reservations being generally poor, most of its residents generally turns to alcohol. For the Navajo and other tribes, rates of alcoholism are estimated to be more than twice the national average. Those in the Native American Church say that the effects of mescaline, which is one their medicine helps keep them sober and healthy in body and mind according to Halpern’s research. A very early advocate of using psychedelics toward the treatment and rehabilitation of addicts was William Wilson, who founded Alcoholics Anonymous in 1935.  He believed as Harpner, that if harnessed properly, the chemical compounds of psychedelics could be used to treat some addictions and mental illnesses. After observing alcoholics undergoing LSD treatment and taking the drug himself in 1956, Wilson became convinced that it might benefit alcoholics. The religious experience that one has under the effects of those drugs is what helped him to stop drinking. Even though many researchers still believe that suggesting the use of psychedelics in the treatment of alcoholism is controversial and borders on insanity, researchers continues. Mescaline induces a psychedelic state similar to those of LDS or psilocybin (Salvia). A brain imaging on rats done by Palenicek et al. (2008) showed that administration of mescaline increases the neural activity particularly in the striatum limbic system in the right hemisphere. Due to the similar structures between mescaline, NE and epinephrine, one could expect the effects to be similar. They include; increased heart rate, increased body temperature, nausea, dizziness, heavy perspiration, dilation of pupils, dry mouth and anxiety (Kovacic, 2009).  As described in Aldous Hurley’s book ‘The doors of perception’ (1953), the psychological effects include a increase in color prominence, recurring visual patterns that self-transform without eye movement. A unique psychological characteristic of mescaline is the geometricization of three dimensional objects, they look distorted or flattened as in a Picasso cubic painting. Another study shows that mescaline elicits increased feelings of sympathetic arousal (Anderson, 1996).
Following is a complete list of positive behavioral changes that mescaline causes; feelings of insight, brightening of colors, closed and open eye visuals mood lift, euphoria, increased giggling and laughing, increase in energy (stimulation) increased tactile sensation, happy, dreamy feelings, feelings of hope and increased access to spiritual ideation as is the aim of the administration of the drug in the religious ceremonies. The behavioral changes that do no have a direct impact on the mood are; general change in consciousness (as with most psycho-actives), a loss of appetite, a change in body temperature regulation, unusual thoughts and speech, unusual focus on either small details or large concepts; changes in meaning or significance of experiences, mild to extreme distractibility depending on the dosage, changes in perception of time, changes in perception of « reality », changes in self control, unusual body sensations, ego softening, pupil dilation, body tremors, urge to urinate and restlessness (Meyer, 2013).  Some negative behavioral changes that can be experienced either during the onset of mescaline or if you are ‘bad tripping’ include nausea, dizziness and vomiting, fear or paranoia, tremors in you limbs especially the extremities, visions and insomnia, shortness of breath, headaches, increase blood pressure and heart rate. While it has often been reported that bad tripping is caused by a variety of factors not limited to the environment and the mind set, some bad experiences are usually overcome when people take care of the person with the bad experiences. Unfortunately in some cases, people do end up in the hospital to administer some counteragents. Intoxication can be alleviated or stopped with chlorpromazine or valium (Kulam, 2007).  Face-test studies were done under mescaline-induced psychosis. The maximum effect of the drug is triggered by preferential actions on the serotonergic muscles. The behavioral effects for mescaline via intra-cerebroventricular administration were tested. The rats exposed to mescaline showed enhanced spontaneous motility with no effect on their exploratory behavior. The influence of mescaline on behavior may be related to change in the brain’s cholinergic system. The effects of the drug can least at their maximum effect from 5 to 8 hours and its after effects can be felt from 6 to 8 hours (Anderson, 1996).  Peyote is part of the groups of phenethylamine hallucinogens and is part of the catecholamines family, as such its mechanism of action has some similarities to those of norepinephrine and the psychostimulant amphetamine. That is also due to the structural similarities between the three compounds.  Mescaline is a non selective, serotonin receptor agonist that involves 5-HTP receptors. Mescaline binds to and activates the serotonin 5-HT (2A) receptor. It increases serotonin via activation of those receptors. The serotonergic system is intimately involved in the explanation for the psychoactive effects of phenethylamine hallucinogens as it plays an important role in a variety of processes, such as anxiety, cognition, aggression, learning, memory, nausea, sleep and mood. Two specific receptor subtypes are involved; 5-HT(2A) and 5-HT(2C). Mescaline activates those specifically, they are located in the cortex. 5-HT(2A) specifically, is crucial in the mechanism of action of the compound in the origin of the hallucinogenic state experienced by humans. 5-HT(2A) (Meyer, 2013). The full explanation of the cause of these experiences still remains unsure until today however two theories are potentially plausible. The first is that the activation of 5-HT(2A) receptors increases the excitation of the pyramidal neurons in layer V of the prefrontal cortex, which are glutamate-mediated. Hence, excess glutamate is being released from the thalamus which interferes with the thalamic filtering of sensory information. No ‘filtering’ takes place and you are left with an excessive strain due to the overloading of information on your cortex, which results in the visions, distortions and overall cognitive disturbances that are know effects of hallucinogens. The second explanation is simply that the activation of 5-HT(2A) receptors disturbs the usual activity of excitatory glutamatergic networks within the prefrontal cortex. The increased excitation of prefrontal cortical pyramidal neurons appears to be a critical feature of hallucinogenic activity. Further studies and research still need to be done concerning the cause of the psychological illusions created by hallucinogens.  Approximately half of the initial dosage of mescaline is excreted after 6 to 8 hours, however studies have shown that 50 to 60% of mescaline is not metabolized and leaves the body unchanged. The other 50 or 40% are going the liver protein 26 and are broken down by the liver protein through deamination to be excreted in urine as 3,4,5 trimethoxyphenyacetic acid. The LD50 for mescaline has been measured on animals and has been found, in rats to be 132 mg/kg I.P (Cochin et al, 1951). As a result the plateau phase will last generally between 3 to 5 hours.  Throughout the years peyote has had many ‘street names’ such as dry whiskey, divine herb, devil’s root and medicine of God. Today, mescaline is not as available on the streets as other hallucinogens such as LSD or psilocybin because its costs more to synthesize it and the demand for it is not high enough on the drug market.  Hallucinogenics do not produce physical withdrawal symptoms after chronic use and do not posses the high degree of abuse potential present in other types of drugs such as nicotine or cocaine. Peyote (mescaline) is 1000 to 3000 times less potent than LSD according to Kovacic’s study in 2009. Mescaline does not produce tolerance with repeated use, as LSD does. This is due to the absence of the down- regulation of 5-HT(2A) receptors after the drug has been taken. A short term tolerance can be built though that last a few days if you consumed a normal amount on a daily basis. Overdosing on peyote is incredibly easy due the uncertain amount of mescaline in the buttons. The average 76 mm (3.0 in) button contains about 25 mg mescaline. A study in 2007 showed no long term problem associated to cognitive functioning with the consumption of peyote. The hallucinogen does not possess any addictive potential, however it has negative physical effects after the coming down from the high.  While recognizing that psychedelics are toxic substances that should not be treated or ingested lightly, Meyer et al. (2013) states that the drug compound do have beneficial uses. They are naturally occurring substances that are fundamentally valuable and that can provide treatment to a variety of mental illnesses. Psychopharmacologists have worked in the past and are still working today to harness the mind-revealing power of psychedelics to help alleviate the pain and suffering caused by two deadly chronic diseases that have long been notoriously resistant to treatment: alcoholism and addiction. Today, more than 18 million Americans abuse alcohol, and another 1.8 million abuse cocaine or heroin.The study made Albaugh & Anderson (1974) states that he Native American Church (NAC) has proven itself to be effective in helping to minimize the symptoms of alienation and loneliness and isolation for many subjects. It allowed them to express their most inner feelings very cathartically and safely. The helps their alcoholic members find a sense of identity and purpose with the experience mescaline. In abnormal psychology, while the physical effects of withdrawal are what makes the addict want more, the psychological effect is what the addict succumbs to. Physical effect are usually less felt 48 hours after withdrawal, it the mind that still wants to be able to find its peace and escape in the consumption of the substance. What mescaline provides is the opposite. It provides an experience where ones realizes that they are wasting their potential and could fulfill their lives with a purpose once again. This essay doe snot propose that the pharmacological effects of peyote or the NAC by itself is a cure for alcoholism, as alcoholism does not have a cure. It is a chronic condition that is resistant to treatment. In conclusion, mescaline, which is present in the cactus peyote, is a hallucinogen that can be found in South America and that has a very potent effect on its subject that can last up to 6 to 12 hours. It is a mind-altering substance that can cause hallucinations but mostly makes one feel a euphoria due the consumption of the little buttons on top of its plant. Most easily consumed if boiled in hot water and drunk as an herbal tea. ReferencesAlbaugh, B.J. & Anderson, P. (1974) Peyote In the Treatment of Alcoholism Amongst American Indians. American Journal of Psychiatry 131(11), 1247-1250Anderson, E. F. (1996). Peyote: the divine cactus. Great Plains Research: A Journal of Natural and Social Sciences, 353-354. from http://digitalcommons.unl.edu/greatplainsresearch/350El-Seedi H, R., De Smet P, A., Beck, O., Possnert G & Bruhn JG (2005). Prehistoric peyote use: alkaloid analysis and radiocarbon dating of archaeological specimens of Lophophora from Texas. 101 (1–3): 238–42. doi:10.1016/j.jep.2005.04.022. PMID 15990261. Halpern, J.H., Sherwood, A., Hudson., Yurgelun-Todd., Pope, H. (2005) Psychological and Cognitive Effects of Long-Term Peyote Use Among Native Americans: Biological Psychiatry 58(8):624-631. doi:10.1016/j.biopsych.2005.06.038Kapadia, G. J., Fayez, M. (1970), Peyote constituents: Chemistry, biogenesis, and biological effects. Journal of Pharmacy. Science., 59: 1699–1727. doi:10.1002/jps.2600591202 Kovacic, P., Somanathan, R. (2009). Novel, unifying mechanism for mescaline in the central nervous system: Electrochemistry, catechol redox metabolite, receptor, cell signaling and structure activity relationships. Oxidative Medicine and Cellular Longevity, 2(4), 181–190. Kulma, A., Szopa, J (2007). Catecholamies are active compounds in plants. Plant Science. 172 (3): 433–440. doi:10.1016/j.plantsci.2006.10.013. Meyer, J. S., & Quenzer, L. F. (2013). Psychopharmacology: drugs, the brain, and behavior. Sinauer Associates, Inc. Retrieved January 16, 2018, from https://www.erowid.org/plants/peyote/ peyote_effects.shtml#ref1 Nadelmann, E. (2015, June 11). The War on Drugs has got to end: Ethan Nadelmann speaks at TEDGlobal 2014. Retrieved January 22, 2018, from https://blog.ted.com/ethan-nadelmann-speaks-at-tedglobal-2014/Palenicek T, Balikova M, Bubenikova-Valesova V, Horacek J.(2008) Mescaline effects on rat behavior and its time profile in serum and brain tissue after a single subcutaneous dose. Psychopharmacology (Berl) 2008;196:51–62. doi: 10.1007/s00213-007-0926-5Stork, C. M., Schreffler, S.M. (2014) Peyote: Encyclopedia of Toxicology (3). 841-843       doi:10.1016/B978-0-12-386454-3.00765-X

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