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Psychology 572 Spring, 2004
Dr. John M. Morgan Tuesday & Thursday, 8am to 9:20
Natural Resources 201
The following is a research paper regarding hallucinogens.
Marcella Strang wrote about LSD and Psilocybin – Serotonergic Hallucinogens: Route of access, brain metabolism, and neurochemical effects.
Jamaica Chenoweth wrote about physiological changes and primary mood changes.
Teresa Gauthier is the author of the section entitled Primary Behavior Changes and Side Effects of Hallucinogens.
Finally, Denise Thornton wrote about the effects of hallucinogens reported by users.
LSD and Psilocybin – Serotonergic Hallucinogens: Route of access, brain metabolism, and neurochemical effects
The hallucinogens are a group of drugs that can spectacularly alter human consciousness. Some of the drugs included in this group are LSD, mescaline, psilocybin, peyote and DMT. This paper will focus on two of the most commonly used hallucinogens – LSD and psilocybin.
LSD (lysergic acid diethylamide)
LSD is a laboratory-derived chemical that in its pure form is a liquid, without smell, color, or taste. Distributors of the drug, to make handling easier, usually dissolve the drug onto absorbent paper or sugar cubes. Users of the drug swallow the drug or dissolve it on the tongue. The gastrointestinal system quickly absorbs the drug, where it is rapidly distributed throughout the body. LSD is metabolized by the liver, where most of it stays, with only the tiniest amount reaching the brain. Within the brain, the highest levels of LSD are in the visual system, especially within a part called the lateral geniculate nucleus, or LGN. LSD decreases the response of the LGN, which acts a visual relay center. The LGN receives nerve impulses from the retina and sends them to the occipital cortex of the brain, an area also known as the visual cortex. LSD acts to decrease the responsiveness of the LGN to signals from the retina. How this affects the production of visual hallucinations is unclear (DeGracia,1997).
LSD is also concentrated highly in parts of limbic system. The limbic system is dedicated to regulating emotion, aggression, docility, and memory.
Also, LSD concentrates in areas of the reticular formation. The reticular formation mediates the level of arousal and alertness in the brain. It begins in the medulla, and runs up through the brain stem into the forebrain. The textbook authors call it "the volume dial of consciousness" (Palfai & Jankiewicz, 2001).
LSD and psilocybin are both 'serotonergic' in action. This means they act on the neurotransmitter serotonin. In fact, LSD and psilocybin are some of the most extreme serotonergic agonists. The chemical structure of LSD resembles that of serotonin. LSD appears to work by blocking 5-HT (the chemical name for serotonin) receptors at the synapse, resulting in a rebound effect in which serotonin is overactive and receptors are hypersensitive Since the drug is metabolized quickly, takes up to two hours to produce a noticeable effect, and has a long duration of action, it seems that LSD works to imbalance the brain's natural serotonin system. (Palfai & Jankiewicz, 2001).
LSD-25 (lysergic acid diethylamide)
Effects on subtypes of 5-HT receptors
LSD inhibits the activity of the 5-HT1a subtype of serotonin receptor. Many of the 5-HT1a receptors are located in the raphe' nucleus of the brain stem. However, this is probably not the cause of the hallucinogenic effect, since other chemicals that inhibit these receptors are not hallucinogenic (Palfai & Jankiewicz, 2001). However, the raphe' nuclei are known to have an important role in regulating the autonomic nervous system, patterns of sleep and wakefulness, and states of arousal (DeGracia, 1997).
LSD also has an affinity for 5-HT2 receptors – an affinity it shares with mescaline, an andrenergic hallucinogen. Many 5-HT2 receptors are located in the cerebral cortex, and are linked to the perceptual and mental effects of hallucinogens. The cortex is the most advanced area of the brain, receiving information from the thalamus and making higher-level processing possible. LSD's effects on the 5-HT2 receptors are the likely source of the hallucinogenic effects of the drug (Palfai & Jankiewicz, 2001).
LSD's third effect is to activate the NE neurons located in the locus coeruleus of the brain. This is accomplished through a modulating effect of LSD on the 5-HT neurons, which then affect the NE neurons. The NE neurons receive sensory information from the body and then direct the flow of that information – downward to the reticular formation, and upward to the hippocampus, hypothalamus, and amygdala. In animal studies. researchers have shown that LSD increases the responsiveness of the locus coeruleus to stimuli (Palfai & Jankiewicz, 2001).
Psilocybin (and psilocin)
Psilocybin is an active hallucinogenic compound found in a variety of mushroom that grows in Mesoamerica and what is now the southwestern U.S. These "magic mushrooms" have a long history of ceremonial use among tribes of the region. However, today's "street" users consume the mushroom purely for its hallucinogenic effects, with a notable absence of ceremony.
Researchers have isolated the psychoactive compound of psilocybin found in "magic" mushrooms. Psilocybin (and its metabolite, psilocin) are serotonin-like compounds that are chemically similar to LSD. Psilocybin is the only phosphorous- bearing indole compound in nature, which makes it quite stable. (Indole refers to a double organic ring around the substance.) When metabolized, the phosphoric acid is removed, and the psilocybin becomes psilocin, which is virtually identical. The action of psilocybin is very like that of LSD, but is considerably less active and has shorter effects.
Users of psilocybin generally consume it by chewing and swallowing mushrooms that contain the compound. The amount of psilocybin can vary over species, so users do not know exactly what dose they will receive. The amount eaten can vary from 2 to 40 mushrooms. However, psilocybin does not have as strong an effect on the brain as does LSD (Palfai & Jankiewicz, 2001).
Research undertaken in Switzerland shows that psilocybin stimulates glucose production in the right, frontal cortical regions of the brain. They call this effect "right brain hyperfrontality" (Lyvers, 2003). Researchers presume this reflects a strong activation of excitatory 5-HT2 receptors in the cortex. This supports other research showing that LSD's hallucinogenic effects are related to stimulation of these receptors(Vollenwieder, et al., 1997).
In summary, both LSD and psilocybin, along with other serotonergic hallucinogens, act on several subtypes of 5-HT receptors, with the 5-HT2 subtype most closely related to the drugs' hallucinogenic effects.
DeGracia, D. (1997). Background information about psychedelic drugs. Retrieved April 5, 2004, from source.
Lyvers, M. (2003). The neurochemistry of psychedelic experiences.Science & Consciousness Review, 1, 1-5.
Palfai, T. & Jankiewicz, H. (2001). Drugs and Human Behavior. New York: McGraw Hill Primis Custom Publishing.
Vollenweider, F.X., Leenders, K.L., Scharfetter, C., Maguire, P., Stadelmann,
O. & Angst, J. (1997). Positron emission tomography and fluorodeoxyglucose
studies of metabolic hyperfrontality and psychopathology in the psilocybin model
of psychosis. Neuropsychopharmacology, 16, 357.
Physiological Changes and Primary Mood Changes
By Jamaica Chenoweth
Lysergic Acid Diethylamide
LSD is absorbed easily through the gastrointestinal tract with as little as 20micrograms affecting mood and perception. The amount needed is as little as a period at the end of a sentence and less than one percent actually reaches the brain. It is metabolized through the liver and the metabolic products are excreted though the small intestine, leaving one percent excreted and unchanged in the urine, making LSD largely undetectable in drug tests. LSD has a very low toxicity in human beings; in fact an elephant must ingest 297 milligrams before it becomes lethal, which is nearly 6,000 times the amount a human would need to produce psychological effects in humans. Most of the actions of the drug are caused by serotonin receptors (the 5HT2 subtype), which it acts as an agonist for. These receptors are found in the cortex and limbic system, where LSD binds to those as well as dopamine and norepenephrine receptors. The frontal lobes are effected, changing our ability to consider several courses of action at once and put a series of thoughts together. It also changes the temporal cortex, involved in hearing, and the occipital lobes which comprise the visual pathways and connect to the thalamus. The raphe nucleus, which controls sleeping and dreaming is largely stimulated as the reticular formation, which filters out distracting stimuli is aroused to let in more than the usual incoming sensory messages to disrupt visual, auditory, and cognitive thinking abilities with distorted perceptions. (Avis, 1999)
Ergotism, the form of natural hallucination without the synthesis of the ergot mold into LSD, causes the constriction of blood vessels due to the overall physiological effects of erogot, may cause such physiological symptoms as muscle spasms and convulsions if taken at high enough doses because involuntary muscles are stimulated. (Palfai, 1997)
Primary mood changes are dose related, with most individuals using small amounts of LSD to produce the effects needed for a hallucinogenic experience. Synesthesia, or "seeing sounds, hearing colors," and time distortion are the most common reports or psychological changes in users. These individuals report feeling that time moves in terms of seconds as minutes and minutes as hours, slowing down the perception of everything around them. At much higher doses, a distortion of body image or even a loss of the boundary between the self and their environment is reported, which can lead to users experiencing mystical or religious experiences and the resurfacing of old memories that may play into the hallucinogenic occurrence. The higher the dosage, the more adverse reactions that may take place, including paranoia and psychotic behaviors. LSD is not known for causing long term psychosis, but may trigger these symptoms, such as changes in personality, in someone who is otherwise susceptible, or users with a prior psychiatric history, in which case "bad trips" may happen. (Avis, 1999)
Found in mushrooms, the pro-drug is converted into an active drug within the body as psilocin, which is unstable and cannot be taken directly. It effects the same areas of the brain as LSD but with less intense actions and shorter acting results. The glucose of the brain becomes faster acting in areas such as the frontal lobes, temporal cortex, basal ganglia, sensorimotor cortex, and occipital lobes. (Avis, 1999)
Depending on the dosage, sympathetic reactions will occur, but most effects range from a mild, calming bodily sensation to adverse perceptual changes that invoke more illusions than hallucinations, the difference being seeing a bizarre change in what is already present in the environment to imagining something new that does not exist in the direct visual field. (Palfai, 1997)
Mescaline, the active compound of peyote, acts on the same mechanisms as LSD, and causes symptoms that last for hours, such as nausea from the bitter taste that lasts for hours, vomiting, and diarrhea. The gastrointestinal experiences occur first and are followed by intense images of vivid color and a sense of depersonalization that last for at least 2 hours, while the drug remains within the system for about ten. (Avis, 1999)
Mescaline is absorbed rapidly and is an adrenic enhancer, causing some of the same symptoms of amphetamines, such as widening pupils, increased heart rate/blood pressure, raised body temperature, and EEG arousal. The behavioral effects include being easily startled and trembling in the limbs. Reports of objects differing in size with more vivid colors and patterns occur even with the eyes closed. (Palfai, 1997) Bibliography
Avis, Harry. Drugs and Life, 4th edition, WBC McGraw-Hill, Boston, 1999.
Palfai, Tibor, Jankiewicz, Henry. Drugs and Human Behavior, 2nd edition, Brown & Benchmark Publishing, 1997.
By Teresa Gauthier
A hallucinogen is a substance that produces changes in perception, thought, and feeling. These changes range from distortions of what one senses (illusions) to sensing things that don't really exist (hallucinations) (Steiner, 1999). While many drugs produce hallucinations at high doses, hallucinogens produce these effects at low to medium, or "normal" doses (Drug Dependency Services, 1999).
A wide variety of drugs are classified as hallucinogens. Some of these drugs are obtained from natural sources while others are manufactured synthetically. The hallucinogens obtained from natural sources include mescaline (from the peyote cactus) and psilocybin (from magic mushrooms). Cannabis (from the marijuana plant) is not normally included in this group, but, in large doses, it can produce hallucinations. The hallucinogens manufactured synthetically include LSD (d-lysergic acid diethylamide), PCP (phencyclidine), DMT (dimethyltryptamine), MDA (3,4 methylenedioxyamphetamine), MDMA (methylenedioxymethamphetamine), and STP or DOM (2,5 dimethoxy-4 methylamphetamine) (Drug Dependency Services, 1999).
Additionally, hallucinogens can be grouped into sub-categories based on whether they are norepinephrine-like (mescaline, STP, MDA, MDMA), which produce stimulant-like sensations, or serotonin-like (LSD, psilocybin, and DMT), which alter moods (Drug Dependency Services, 1999).
There are several terms used to describe hallucinogens that are related to their effects. The term "psychotomimetic" is used and refers to the similarities between the drugs' effects and the symptoms of psychosis. The term "psychotogenic" is also used and is translated as "psychosis causing." And, finally, "psychedelic," the most commonly used term, which means "mind manifesting" and refers to the effects of hallucinogens that involve the expansion of consciousness (Steiner, 1999).
Primary Behavior Changes/Effects
Hallucinogens produce a wide range of effects that are both physical and psychological. Hallucinogens produce their effects by disrupting the interaction of nerve cells and the neurotransmitter serotonin (particularly the serotonin 1 and serotonin 2 receptors). The serotonin system is distributed throughout the brain and spinal cord and involves the control of behavioral, perceptual, and regulatory systems (Kuhn, Swartzwelder, & Wilson, 1998).
The effects of hallucinogens are unpredictable and depend on many factors, such as the amount of the drug taken, the route of administration, the person's size, weight, mood, expectations, and health, whether other drugs are taken concurrently, the environment in which the drug is taken, and previous drug experiences. The user typically notices the first effects of the drug somewhere between 30 to 90 minutes after taking it, and these effects generally last from 30 minutes to several days (Drug Dependency Services, 1999). Because there are no distinct effects belonging to the individual drugs within the hallucinogen classification, the effects listed in this paper will refer to all of the hallucinogenic drugs (Steiner, 1999).
The physical effects of these drugs include increased heart rate and blood pressure, dilated pupils, increased body temperature, dizziness, nausea, loss of appetite, chills, flushing, shaking, abnormal rapid breathing, muscle weakness, numbness and poor coordination (Bezchlibnyk-Butler & Jeffries, 1999). The psychological and behavioral effects that occur from taking hallucinogens include alterations of perception and body awareness, disturbed sense of time and self, impaired attention and short-term memory, depersonalization, mystical or religious experiences, euphoria, grandiosity, anxiety, visual distortions, hallucinations (primarily visual), erratic behavior/emotions (Bezchlibnyk-Butler & Jeffries, 1999). Additionally, hallucinogens can produce distortions of sensations, such as "hearing" colors and "seeing" sounds. These effects may be experienced as pleasant for some and as "bad trips" for others (Drug Dependency Services, 1999).
Of the various effects and behavior changes caused by hallucinogens, there are certain reactions that occur most often and, therefore, stand out. For example, most users describe being "flooded" with visual experiences and distortions, including the sensation that light is intensified, colors are more vivid, details are sharper, sounds are louder, the perception of space is enhanced, and images are numerous and long- lasting, resulting in an abundance of illusions and hallucinations. Additionally, users often describe a change in their awareness of self. This may include a fusion of self and object, a sense that the body is floating and that body parts are shrinking or getting larger, and a feeling that one is empty inside or that one is the same as the universe. This particular type of reaction is referred to as depersonalization, detachment or dissociation. Finally, users often have the experience of their moods and emotions shifting erratically from one extreme to another. This can be so unsettling to the individual that psychiatric hospitalization is sometimes required (Steiner, 1999).
Because hallucinogens powerfully effect the brain, distorting the way the senses work and changing impressions of time and space, people who use these drugs can experience negative effects and behavior changes, referred to as side effects. These side effects typically occur when hallucinogens are used improperly, such as when taking high doses of the drug or when involved in chronic use of the drug. As with the primary behavior changes and effects of hallucinogens, the side effects also involve the serotonin receptors distributed throughout the brain and spinal cord.
The most common side effects resulting in high doses of these drugs include confusion, restlessness, anxiety, emotional lability, panic, mania, paranoia, "bad trips," cardiac depression, respiratory depression, hypotension, convulsions, and coma (Bezchlibnyk-Butler & Jeffries, 1999). The side effects resulting from chronic use of hallucinogens include anxiety, depression, personality changes, tolerance (tachyphylaxis), "wooly" thinking, delusions and hallucinations (persisting for months after drug discontinuation), and flashbacks (recurrent psychotic symptoms, sometimes occurring years after discontinuation) (Bezchlibnyk-Butler & Jeffries, 1999).
Perhaps the most troubling side effect of hallucinogens is a "bad trip," which can be either physical or psychological in nature. Bad trips are characterized by strong feelings of fear and anxiety. They occur when negative feelings dominate the user's experience. They often include unpleasant hallucinations, such as spiders crawling on your skin. These hallucinations can be so intense that the user feels as though they are "going crazy." Bad trips can also lead to risky behavior, such as running across a busy street or trying to fly. They can lead to feelings of paranoia and fear of persecution, as well as to feelings of superiority. The reasons for bad trips are unknown. They occur more frequently among first-time users. To help someone through a bad trip, you should do the following: make sure that the user is safe; move and speak calmly and confidently; address the user by name and remind them of who they are; tell them who you are; and, if possible, don't leave them alone. It generally takes several hours for the negative effects to fade away, although there have been incidents where users experienced bad trips for several days, weeks, or even months after taking the drug. Occasionally, medical assistance is required, especially if the user becomes violent toward themselves or others (DF Australian Drug Foundation, 2003).
Another disturbing side effect related to taking hallucinogens is "flashbacks," or posthallucinogen perceptual disorder (PHPD). Flashbacks are spontaneous, repeated, sometimes continuous recurrences of some of the sensory distortions originally produced by a hallucinogen. The experience may include hallucinations, but it most often consists of visual disturbances such as seeing bright or colored flashes and false motion on the edges of the field of vision. This condition is typically persistent, in some cases remaining unchanged for years after the individual has stopped using the drug. There is no established treatment for PHPD, although antidepressant drugs have been helpful in reducing the symptoms. In addition, psychotherapy may be useful in helping the patient deal with the confusion and fear associated with this disorder (Kuhn, et al, 1998).
Finally, a dangerous, yet fairly uncommon, side effect related to taking hallucinogens involves the worsening of symptoms in people who are already psychotic. People with a family history of, or a predisposition to, mental illness should be especially careful about taking hallucinogens. Though rare, hallucinogenic drug experiences have been known to reveal psychotic symptoms in such individuals (Kuhn, et al, 1998).
Bezchlibnyk-Butler, K.Z., & Jeffries, J.J. (Eds). (1999). Clinical handbook of psychotropic drugs. Toronto: Hogrefe & Huber Publishers.
DF Australia Drug Foundation (2003). How drugs affect you: Hallucinogens. Retrieved April 4, 2004, from http://www.nevdgp.org.au/geninf/adf/hdayha.htm
Drug Dependency Services (1999). Information on hallucinogens from DDS. Retrieved April 4, 2004, from http://www.druginfosite.ca/hal/html
Kuhn, C., Swartzwelder, S., & Wilson, W. (1998). Buzzed: The straight facts about the most used and abused drugs from alcohol to ecstasy. New York: W.W. Norton & Company, Inc.
Steiner, W. G. (1999). Head Sounds: Hallucinogens. Retrieved April 4, 2004, from http://www.britannica.com/psychedelic/textonly/hallucinogen.html
Effects of Hallucinogens Reported by Users
People may use hallucinogenics for the mind-altering effects, he vision, the feelings of well-being, the approval of their peers, stress reduction, rebellion against authority, and to achieve states of heightened mental awareness (crystalinks.com). Withdrawal states for chronic hallucinogen use are very rarely reported, and no detoxification is necessary ( Schatzberg, A.F., Cole, J. O., DeBattista, 2003).
Peyote Cactus (Lophophora williamsii)
Peyote is a hallucinogenic cactus that grows naturally in the desert regions of northern Mexico and the Southern United States. Researchers estimate that it has been in use for about 3,000 years as a shamanic teacher plant that can give visions of an alternate reality or of the spirit world (Schultes , R.E. & and Hoffman, A.,1992). An Indian explained to an anthropologist, "God made Peyote. It is His power. It is the power of Jesus. Jesus came afterwards on this earth, after Peyote…. God (through Peyote) told the Delawares the same things that Jesus told the whites. It causes those devouring it to be able to foresee and to predict things…."
Peyote eaten in ceremony has assumed the role of a sacrament in part because of the sense of well-being that it induces and the psychological effects (richly colored visions) often experienced by those who indulge in its use. Peyote is considered sacred by native Americans, a divine "messenger" enabling the individual to communicate with God without the medium of a priest. Those in touch with the supernatural realm could heal the sick, ensure the fertility of the world, predict the future, and resolve the problems of existence.
Lysergic acid diethylamide (LSD)
In 1938 a chemist, Albert Hofman, working on a blood stimulant for Sandoz Pharmaceuticals, synthesized LSD. He discovered its hallucinogenic properties in 1943 by accidental absorption through the skin. He later purposefully administered a dose to himself in order to conduct an experiment. He chronicled his reactions:
He reports seeing "an uninterrupted stream of fantastic pictures, extraordinary shapes with intense, kaleidoscope-like play of colors." The symptoms lasted for about 2 hours.
The initial effects begin in 20 – 40 minutes after ingestion. Initial symptoms include a sense of euphoria and dizziness which give way to auditory and/or visual hallucinations. LSD users may experience a feeling of detachment. Perceptions are altered. Senses may appear to mix; the use may see noise or hear visual stimuli. Effects taper off in about 6-8 hours and are completely gone after a good night's rest. LSD has been used in western cultures in a similar manner as peyote has been used for centuries; to enrich one's awareness and in hopes of spiritual transformation.
There is no difference in principle between sharpening perception with an external instrument, such as a microscope, and sharpening it with an internal instrument, such as one of these...drugs. If they are an affront to the dignity of the mind, the microscope is an affront to the dignity of the eye and the telephone to the dignity of the ear. Strictly speaking, these drugs do not impart wisdom at all, any more than the microscope alone gives knowledge. They provide the raw materials of wisdom, and are useful to the extent that the individual can integrate what they reveal into the whole pattern of his behavior and the whole system of his knowledge (Watts, A.).
There are two primary conditions for the quality of an LSD trip; set and setting. Set refers to the expectations of the user. Setting refers to the environment in which the drug is ingested. A user's mood is likely to shift. If the user was in an anxious state there is likelihood that a bad experience will occur. Users experiencing a bad trip are usually easily "talked down" by a trusted friend. Because of this, LSD would optimally be used in the presence of supportive, trusted friends.
Marijuana (Cannabis sativa)
Marijuana has been used since the beginning of time, yet there are still many mysteries about it. Marijuana is a preparation of the crushed flowers and buds of female hemp plant. The existence of the plant has been reported as early as 1500- 1200 BC. in China, and cannabis has been described as an analgesic as early as 200 AD (Walton, 1938).
Marijuana is easy to grow, especially in temperate climates. The Pacific Northwest region of the US reportedly produces some of the highest quality marijuana. The amount of THC (the active ingredient in marijuana) varies greatly from plant to plant. Controlled studies are difficult to perform because of this inconsistency.
The user of marijuana feels the initial effects of the "high" between 7 seconds (when smoking) and up to 30 minutes (after eating). This involves a relaxed and peaceful, yet sometimes euphoric state of mind. It can cause hallucinations at high doses. The effects last from 2 to 4 hours after the drug is ingested, and it usually leaves the user in a relaxed state for several hours after the high. Short term memory may be inhibited while the user is high Thoughts may seem unclear, and it might be difficult for a user to concentrate on logical-complicated concepts like mathematics (Marc Anderson, M., 1992).
An effect commonly called "the munchies" by users is often reported. It is unclear whether this is a physiological hunger or the enhancement of the enjoyment of eating. More research needs to be done on this aspect of marijuana use. However, the increase in appetite, along with a suppression of feelings of nausea, has medical value. Patients wasting from AIDS or nauseous from chemotherapy have benefited from marijuana use. Some medical providers have expressed hesitation in prescribing marijuana because of the lack of control of dosage.
The effects of marijuana are so subtle that participants in a research study (even those who were regular users of marijuana) were often not able to determine whether they had received a high or low dose. Participants in this study who had never smoked marijuana before the experiment reported that they believed they had received a placebo even when they had received the high dose. In fact, many users report no sense of being high the first time they tried marijuana. Friends often instruct the first time user in what to expect. This expectation may enhance the effects.
Marijuana use is so popular in the US that researchers conducting the experiment I discussed above had a difficult time finding college students who had never tried marijuana. It took them two months of interviews to fill the positions. They report that they had no difficulty finding regular users who were willing to openly discuss their marijuana use with the psychiatrist conducting the interviews.
Anderson, M. (1992). The health effects of marijuana on humans. http://hepenthes.lycaeum.org
Schatzburg, A.F., Cole, J.O., & DeBattista ,C. (2003). Manual of clinical psychopharmacology. Psychiatric Publishing: Washington, D.C.
Schultes, R.E. & Hoffman, A. (1992). Plants of the gods-their sacred, healing and hallucinogenic powers. Healing Arts Press: Vermont
Watts, A. the joyous cosmology.www.deoxy.org