WHAT HALLUCINOGENS DO TO THE BRAIN

WHAT HALLUCINOGENS DO TO THE BRAIN

It is extremely hard to portray what a man encounters under the influ­ence of these medications in light of the fact that each experience is so individualized. The personality and measure of the medication, how it is taken, the client's desires, and the client's past experience all assume a part. There are some regular impacts, in any case. Frequently, an outing starts with sickness; a sentiment unsteadiness; and gentle increments in circulatory strain, heart rate, and relaxing. At that point the client typically feels a slight twisting of tactile discernment. Visual impacts prevail, with faltering pictures and twisting of size (things may appear to be substantially bigger or littler than they are). 

At high measurements, clients encounter deceptions, pseudohallucinations, or hal­lucinations that are very individual and significantly impacted by the setting. They can run from basic shading examples to complex scenes, regularly with the medication taker feeling like he is watching his activities from out­side his body. The disarray of faculties, or synesthesia, for example, seeing sounds and hearing hues, is generally revealed. The feeling of time is twisted, so minutes can appear like hours. At the pinnacle of the medication encounter, the client much of the time depicts a feeling of significant understand­ing or illumination. Once in a while there is a feeling of unity with the world, which is once in a while kept up after the medication encounter is finished. Pro­found rapture or nervousness can happen. As the medication impact melts away, the client typically feels a kind of extraordinary sense and exhaustion. 

Albeit persuasive, phenomenal, and engaging reports possess large amounts of the writing, a standout amongst other portrayals of the stimulating background was composed by Dr. Albert Hofmann, the physicist who initially orchestrated LSD. The report is particularly convincing in light of the fact that Dr. Hofmann composed it when the impacts of the medication had at no other time been portrayed, so he couldn't have been affected by desires. 

This was in the period when logical self-experimentation was more com­mon than it is today, so after an unplanned involvement in the research facility that alarmed him to the significant impact of the medication, he took some of it deliberately and recorded what happened. He reports two encounters in his book LSD, My Problem Child that show the mind boggling scope of encounters that can happen even inside a similar person. 

Last Friday, April 16,1943,1 was compelled to intrude on my work in the lab amidst the evening and continue home, being influenced by an amazing fretfulness, consolidated with a slight dazedness. At home I set down and sank into a not disagreeable inebriated like condition, described by a to a great degree empowered creative energy. In a dreamlike state, with eyes shut (I observed the light to be offensively glaring), I saw a continuous stream of phenomenal pictures, exceptional shapes with extraordinary, vivid play of hues. After somewhere in the range of two hours this condition blurred away . . . 

The unsteadiness and vibe of blacking out turned out to be so solid now and again that I could never again hold myself erect, and needed to rests on a couch. My surroundings had now changed themselves in additionally startling ways. Everything in the room spun around, and the natural protests and household items expected peculiar, undermining shapes. They were in contin­uous movement, vivified, as though determined by an inward eagerness. The woman adjacent, whom I hardly perceived, brought me drain—over the span of the night I drank more than two liters. She was never again Mrs. R., but instead a malicious, deceptive witch with a hued veil. 

Far more terrible than these satanic changes of the external world, were simply the adjustments that I saw, in my inward being. Each effort of my will, each endeavor to put a conclusion to the deterioration of the external world and the disintegration of my personality, appeared to be squandered exertion. An evil spirit had attacked me, had claimed my body, brain, and soul. I bounced up and shouted, endeavoring to free myself from him, yet then sank down again and lay defenseless on the couch. The sub­stance, with which I had needed to try, had vanquished me. It was the devil that contemptuously triumphed over my will. I was seized by the frightful dread of going crazy. I was taken to a different universe, somewhere else, some other time. My body appeared to be without sensation, dormant, weird. Is it accurate to say that i was biting the dust? Was this the progress? On occasion I trusted myself to be outside my body, and afterward saw unmistakably, as an outside onlooker, the total disaster of my circumstance;

CHROMOSOMAL DAMAGE

CHROMOSOMAL DAMAGE

We have one final myth to discuss: the idea that LSD will break chromo somes. This concern, based on scanty research, was raised during the 1960s. While women who used LSD during pregnancy have given birth to children with birth defects, this rate is not higher than that of the general population. Furthermore, most of these women also used other drugs during pregnancy. Most animal research has not shown remarkable effects of LSD on the developing fetus. Some concern about the effects of LSD goes back historically to the widespread use of related ergot alkaloids to induce abortion. However, LSD itself does not have this effect. Never‑

theless, women who are pregnant, or who might be, should avoid drugs in general.

DEATH

Conventional LSD-like hallucinogens are fairly unlikely to produce seri­ous physical effects. However, some newer and fortunately rare designer hallucinogens have blurred the lines between stimulants and hallucinogens. For example, one of these-25I-NBOMe, 4-lodo-2,5-dimethoxy-N-(2- methoxybenzyl) phenethylamine—has been reported to cause deaths. This drug and some like it sometimes are marketed as bath salts, and sometimes as LSD. 'The particular problem with this drug is its extraordi­nary potency: like LSD, it has big effects at very small doses. This drug and several close relatives may represent serious risks to human users, but almost nothing is known about them.

lhe belladonna alkaloids represent a particular danger. These drugs prevent the action of one of the major neurotransmitters in the body (ace­tylcholine) at many of its synapses. At doses that cause hallucinations, they increase heart rate and body temperature to dangerous levels: death can result. It is important to understand that there is not a dose that pro­duces significant behavioral effects that is not toxic: the behavioral effects, like delirium, are signs of overdose. These effects are easily treated by medical personnel if they know what the intoxicating drug is. Therefore, it is extremely important to seek medical attention.

PCP also can cause dangerous side effects or death from overdose (two to five times a single recreational dose). As the user increases the dose, general anesthesia can result (remember, this was the reason the drug was invented). However, a number of dangerous effects occur after high doses, any one of which can be lethal. Body temperature can rise to 108 degrees Fahrenheit, blood pressure can rise so much that a stroke occurs, breathing can cease, or a prolonged period of seizure activity can result. PCP can also cause a prolonged state resembling paranoid schizo h enia. This most often happens in people who use PCP for a long time; however, an abnormal psychiatric state that persists for days can result from a single use. The acute delirium caused by PCP or ketamine can be alleviated with benzodiazepine drugs, such as Valium.

Designer Mescaline-like Drugs

Designer" Mescaline-like Drugs

A large number of variations on the structure of mescaline were first "designed" during the original chemical studies of mescaline. The names sound like an alphabet soup: DOM (2, 5 dimethoxy-4-methylphenyliso­propylamine, also known as STP), MDA (methylenedioxyamphetamine), DMA (dimethoxyamphetamine), MDMA (methylenedioxymethamphet­amine, or Ecstasy). All of these drugs are less specific than mescaline and produce strong amphetamine-like effects in addition to hallucinations. As a result, all are more toxic than mescaline and appear much more rarely on the street today. Ecstasy provides a unique profile of effects, dis­cussed in the "Ecstasy" chapter.

'fhe spices nutmeg and mace deserve a final note as we discuss the mescaline-like hallucinogens. Someone who takes several teaspoons of nutmeg (if he can figure out how to avoid the overwhelming taste) might experience a very mild hallucinogenic state that includes perceptual dis­tortions, euphoria, and sometimes mild visual hallucinations and feelings of unreality. The active compounds in nutmeg and mace are myristicin and elemicin, compounds with structures somewhat like mescaline. These compounds are very weak hallucinogens, and the dose required to evoke changes in perception causes a number of unpleasant side effects including vomiting, nausea, and tremors. Furthermore, an aftereffect of sleepiness or a feeling of unreality can persist into the next day.

OTHER LSD-LIKE HALLUCINOGENS

OTHER LSD^-LIKE HALLUCINOGENS

There are many other molecules with chemical structures that resemble serotonin (tryptamines) or amphetamine (phenethylamines) that scien­tists or bootleg drug preparers have made. 2C-B is one example, but there are many, and odd variants pop up all the time. Those that have been stud­ied scientifically owe their hallucinogen properties to the same mechanism as LSD. However, each one has the potential to exert additional effects due to interactions with multiple receptor types, and so the effects can be indi­vidual and perhaps not what the user expects. A former synthetic chemist, Alexander Shulgin, and his wife published two books that describe the synthesis and use of these drugs, which some use as a guidebook. Those with amphetamine-like structures often have amphetamine-like activities along with their hallucinogenic properties, which can lead to dangerous levels of sympathetic nervous system stimulation and increased heart rate and blood pressure, for example. All such drugs are illegal in the United States (see the "Legal Issues" chapter).

DMT

Dimethyltryptamine (businessman's special) is one of the other serotonin­like hallucinogens that appear on the drug scene in North America. The compound originally derives from the beans of the tree Anadenanthera peregrine (sometimes referred to as Piptadenia peregrine), which grows in northern and central South America, and related species in southern South America. It has been used by South American tribes as a halluci­nogenic snuff called yopo or cohoba. However, it is most often available today as the pure compound, which users prepare as a tea or smoke by itself or in conjunction with marijuana by first soaking the leaves in a solution of DMT and then drying and smoking them. The drug takes effect very rapidly: the entire experience develops and finishes within an hour. Probably because the onset of action is so fast, DMT causes anxi­ety attacks much more frequently than LSD, although the basic experi‑

ence is similar.

Some serotonin-derived compounds, such as 5-methoxy dimethyl­tryptamine (5-Me0-DMT) or bufotenin, are found in the skins of some toads, including the Colorado River toad. Milking the glands on the back of the toad to obtain the hallucinogens, which are then smoked or ingested, was an old Native American trick that has been repopularized to the extent that the Wall Street Journal reported it. The high that is produced is extremely brief and accompanied by much worse side effects than most hallucinogens, including increased blood pressure and heart rate, blurred vision, cramped muscles, and temporary paralysis. These are due mainly to the bufotenin. The same compounds also appear in the seeds of a number of trees that grow in the Caribbean, Central America, and South America (Piptaclenia peregrina). The powdered seeds provide the basis for hallucinogenic snuffs used by indigenous peoples and have been identified as a component of voodoo powders. DMT, 5-Me0-DMT, and some other variants including 4-Acetoxy-DMT and 5-Me0-DiPT (N)N^-diisopropy1-5-methoxy-tryptamine) also show up in pill form. The basic effects of these drugs are similar, although the duration of action varies.

Peyote Cactus (Mescaline)

The peyote cactus has likely been used as a hallucinogen by native tribes in Mexico for thousands of years, and its use by North American tribes is an accepted part of their histories. The species that is typically the source of hallucinogens in the United States is a cactus that grows in northwest Mexico: Lophophora williarnsii. It produces mescaline, the active halluci­nogen, as well as many other compounds. The dried "button" of the cac­tus is the usual form in which the drug is sold, although it also appears in other dried forms (powders, etc.), as well as in a tea. While it can be smoked, the button is usually swallowed without chewing, and the active agent is absorbed from the stomach and intestine. There are other cacti that produce hallucinogens, including the San Pedro cactus (Trichocereus pachanoi), which grows in the Andes Mountains of South America.

Mescaline's chemical structure does not resemble LSD or psilocybin and the other serotonin-like hallucinogens. Instead, the structure looks more like amphetamine. The physical effects also resemble those of amphetamine—dilated pupils, increased heart rate, and increased blood pressure. The mental effects as described by ritual and recreational users, however, are surprisingly similar to LSD. Nausea and vomiting are com­mon, especially soon after ingestion of the cactus buttons. After a user ingests a number of cactus buttons, he often feels an increase in sensitiv­ity to sensory images and sees flashes of color followed by geometric pat­terns and sometimes images of people and animals. Time and space perception are distorted, as with LSD, and people often feel that they are outside themselves. The effects of ingesting pure mescaline versus the cac­tus button are similar but not identical, because there are at least thirty other compounds in the cactus.

The ritual use of this cactus by the shamans of native tribes, such as the Huichol in Mexico, persisted into recent times, and North American tribes adopted it in the late nineteenth century. The ritual use by North American tribes was then integrated with a number of Christian prac­tices in the form of the Native American Church. The use of peyote as a part of this church's religious rituals has been protected by the First Amendment and then later by the Religious Freedom Restoration Act (1993). The act states that the government can limit a person's exercise of religious freedom only if "it is in furtherance of a compelling govern­ment interest, and is the least restrictive means of furthering that com­pelling interest." Although the 1993 law was declared unconstitutional by the US Supreme Court in 1997, some states have since enacted protective legislation for religious use to replace the protection no longer provided by federal law.

INDIVIDUAL HALLUCINOGENS

INDIVIDUAL HALLUCINOGENS

Lysergic acid diethylamide (LSD) is probably the best known and most commonly used hallucinogen in the United States. It is also the most potent of commonly used hallucinogens. The effects of LSD depend upon the dose. Typical doses today are between 50 and 150 micrograms (typical doses of the sixties were 100 to 200 micrograms). These levels are enough to produce full-blown hallucinations in nontolerant individuals, although some experienced users take multiple "hits."

Because LSD is so potent and so easily dissolved, it is most often diluted and dissolved in liquid and then absorbed into a piece of blotter paper. No other drug is potent enough to be used in this form. Most of the LSD sold in this format is synthesized in just a few laboratories in northern Cali­fornia, and the product is almost invariably pure LSD. However, enter­prising drug dealers sometimes sell other compounds as LSD. I.SD is also sold in gelatin squares (window pane) and in tiny pills (microdots).

Although LSD itself was originally synthesized in a laboratory in the 1940s, the hallucinogenic and toxic effects of lysergic acid derivatives (the ergot alkaloids) have been recognized for thousands of years. Certain spe­cies of morning glory seeds that provided a drug called ololiuqui (the exact species are not clear but may include Turbina corymbosa) or tlitlitzin (Ipo­moea violacea) in ancient Mexico contain a related chemical, lysergic acid amide. A tea made from the seeds, an alcoholic beverage made by extraction of the seeds with a favorite form of alcohol, and chemically extracted hallu­cinogens all cause an LSD-like hallucinatory experience. As with most plant hallucinogens, the seeds contain other chemicals, and the combina­tion can cause nausea, vomiting, and other unpleasant side effects. Lysergic acid compounds were recognized in the Middle East several thousand years ago through the poisonings that resulted when a fungus (Claviceps pur­purea) infected rye that was used to prepare bread. This fungus produced a number of LSD-related ergot alkaloids and amino acids that caused halluci­nations and constriction of the blood vessels that could lead to gangrene, loss of limbs, spontaneous abortion, and sometimes death. The disease caused by eating ergot-infected rye became known as St. Anthony's fire, after the patron saint of the order of monks founded to care for the victims of these poisonings and the burning sensation caused by the intense con­striction of blood vessels. This plant product was well understood in medie­val Europe, and midwives used its ability to cause uterine contractions to accelerate labor.

As the LSD experience begins, many people report unusual sensations, including numbness, muscle weakness, or trembling. A mild fight-or-flight response occurs: heart rate and blood pressure increase a little, and pupils dilate. Nausea is quite common. These changes are rarely large enough to be dangerous, although they can be in individuals with underlying heart disease. Some users report phantom pains. Internet discussions of halluci­nogen experiences usually reveal several conversation threads about partic­ular pains. A recent look at these found complaints ranging from chest pain to testicular pain. Rapid tolerance develops to LSD. Probably this effect, as well as the lin­gering exhaustion from a drug experience that lasts so long, is the reason why most users take LSD at fairly widely spaced intervals (once a week to once a month). The tolerance diminishes quickly, so that a week's absti­nence is usually enough to restore sensitivity to the drug.Hallucinogenic mushrooms are probably the second most frequently used hallucinogen in the United States. The popular cottage industry that has arisen promoting sales of home-growing kits has increased public aware­ness of these agents. However, there is probably almost as much misinfor­mation about "shrooms” as there is about LSD.

The shrooms to which most users refer belong to several genera of mushroom (Psthicybe, Panaeolus, and Conocybe). The most commonly used species in the United States are Psilocybe mexicana and Psilocybe cya­nescens. These mushrooms contain two related compounds: psilocin (4-hydroxy-N, N-dimethyltryptamine) and psilocybin (4-phosphory­loxy-N, N-dimethyltryptamine). Although many people think that psilo­cybin is the active agent, this is probably not the case. Only after the liver has removed the extra chemical group (a phosphate group) can the remainder of the molecule (psilocin) enter the brain. Although there are rumors that phosphorylated serotonin or phosphorylated DMT are alter­native hallucinogens that provide a unique new high, these molecules have an additional piece that slows entry into the brain and actually prevents rather than promotes psychoactivity. Psilocybin is distributed both in the dried mushroom form and as a white powder of purified crystalline com­pound. A typical dose is four to ten milligrams (two to four mushrooms of the genus Psilocybe cyanescens).

Use of these mushrooms is ancient. Statues of mushrooms dating from AO 100 to 1400 appear throughout Mexico and Central America, and a group of statues from central Guatemala that are even older (about 500 fig) are widely interpreted as mushroom stalks associated with mushroom wor­ship. Use of teonanactl, or "flesh of the gods," persisted in Mexico until the arrival of the Spanish, who attempted to extinguish its use. Ethnobotanists, including R. Gordon Wasson, Richard Schultes, and others, worked in cen­tral Mexico in the 1930s to identify almost twenty species of mushrooms belonging to the genera Psilocybe (the majority), Conocybe, Panaeolus, and Stropharia that were used for healing and religious purposes.

Psilocybin has come full circle in some ways, from careful ritualistic use by native peoples to college students' recreational shroom use during spring break and at weekend parties to the object of current research and religious interest regarding its ability to cause persevering beneficial psy­chological effects. This experience is generally viewed as a milder and shorter LSD-like experience. At low doses, psilocybin causes simple feel‑ings of relaxation, physical heaviness or lightness, and some perceptual distortions (especially visual). At higher doses, more physical sensations occur, including lightheadedness; numbness of the tongue, lips, or mouth; shivering or sweating; nausea; and anxiety.

The psychological effects mirror those of LSD. The records of a group of scientists who gave LSD, psilocybin, and PCP to college students during the mid-1960s provide a good description of the effects in contemporary terms. They published the verbatim transcripts of the experiences of three students. The following is an excerpt from a transcript of a female college senior (who previously had never taken hallucinogens) that was recorded during a psilocybin experiment.

About an hour after the drug: "When I close my eyes, then I have all these funny sensations. Funny pictures, they're all in beautiful colors. Greens and reds and browns and they all look like Picasso's pictures. Doors opening up at triangular angles and there are all these colors ... an unreal world. It must be my subconscious or something. If I open my eyes, now the screen is, the dome gets darker. Looks like something is moving on the outside. Right along the edge. Some writhing. There's a figure—isn't exactly a figure, huge wings like a hawk, head of a hawk, but legs of a man beneath a bed. Now it's gone."

About two hours after the drug: "Ho, ho, I wonder if, I know I can sing as I sang before, but there's some flower vines running up. They start at one point, like at the bulb, and then they go up over an archway or something. And they have flowers on them: the vines are green ... I have the feeling that someone is sticking their high-heeled shoe into the cotton in my right hand. But I can't feel it, it's not there. When I move my hand, my hands are very wet. And the lower part of my body, body, well, my body's bent. Freud. I think he went too far. Ohh. I'm moving. I look like I'm just moving. I just looked down at my body I wish I had a mirror. I suppose that wouldn't help my seeing.... Now I can see a fire. It looks like a key and there's the crackling again. There's a cage and someone is opening the door of the cage. And there's a spider inside. But I'm not going in. I could stay here forever. It's so pleasant. Move slowly up and down, up and down, back and forth, ripple and wave. I keep my eyes closed now and I see a purple flower."Trips are not always as benign as this one, and in some cases they can be terribly frightening. The following is a description of a very unpleasant trip experienced by a friend of ours.

"It was late in the evening and I had been hanging out with two friends since the afternoon. We were all pretty tired, but decided to take some mushrooms. I remember as the trip began that every time I closed my eyes huge, vividly colored plants would seem to grow really rapidly in the darkness behind my eyelids. I found this pretty interesting and entertaining. It happened every time I closed my eyes—as though the process and the images were completely beyond my control." Later that night, after a botched attempt to go to a party and a brief spell of uncon­sciousness, our friend "lay there looking up into the darkness and per­ceived the darkness to begin to move ever so slightly in a circular motion. It was not a dizzy feeling that happens sometimes to people who are really drunk and think that the room is moving. I had not been drinking heavily at all. In my mind it was the darkness that was moving. I already felt pretty unsettled because of having passed out, and the sense of moving darkness was quite frightening. As I stared into the darkness it began to swirl slightly faster, and I had the feeling that it was moving toward ne—bearing down on me. Lightly at first, but the force seemed to increase as the swirling gained speed. Before long I was consciously fighting with that swirling dark force, having to push hard against it with my mind to keep it at bay. the process continued. The swirling got faster, and the darkness now seemed bent on overtaking me. I was overcome with the thought that if I let it get all the way to me I would he dead. So, I mustered all the concentra­tion and focus I could to continue holding it off. I struggled for some time, but very slowly it seemed to wear me down.

"I remember thinking that it was going to win, and! was going to die. I held it off with all the will I could muster, and finally, feeling quite exhausted, gave up with the thought that fighting that force was useless and I should just let it take me. So I did. I relaxed and felt that at least I was facing my death calmly The swirling malevolence seemed to enter my body in the middle of my belly. Then everything was calm and quiet again. I really thought I was dead. After a brief moment, I remember sud­denly feeling that an intense white light was bursting from within me, moving outward. It was as if single, white laser beams were shining out through each and every pore of my skin. Later I remember interpreting the experience in terms of my fear of, and struggle with, my image of my own death. But while it was going on, I was more afraid than I can ever remember having been."

A Cautionary Note on Mushrooms: Psilocybin mushrooms are not the only ones that produce discernible mental effects. However, they are the only mushrooms in wide use in North America. The other well-described hallucinogenic mushrooms can be dangerous. Amanita muscaria, which we discussed at the beginning of this chapter, contains a number of com­pounds that produce hallucinations, including muscimol and ibotenic acid. These compounds can cause a marked intoxication in which speech is slurred, coordination is impaired, and users experience nausea and often vomit. After this phase, a dreamy/sleepy state ensues followed by an intense hallucinogenic experience. However, this mushroom also con­tains muscarine, which stimulates acetylcholine receptors in the body. This compound mimics stimulation of the parasympathetic nervous sys­tem, causing intense salivation, nausea, vomiting, spasm of the bronchi­oles (breathing tubes), slowed heart rate, and extremely low blood pressure. These last two effects can theoretically lead to shock and death, although muscarinic effects are usually mild. Recreational use of amanita is rare, because the experience is often unpleasant and the mushrooms are not widely available.

Scientists are currently exploring both the basis of the hallucinogenic properties of psilocybin and its therapeutic potential. Studies in Switzer­land by Franz Vollenweider have provided a quantifiable rating scale for its behavioral effects, confirmed the role of 5-HT2 receptors in its actions (see the following), and produced brain scans conducted in people who were experiencing drug effects. Studies by Roland Griffiths in the United States have investigated its effects in certain clinical situations like end­of-life care and in the treatment of migraines, and laboratory studies are underway. These studies have established dosage ranges that cause signif­icant effects (twenty to thirty milligrams), and participants report perse­vering insight as a result of the experience. These studies, among the first in the United States in decades, used careful experimental controls, recruited both hallucinogen users and nonusers, and were reported in the peer-reviewed scientific literature.