FLASHBACKS

FLASHBACKS

The issue of flashbacks, or posthallucinogen perception disorder (PITPD), is clearer. Flashbacks are the reemergence of some aspect of the hallucino­genic experience in the absence of the drug. They are most commonly reported in frequent I.SD users, although isolated case reports exist about flashbacks in individuals after use of other serotonin-like hallucinogens. The most common form includes altered visual images, wavering, altered borders to visual images, or trails of light. While flashbacks can occur after a single use of the drug, they may become increasingly common as the number of hallucinogenic experiences increases. Use of other drugs, like marijuana and alcohol, and even extreme fatigue, can trigger this phenomenon. The overall incidence is hard to judge because use of other drugs or psychiatric conditions must be ruled out. By our best guess, inci­dence for the common user is low.

People's reactions to flashbacks vary widely. Some users experience anxiety and depression while others view flashbacks as an acceptable side effect of an otherwise positive experience. In many cases, flashbacks diminish with abstinence, although symptoms that persist for years have been reported.

Persistent symptoms might actually reflect long-term changes in how the brain processes sensory images. Studies of vision of habitual LSD users (when they are not under the influence of the drug) show that their brains may continue to respond to visual stimuli after the stimuli are removed. This response suggests that repeated LSD usage may cause some neuroplastic changes that persist. In the "Brain Basics" chapter, we dis­cuss the brain's capacity to remember all sorts of experiences, including repeated drug applications.

PHYSICAL AND PSYCHOLOGICAL PROBLEMS

PHYSICAL AND PSYCHOLOGICAL PROBLEMS

LSD, psilocybin, and mescaline do not generally cause dangerous phys­ical reactions; and blood pressure, body temperature, and other vital signs remain reasonably stable unless there are acute anxiety reactions. A user is in little danger of seizures or coma. Furthermore, there is lit­tle evidence that these drugs activate the pleasure centers, and addic­tion and physical dependence do not occur. In this sense, they are remarkably safe. However, the psychological consequences for some users can be extreme. The bad trip, in which the drug user feels acute anxiety and perhaps fears that he will not be able to return, is the most common. Fortunately, this reaction ends as the drug is eliminated from the body. Acute anxiety can usually be treated with a dose of a benzodiazepine (a Valium-like drug—see the "Sedatives" chapter). "Talking down" can be helpful, but it is not always practical. While antipsychotic medications like Thorazine (chlorpromazine) were once popular, they are not always effective on bad trips and, in fact, can make things worse. Now that we understand that many hallucinogens act on serotonin-2 receptors, it's possible that an antagonist (blocking) treatment will become available that would terminate the trip immedi­ately. Research studies show that a 5-HT2 antagonist called ketanserin effectively blocks most psychoactive effects of psilocybin. Such drugs exist but have not yet been investigated or approved for this purpose in the United States. Similarly, the narcotic antagonist naloxone should stop a Salvia trip, but this hasn't been tested yet.

What about the myth that taking LSD will make you crazy? Hallucino­gens can worsen the symptoms of people who are already psychotic, but we don't know if they can cause psychosis. They certainly don't very often. However, a number of studies have shown that hallucinogen users are dis­proportionately represented among psychiatric inpatients, and that one to five people out of one thousand who take hallucinogens experience an acute psychotic reaction.

There is a "chicken and egg" problem in understanding this statistic. Most people who are hospitalized for a psychotic reaction to hallucino­gens have never before been seen by a psychiatrist. So, it is impossible to know whether they were completely healthy before the drug experience We do know that a small number of people have very serious reactions to LSD and similar drugs, including prolonged psychotic states. Also, people with a family history of, or other predisposition toward, mental illness should be particularly careful. Sometimes a hallucinogenic experience can bring out symptoms in such individuals

DANGERS AND MYTHS

DANGERS AND MYTHS

RESEARCH ON HALLUCINOGENS

One myth we want to dispel is that there is no credible scientific research conducted on hallucinogens. Research on hallucinogens (including LSD) can be legally conducted in the United States and Europe. Admittedly, the research history of hallucinogens is colorful and not always credible, ranging from military experiments on unsuspecting subjects to the blithe self-experimentation of Dr. Timothy Leary in the sixties. However, in recent years, research by credible biomedical researchers has expanded, focusing on a variety of topics ranging from what hallucinogen experi­ences can tell us about psychosis to the specific mechanisms by which these drugs act to cause persevering effects on religious insight.

IDENTIFICATION

Users can never really be sure which hallucinogen they are taking. Blotter-paper-like preparations are most likely to be actual LSD because other hallucinogens are not potent enough for an effective dose to be delivered in this way. However, a pill/capsule/powder could be anything, or any combination of things. Laboratory analyses of blood from people admitted to emergency rooms for LSD toxicity indicate that in some urban settings, only about 50 percent of the drug samples that were thought to be LSD by their possessors actually were LSD. Finally, any drug that has been synthesized in an underground laboratory can contain various by-products that arise from poor chemical synthesis.

Hallucinogenic mushrooms represent another identification problem. It takes an educated and practiced eye to identify any mushrooms in the field, and this is always a dangerous proposition. Many mushroom spe­cies, including the aforementioned Amanita muscaria, contain psycho­active compounds that are extremely dangerous or lethal. Other species (Amanita phalloides, for example) contain toxins that produce fatal damage to the liver and kidneys. While simple "home" tests are much touted ("if the stem turns blue, it is psilocybin"), none of these are fool­proof A number of mail-order operations exist that claim to send out psilocybin-containing mushrooms, but the identity of the spores for "grow your own" operations can be very difficult to establish.

ENLIGHTENMENT OR ENTERTAINMENT?

ENLIGHTENMENT OR ENTERTAINMENT?

The use of hallucinogens by many indigenous peoples is tightly controlled by their cultures, which restrict such drugs to ritual use for purposes of healing, enlightenment, or prophecy. In many cases, only particular indi­viduals in a society are permitted to use the drugs at all.

Has the use of hallucinogens evolved from this spiritual purpose to recreational use/abuse in contemporary society? If you talk to college stu­dent users, the reasons they give for using these drugs vary tremendously. Some clearly and simply aim for a novel and exciting experience. How­ever, interviews with regular and heavy users reveal a substantial percent­age who use the drug for the sense of enlightenment they feel they gain by separating from themselves.

The difference between the novelty seekers and those seeking enlight­enment may simply be in how they frame the experience. For example, many users report a sense of "dissolving boundaries" while under the influence: A user might be sitting on the ground and feel that the boundary between the ground and his body no longer exists. This feel­ing could lead to the very exciting (or unsettling) feeling of being sucked into the earth, or it could lead to a calming sense of "oneness" with Mother Earth.

Dr. Timothy Leary (1920-1996) provides an example of varying per­spectives on LSD. He started out as a professor at Harvard, pursuing a traditional academic study of the potential therapeutic utility of halluci­nogens. The stories his subjects told him convinced him that LSD had tre­mendous spiritual value, and he became famous (and lost his job at Harvard) for his advocacy of the free use of LSD. Today he is better known for coining the phrase "turn on, tune in, drop out" during the 1960s than he is for his academic research.

Unfortunately for LSD advocates, their attitudes conflict directly with the illegal status of these drugs. Both sides can argue this issue persua­sively, but the fact is that the majority of Americans prefer that use of such drugs be tightly restricted, as native societies seem to have decided as well. One person's enlightenment can be another person's hell.

BELLADONNA ALKALOIDS

BELLADONNA ALKALOIDS

The belladonna alkaloids work by a completely different mechanism, which explains the different state that they cause. They act by prevent­ing the actions of the neurotransmitter acetylcholine at one of its recep­tors. Acetylcholine is the neurotransmitter that nerves use to stimulate muscle and allow movement, and it is also the neurotransmitter mim­icked by nicotine. It has two types of receptors: one is stimulated by nic­otine, and the other (called the muscarinic receptor, because researchers discovered that it was stimulated by the compound muscarine from the Amanita muscaria mushroom) slows the heart and probably helps to

form memories. We'll describe this in more detail in the chapter on PCP, KETAMINE, AND DEXTROMETHORPHAN

All three drugs block the actions of the neurotransmitter glutamate at one of its receptors, although PCP and ketamine are much better at it than dextromethorphan. This blockade can, on its own, produce most of the effects of these drugs, including feeling disconnected from your body or environment after either recreational use or medical use in anesthesia. This feeling has made it impossible to use these drugs to treat stroke, a medical use for which there was great hope when the ability of these drugs to limit stroke-induced brain damage was discovered. However, in clinical trials of these drugs, patients hallucinated. As you can imagine, it was terrifying for patients to wake up in the hospital, seriously ill, afraid that the stroke rather than the treatment was causing hallucinations.

PCP and to a lesser extent ketamine act like amphetamine to release the neurotransmitter dopamine. This accounts for the locomotor activation that PCP-intoxicated people can experience. Scientists once thought that these drugs directly affected dopamine neurons, but now they think PCP effects are the result of glutamate receptor blockade. In any case, this causes sonic good feelings and is why both drugs are somewhat addicting.

These drugs also decrease sensations of pain to a varying extent. NMDA receptor blockade likely plays a major role in the effect, but it also may reflect some activity on a group of receptors called "sigma" receptors that when activated cause a spectrum of effects including hallucinations and a loss of pain sensations. These receptors were once classified as opi­ate receptors, but they are not anymore. We do not know what they do in regulating normal brain function. Interest in this system has risen in recent years because researchers found that drugs that specifically stimu­lated this receptor system produced hallucinations without affecting the other opiate systems. Dextromethorphan is also a very weak stimulant of this receptor, which might contribute to its effects.

The most useful drugs are those that are most selective. PCP, ketamine, and dextromethorphan suffer from being the opposite—they block the action of the major neurotransmitter in the brain that excites other neu­rons, and so they affect many important brain functions.

HOW HALLUCINOGENS WORK

HOW HALLUCINOGENS WORK

Neuroscientists know less about stimulants than most other psychoac­tive medications. To some degree, this is on account of mental trips can be contemplated most accu­rately in people. Nobody would volunteer for the watchful mind injury contemplates that can figure out where basic medication impacts live, however imaging examinations in living people have demonstrated helpful. Also, we do have a considerable measure of data about the neurotransmitter frameworks required from examines in creatures. Since there are such a variety of stimulating medications, it will not shock anyone that there are a few diverse neurochemical courses to hal­lucinatory states and that each medication creates a to some degree particular state caused by an unmistakable component of activity. 

LSD, PSILOCIN, MESCALINE, AND DMT 

The doubt that medications like LSD have something to do with the neu­rotransmitter serotonin (5-HT) has been common since researchers initially depicted the similitude of the synthetic structures of LSD and psilocin to serotonin in the 1940s. It has been a long and convoluted street from this ini­tial doubt to an atomic comprehension of what these medications do. Sero­ton in is an essential neurotransmitter that manages rest, tweak eating conduct, keep up a typical body temperature and hormonal state, and maybe restrain powerlessness to seizures. Medications that improve the greater part of the activities of serotonin are valuable for treating sadness and sup­pressing gorging. How, at that point, can drugs that influence serotonin deliver such odd consequences for observation without disturbing a number of these different activities of serotonin? 

Some portion of the trouble in understanding drugs originated from utilizing LSD as a test psychedelic drug. The greater part of the early test frameworks included organs other than the cerebrum. For instance, serotonin can make the core of a mollusk beat quicker, so these hearts were an early most loved test framework. Researchers would hang the shellfish heart from a wire joined to a pen that would move if the heart muscle contracted. At the point when serotonin was trickled on the heart, it contracted. LSD kept the impacts of serotonin on shellfish hearts and other test frameworks, and for a considerable length of time it was felt that drugs acted by keeping the activities of serotonin. At the point when more advanced trial of serotonin activity in the cerebrum ended up plainly accessible, they appeared to help this thought. Researchers measuring the rate at which serotonin neurons were terminating demonstrated that LSD restrained their terminating. Notwithstanding, this didn't bode well, since closing down the serotonin neurons so significantly ought to have influenced the greater part of alternate procedures that depend on serotonin, however I,SD did not deliver such impacts. Besides, mescaline did not have an indistinguishable impact from LSD in these sorts of investigations, but since the structure of mescaline, not at all like alternate medications, did not look like sero­tonin, researchers were ready to expect that mescaline was working in some extraordinary way. The response to the subject of what psychedelic drugs need to do with sero­tonin needed to sit tight for researchers to find that the neurotransmitter sero­tonin follows up on various distinctive receptors. No less than thirteen sorts of serotonin receptors are currently perceived, and we realize that some appear to have particular impacts on conduct. Just a single of these (as we officially depicted) can trigger mind flights. The thirteen receptors can be gathered into huge classes (1-7), which themselves are subdivided. For all intents and purposes all serotonin-like drugs are agonists (they empower) at two sub­types of the 5-HT2 receptors (5-1-IT2a and 5-HT2c). Analysts feel that the psychedelic action comes about because of the incitement of 5-HT2a. Up until this point, each trial medicate tried that empowers the serotonin-2a receptors causes mental trips. We don't know how this happens, yet we are almost certain that animating these receptors can do it. The greater part of these receptors are in the cerebral cortex, where we think drugs have 

their real activity. 

One puzzle that remaining parts about serotonin drugs is the reason the antidepres­sant drugs that expansion the measure of serotonin in the neural connection (see the "Cerebrum Basics" section) don't for the most part cause mental trips. These medications increment serotonin wherever in the mind, including destinations that have 5-HT2a receptors, yet in spite of the fact that an uncommon patient taking one of these medications encounters mental trips, when the 5-HT2a receptors are animated in adjust with the greater part of the other serotonin frameworks, there are for the most part no 

stimulating impacts.