Intoxicants Outline • • • • • Psychoactive and recreational drugs Tobacco opium Cocaine Marijuana • Chapter 20 Psychoactive Drugs • Psychoactive drugs alter brain function , which results in changes in mood, behavior, perception, etc. • In addition to recreational use, psychoactive drugs are consumed for religions purposes in some cultures, and for medical and therapeutic reasons. • Virtually all human cultures have used psychoactive drugs, and archeological evidence shows that drug use existed in prehistoric times. – Sumerian clay tablets from 4000 BC refer to opium as the “joy plant”. They discuss how to collect and process the poppy juice. • Basic categories: – Stimulants enhance nervous system activity, increase alertness, reduce fatigue and hunger. Examples: amphetamines, cocaine, nicotine – Depressants dull awareness, reduce physical performance, and induce a dream-like state. Examples: alcohol, barbiturates, morphine – Hallucinogens alter how reality is perceived. Examples: LSD, mescaline Nerves • The nervous system works by having individual nerve cells (neurons) transmit messages to each other. • Signals in the nervous system travel as electrical waves down the bodies (the axons) of nerve cells. • The signals from different cells are combined with each other at synapses. – A synapse is the connecting point between an input cell (or more than one input cell) and an output cell. – When the input cells stimulate the output cell sufficiently, it fires, sending an electrical wave on to the next synapse. Synapses • Each nerve cell releases a specific neurotransmitter chemical, which crosses a small gap (the synapse) and binds to a receptor molecule on the surface of the receiving cell (the “post-synaptic neuron”). – After transmitting the signal , the neurotransmitter chemicals are taken back into the transmitting cell, for re-use. • • Most psychoactive drugs work by affecting the transmission process of a specific neurotransmitter: mimicking its action, or blocking its action, or preventing re-uptake by the transmitting cell. Different types of neurotransmitter have different functions in the body and the brain. Transmission of a Nerve Impulse Across a Synapse The Reward Circuit • A common feature: recreational drugs affect the reward circuit (mesolimbic system) in specific areas of the brain by increasing or prolonging the release of the neurotransmitter dopamine. You feel good when the nerve cells release a lot of dopamine. This can be caused by drugs, or by other pleasurable or positive experiences. – This is the cause of euphoria, common to all addictive drugs. – It causes you to want to repeat the actions that stimulated the euphoria. – Why an increase in dopamine in certain nerve cells of your brain causes “me” to “feel good” seems to reach the interface between biology and philosophy. – Medical psychoactive drugs, as opposed to recreational psychoactive drugs, avoid stimulating the mesolimbic system. • • • Morphine and endorphin work by disabling neurons that inhibit the release of dopamine in the reward system. Stimulants like cocaine and amphetamine stimulate the release of dopamine or prolong its action by preventing its removal (re-uptake) from the synapse. Other drugs use other mechanisms. Tolerance • Addiction is a complicated phenomenon. One important feature for most addictive drugs is that tolerance for the drugs develops. It takes a higher dose of the drug to achieve the same effect, and the effects aren’t as rewarding as they initially were. – Also, previously pleasurable activities aren’t as rewarding as they used to be. • Tolerance is the brain trying to stay in balance. The brain cells respond to the flood of dopamine by “down-regulating”: decreasing the number of dopamine receptors in the receiving cell. This makes the nerve cells harder to stimulate. • Most psychoactive drugs also affect other brain systems in addition to the reward circuit, which gives them their specific effects, including the negative effects. Substance Dependence and Drug Abuse • • • • • This area is filled with a mixture of physical effects, psychological effects, and moral judgments that are just about impossible to separate. Definitions change frequently. Substance dependence , or drug addiction: when an individual persists in using alcohol or other drugs despite problems caused by that use. The craving to obtain and use the drugs can overcome all other needs. Substance abuse involves physical dependence and psychological dependence. Physical dependence on a drug means that persistent use produces tolerance and withdrawal symptoms. – Tolerance: it takes an increasing dose to achieve the same effect – Withdrawal: abrupt discontinuation of the drug leads to unpleasant physical symptoms. Psychological dependence: goes with the concept of selfmedication. Mental states like depression, stress, social anxiety can all be relieved by different drugs. People take specific drugs when they find that the drugs relieve their symptoms. The bad side effects and consequences seem less important. Drug Risks • • All cultures regulate drug use: which drugs are allowed and forbidden, who can take them, and under what conditions. Why? Partly cultural tradition and history. – Some drugs are reserved for religious leaders. – Conversely, some drugs are seen as immoral: unearned pleasure. – In the US, specific drugs have been banned because they are perceived to cause harm to individuals and society. Current political categories aside, we are a generally conservative society: laws tend to stay on the books even if their original rationale is gone. • Two main problems: – Many banned drugs have a high potential for addiction. – Many banned drugs have a high risk of causing harm to the user. • An important aspect of high risk: the ratio between effective dose and lethal dose. – The dose of opiates (such as heroin) needed to get high is s only a few times greater than the lethal dose for respiratory failure. This makes overdosing very easy. – The effective dose for marijuana is so much less than the lethal dose that it is almost impossible to overdose on marijuana. Drugs Classified by Addictive Potential and Effective Dose/Lethal Dose Ratio Tobacco • • • • • Tobacco is a New World crop, first cultivated around 5000 BC. The native Americans apparently didn’t use it recreationally, but rather ceremonially, to seal bargains, or to mark major life events. – Also, in high doses, tobacco induces hallucinations, so it was used by spiritual leaders. “entheogenic”: psychoactive substances used in a religious or spiritual context. – Also used in medicine, to cure pain, fatigue, and a lot of other problems. Consumed in many ways: smoking and chewing, but also drinking tobacco juice, licking tobacco paste, tobacco enemas, and even direct application to the eyes. Both pipes and cigars (tobacco rolled up in leaves) were used. Although the habit started in South America, it was widespread in North America as well. Aztec feast: guests presented with pipes filled with tobacco European Discovery of Tobacco • • • • Columbus first saw tobacco at his very first encounter with native Americans on October 12, 1492: they offered him some dried leaves, but Columbus had no idea what they were used for. The Spanish first saw it being smoked on the island of Cuba a few weeks later. The natives rolled the dried leaves in palm or maize leaves “in the manner of a musket formed of paper”. They lit one end and “drank” the smoke from the other end. Rodrigo de Jerez, one of Columbus’s crewmen on the Santa Maria was apparently the first European smoker. When he got back to Spain, the Inquisition imprisoned him for he sinful and infernal habit. He was release 7 years later, after the habit had caught on. It caught on throughout the Old World very quickly: used in Turkey, China, and Japan by 1600. Sir Walter Raleigh • • • • • • Walter Raleigh learned to smoke from Sir Francis Drake. Raleigh then taught Queen Elizabeth I how to smoke, and introduced the smoking pipe to England. Raleigh was an adventurer who became close to Queen Elizabeth (who was known as “the Virgin Queen: Virginia was named after her). Elizabeth liked having Raleigh at court. However, he secretly married one of her attendants, which annoyed Elizabeth, and she imprisoned him. After they reconciled, Elizabeth funded Raleigh’s colony (Roanoke) in America, which was the first English settlement in the New World. The colony failed and all inhabitants vanished. The big problem: no resupply from England due to a war with Spain (Spanish Armada). After Elizabeth died in 1601, James I took the throne. James didn’t like Raleigh, and imprisoned him for 13 years, then executed him for treason. Early Attempts to Ban Tobacco • James I of England published “A Counterblaste to Tobacco” in 1604: – "Smoking is a custom loathsome to the eye, hateful to the nose, harmful to the brain, dangerous to the lungs, and in the black, stinking fume thereof nearest resembling the horrible Stygian smoke of the pit that is bottomless.“ – He then imposed a 4000% tax on tobacco. • Murad IV, Sultan of the Ottoman Empire (Turkey) banned it in the 1620’s, imposing the death penalty. A popular Turkish cigarette is named after him. • Chongzhen, Chinese emperor, banned it in 1642. • The Patriarch of Moscow sentenced smokers to having their nostrils slit and the skin whipped off their backs in 1634. • Pope Urban VIII condemned it in 1642. • None of these attempts was successful: tobacco is very addictive. Tobacco in the American Colonies • • • The first successful English colony in what is now the US was at Jamestown, Virginia, stared in 1607. The Jamestown colony had many problems: bad water supply, disease, no knowledge of how to grow crops under existing conditions, and especially, very bad relations with the natives, who resented having their land taken away from them. Also, it wasn't profitable: the backers in England wanted them to find gold or something else valuable, the way the Spanish had done further south. John Rolfe started growing tobacco at Jamestown in 1612 It became the cash crop that made up for the lack of gold, and by 1640 Virginia was economically successful. – John Rolfe also married Pocahantas. • • African slaves first came to Jamestown in 1619, to work in the tobacco fields. Between 1617 and 1793, tobacco was the most valuable export from the American colonies. Nicotine • Nicotine is the active ingredient in tobacco. It is an alkaloid: bitter, nitrogencontaining compounds that are “secondary metabolites”. – Secondary metabolites are not part of the common macromolecules: proteins, carbohydrates, lipids, and nucleic acids that are found in all cells. – Secondary metabolites vary greatly between species, and are thought to mostly protect the plants from predators. • • Nicotine can be sprayed on plants as a natural insecticide. Nicotine is quite poisonous: the LD50 (dose needed to kill 50% of humans) is 4060 milligrams. Smoking a typical cigarette delivers about 1 mg. – however, a cigarette contains about 9 mg of nicotine: most of it is destroyed by burning the tobacco. • • • It is absorbed easily through the lungs and skin, but not by eating it: it is mostly destroyed by stomach acids. Most cases of nicotine poisoning come from nicotine insecticides. It is metabolized quickly, with a half-life of about 2 hours. This contributes to the need to keep smoking. Nicotine addiction is considered one of the hardest to break, comparable to opium. More Nervous System • Nicotine binds to receptors for one of the main neurotransmitters, acetylcholine: it mimics the action of acetylcholine itself. • Nerve cells that use these receptors are found in the brain and in the peripheral nervous system. • It is thought that stimulating the brain receptors increases the level of dopamine in the brain’s pleasure center, leading to feelings of euphoria and relaxation. – The primary focus of most psychoactive drugs is the brain’s pleasure center. (also called reward system), The drugs stimulate dopamine release, or inhibit its uptake. • Nicotine also stimulates brain cells involved in learning and memory. • In the peripheral nervous system, stimulation of the acetylcholine receptors leads to a release of epinephrine (adrenaline). – This increases heart rate, blood pressure, and blood glucose, and increases alertness and decreases reaction time. The “fight-or-flight” response. – Epinephrine also decreases appetite: a well-known effect of smoking. – Also, it decreases pain and anxiety. The Tobacco Plant • Nicotiana tabacum is the cultivated tobacco plant: all commercial tobacco products use this species. – Other members of the genus Nicotiana also produce nicotine and are smoked in various parts of the world. – A species native to Australia, N. suaveolens was independently domesticated. They chewed it, mixed with wood ash to release the alkaloid flavor. It • Nicotiana is a member of the Solanaceae (nightshade) family, which also contains potato, tomato, chili peppers, petunia, and belladonna. – Many of the Solanaceae produce useful and/or poisonous alkaloids. • Nicotine is formed in the roots, then transported to the leaves and other parts of the plant through the phloem. • The flowers have long tubes, making them best suited for hummingbirds as pollinators. Growing Tobacco • Tobacco likes a warm moist environment. It is an annual, so it can be grown in temperate regions, even in Alaska and Canada. • Tobacco is grown from seed. It is self-fertilizing and highly inbred, so good varieties breed true. • The seeds are very tiny. They are sown directly on the soil of greenhouse seedbeds, because germination is activated by light. After the plants have reached a certain height, they are transplanted into the fields. – They are often fertilized with the mineral apatite, which partly starves them for nitrogen and improves the taste. • The plants need a lot of nutrients: this used to deplete soil very quickly, but modern fertilizer works very well. • The top buds and side branches are removed, so the upper leaves get larger. Harvesting and Curing • Most tobacco is harvested by cutting the plant stalk near the base. – It is also possible to harvest a few leaves at a time, as they begin to turn yellow. – Leaves from different levels of the plant have different strengths and flavors. • Then, it is "color-cured" by hanging the plants upside down until all the green color is gone. After this, the leaves are completely dried. • Curing is necessary to develop a smooth flavor. This is an oxidation or fermenting process that involves storing it at elevated temperatures while keeping the leaves at about 20% moisture content for up to a year while enzymes in the dried leaves degrade the compounds that cause harsh flavor and cause good flavors to emerge. Processing • Processing is mostly a matter of cutting it up: fine shreds for cigarettes, larger shreds for cigars, very fine for snuff and dip. – It can also be mixed with flavors like menthol or honey. • It then needs packaging: hand-rolling of cigars is common, but cigarettes are rolled with a machine. • Methods of consumption: – Smoking cigars, cigarettes, pipes. – Chewing: keeping tobacco in your mouth stimulates the salivary glands. This led to the need for spittoons, which was disgusting enough to fall out of fashion in most places. – Snuff: very fine tobacco that was snorted up the nose, and then sneezed out. Very popular in the 1700's. Fred Ott taking a snuff and then sneezing, taken by Thomas Edison's laboratory, 1894 Opium • Opium is the product of the opium poppy, Papaver somniferum. • Opium is the dried latex produced by cutting immature fruits (seed pods). • The main active ingredient in opium is morphine; codeine is a related compound also found in opium. These compounds relieve pain and induce sleep. • Opium is an Old World crop, and it has been used medically and recreationally since ancient times in Middle East, Egypt, and around the Mediterranean Sea. • Two methods of ingesting opium : – smoking it, which vaporizes the active ingredients – Dissolving it in alcohol, as opium-laden wine. As a medical compound this was called laudanum, and it was very popular as medicine and for recreational use in the 1800’s. Morphine and Heroin • Morphine was first isolated from opium in 1806. It was the first active principle isolated from a plant, leading to the idea that plant-based medicines could be simplified to single chemical compounds, with the rest of the plant being irrelevant. – The big advantage of this is that dosage could be precisely controlled. The plant product varies in strength depending on how much morphine is present in it. – Invention of the hypodermic needle allowed direct intravenous injection, bypassing the digestive system • Opium and morphine have long been know to be addictive. – Heroin was originally marketed as a non-addictive morphine substitute. – More recently, oxycodone, a deriviative of codeine was thought to be less addictive than morphine. – After World War 2, methadone became available to treat heroin addiction and withdrawal symptoms. Methadone gives less of a high, and it blocks the action of morphine and heroin. It is also fairly long acting, so it can be administered only once a day. – Many other morphine derivatives have been created, but morphine remains the best at killing pain. – All known opioid compounds are addictive. Endorphin and Pain • Morphine binds to specific receptor molecules in the nervous system: the opioid receptors. – This fact was discovered by Candace Pert and Solomon Snyder in 1973: they found that radioactive morphine bound to a specific protein in extracts of brain cell membranes. Nobel Prize. – Since then, receptors for most other psychoactive drugs have been isolated. • As a consequence of this, it was discovered that the nervous system contains a group of proteins called endorphins, which bind to the opioid receptors and relieve pain. – Endorphins (“endogenous morphine”) are your body’s natural analgesic system. Pain control through methods like hypnosis probably work by stimulating endorphin production. – Endorphin is released into the blood and brain from the pituitary gland. Like morphine, it produces analgesia (pain relief) and a feeling of well-being. Endorphins, Substance P, and Pain • When bound to the opioid receptors, both morphine and endorphin block the release of substance P, the neurotransmitter chemical that signals pain in the body. – When you injure yourself or burn yourself, specific pain nerves signal this fact to your spinal chord, and then other nerves carry it to your brain by releasing substance P. – Substance P is also released into the blood to stimulate wound healing and infection fighting. • Opioid receptors are found in many places not directly involved with pain: control of the respiratory system and gut movements, for example. – Thus, morphine use can kill by suppressing breathing, and it also works to stop coughing. – It can also be used to stop diarrhea, and it induces constipation. Other Uses of Opium Poppies • The opium poppy produces a very nice ornamental flower. It is illegal in the US (a Schedule II narcotic), but this law is apparently not enforced for ornamental plants. It can be found in flower and garden shops, and it used to be available from seed catalogs. – Most perennial ornamental poppies in American gardens are Papaver orientale, a different species. However, morphine is also found in this species. • Poppy seeds also come from the opium poppy. It can be used as a garnish or in large amounts as a pastry filling. • Poppy seeds contain only small amounts of morphine. It is possible to have a positive drug test for 24 hours after eating poppy seed baked goods. – In Poland there was an industry devoted to extracting morphine from poppy seeds. Cocaine • The coca plant (Erythroxylum coca) is native to the lower slopes of the Andes Mountains in Peru, Bolivia, and surrounding countries. • The dried leaves of the coca plant are traditionally chewed with lime, to release the cocaine alkaloid. • Coca use is quite old: traces have been found in 3000 year old mummies. • It was an important trade item. • It was viewed as essential for the ability to live and work at high altitude. It relieves altitude sickness and overcomes fatigue, hunger, and thirst. • At times, usage was restricted to the upper classes. • After the Conquest, the Spanish initially banned its use. Later, they encouraged its use among the natives to increase labor output in the gold and silver mines. Cocaine History • Coca became popular in Europe around 1850. This led to the appearance of coca wine (e.g. Vin Mariani) and the original version of Coca-cola. Also, pure cocaine was extracted in 1859. – Coca Colla (sic) is an energy drink made in Bolivia, made from coca leaves. – Red Bull uses de-cocainized coca leaves as a flavoring. • In the early 1900’s, the addictive nature of cocaine was recognized, and it became illegal in most countries. • Still legal in South America, where it is used in tea (mate de coca), cookies, candy, and toothpaste. • Cocaine is a topical anaesthetic, used today for eye and nasal surgery. It both numbs the tissue and constricts blood vessels, reducing bleeding. More Cocaine History • • • • • Sigmund Freud, Thomas Edison, Jules Verne, and John Philip Sousa used it. So did the fictional character Sherlock Holmes, in Arthur Conan Doyle’s novels. Some 1885 advertising: cocaine products “supply the place of food, make the coward brave, the silent eloquent and ... render the sufferer insensitive to pain.” Outlawed in 1914 in the US, at the same time as opium derivatives. Cocaine became popular again in the 1970’s, among well-off younger people in high pressure jobs. Eventually the bad side effects caused it to lose popularity. Crack cocaine is a form that can be smoked: it vaporizes easily. Invented around 1980. Cocaine powder is usually snorted up the nostrils or injected. Regular cocaine is a salt: cocaine chloride. Crack is the free base form, made by heating cocaine with baking soda. Crack is not soluble in water. – An earlier craze fro pure freebase cocaine involved the use of ether as a solvent, which had a tendency to catch fire. Crack manufacture eliminates the use of ether. – Crack is thought to produce a faster and more intense high than cocaine. Cocaine and the Nervous System • Cocaine inhibits the re-uptake of dopamine in the synapses of the brain's reward circuit, which means that the dopamine stimulates the receiving nerve cell much longer than is normal. – Gives feelings of euphoria and supreme confidence, plus loss of appetite, increased energy and alertness. • • • • As it wears off, dopamine levels in the brain drop, leading to depression and paranoia, and the desire for more cocaine. Tolerance develops quickly: it takes more to achieve the original high. Cocaine is a stimulant: it constricts blood vessels and increases heart rate and blood pressure. This sometimes leads to cardiac arrest, occasionally even on the first use. Cocaine passes through the placenta from a pregnant woman into her fetus. Babies can be born addicted. However, most seem to suffer little long term effects. Marijuana • Cannabis sativa, in the same family as hops and figs. It’s an Old World crop, native to China. – Emperor Shen Numg used it as part of traditional medicine. • The same plant produces both the psychoactive resin and a useful fiber. However, different strains are bred for different purposes. – Locally, wild marijuana plants (“ditch weed”) are escapes from the hemp industry that used to be here. It was virtually no psychoactive properties. – Hemp fibers are processed much like linen: retting, then beating the dead plant cells away from the fibers. • The plants have imperfect flowers, with male and female flowers on separate plants. Most of the resin is produced by the female flowers before they are fertilized. History • The Scythians were a nomadic group on the steppes of western Asia who eventually settled down to become the Slavs. They piled marijuana plants onto small fires in enclosed tents and breathed the fumes. – Smoking pipes or cigarettes was a New World invention, and it came to Europe with Columbus. • Marijuana use became popular throughout India, Asia, and Africa by 500 BC. • According to Marco Polo, who wrote the story in 1297, the Persian leader Al-Hasan ibn-al-Sabbah, called The Old Man of the Mountain, led a fanatical sect, whose followers would kill their enemies after working themselves into a frenzy with marijuana. The sect’s name, hashishin, got transmuted to “hashish” and “assassin”. – Note that it used to be a drug that incited violence, but now it is drug that induces lethargy. Probably something cultural here. Recent History • It got popularized in Europe following Napoleon’s expedition to Egypt in the early 1800’s, and hashish clubs existed in Paris by the 1850’s. • Came to the US from Mexico or the Caribbean early in the 20th century, but it was primarily used by the lower classes, including musicians who felt it enhanced their creativity. Especially popular with jazz musicians. Some songs: Benny Goodman’s “Texas Tea Party”, Cab Calloway’s “That Funny Reefer Man”, Ella Fitzgerald’s “When I Get Low, I Get High”. • Banned in the US in the 1930’s • Usage revived during the 1960’s youth culture. Current Status • • It remains illegal, but widely used: latest survey suggests 16.7 million Americans have used it within the past month. It is certainly the most widely used illegal drug in the US, Medical uses. Marijuana has long been used for various conditions. Although the federal government bans it, many states have passed laws allowing usage as an aid to chemotherapy: it relieves nausea, a serious side effect of chemotherapy since the patient often doesn’t get enough nutrition. and to reduce pressure in the eyeball in glaucoma, plus pain relief and a variety of other conditions. Many multiple sclerosis patients take it to alleviate muscle pain and tremors. – It is still classified as a Schedule I drug, with no medical value. Many doctors disagree with this, and would like to see it classified as Schedule 2, which allows prescriptions to be written. – Almost all states distinguish between marijuana and other Schedule 1 drugs. Growing Marijuana • It's illegal. It's even illegal to have wild plants with no psychoactive effects on your property. • Most American marijuana used to come from Mexico. The War on Drugs led to a crackdown on smuggling, which stimulated the domestic industry. Plant breeding techniques have led to much stronger strains. Also, the use of sensimilla, unfertilized female flowers, became widespread. As part of this, much marijuana is grown from cloned plants, not seeds. This ensures the plants will be female as well as allowing good hybrids to be propagated. The primary growing are is northern California, but it grows just about anywhere. • Also, much indoor cultivation, with specific rapid flowering dwarf varieties available. • It may be the number one cash crop in the US. Cannabinoid Receptors • Marijuana receptors in the nervous system. • Based on the morphine model, receptors for THC were found, and shortly thereafter, the natural endocannabinoid anandamide, found in the nervous systems of all vertebrate animals. – The cannabinoid receptor may be the most widely distributed receptor in the brain. – Involved in a mechanism that transmits information backwards across the synapses. Pain suppression, for example, seems to work by suppressing the ability of pain nerves to release their neurotransmitters. • Receptors found in areas affecting movement and coordination, short term memory, hunger – Maybe less short term memory is good for getting over the many daily insults and injuries we all suffer. • Notably, no receptors in areas affecting respiration and cardiovascular function: perhaps why there are no known cases of death from overdose. – It is possible to kill rats and other experimental organisms with THC, but it takes about 1000 times as much THC to kill as is normally administered. For alcohol, cocaine, or heroin, the lethal dose is about 10 times the effective dose. Peyote • Peyote is a cactus, Lophophora williamsii, that grows in the Chihuahuan desert of west Texas and northern Mexico. It produces the hallucinogenic compound mescaline. – It is a slow growing perennial, taking 3 years or more to mature. – Very little is cultured or grown commercially • It has been used since pre-Columbian times in religious ceremonies to induce spiritual revelations. • Its use was banned in the US for many years, but as of 1996 it was legal to use as part of a “bonafide religious ceremony”, at least if you have some native American ancestry and/or are part of the Native American Church. Psychedelic Drugs • “psychedelic” means “mind-expanding”, and allegedly open the mind to previously unknown perceptions. – Also called “hallucinogens”: generate visions of things that aren’t really there. Or “entheogenic”: revealing the god within us. Or “psychotomimetic”: mimicking serious mental illness. – It’s a matter of point of view. • Bright colors, euphoria, sensory alterations including synesthesia: stimulation of one sense is experienced as another sense, for example seeing musical notes. Also, profound thoughts and a sense of oneness with the world. • Several drugs from a variety of origins produce psychedelic states: mescaline (peyote cactus), ergine (morning glory seeds), psilocybin (certain mushrooms), LSD (synthetic derivative of ergot fungus), bufotenin (secreted by some toads), plus many others. • Psychedelic states can also be induced by meditation, fasting, physical pain, and several other non-drug related activities. Neurological Effects • Psychedelic drugs stimulate the serotonin receptors • Serotonin is found in all but the simplest animals. – In nematodes (round worms), serotonin is released when food is found. – In lobsters it helps gauge social dominance. • Psychedelic drugs also stimulate the reward circuit, leading to euphoria in addition to other effects. • The effective dose of mescaline is about 1000 times higher than LSD: a typical dose of mescaline is about 250 milligrams while a typical dose of LSD is about 250 micrograms. (1 milligram = 1000 micrograms). Kava • Kava (or kava-kava) (Piper methysticum) is a plant in the same genus as black pepper. It is native to the Pacific Islands. Ground up roots are widely consumed there, producing mile euphoria and relaxation. It relaxes you without harming your mental clarity. It is used in social situations as part of conversation, similar to beer and wine. • Traditional preparation involves having unmarried women chew the roots until the fiber is disrupted, then spit it into a bowl, where it is mixed with water. The pulp is then strained out. – These days it is grated or processed with a blender. • Kava has been alleged to cause liver damage, at least if used as a dietary supplement. However, more recent studies haven’t shown any effect on the liver. The effect may be due to manufacturers using leaves and stems instead of roots. It remains legal in the US. Khat • Also “qat”. Catha edulis is a shrub native to East Africa, and widely used there and in Arabia. It contains a stimulant that produces excitement, euphoria, and loss of appetite. • The leaves are chewed. It must be used fresh: its active ingredient breaks down within 48 hours. It is rather rare in the US and Europe because of this. • Khat is used in a similar social context as coffee. • Production in Yemen uses 40% of the available agricultural water. • It is not regulated in many countries, but it is banned in the US. • Its active ingredient, cathinone, is similar in action and structure to amphetamine.