The document provides an overview of the four main classes of hallucinogenic drugs: serotonergic hallucinogens like LSD and psilocybin; methylated amphetamines like MDMA; anticholinergic hallucinogens found in plants; and dissociative anesthetics like PCP. It discusses the history of hallucinogen use from the 1960s counterculture movement to current trends, physiological and psychological effects of different classes of drugs, risks and adverse effects, and mechanisms of action in the brain.

1. HALLUCINOGENS CHAPTER 12

2. Overview Hallucinogens are a group of drugs that have the capacity to alter perceptual, cognitive, and emotional states. They can alter consciousness in profound and bizarre ways They are confusing because so many different drugs act in a variety of ways and thus have been classified in many different ways over the years Hallucinogens are divided into four classes: serotonergic hallucinogens, methylated amphetamines, anticholinergic hallucinogens, and dissociative anesthetics

3. Serotonergic hallucinogens include the synthetic compound LSD and related drugs, such as mescaline (from the peyote cactus) and psilocybin (from certain mushrooms), along with many other less well known compounds. All produce vivid visual hallucinations and a variety of other effects on consciousness. They also have in common the action of influencing serotonin transmission in the brain Methylated amphetamines include MDA and MDMA (ecstacy). They are structurally related to amphetamines and produce alterations in mood and consciousness with little or no sensory change. They act like amphetamine and cocaine on dopamine, norepinephrine, and serotonin synapses

4. Anticholinergic hallucinogens include drugs like atropine and scopolamine found in plants such as mandrake, henbane, belladonna, and jimson weed. These drugs produce a dreamlike trance where the user awakens with little or no memory of the experience The fourth class of hallucinogens, referred to as the dissociative anesthetics, include phencyclidine (PCP or angel dust) and the related compound ketamine. They have the ability to produce surgical anesthesia while the individual remains at least semiconscious

5. History Despite the long history of hallucinogenic drug use, these drugs had virtually no impact on European or American culture until the 1960s when their use exploded The “psychedelic” movement began with the discovery of LSD by the Sandoz chemist Albert Hoffman in 1938 LSD underwent several animal tests and was then shelved until 1943 when Hoffman decided to reexamine its properties. When he accidentally spilled some on his hand, he became the first person to experience the effects of LSD

6. In the 1960s, LSD was made popular by the counterculture figures Timothy Leary and Ken Kesey. Sandoz began to distribute LSD to psychologists and psychiatrists for use as an adjunct to psychotherapy as it was assumed the drug would break down the patient’s ego defenses and thus facilitate the psychotherapy process Psychiatrists were encouraged to try LSD themselves so they would better understand the subjective experience of schizophrenia, as the drug was also thought to mimic psychosis

7. Leary was a Harvard psychologist who advocated the use of LSD and other hallucinogens for spiritual enlightenment and coined the now famous expression “Turn on. Tune in. Drop out”. Kesey, author of “One Flew Over the Cuckoo’s Nest, threw large parties where hundreds of people were “turned on to LSD” in a single night The Grateful Dead, Jefferson Airplane, and Jimi Hendrix advocated use through their music which later became known as “acid rock” By the late 1960s, positive statements about LSD were being counterbalanced with increasing negative publicity and it became the most controversial drug in the world

8. LSD use declined in the 1980s and then use of it and other hallucinogens increased again in the 1990s. LSD use decreased again in recent years, however, other hallucinogens such as MDMA (ecstacy) have emerged as popular drugs Though MDMA remains the prototypical “club drug”, LSD remains popular as well with nearly half (48.6%) of the clients in substance abuse treatment under 18 yrs old reporting use compared to only 32.3% reporting MDMA use. For clients (18-32 yrs old) the pattern was similar with 42.9% reporting use of LSD compared with 37% using MDMA .

9. Mechanisms of Action of LSD-like Drugs LSD and other drugs in this class mimic serotonin. Serotonin is distributed widely in the brain and this may account for the many varied effects of LSD-like hallucinogens. It also plays an important role in mood, which is consistent with the powerful emotional effects of these drugs. Mescaline is similar to LSD in that it produces vivid visual hallucinations, and tolerance to its effects develop rapidly. Its structure is more similar to amphetamines and thus has been classified as having a different mechanism from LSD There is cross-tolerance between LSD, mescaline, and other drugs of this class suggesting a common mechanism of action

10. Pharmacokinetics of LSD-like Drugs LSD is the most potent with doses as small as 25 micrograms producing effects. Street doses range from 75 to 250 micrograms and are distributed as blotter acid, windowpane, or in tablet form Effects are noted within 20-60 minutes and last 8-12 hours The drug cannot be detected in the urine more than 72 hours after use Psilocybin is ingested by eating the mushrooms or drinking a brew containing them Typically 5-10 grams of mushrooms are taken containing 10-20 milligrams of psilocybin. Psilocybin is about 1% as potent as LSD

11. Mescaline is usually taken by consuming 5 to 20 peyote buttons containing 200-800 milligrams of mescaline Mescaline is about 1/3000 as potent as LSD, with 200 milligrams considered an effective dose Duration of action is about 8-12 hours Another serotonergic hallucinogen is DMT from the bark of the Virola. It is taken as snuff or by smoking it Its effects begin within minutes but last only about 30 minutes

12. Effects of Serotonergic Hallucinogens Physiological effects are similar to amphetamine and cocaine in that they include pupil dilation, increased heart rate and blood pressure, increased body temperature, and increased sweating. Psychological effects vary among individuals and may vary from one experience to the next Most common are profound changes in visual perception which include form constants such as spiral explosions and a lattice pattern, flashing lights, increased brightness and intensity of colors, trails or plumes around objects, and the sense of movement in stable objects, e.g., walls breathing

13. Synesthesia is also common Synesthesia – An effect sometimes produced by hallucinogens characterized by the perception of a stimulus in a modality other than the one in which it was presented (for example, a subject may report “seeing” music) Mood is extremely labile and bizarre cognitive experiences may occur. There may be “magical” thinking where the user believes they posses telepathic or clairvoyant abilities

14. Adverse Effects Many adverse effects have been linked to LSD and other drugs in this class It was believed that LSD produced chromosome damage and would thus cause birth defects in offspring. Research does not support this. As with most drugs, however, there is risk of fetal damage if taken by pregnant women Acute panic or paranoid reactions led to walk-in crisis centers in the 1960’s The psychological state of the user and setting are important. A calm and comfortable setting and low doses of LSD will reduce the frequency of bad trips

15. Individuals should be aware and frequently reminded they are under the influence of a drug. One of the few documented LSD suicides took place after a man was administered the drug without his knowledge Another phenomenon associated with LSD is the flashback , or the DSM-IV diagnosis: hallucinogen persisting perception disorder Flashback – A sudden recurrence of an LSD-like experience Flashbacks are brought on by stress, fatigue, entering a dark environment, or marijuana use

16. More than 50% of LSD users report flashbacks Treatment with benzodiazepines or antidepressants may relive symptoms LSD has also been linked to long-term psychiatric disorders (Charles Manson and his family) It is difficult to determine whether LSD caused the psychosis or it made the symptoms of psychotic individuals more flagrant Also, users of LSD who are diagnosed with psychosis often have extensive histories with other drugs as well

17. Methylated Amphetamines MDMA (ecstasy) is one of the most controversial illegal drugs in the world today due to its enormous increase in popularity despite reports of brain damage and death After marijuana, it is the most widely used illegal drug in Europe and more than 8 million people are thought to have used it at least once Its popularity is attributed to publicity about its therapeutic benefits, its nicknames of “ecstasy and the “love drug”, and more recently, its association with the “club” or “rave” subcultures.

18. Both MDMA and MDA produce effects similar to LSD but without the visual hallucinations Produce a mild euphoria with openness and lack of defensiveness which led to some psychotherapists advocating their use as an adjunct to therapy in the past and consideration today for it’s use in the treatment of posttraumatic stress syndrome and anxiety in terminally ill cancer patients In a 2003 study comparing the psychological effects of MDMA with amphetamine, participants reported stronger reinforcing effects for MDMA than amphetamine at all doses tested and they consistently reported they liked the MDMA better .

19. DRUGS AND CULTURE BOX 12.3 “Hallucinogenic Ibogaine: New RX for Addiction” Iboga is a shrub native to West Africa with hallucinogenic properties that has been used for centuries in ceremonies There have been claims since the 1960’s by ex-addicts that it helped with their recovery from dependency on alcohol, cocaine, and heroin Most treatment experts have been skeptical but recent data shows that Ibogaine reduces alcohol consumption in rats and other studies have suggested neurochemical actions are more complex than previously thought

20. History and Epidemiology Methylated amphetamines were developed in the 1900s but attracted little attention until recently MDMA was patented in 1914 but not marketed or much studied until years later DOM was first reported on the street in the late 1960s when its potent hallucinogenic effects and very long duration of action (as long as 24 hours) led to many bad trips MDA, also surfacing in the 60s, was called “mellow drug of America” because it had fewer perceptual effects than LSD

21. Effects of Methylated Amphetamines MDMA, MDA, and MDE are similar in effects Absorbed rapidly with a duration of action 6-8 hours Effects are similar to those of amphetamines and include increased heart rate, blood pressure, pupil dilation with such physical effects as muscle tension, teeth-grinding (bruxism), increased body temperature, appetite suppression and insomnia Psychological effects are euphoria, increased emotional warmth, lowered defensiveness, and increased communicative ability Commonly reported after effects are drowsiness, muscle pain, depression, paranoia, and anxiety

22. Toxicity There have been numerous reports of toxic reactions and deaths Toxic reactions include dehydration, heat stroke and heat exhaustion, muscle breakdown, kidney failure, stroke, seizures, and heart attacks Most occur after high doses or multiple doses (stacking) but some serious reactions and even death have occurred after relatively low doses Often contains other drugs that may be more toxic than MDMA Common adulterants are caffeine, MDA, dextromethorphan, and ephedrine

23. Residual Effects of MDMA Studies have shown that after several administrations of high doses of MDA, rats had a depletion of serotonin due to degeneration of serotonergic neuron terminals Primate studies produced similar results after administration of a single high dose (20mg) or after several low doses (5mg) over consecutive days The effects persist for as long as 7 years in primates As serotonin modulates sleep, mood, and many other functions, depletion could lead to serious problems MDMA and related drugs pose a serious risk of acute toxic effects and possible long-term deficits in psychological functioning

24. Specifically, studies have linked sleep problems, depressed mood, memory and attention deficits, and other cognitive impairments to MDMA use It is difficult to generalize the data on neurotoxicity of MDMA from studies on nonhumans to humans due to the enormous variability in dosages of MDMA tablets taken (average dose of 70-100mg up to 300mg) and variability in amount taken (2-3 tablets up to 15 in a night. Though the jury is still out on the long-term effects of MDMA use, accumulating scientific literature is clearly not reassuring

25. Anticholinergic Hallucinogens Atropine and scopolamine block acetylcholine receptors in the brain In low doses they are used for a variety of medical purposes. atropine, if administered rapidly after exposure, is an antidote for nerve gas Anticholinergic hallucinogens produce such physiological effects as dry mouth, blurred vision, loss of motor control, and increased heart rate and body temperature They can be fatal as they cause respiratory failure at doses only slightly higher than the effective dose

26. Dissociative Anesthetic Hallucinogens A large group of drugs but only two – phencyclidine (PCP, angel dust) and its close analogue ketamine, have been used enough to warrant discussion PCP was synthesized in 1956 and marketed as a veterinary anesthetic and tranquilizer when clinical trials with humans produced hyperexcitability, delirium, and visual disturbances in some patients In the 1960s, PCP was sold as a “rip-off” drug as THC, MDA, or mescaline but in the 70s it emerged as a drug of preference Typically used in powder form sprinkled on a cigarette or joint

27. PCP is no longer widely used in veterinary medicine, but ketamine is, and ketamine abuse has become more common due to its inclusion among the “club” drugs PCP is absorbed rapidly after smoking or injection, with peak concentrations noted 5-15 minutes after smoking The drug remains in the system unmetabolized for more than two days and is detectable in urine for several weeks after a single use

28. Effects of PCP and Ketamine A moderate dose (1-10mg) produces feelings of euphoria and numbness, slurred speech, and motor discoordination resembling alcohol intoxication The user may be catatonic and rigid with a blank stare, or aggressive and hyperactive Effects include profuse sweating, increased heart rate and blood pressure, rapid, jerky eye movements (nystagmus), blurred or double vision, changes in perception of body image, and distortions of the tactile senses Overdoses (more than 20mg) may result in seizures, prolonged coma, and death from respiratory failure

29. PCP produces bad trips in 50-80% of users Toxic psychosis produced by PCP is characterized by paranoia and violence and may persist for several days Long-term psychotic episodes and depressions can last 7 to 30 days or longer Talking the subject down is generally unsuccessful and physical restraint and intensive medical care is often necessary PCP is far more likely than other hallucinogens to produce medical or psychiatric complications

30. DRUGS AND CULTURE BOX 12.3 “Hallucinogenic Ibogaine: New RX for Addiction” Iboga is a shrub native to West Africa with hallucinogenic properties that has been used for centuries in ceremonies There have been claims since the 1960’s by ex-addicts that it helped with their recovery from dependency on alcohol, cocaine, and heroin Most treatment experts have been skeptical but recent data shows that Ibogaine reduces alcohol consumption in rats and other studies have suggested neurochemical actions are more complex than previously thought

31. Enough of this drug stuff already !