Hallucinogens
(Ch. 16)

• HALLUCINOGENS COME IN MANY DIFFERENT FORMS, AND FROM ALL OVER THE WORLD, WITH LSD PROBABLY BEING THE MOST WELL KNOWN
• These drugs were once referred to as belonging to the class phantastica - drugs that can create in our minds a world of fantasy: peyote, psilocybin and LSD
• In the 1960s, these drugs provided users with the ability to "see into their own minds" - and the term psychedelic was widely used to refer to this
• Because these drugs are capable of producing hallucinogens and some altered sense of reality, a state that could be called psychotic, they have also been referred to as psychotomimetic - a term that implies that these drugs produce dangerous effects and produce a form of mental disorder.
• In the 1990s, proponents have made popular a new term, entheogen, implying that the substances create spiritual or religious experiences
• These drugs all produce hallucinations - therefore, they are most often referred to as hallucinogens

LSD BELONGS TO THE INDOLE HALLUCINOGENS
 
• The basic structure of the neurotransmitter serotonin is referred to as an indole nucleus (LSD and psilocybin also contain this structure)
• d-Lysergic Acid Diethylamide (LSD) is the most potent of all hallucinogens and is not found in nature. It was originally synthesized from ergot alkaloids extracted from Claviceps purpurea
• LSD has been studied quite extensively, but no therapeutic uses for it have been found
• LSD has had a rather notorious history since its discovery by Dr. Albert Hofmann in 1938
• LSD is usually active when only 0.05 mg is taken, and in some people a dose of 0.03 - 0.10 mg is effective.
• The major emphasis of LSD research had to do with its alleged ability to to access the "subconscious mind" (dreams and there association to psychoanalysis)
• In 1968, NIMH stopped its in-house LSD research on humans and stopped funding university human research on LSD in 1974. The National Cancer Institute and the National Institute on Alcohol Abuse and Alcoholism stopped supporting psychedelic research in 1975 because it was nonproductive
• In June 1975, the Rockefeller Commission reported that the CIA and the US Army conducted unethical research on human subjects. The three major failures were: many of the volunteers were not really volunteers, many of the participants could not really quit an experiment if the wanted to, and the participants were not told the nature of the experiment. Many experiments had to do with giving LSD to unsuspecting civilians.
• Recreational use increased during the 1960. It provided new sensations, hope of a potent aphrodisiac (which never materialized) and a feeling of kinship among other drug users
• In 1966, Timothy Leary started his own religion, the League of Spiritual Discovery, with LSD as the sacrament - he was later arrested on drug charges and sent to prison - released in 1976
• LSD use peaked in 1967-68, after which it tapered off because of widely publicized reports of "bad trips," prolonged psychotic reactions, chromosome damage, self-injurious behavior and "flashbacks." Concerned, many people began to avoid hallucinogens, whereas others shunned the synthetic LSD for the natural experiences produced by psilocybin or mescaline

1. THE PHYSIOLOGICAL EFFECTS OF LSD ARE NOT GENERALLY CONSIDERED AS IMPORTANT AS THE PSYCHOLOGICAL EFFECTS

• LSD is a very potent (if not the most potent) psychochemical known
• Absorption from the gatsrointestinal tract is rapid and most users take LSD through the mouth. It is not readily enter the brain
• LSD is metabolized in the liver and excreted as 2-oxy-lysergic acid diethylamide, which is inactive
• Tolerance develops rapidly, repeated daily doses become completely ineffective in 3-4 days. Cross tolerance has been shown between LSD, mescaline and psilocybin and the effects of each can be blocked or reversed with chlorpromazine (antipsychotic). Most behavioral effects of LSD and the catechol hallucinogens can be blocked by drugs that act as serotonin-receptor antagonists
• LSD is a sympathomimetic agent, and the autonomic signs are some of the first to appear after LSD is taken
• The serotonin receptors are the primary, but not only, binding sites for LSD. Many of the primary CNS effects of LSD are by actions on the serotonin systems - at the present time, the best evidence seems to indicate that LSD and other hallucinogens, including mescaline and psilocytin act by stimulating the "serotonin-2" subtype receptors.
• Modification of perception, especially visual, is common to all users. "Synthesia" a "mixing of the senses"- sounds may appear as visual images (effective dose 0.03 - 0.10 mg)
• Enhanced emotionality is also experienced - from intense "beauty" to sadness and fear
• Two types of overall reactions are experienced: characterized as "expansive" (a good trip) and "constricted" (a bad trip)
• Adverse reactions of LSD use are usually caused by impurities in the drug, chemical composition or the quantity used (this is true for all drugs obtained on the streets). They include: panic reactions, prolonged psychotic reaction, and flashbacks
• Beliefs about LSD: increases creativity (no evidence); has therapeutic value (research has shown that it doesn't); and causes chromosomal damage (there is no evidence to support this)
• LSD, in and of itself, does not kill the user, but the user may in some way kill him/herself as a result of taking the drug
• LSD is in the classification of indole hallucinogens as are:
• psilocybin (from mushrooms) - the hallucingenic effects are quite similar to those of LSD and the catechol hallucinogen mescaline. Psilocybin has its CNS effects only after it has been changed in the body to psilocin (which is more lipid soluble),
• morning glory seeds, and
• Dimethyltryptamine (DMT) - on a world-wide basis DMT is one of the most important naturally occurring hallucinogenic compounds. It is ineffective when taken orally and must be inhaled, smoked or injected

1. ANOTHER CLASSIFICATION OF HALLUCINOGENS IS THE CATECHOL HALLUCINOGENS

• Mescaline is taken from the peyote plant, which is still legal for Native American Indians who are members of the American Indian Church ( a pan-American Indian religion; proven by a certificate of membership). Only the part of the cactus that is above ground is easily edible, but the entire plant is psychoactive. The upper portion, or crown, is sliced into disks that dry and are known as "mescal buttons" It is this part that is used as a sacrament in religious worship.
• Amphetamine derivatives:
• 2,5-dimethoxy-4-methylamphetamine, or simply DOM (also referred to as STP - as in serenity, tranquility and peace) is used on the street and is known for its long experience (because of the very big dose). Its effects are highly similar to mescaline and LSD. Its effects were enhanced rather than blocked by chlorpromazine
• 3,4 methylenedioxy amphetamine (MDA) and
• 3,4-methylenedioxy methamphetamine (MDMA); also called "ecstasy" on the street) appears to increase empathy but may cause permanent brain damage
• PCP - [1-(1-phenylcyclo-hexyl) piperidine hydrochloride]; is associated with violent behavior, which may be the result from the side effects of the drug (namely suspicion and its anesthetic properties). In the 1950s it was reported that PCP (brand name Sernyl) caused disorganized thinking, suspiciousness, and a lack of cooperation among normal psychiatric patients - which resembled schizophrenia. In 1965, Parke-Davis withdrew Sernyl as an investigative drug for humans. In the 1970s PCP crystals were sprinkled into a variety of substances, including marijuana, which eventually became known as "angel dust." The PCP receptor is found in close association with receptors for glutamate, an excitatory neurotransmitter.

1. A THIRD CLASSIFICATION IS THAT OF ANTICHOLINERGIC HALLUCINOGENS

• The potato family contains all the naturally occurring agents of the drugs discussed
• These agents have powerful peripheral and central effects
• The agents can be found in several different types of plants
* Belladonna (atropine) has been used since before the Middle Ages
* The mandrake plant can be traced to the Bible and is associated with love
* Henbane is known as the poison that killed Hamlet’s father
* Datura goes far back in history and has had many uses. The distribution of the Datura species is worldwide, but they contain three alkaloids - atropine, scopolamine and hyoscyamine - in varying amounts
• The Amita muscaria is the poisonous Russian mushroom that is "reusable" since it is excreted unchanged in the urine