Chapter 14: Hallucinogens
Categorizing Hallucinogens
LSD
Mushrooms
Mescaline
DOM, MDA, MDMA (Ecstasy)
PCP
Salvia
Animism and Religion
Follower of this, who has access to, and influence in, the world of spirits, is known as a Shaman
Plants evolved to produce chemicals that alter the biochemistry of animals.
Humans discovered that some plants alter perceptions and emotions.
Animism: Belief that animals, plants, rocks, and other natural features derive their special characteristics from a spirit contained within the object.
Eating a plant transfers its spirit to the consumer, potentially granting special powers or insights.
Psychoactive plants have been important in medicine and the development of spiritual/religious traditions.
Terminology
Naming this family of drugs is a complex issue.
Phantastica: Drugs that create a world of fantasy in our minds
Psychedelic: “Mind-viewing,” a term that controversially implies a beneficial, visionary type of effect
Psychotomimetic: “Mimicking psychosis”—by producing hallucinations and some altered sense of reality, these drugs produce a state that could be described as psychotic
Entheogen: Substances that create spiritual or religious experiences.
Entactogen: Substances that enhance feelings of empathy.
Hallucinogens: A drug that produces profound alterations in perception, including unusual visual sensations and often changes in the perception of one’s own body.
Classification
Hallucinogens can be classified by:
Chemical structure
Known pharmacological properties
How much loss of awareness they cause
How dangerous they are
Two Major Groups:
Classical phantastica: Alter perceptions while allowing the user to remain in communication with the present world.
Deliriants: Produce more mental confusion, greater clouding of consciousness, and a loss of touch with reality.
Phantastica: Major Groups
Indole Hallucinogens:
Drugs that have the indole structure also found in the neurotransmitter serotonin.
Examples: LSD, psilocybin.
Catechol Hallucinogens:
Drugs that have the catechol nucleus that forms the basic structure of the neurotransmitters norepinephrine and dopamine.
Examples: mescaline, MDMA (Ecstasy).
Indole Hallucinogens examples
d-lyseric acid diethylamide (LSD)
Psilocybin
LSD: Discovery
LSD is not found in nature; it is synthesized from alkaloids extracted from the ergot fungus Claviceps purpurea.
Eating grain infected with this fungus causes ergotism.
During famine, infected grain might be consumed, leading to outbreaks.
Associated with Saint Anthony's fire and the 1692 Salem witch trials.
1938: Synthesized by Dr. Albert Hofmann of Sandoz Laboratories in Switzerland.
1943: Dr. Hofmann took a large dose and described its effects.
Potency of the drug attracted attention because a very small dose produces effects.
Comparable effects from mescaline would require 4,000 times the dose.
LSD: Early Research
Between 1953 and 1966, large quantities of LSD were produced for research into several potential uses:
In psychotherapy, to help patients bring up repressed memories and motives.
As a possible treatment for alcohol dependence.
In terminal cancer patients, to help them explore their feelings about their own mortality.
Most research on LSD was found to contribute little to our understanding of the effects of the drug.
Most research since 1975 has been conducted on animals to understand the drug’s action at the neural level.
LSD: Secret Army/CIA Research
1975 report on the 1953 suicide of a biochemist who had secretly been given LSD by CIA agents.
First public exposure of Army/CIA use of LSD.
Use of hallucinogens for warfare and for interrogation of prisoners and spies.
Army/CIA-sponsored research was poorly done and violated many ethical codes.
Participants were not volunteers, could not leave the experiment, and/or were not told the nature of the experiment.
LSD: Recreational Use and Timothy Leary
Experiments by psychologist Timothy Leary and Dr. Richard Alpert on Harvard graduate students.
Began with proper supervision and controls but were later changed in ways that called into question the scientific validity of the research.
1966: Leary started a religion, the League of Spiritual Discovery, with LSD as the sacrament.
1966: AMA called for greater controls on LSD and other hallucinogens due to the risk of panic and psychosis in some users.
Use peaked in 1967 and 1968, then fell due to reports of problems associated with its use.
Leary served time in prison on drug charges and later stopped advocating the use of LSD or any drug.
LSD Pharmacology
LSD is odorless, colorless, tasteless, and one of the most potent psychochemicals known.
No known human overdose deaths.
is about 400 times the behaviorally effective dose.
Absorbed rapidly through the gastrointestinal tract.
LSD is usually taken orally.
Half-life is about three hours.
LSD is metabolized by the liver.
Excreted as the inactive chemical 2-oxy-lysergic acid diethylamide.
Tolerance develops rapidly, within three to four days of daily doses.
Recovery from tolerance is also rapid.
Cross-tolerance occurs among LSD, mescaline, and psilocybin.
Physical dependence to LSD or other hallucinogens has not been shown.
LSD is a sympathomimetic agent.
Autonomic signs appear quickly following administration: dilated pupils, elevated temperature and blood pressure, increased salivation.
Indole structure of LSD resembles that of serotonin, implying that LSD works by acting at serotonin receptors.
Effects are complex due to the number of, and variation among, subtypes of serotonin receptors and LSD’s different effects on them.
Best evidence indicates that LSD acts by stimulating the serotonin-2A subtype of receptor.
The LSD Experience
Modification of perceptions.
Visual images: Users see shapes and patterns, usually with intense colors and brightness.
Users report an altered sense of time, changes in the perception of their own bodies, and alterations of auditory input.
Synesthesia (“mixing of senses”), in which sounds may appear as visual images or visual pictures might alter in rhythm with music.
Enhanced emotionality.
Images may be perceived as beautiful and awe-inspiring or as intensely sad or frightening.
The LSD Experience: “Trips”
Typically last six to nine hours.
Autonomic responses occur over the first 20 minutes.
Alterations in mood, perception, and sensation begin in the next 30 to 40 minutes.
Full intoxication occurs within one hour.
Loss of self-awareness and loss of control of behavior may occur.
Unique and variable experiences.
Expansive and pleasant—user feels she or he is uncovering great secrets or profundities.
Constricted and negative—user experiences paranoia and feelings of persecution.
Form-constants
May be combined with complex images
Synesthesia
Mixing of senses
Each trip is a unique experience
Impact on creativity
Unlikely to be enhanced successfully
Therapeutic usefulness?
LSD: Adverse Reactions
Impossible to determine true incidence of adverse reactions.
Some bad reactions may be due to impurities in street LSD and/or preexisting psychological conditions in the user.
Panic reactions.
Flashbacks
Recurrence of symptoms weeks or months after an individual has taken LSD.
Rare, variable, and unpredictable in occurrence.
DSM-5 classifies them as Hallucinogen Persisting Perception Disorder.
Psilocybin: “Magic Mushrooms”
Long history of use among natives of Mexico.
Psilocybe mexicana is the most well-known psychoactive mushroom.
Primary active ingredient is the indole psilocybin.
Dried mushrooms are 0.2 to 0.5 percent psilocybin.
Effects are similar to LSD and mescaline, and cross-tolerance exists among the three.
Effects depend on dose.
Up to 4 mg causes relaxation and some body sensations.
Higher doses cause perceptual and body-image changes, with hallucinations in some individuals.
Sympathetic arousal symptoms.
May only be active after converted to psilocin
Psilocybin
Good Friday study (1962) by one of Timothy Leary’s followers.
Seminary students were given psilocybin or a placebo 90 minutes before attending a religious service.
Study looked at the effect and magnitude of changes caused by the drug and at the durability of the changes.
Researchers concluded that under certain circumstances, the drug enhances mystical or religious experiences.
Most current production is from local, amateur growers.
“Shrooms” might be consumed at a party in combination with alcohol.
Peyote
Peyote (from the Aztec peyotl) is a small, spineless, carrot-shaped cactus, Lophophora williamsii Lemaire.
Mostly subterranean, with only the pincushion-like top appearing above ground.
Long pre-Columbian history of use among Mexican Indians, who used the plant ceremonially.
Upper portion (crown) is sliced into disks and dried, creating so-called mescal buttons
Not the same as mescal beans or mescal liquor
Mescal beans may produce some hallucinogenic effects but are highly toxic
Dried buttons remain psychoactive indefinitely
Mescaline is the primary active agent
Peyote cult moved north and became widely established among Indians of the plains by the late 19th century
Native American Church is an amalgamation of Christianity and traditional beliefs and practices of Native Americans, with peyote use incorporated into its ceremonies
Peyote and Mescaline Use
Peyote use:
In religious ceremonies
As a treatment for illness
Worn as a protective amulet
Current laws governing the use of peyote as a sacrament vary from state to state
Mescaline was isolated and synthesized by 1918.
Peyote includes many other psychoactive alkaloids, but mescaline has been identified as primarily responsible for the visual effects.
Users may experience bad trips as well as nausea and physical discomfort.
San Pedro cactus: Another mescaline-containing cactus, Trichocereus pachanoi, has also been used for thousands of years, but its recreational use is limited by frequent adverse side effects.
Mescaline: Pharmacology
Rapidly absorbed if taken orally.
Half-life is about 6 hours.
Effects:
Low dose effects are primarily euphoric.
Higher doses cause the full set of hallucinogenic effects.
Most mescaline is excreted unchanged.
Psychoeffective dose causes sympathetic arousal.
is about 10 to 30 times the dose needed to cause behavioral effects.
Tolerance develops more slowly to mescaline than to LSD.
Cross-tolerance between LSD and mescaline.
Amphetamine Derivatives
A group of synthetic hallucinogens.
Chemically related to amphetamines.
Due to chemical structure, they have few stimulant effects and act much more like mescaline.
Examples:
DOM
MDA and other “designer drugs”
MDMA (Ecstasy).
DOM and MDA
DOM:
2,5-dimethoxy-4-methylamphetamine
Earlier street name was STP (“serenity, tranquility, peace”).
Effects similar to mescaline and LSD.
MDA and others:
Group includes “designer drugs” that are not all specifically listed as controlled substances.
MDMA: “Ecstasy”
Similar in structure to MDA but acts differently.
Prior to the scheduling of MDMA, some psychiatrists used it in practice because it was viewed as having a special ability to promote empathy, aiding in therapy.
Effects:
Heightened sense of “closeness” with others.
Increased heart rate and blood pressure.
Euphoria and increased sociability.
Other autonomic effects.
Some research has found that MDMA may cause brain damage.
Selective destruction of serotonin neurons.
Strong evidence from animal studies but limited evidence of long-term neurotoxic effects in humans.
Listed as a Schedule I drug but continues to be studied as a potential psychotherapeutic agent.
3,4 methylenedioxymeth- amphetamine § a stimulant and psychedelic
Taken in tablet form
Chemically similar to methamphetamines
Some caveats about MDMA research…
MDMA (Ecstasy) Short Term Effects
Feelings of mental stimulation
Emotional warmth
General sense of well being
Decreased anxiety
Enhanced sensory perception
From: National Institute on Drug Abuse Research Report (2006)
MDMA (Ecstasy): Undesirable Effects
Anxiety
Restlessness
Irritability
Sadness
Impulsiveness
Aggression
Sleep disturbances
Lack of appetite
Reduced interest in and pleasure from sex
From: National Institute on Drug Abuse Research Report (2006)
MDMA (Ecstasy): Health Effects
Nausea
Chills
Sweating
Involuntary teeth clenching
Muscle cramping
Blurred vision
Overdose:
High blood pressure
Faintness
Panic attacks
Loss of consciousness and seizures
From:National Institute on Drug Abuse Research Report (2006)
MDMA and the Brain
Compared to meth:
causes greater serotonin release
somewhat lesser dopamine release
Monkey studies suggest that MDMA destroys serotonergic neurons (Hatzidimitriou et al, 1999)
Deliriants
Compared to “phantastica,” deliriants tend to produce more mental confusion and a loss of touch with reality.
Deliriants act through a number of different brain mechanisms.
PCP (Phencyclidine)
1-(1-phenylcyclohexyl) piperidine hydrochloride
Initially appeared to be a good anesthetic.
It does not depress blood circulation or respiration or produce heart rate irregularities as some anesthetics do.
Mechanism of action of PCP
PCP alters many neurotransmitter systems
Sigma receptor may be selective for PCP and similar drugs
Effects: Reactions to the drug were found to be unpredictable.
Some patients experienced changes in body perception, hallucinations, and prolonged confusion.
Some patients became angry, uncooperative, or unmanageably manic.
Most users experienced diminished pain, touch, and position sense, as well as nystagmus.
Overall, PCP causes a dissociative state that resembles schizophrenia much more than the LSD state.
By 1960, PCP had been characterized as:
An excellent anesthetic for monkeys
A medically safe but psychologically troublesome anesthetic for humans
A hallucinogen different from LSD and mescaline, with profound effects on body perception
Currently, PCP is licensed for use as an animal anesthetic
PCP: Recreational Use
Has had brief, sporadic periods of popularity.
Relatively inexpensive and easy to manufacture.
Sprinkled onto oregano, parsley, or alfalfa and sold as marijuana.
Called “angel dust.”
Joints made with PCP containing marijuana or another plant substance.
Called “killer joints” or “sherms.”
Some users develop psychological dependence on PCP.
Animal studies also indicate a dependence-producing potential.
A few but not all PCP users have been reported to behave violently.
Urban legends of superhuman strength among PCP users are most likely false, BUT
Police attempting to arrest PCP users have had trouble subduing them due to the anesthetic effects of PCP.
Salvia Divinorum (“Diviner’s Sage”)
Used for centuries in Oaxaca, Mexico, in religious ceremonies.
Traditional methods of use:
Chewing the leaves
Drinking a tea made from the crushed leaves
Smoking the dried leaves
Produces a hallucinatory effect
Recreational use reported in Mexico and the U.S.
Not currently listed as a federally controlled substance in the U.S. but is outlawed in several states.
Mechanism of action:
Active ingredient is salvinorin A, a highly potent agent.
Salvinorin A binds selectively to the kappa opioid receptor, acting as an agonist (a unique pharmacological effect).
New Research on Hallucinogens as Therapeutic Agents
Psilocybin research on terminal patients
MDMA research on PTSD and trauma
LSD research on terminal patients and fear of death