Pemoline (Cylert)

Pronunciation: PEM-oh-leen
Chemical Abstracts Service Registry Number: 2152-34-3
Formal Names: Cylert
Informal Names: Popcorn Coke
Type: Stimulant.
Federal Schedule Listing: Schedule IV (DEA no. 1530)
USA Availability: Prescription
Pregnancy Category: B

Uses.
In the United States pemoline became available for medical purposes during the 1970s. It is used to treat depression, weariness, and attention deficit hyperactivity disorder (ADHD). The drug’s stimulant effects are described as greater than caffeine but less than amphetamine. Unlike many scheduled stimulants, pemoline is unrelated to amphetamine.

Studies find pemoline useful in reducing symptoms of depression, and experimental usage of pemoline with monoamine oxidase inhibitor (MAOI) antidepressants has helped depressed persons who obtain insufficient relief with other drugs.

Pemoline has eliminated drowsiness felt by persons taking antihistamines. The drug has been proposed for workplace usage to reduce fatigue but has not been tested extensively for that purpose. Tests have found that the drug improves ability to perform arithmetic when users are tired. In a different but more robust experiment, members of the U.S. Navy Special Warfare group stayed awake 64 hours around the clock while using pemoline. Though their performance appeared to decline as the experiment continued, they not only did better than participants who used placebos, but they also did better than persons using methylphenidate. In England, Royal Air Force experimenters concluded that pemoline can help keenness and capabilities during long shifts of duty. A Russian report endorses the drug’s usefulness for “urgent increase” of functioning but notes that persons using pemoline cannot maintain initial ability if body temperature rises and oxygen supply declines, nor does the drug help persons push past emotional strain or fulfill complicated task requirements.

During the 1980s and 1990s sports officials in Belgium found the drug was frequently used by cyclists seeking a competitive edge. Multiple sclerosis patients using pemoline sometimes report less exhaustion than those using a placebo, but investigators who rigorously reviewed studies about multiple sclerosis fatigue found no evidence of pemoline improving weariness.

An instance is known of an elderly man taking pemoline to help him stay awake during lectures, but the regimen seemed to promote prostate trouble. Pemoline has been successfully used against narcolepsy.

Studies find pemoline about as effective as either dextroamphetamine or methylphenidate in helping children with ADHD. Pemoline has been used successfully against ADHD in teenagers and adults as well. Growth rates are below normal in some youngsters with ADHD, and pemoline itself can temporarily hold back such development but without long-term harm—youngsters
develop normal adult weight and height. Those deficient growth rates may be treated with growth hormone. One study found, however, that pemoline seems to make the hormone treatment less effective in some patients. As the age of ADHD patients grows, so can unwanted effects that they experience from pemoline.

Animal experiments in the 1960s indicated that pemoline boosts learning ability. The lure of a “smart pill” had understandable appeal to suffering students and teachers, but when the drug was tested on college students, no improvement in learning ability occurred. The same dismal outcome occurred when elderly persons received the drug; indeed, some performed worse than
elderly persons receiving a placebo. Group results in still another experiment showed either no improvement or worsening of learning scores when people used the drug. In contrast, long-term daily administration of the drug seemed to improve memory in some persons entering senility.
A review covering 10 years of pemoline reports found none attributing euphoria to the drug, a lack that sets it apart from other scheduled stimulants.

Unlike some other stimulants, pemoline also seems to have little effect on pulse rate or blood pressure.

Drawbacks.
The drug can bring on tics and partial muscle movements, in a particularly severe way if an overdose occurs. An instance is known of muscle damage in an adult misusing pemoline. Pemoline is also known to reduce appetite and salivation, increase crankiness, bring on headaches and stomachaches, cause skin rash, and interfere with sleep. Hallucinations from
pemoline have been reported.

In rats and mice pemoline can cause self-harm behavior, and the amount needed to induce such behavior declines when a certain kind of brain damage is present, damage that is often seen in mentally retarded humans. Those findings suggest that such persons receiving pemoline may need monitoring to guard against self-injury. Long-term excessive usage may generate temporary psychotic behavior, but such an outcome appears untypical.

Probably the most serious unwanted results of taking pemoline can be hepatitis and other liver injury, injury so severe as to require a transplant. Damage can continue to worsen after the drug is stopped, and people have died from liver failure induced by pemoline. Victims tend to be children. Such an adverse effect is particularly disquieting because it occurs at therapeutic dosage, rather then being created by reckless abuse. A child can take pemoline for months before harm is apparent, or alarming symptoms can arise after just a week of use.

Methylphenidate is suspected of contributing to liver trouble in persons who are also taking pemoline. Debate exists about how dangerous pemoline is to liver function when no other drugs are being taken, but the debate has limited practical significance because many patients taking pemoline receive other drugs as well. Because of concern about liver damage, parents are supposed to sign a written consent form before their children begin pemoline therapy.

Abuse factors.
Although pemoline is a scheduled substance, a review of reports covering the first 10 years of its medical availability in the United States found little evidence of addiction or abuse. A Norwegian review of pemoline use boldly described it as “a stimulant which cannot be abused.”

1 When given a choice of drugs, animals show no particular interest in pemoline, a sign of low abuse potential. Nonetheless, a case report does exist of a pemoline addict who developed a paranoid psychosis that went away after stopping the drug. A British medical practitioner reported that drug misusers were supplementing their amphetamine habit with pemoline.

An experiment tested pemoline’s ability to help reduce cocaine usage among persons receiving methadone treatment (meaning the persons were addicted to cocaine and heroin both). Results were unencouraging. In contrast, favorable response in an ADHD alcoholic caused researchers to predict that pemoline may be useful for treating alcohol addiction. Mice experimentation
shows that pemoline reduces effects produced by THC, considered the primary drug in marijuana.

Drug interactions.
Pemoline is suspected of interfering with epilepsy medicines.
It can boost mono amine oxidase inhibitor (MAOI) antidepressants and
urinary acidifers (the latter action interfering with pemoline’s psychostimulant
effects).

Cancer.
Rat experiments do not indicate any cancer risk from pemoline.

Pregnancy.
Experiments with rabbits and rats reveal no harm to fetal development, but influence on human fetal development is unknown.

Additional information.
When tested on mentally handicapped workers, magnesium pemoline (CAS RN 18968-99-5) brought on the kinds of temperament modification associated with caffeine but failed to increase either productivity or time worked. Two cocaine addicts who appeared to have mild ADHD were able to reduce their intake of cocaine while receiving magnesium pemoline, a result leading the scientific investigators to wonder if magnesium pemoline might have potential for helping to break cocaine addiction. Animal experiments have shown that both pemoline and magnesium pemoline can provide protection against atomic radiation.

Additional scientific information may be found in:
Bostic, J.Q., et al. “Pemoline Treatment of Adolescents with Attention Deficit Hyperactivity
Disorder: A Short-Term Controlled Trial.” Journal of Child and Adolescent Psychopharmacology 10 (2000): 205–16.

Elizur, A., I. Wintner, and S. Davidson. “The Clinical and Psychological Effects of
Pemoline in Depressed Patients—A Controlled Study.” International Pharmacopsychiatry
14 (1979): 127–34.

Honda, Y., and Y. Hishikawa. “Long Term Treatment of Narcolepsy and Excessive Daytime Sleepiness with Pemoline (Betanamin).” Current Therapeutic Research:
Clinical and Experimental 27 (1980): 429–41.

Langer, D.H., et al. “Evidence of Lack of Abuse or Dependence Following Pemoline
Treatment: Results of a Retrospective Survey.” Drug and Alcohol Dependence 17
(1986): 213–27.

Newlands, W.J. “The Effect of Pemoline on Antihistamine-Induced Drowsiness.” The
Practitioner 224 (1980): 1199–1201.

Shevell, M., and R. Schreiber. “Pemoline-Associated Hepatic Failure: A Critical Analysis
of the Literature.” Pediatric Neurology 16 (1997): 14–16.

Sternbach, H. “Pemoline-Induced Mania.” Biological Psychiatry 16 (1981): 987–89.
Valle-Jones, J.C. “Pemoline in the Treatment of Psychogenic Fatigue in General Practice.”
The Practitioner 221 (1978): 425–27.

Note
1. N. Lie, “Sentralstimuleren Midler ved AD/HD Hos Voksne. Kan De Misbrukes?
[Central Stimulants in Adults with AD/HD. Can They Be Abused?],” Tidsskrift for den
Norske Laegeforening 119 (1999): 82–83. Abstract in English.

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PCP (Phencyclidine)

Pronunciation: pee-see-pee
Chemical Abstracts Service Registry Number: 77-10-1. (Hydrochloride form 956-90-1)
Formal Names: Phencyclidine
Informal Names: Ace, Ad, Alien Sex Fiend (with heroin), Amoeba, Angel, Angel Dust, Angel Hair, Angel Mist, Angel Poke, Animal Trank, Animal Tranq, Animal Tranquilizer, Aurora Borealis, Belladonna, Black Dust, Black Whack, Blotter Acid, Blue Madman, Boat, Bohd, Bush, Busy Bee, Butt Naked, Cadillac, Cannabinol, Cigarrode Cristal, CJ, Clicker, Clickum, Cliffhanger, Columbo,
Cozmo’s, Crazy Coke, Crazy Eddie, Crystal, Crystal Joint, Crystal T, Cycline, Cyclone, D, Detroit Pink, Devil’s Dust, Dipper, DMT, DOA, Do It Jack, Domex, Drink, Dummy Dust, Dust, Dusted Parsley, Elephant, Elephant Trank, Elephant Tranquilizer, Elysion, Embalming Fluid, Energizer, Erth, Fake STP, Flake,

Flying Saucer, Fresh, Fuel, Good, Goon, Goon Dust, Gorilla Biscuit, Gorilla Tab, Green, Green Leaves, Green Tea, Happy Sticks, HCP, Heaven & Hell, He-Man,
Herms, Hinkley, Hog, Hog Dust, Horse Tracks, Horse Tranquilizer, Ice, Ill, Illy Momo, Jet Fuel, Juice, K, Kap, Kay Jay, K-Blast, Killer, KJ, Kool, Koolly High, Krystal, KW, LBJ, Leaky Bolla, Leaky Leak, Lemon Drop, Lemon 714, Lenos, Lethal Weapon, Little One, Live One, Log, Loveboat, Lovely, Mad Dog, Madman, Magic, Magic Dust, Magic Mist, Mean Green, Mint Dew, Mint Leaf, Mint Weed, Missile, Mist, Monkey Dust, Monkey Tranquilizer, More, New Acid,
New Magic, Niebla, Octane (mixed with gasoline), Oil, Omen, OPP, Orange Crystal, Ozone, P, Parsley, Paz, PCPA, Peace, PeaCe Pill, Peace Weed, Peep, Peter Pan, Pig Killer, Pikachu (mixed with MDMA), Pit, Polvo, Polvo de Angel, Polvo de Estrellas, Puffy, Purple Rain, Red Devil, Rocket Fuel, Scaffle, Scuffle, Selma, Sernyl, Sernylan, Sheets, Sherm, Sherman, Sherm Stick, Skuffle, Smoking, Snort, Soma, Space Base (mixed with crack cocaine), Space Cadet (with crack), Space Dust (with crack), Speedboat (with crack and marijuana), Spore, Squirrel (with crack and marijuana), Stardust, Stick, STP, Super, Super Grass (with marijuana), Super Joint, Super Kool, Super Weed, Surfer, Synthetic Cocaine, Synthetic THT, TAC, T-Buzz, Tea, Tic, Tic Tac, Tish, Titch, Trank, Wac, Wack, Water, Weed, Wet (alone or with marijuana), Wet Daddy, Whack (with crack or heroin), Whacky Weed, White Devil, White Horizon, White Powder,
Wicky Stick (with crack and marijuana), Wobble Weed, Wolf, Wooly (with marijuana), Worm, Yellow Fever, Zimbie, Zombie Dust, Zombie Weed, Zoom

Type: Depressant.
Federal Schedule Listing: Schedule II (DEA no. 7471)
USA Availability: Prescription

Uses.
This substance was invented in the 1920s, but not until the 1950s was it introduced as a drug, intended as a human and veterinary anesthetic. Human medical use soon ended because of psychological effects discovered during tests on patients. PCP is related to ketamine and, like that substance, has hallucinogenic qualities. Depending on how PCP is used, it can have stimulant, depressant, or hallucinogenic actions. In monkeys PCP is about 10 times stronger than ketamine.

Drawbacks.
PCP can make people feel aloof from the world around them, cause numbness, interfere with movement, and distort perception of time. Hallucinations, floating sensations, euphoria, and mania can occur. People may forget what they did while under the drug’s influence; such amnesia can last for 24 hours after a dose. Although euphoric effects are well documented,
one group of researchers noted bouts of depression brought on by chronic use of the substance, though not by intermittent use. Yet the same researchers also found people successfully using the drug as an antidepressant, and animal studies suggest PCP may have antianxiety properties. The substance reduces appetite in dogs. Rats lost weight when they chronically received PCP.

Law enforcement authorities say the drug can make people hostile and give them extra physical strength, and the same has been experienced by medical personnel dealing with overdose emergencies. Researchers, however, have generally not observed such results from PCP (although one of the very first studies in the 1950s noted violent reactions from about 5% of surgery patients who received the drug as an anesthetic). A study examining PCP cases at a
Los Angeles psychiatric hospital emergency room explicitly noted that wild conduct among PCP patients was uncommon. Perhaps police simply have more dealings with hostile individuals; for example, alcohol can embolden belligerent persons, but violence is not considered an inherent effect of alcohol.

Persons who become violent after taking PCP already have such a history without the substance, and during a police encounter they may well be under the influence of alcohol or other drugs as well. Military research found that PCP hostility did not occur unless persons were under stress, and not all stressed individuals reacted that way. The military study also found that psychotic
episodes did not occur with normal persons; someone had to be prone to psychosis in order for such behavior to occur while using the drug (a finding supported by other studies as well). In mice research PCP reduces violent behavior. Most species, including monkeys, act more docile after taking the drug. Some violent human episodes are described as coming not from aggression
but from a PCP user’s panic when police or medical personnel try to restrain the person. One group of addicts spoke of the substance lowering inhibitions, which is not the same as causing violence, although an already enraged person who loses inhibitions may engage in stormy behavior. In addition, users who attract attention from police or emergency medical personnel
are not necessarily representative of recreational users in general, either in personality or size of dose or reaction to the dose.

PCP’s physical effects include increased salivation, body temperature, pulse rate, and blood pressure. Case reports about humans indicate that PCP can raise blood pressure so high that a medical emergency occurs. The drug can bring on dizziness and double vision, create seizures, and cause muscle discoordination and damage. Numbness caused by PCP can promote injury due to lack of pain signals that ordinarily warn a person to stop doing something.

Cases of kidney failure and liver destruction have been associated with the
substance.

The higher one rises in the traditional evolutionary scale (for example, from mice to rats to humans), the lower the dose necessary for PCP to create anesthesia. Two observers who noted that trend concluded that human brains are exquisitely sensitive to PCP. Animal experiments reveal brain damage when the substance is used chronically for as little as five days. PCP addicts
have complained of memory trouble. A small human study found impaired ability for abstract thinking and for physical movement in response to signals, impairment measured years after the persons said they had stopped using PCP. Moreover, users of the drug may have normal scores on intelligence tests but have emotional disabilities and be crippled in their ability to cope with
problems. Those latter defects may be caused by the drug or may instead be reasons why people resort to the drug.

Abuse factors.
Initially PCP was a Schedule III drug, but in 1978 government authorities shifted it to Schedule II because of recreational use. At about that time a Los Angeles psychiatric hospital emergency room tested 145 consecutive patients for PCP; 63 were positive (over 40%).

A study of 200 recreational users found differences in effects reported by persons who took a little of the drug once a month and by persons who took a lot every day for years. Heavy users felt more pepped-up, violent, and suicidal. Regular users of PCP are known for self-destruction; one study found that 24% of regular users had tried to commit suicide, and 36% had overdosed
on other drugs. A study of PCP users who were treated at a charity hospital found no behavioral difference between black or white males, but black females acted much stranger and more aggressively than white females. The meaning of that finding is unclear—it could be racial, could be cultural, could be a statistical oddity that would disappear after more research.

When monkeys were given a choice between water or PCP, the animals showed no preference; such indifference is a sign of low addictive potential.

An experiment measuring rats with prenatal exposure to PCP found the animals were more sensitive to the drug than were rats lacking prenatal exposure— the opposite of tolerance. Dependence has been reported in monkeys that receive PCP. Pigeons that received the drug every day for 215 days did not develop dependence. Human research has found tolerance but not dependence among users, although dependence is suspected.

Various cold remedies contain doxylamine succinate, which can cause a false-positive drug test for PCP.

Drug interactions.
In a rat experiment neither alcohol nor PCP affected blood pressure, but blood pressure rose when they were used simultaneously. They also speeded up the heart. One human study found that PCP may be more likely to induce excitability in alcoholics than in nonalcoholics, possibly meaning that alcohol increases the likelihood of a manic reaction. In mice marijuana has reduced hyperactivity caused by PCP.

Cancer.
Not enough scientific information to report.

Pregnancy.
Two studies published only a few months apart in the 1980s gave different impressions about the prevalence of PCP use among pregnant women. In one study a group of 2,327 pregnant women were tested for PCP use; 19 were taking the drug. Those 19 were typically polydrug abusers. A different study of 200 pregnant women found 24 using PCP, a rate 15 times
higher than in the other group.

If a pregnant woman uses PCP, it passes into the fetus. Reports exist of PCP being detected in newborns three months after the mothers claimed to have stopped using the drug during pregnancy, which would mean that the drug remains in a fetus months after a pregnant woman stops taking PCP. Whether the women’s claims of abstinence were confirmed by laboratory testing during those months of pregnancy is unclear, however. In mice and pigs PCP builds
up in the fetus, reaching levels 7 to 10 times higher than in the female’s bloodstream.

The drug is suspected of causing birth defects. At dosage levels high enough to poison the pregnant female, birth defects have been produced in rats and mice. Rats with prenatal exposure to PCP show defective memory and learning ability. The substance is suspected of harming fetal brain development in humans. Pregnant women who use the drug tend to produce infants who are smaller than normal. In a group of 83 infants with prenatal PCP exposure,
almost half had a head circumference below the 25th percentile (meaning that 75% of infants in the general population have bigger heads and, by implication, larger brains). Some were below the 10th percentile. Smaller-than-normal infant skulls may interfere with physical growth of the brain. People who abuse one drug tend to abuse others as well; one study of 41 women who
used PCP during pregnancy found that most had also been using cocaine.

Two studies of women who used PCP during pregnancy found that all were poor; most were unmarried, were in an ethnic minority, and had received inadequate prenatal care. Such factors confound efforts to confirm what effect PCP alone has on pregnancy.

Offspring of mothers who have been using PCP can exhibit symptoms similar to those seen in infants undergoing opiate withdrawal—even though the drug is not an opiate, and research has yet to demonstrate that PCP dependence occurs. Infant distress may be real, but the newborn may be responding to the unpleasant effects of the drug itself rather than responding to sudden
absence of the drug.

A year after birth, a group of 57 babies with prenatal PCP exposure showed normal development in mental ability and physical coordination, although almost half were ill-tempered. About 15% had trouble sleeping, and the same percentage lacked normal emotional attachment. Those findings are consistent with other studies. Home environment, of course, may influence behavior as much or more than prenatal drug exposure. Factors noted above (lack of money, absent father, being in a disadvantaged ethnic minority) can weaken home life. Still, the kinds of brain function damage seen in animal studies are the kinds of damage that should interfere with children’s abilities to socialize normally—exactly the kind of deficit seen in children who have prenatal exposure to PCP.

In mice PCP not only passes into maternal milk, but milk levels are 10 times higher than maternal blood levels.

Additional information.
PCP is related to the Schedule I hallucinogens PCE (CAS RN 2201-15-2), PCPy (2201-39-0), TCP (21500-98-1), and TCPy (22912- 13-6).

Rat experimentation measured PCPy as about the same strength as PCP.
Other laboratory measurement shows TCP as stronger than PCP, and PCE as stronger than TCP. French military experiments found that TCP could protect rats and guinea pigs from the chemical warfare agent soman.

“Cannabinol” is a nickname for PCP and refers to THC, which is the active chemical in marijuana and dronabinol, but PCP is not THC. Likewise “DMT” and “STP” (DOM) are nicknames for PCP, but they are all different drugs.

Additional scientific information may be found in:
Baldridge, E.B., and H.A. Bessen. “Phencyclidine.” Emergency Medicine Clinics of North
America 8 (1990): 541–50.

Brecher, M., et al. “Phencyclidine and Violence: Clinical and Legal Issues.” Journal of
Clinical Psychopharmacology 8 (1988): 397–401.

Giannini, A.J., R.K. Bowman, and J.D. Giannini. “Perception of Nonverbal Facial Cues
in Chronic Phencyclidine Abusers.” Perceptual and Motor Skills 89 (1999): 72–78.

Graeven, D.B., J.G. Sharp, and S. Glatt. “Acute Effects of Phencyclidine (PCP) on
Chronic and Recreational Users.” American Journal of Drug and Alcohol Abuse 8
(1981): 39–50.

Harry, G.J., and J. Howard. “Phencyclidine: Experimental Studies in Animals and
Long-term Developmental Effects on Humans.” In Perinatal Substance Abuse: Research
Findings and Clinical Implications, ed. T.B. Sonderegger. Baltimore, MD:
Johns Hopkins University Press, 1992. 254–78.

Khajawall, A.M., T.B. Erickson, and G.M. Simpson. “Chronic Phencyclidine Abuse and
Physical Assault.” American Journal of Psychiatry 139 (1982): 1604–6.

Pradhan, S.N. “Phencyclidine (PCP): Some Human Studies.” Neuroscience and Biobehavioral
Reviews 8 (1984): 493–501.

Schuckit, M.A., and E.R. Morrissey. “Propoxyphene and Phencyclidine (PCP) Use in
Adolescents.” Journal of Clinical Psychiatry 39 (1978): 7–13.

Sioris, L.J., and E.P. Krenzelok. “Phencyclidine Intoxication: Literature Review.” American
Journal of Hospital Pharmacy 35 (1978): 1362–67.

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Nitrite (Amyl Nitrite, Butyl Nitrite, Cyclohexyl Nitrite, IsoamylNitrite, Isobutyl Nitrite, Nitrous Acid)

Pronunciation: NIGH-tright
Chemical Abstracts Service Registry Number: 8017-89-8 (amyl nitrite); 542-56-3
(isobutyl nitrite)
Formal Names: Amyl Nitrite, Butyl Nitrite, Cyclohexyl Nitrite, Isoamyl Nitrite,
Isobutyl Nitrite, Nitrous Acid
Informal Names: Aimes, Aimies, Ames, Amys, Army, Aroma of Men, Blackjack, Blue Heaven, Bolt, Boppers, Buds, Bullet, Buzz Bomb, Climax, Dixcorama, Hardware, Heart-On, High Ball, Liquid Gold, Liquid Incense, Locker Room, Man Aroma, Oz, Ozone, Pearls, Poppers, Quicksilver, Ram, Rush, Snappers, Thrust, Whiteout
Type: Inhalant.
Federal Schedule Listing: Unlisted, but may be in state schedules
USA Availability: Prescription for some formats; nonprescription for others
Pregnancy Category: X (amyl nitrite, also called isoamyl nitrite)

Uses.
Various chemical subvarieties of nitrite inhalants exist. Isobutyl nitrite is popular in some teenager circles and has been called “the cocaine of poor people.” Although anyone is physically free to use any drug, authorities find that nitrite sniffing has particular appeal to male homosexuals, especially during sexual activity. Aphrodisiac qualities are claimed for the substance. Amyl nitrite sniffers report euphoria and muscle relaxation. Isobutyl nitrite users
report losing their sense of who they are and also becoming calm or, in contrast, becoming prone to wild conduct—differences that may illustrate the impact that someone’s personality and surroundings have on drug experiences.

Regardless of exact content of a nitrite experience, sensations are brief. Some persons have confused nitrites with nitrates; they have a similar spelling but are different substances.

Drawbacks.
Nitrite inhalants have brief action but may incapacitate a person during that time and thus should not be used while engaged in dangerous activity such as driving a car. Unwanted actions of nitrites include feelings of falling and spinning, headache, facial flushing, rapid heartbeat, generalized throbbing feelings, and low blood pressure (low enough to make a person
faint). Less common are nausea, vomiting, agitation, sweating, loss of energy and strength, and loss of bladder and rectal control. In mice experiments involving single and multiple exposures, inhaling isobutyl nitrite can cause anemia, harm the immune system, create nose and lung abnormalities, and disturb the spleen. Similar results are seen with rats. Blood and spleen abnormalities developed in a mice experiment using cyclohexyl nitrite. In a human patient, sniffing isobutyl nitrite caused bronchitis severe enough to affect the trachea. Amyl nitrite (which has a long medical history as a heart medicine) and isobutyl nitrite may each cause methemoglobinemia, a sometimes fatal blood disease interfering with the body’s use of oxygen; this affliction is particularly likely if a person drinks isobutyl nitrite instead of inhaling the
vapor. Isobutyl nitrite interference with the body’s ability to use oxygen may be perilous for persons with inadequate oxygen supply to the heart.

In the early days of AIDS (acquired immunodeficiency syndrome) research, scientists noticed that many victims were nitrite sniffers. Because of this association, at one time nitrite sniffing was suspected to be the cause of AIDS, an excellent example of why association of a chemical with a disease cannot be assumed to demonstrate a cause-effect relationship. The substance is still, however, suspected of worsening the progression of AIDS once the disease strikes. In addition, damage to the immune system caused by nitrite inhalation is suspected of making a user more susceptible to AIDS and to a type of cancer called Kaposi’s sarcoma.

Abuse factors.
Tolerance to amyl nitrite can develop.

Drug interactions.
Although amyl nitrite is used as an antidote for cyanide poisoning, isobutyl nitrite can interact with coffee in a way that produces enough cyanide to poison someone who drinks the combination beverage. Using amyl nitrite with alcohol can cause heart failure. Nitrites are flammable, making them hazardous around flames or lit cigarettes. Persons with glaucoma
are supposed to avoid amyl nitrite. People report burns caused by isobutyl nitrite splashing on skin.

Cancer.
Laboratory tests and animal experiments (the latter involving longterm exposure) indicate that isobutyl nitrite liquid and vapor each cause cancer.

Pregnancy.
In the body nitrite breaks down into chemicals that may promote birth defects. The lower blood pressure produced by amyl nitrite is believed harmful to a fetus. Whether amyl nitrite passes into the milk of nursing mothers is unknown.

Additional scientific information may be found in:
Bradberry, S.M., et al. “Fatal Methemoglobinemia Due to Inhalation of Isobutyl Nitrite.”
Journal of Toxicology: Clinical Toxicology 32 (1994): 179–84.

Covalla, J.R., C.V. Strimlan, and J.G. Lech. “Severe Tracheobronchitis from Inhalation
of an Isobutyl Nitrite Preparation.” Drug Intelligence and Clinical Pharmacy 15
(1981): 51–52.

Haverkos, H.W., and J. Dougherty. “Health Hazards of Nitrite Inhalants.” American
Journal of Medicine 84 (1988): 479–82.

Haverkos, H.W., et al. “Nitrite Inhalants: History, Epidemiology, and Possible Links
to AIDS.” Environmental Health Perspectives 102 (1994): 858–61.

Israelstam, S., S. Lambert, and G. Oki. “Use of Isobutyl Nitrite as a Recreational Drug.”
British Journal of Addiction to Alcohol and Other Drugs 73 (1978): 319–20.

Lange, W.R., and J. Fralich. “Nitrite Inhalants: Promising and Discouraging News.”
British Journal of Addiction 84 (1989): 121–23.

Soderberg, L.S. “Immunomodulation by Nitrite Inhalants May Predispose Abusers to
AIDS and Kaposi’s Sarcoma.” Journal of Neuroimmunology 83 (1998): 157–61.

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Nutmeg (Mace, Myristica fragrans)

Pronunciation: NUT-mehg
Chemical Abstracts Service Registry Number: 84082-68-8
Formal Names: Mace, Myristica fragrans
Type: Hallucinogen.
Federal Schedule Listing: Unlisted
USA Availability: Nonprescription (food)
Pregnancy Category: None

Uses.
Nutmeg is a familiar spice, but when used in larger amounts, it can act as a drug. Nutmeg originated in the Spice Islands of Indonesia. It is a seed coming from an evergreen tree that can reach 45 feet in height. Folk medicine uses nutmeg for treating insomnia, mouth sores, stomach inflammation, gas, diarrhea, and vomiting. Animal research verifies the antiinsomnia and antidiarrhea properties; they have been observed among humans undergoing formal
medical care, and recreational users mention sleep-inducing action. The substance is also used as an aphrodisiac, and laboratory tests show that it kills headlice. Nutmeg may be able to help improve dysentery, infections, and rheumatism. In rabbit experiments, nutmeg lowered cholesterol levels and aided in coughing up mucus. Nutmeg, like many other spices, has antimicrobial actions that appear to retard spoilage of unrefrigerated food.

Nutmeg can produce false positives for marijuana in a field test that law enforcement officers have used to identify an unknown substance, but of course more sophisticated laboratory examination can correct such an error.

Drawbacks.
A nutmeg dose sufficient to produce hallucinations is also sufficient to produce headache, thirst, nausea, constipation, rapid heartbeat, dizziness, and a miserable hangover. Muscular discoordination can be severe enough to mimic multiple sclerosis. Research on cats produced liver destruction. All these results are from dosage quantities much higher than the small
amounts used for spicing foods.

Abuse factors.
Nutmeg is not considered addictive, although a case report notes a patient hospitalized for nutmeg poisoning, who craved the substance so much that he had a supply smuggled to him during his hospital stay. The report said he was never able to go beyond two weeks without nutmeg.

Some researchers are skeptical that nutmeg possesses hallucinogenic qualities, but for centuries numerous users have said otherwise. Betel chewers sometimes add nutmeg to a quid for extra sensations, and mixing tobacco with nutmeg is a practice reported in Asia. Research indicates that human body chemistry converts part of a nutmeg dose into substances related to amphetamine, affecting mood and sometimes causing hallucinations. The effects from a dose can last three days. Overdose requiring medical intervention is possible, although only one fatality is recorded. Nutmeg has received mixed reviews as a recreational drug. Some people call it incomparable; others resort to it only as an act of desperation when nothing else is available. A favorable description says nutmeg is “capable of removing one completely from the
world of reality in a hypnotic trance accompanied by golden dreams and euphoric bliss.”1 In contrast, someone who used nutmeg together with marijuana received emergency hospital treatment for gagging, hot and cold flashes, numbness, blurred vision, double vision, triple vision, and difficulty in controlling movements—among other complaints. Persons who use nutmeg by
itself have also reported bad experiences.

Drug interactions.
In a mice experiment nutmeg boosted actions of alcohol and reduced those of dextroamphetamine. One authority describes nutmeg as a weak monoamine oxidase inhibitor (MAOI), and MAOIs interact badly with many drugs described in this blog.

Cancer.
A laboratory test using a nutmeg extract found evidence that it might cause cancer, and a nutmeg experiment with mice produced DNA changes that might be related to eventual cancer.

Pregnancy.
Male mice that received nutmeg in an experiment did not show chromosome damage. A case report notes a normal full-term infant born to a woman who had experienced nutmeg poisoning during pregnancy, but pregnant women are advised to avoid using nutmeg as a drug.

Additional information.
As with many other natural products, nutmeg’s effects may be produced by the combination of hundreds of chemicals found in the substance. Researchers have identified several chemicals as likely causes of nutmeg’s effects: elemicin, eugenol, myristicin, and safrole. Under laboratory
conditions myristicin can be chemically converted to MDMA and safrole to MDA, but this conversion has never been detected in animals or humans.

Body chemistry does convert myristicin into substances resembling amphetamine.
Myristicin is found not only in nutmeg but in plants related to carrots. An experiment testing myristicin on rats found no poisonous result. Researchers found no evidence of cancer after dosing mice with the substance, but the study did not last long enough to reveal whether cancer would eventually develop. Myristicin’s potential for causing birth defects is unknown. Safrole
has a faint ability to promote cancer; pregnant women are advised to avoid using it as a drug.

Mace comes from the same seed as nutmeg does, but is a different spice. Folk medicine uses mace to reduce inflammation and pain; research indicates it can protect against some chemically caused cancers. Mace is routinely added to areca nut quids.

Additional scientific information may be found in:
Fras, I., and J.J. Friedman. “Hallucinogenic Effects of Nutmeg in Adolescent.” New York
State Journal of Medicine 69 (1969): 463–65.

Lewis, P.W., and D.W. Patterson. “Acute and Chronic Effects of the Voluntary Inhalation
of Certain Commercial Volatile Solvents by Juveniles.” Journal of Drug
Issues 4 (1974): 172.

Lewis, W.H., and M.P.F. Elvin-Lewis. Medical Botany: Plants Affecting Man’s Health. New
York: John Wiley & Sons, 1977. 408–10.

Panayotopoulos, D.J., and D.D. Chisholm. “Hallucinogenic Effect of Nutmeg.” British
Medical Journal 1 (1970): 754.

Sjoholm, A., A. Lindberg, and M. Personne. “Acute Nutmeg Intoxication.” Journal of
Internal Medicine 243 (1998): 329–31.

Van Gils, C., and P.A. Cox. “Ethnobotany of Nutmeg in the Spice Islands.” Journal of
Ethnopharmacology 42 (1994): 117–24.

Weiss, G. “Hallucinogenic and Narcotic-Like Effects of Nutmeg.” Psychiatric Quarterly
34 (1960): 346–56.

Note
1. W.H. Lewis and M.P.F. Elvin-Lewis, Medical Botany: Plants Affecting Man’s Health
(New York: John Wiley & Sons, 1977), 408.

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The Principal Alkaloids in Opium

Alkaloid---Chemical Class---Amount in Opium

Morphine---Phenanthrene---10%–15%
Noscapine---Benzylisoquinoline---4%–8%
Codeine---Phenanthrene---1%–3%
Papaverine---Benzylisoquinoline---1%–3%
Thebaine---Phenanthrene---1%–2%

Adapted from Moraes, Francis, and Debra Moraes. Opium. Oakland, Calif.: Ronin Publishing, 2003, p. 58

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Opium Addiction Treatment

Opium has been used as a medicine for hundreds of years, inevitably creating countless addicts. Scientists have conducted a never-ending search for effective cures for opium addiction, morphine addiction (morphinism), and heroin addiction. For most of its history, opium addiction was treated as a disease with no cure, and doctors concerned themselves with treating the symptoms of addiction rather than the root cause. As a result, other opiates were used to lessen the effects of withdrawal. The addict is placed on a regimen of opiates that slowly decrease over time, weaning the addict from his or her addiction. This process of treatment is still used today.

Over the years, scores of seemingly counterintuitive methods have been tried to cure the addict. When morphine was first isolated and synthesized, it was considered to be, and utilized as, a cure for opium addiction. Later, heroin was created, and used as a treatment for morphinism. In the mid-twentieth century, lysergic acid diethylamide (LSD) likewise was tried as a therapy. The sad truth is that even today there is no real cure for any of the various forms of opiate addiction.

Modern therapy uses a drug called methadone.
Methadone, discovered in the 1940s, is similar to morphine and heroin as a powerful analgesic. When injected, methadone prevents heroin and morphine from working and lessens the withdrawal effects of both. While also an addictive drug, methadone is used to treat heroin and morphine addiction because it is supposedly easier to quit using. Essentially, an addict on the therapy is given a dose of methadone equivalent to that of their heroin or morphine use. The patient receives lower and lower dosages, until they eventually need no drug at all.

Many addicts, however, report that weaning themselves off of methadone is just as bad as coming off of heroin or morphine addiction. Ultimately, primary treatments for opiate addiction rely on replacing one drug for another and are essentially palliative treatments. The user is never “cured” and will always be tormented by the specter of addiction.

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ACTIVE INGREDIENTS IN OPIUM

Seventy-five percent of raw opium consists of ingredients that have no significant biological effects, such as water, sugars, and fatty acids. The remaining 25 percent contains numerous biologically active ingredients that interact with opioid receptors. These agents are termed the opiod alkaloids.

Alkaloids are complex organic molecules, many of which have been used in traditional medicine or as poisons.

Atropine from the deadly nightshade plant dilates the pupil of the eye, and curare is a skeletal muscle relaxant employed in anesthesia, but both agents have also been used as poisons.

Opium contains at least 20 alkaloids and by some claims as many as 50. However, five principal alkaloids are of major interest: these are morphine, codeine, noscapine, papaverine, and thebaine.

Morphine is the most abundant of the opium alkaloids. It constitutes as much as 15 percent of the plant extract.

Morphine has been used as a medicine and narcotic for thousands of years. Therapeutically, morphine has three principal uses: as an analgesic for the relief of acute and chronic pain, as a respiratory depressant, and as an antidiarrheal agent. The analgesic properties are morphine’s most important clinical use.

Codeine is a close chemical relative of morphine, differing in only one chemical group. Once administered, codeine is actually metabolized by enzymatic action, and its actions mimic those of morphine. Codeine is used primarily as a cough suppressant, although it certainly also possesses significant analgesic properties (approximately one tenth those of morphine) as in the relief of pain from toothache.

Noscapaine has only minimal therapeutic and narcotic properties. It can be used as a cough suppressant, but has no apparent advantage over other agents.

Papaverine also has minimal narcotic properties.However, it does have vasodilator (blood vessel relaxant) properties, and because of this property it has been employed for both cognition enhancement and erectile dysfunction.

Thebaine has, despite its chemical similarity to morphine, no narcotic or therapeutic uses. It does, however, cause convulsions at high doses. It is also a useful chemical intermediate in the laboratory for production of other opioid compounds.

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PHARMACOLOGICAL AND OPIOID RECEPTORS

It has been recognized for more than a century that the neurotransmitters of the nervous system produce their biological effects through interaction at specific drug binding sites or receptors. These receptors, many of which have been isolated and characterized in the past two decades, are typically specialized proteins on the cell surface. The function of these proteins is to recognize the neurotransmitter and to enable the molecule to bind to the receptor to trigger a biological response— muscle contraction, hormone or neurotransmitter secretion, or increased cardiac rate, for example. These interactions are typically quite specific and are often viewed in terms of a “lock and key”model. Despite this specificity it is usually found that a number of chemical variations around a particular structure can also be accommodated at the receptor site.

When these chemical variants can also trigger the biological response they
are termed “agonists.” However, some molecules can bind to the receptor and not trigger the response, but rather block the response: these drugs are termed “antagonists.”Thus, for example, the naturally occurring atropine from the Belladonna plant can block the actions of the neurotransmitter acetylcholine in the parasympathetic system by interacting with the same receptors that acetylcholine uses.

The alkaloids in opium, including morphine, also interact with specific receptors (opiate receptors) within the central and peripheral nervous systems. At these receptors, the alkaloids in opium mimic the effects of the body’s natural opiates.

There are actually three major structural classes of opiates that occur in the body: enkephalins, endorphins, and dynorphins. The existence of these endogenous molecules was initially theorized because morphine and related drugs had been shown to exert their pharmacological and therapeutic effects through interaction at specific receptors.Due to the specific locations of these interactions, scientists postulated that there must exist corresponding endogenous physiologically employed molecules. A similar argument was employed in the search for the endogenous equivalent of the cannabinoids found in marijuana and led to the recognition of the so-called “endocannabinoid” system.

There are three principal classes of opiate receptors, designated m, k, and d, and there exist a number of drugs that are specific for each of these receptor types. However, most of the clinically used opiates are quite selective for the mÙreceptor: the endogenous opiates enkephalin, endorphin and dynorphin are selective for the mÙand d, d and k receptors respectively.When activated by opioids these receptors produce biochemical signals that block neurotransmitter release from nerve terminals, a process that underlies their blockade of pain signaling pathways as well as other effects, such as constipation, diuresis, euphoria, and feeding.

Brief administration of opioids leads to the development of acute tolerance, whereby increased quantities of the opioid are required to produce the same end result, but this process is rapidly reversed once the administration is ceased.

However, more prolonged administration leads to classical or chronic tolerance from which state recovery to full sensitivity make take several days. These phenomena are not unique to opioid drugs, but rather are common to virtually all drug-receptor interactions and appear to be a common property of pharmacological receptors. Tolerance may also be associated with the state of physical dependence. The chronic administration of a drug, in this context an opioid, may result in a resetting of homeostatic mechanisms, and maintenance of this new state requires continued drug administration. Cessation of drug administration can then result in the phenomenon of withdrawal, during which the nervous system is excessively perturbed as it readapts to its original drug-free state. It should be emphasized that tolerance and physical dependence are physiological responses to continued administration of opioids and are not, contrary to some popular opinion, predictors of addiction. For example, patients with severe pain from bone cancer require very large amounts of opioids, yet these patients do not become addicted and will not even show withdrawal if the drug doses are reduced slowly over a period of days. Unfortunately, misinformation about opioids has led to patients with severe pain being undertreated.

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OPIUM AND THE NERVOUS SYSTEM

Although the nervous system is often discussed in terms of peripheral and central components, it should be regarded as a highly integrated whole in which the central nervous system (brain and spinal cord) plays a critical information gathering and processing role. The peripheral nervous system is often divided into the autonomic and somatic components. The somatic system controls the voluntary functions of the body, like those of the skeletal muscles. The autonomic system, in contrast, is often referred to as the “involuntary” system. It regulates parts of the body where we execute little or no conscious control, such as the heart, intestines, vasculature, and other internal organs.

The autonomic nervous system is divided into the sympathetic and parasympathetic components, which typically exert opposing effects. The sympathetic system is involved in the “fight or flight” reaction (increased blood pressure and heart rate, and accommodation for increased vision, for example) that prepares the organism for stressful situations. The parasympathetic system conversely establishes a more relaxed situation, for instance, the rest period after a meal. The autonomic nervous system that is responsible for the independent control of the mechanical and secretory functions of the gastrointestinal tract is sometimes called the enteric system.

Drugs that affect the central nervous system may also have a major action in the gut. Thus, the constipating effects of opium alkaloids are exerted through this system and a number of the important withdrawal symptoms reflect the actions of the enteric nervous system. The nervous system is often regarded as a command (efferent) system that sends instructions to be executed. However, there is also a sensory (afferent) component, that receives information from innervated systems and that is vital to the overall integrated nervous response.

Despite the anatomical and functional differences between the various components of the nervous system, they share a fundamental similarity in their use of chemicals (neurotransmitters) to convey information.

The individual unit of the nervous system is the neuron, a specialized cell that both receives and transmits information.

The nervous system contains more than 100 billion neurons and is a major user of metabolic energy in the human body. It is also a region particularly susceptible to injury from toxic chemicals, lack of oxygen, and other assaults. Depending on the nervous region in which they reside, neurons may have different anatomical features and may use different chemical transmitters. Neurons communicate with each other and with their end organs by these chemical signals, which are released from the nerve terminal and interact with specific receptors on adjacent neurons or cells.

The chemical transmitters may be small molecules—notably acetylcholine, norepinephrine, epinephrine, serotonin, dopamine, or histamine. Acetylcholine and norpeinephrine are the dominant neurotransmitters in the parasympathetic and sympathetic nervous systems, respectively.

Dopamine and serotonin are employed primarily in the central nervous system. Neurotransmitters may also be more complex peptides (small proteins) such as substance P, vasopressin, endorphins, and enkephalins. The latter agents are of particular importance to our considerations of opium since they represent the “endogenous” opiates—agents that exist within the body whose actions are mimicked by exogenous, or outside, agents such as morphine, heroin, codeine, and so on. These neurotransmitters serve to convey information between neurons across the synaptic cleft (the junction where two neurons meet) or at the neuroeffector junction (the site between neuron and an innervated organ such as muscle or secretory gland).

Each neuron has specific synthetic machinery that enables it to both synthesize and eliminate a specific neurotransmitter.

For example, neurons of the sympathetic nervous system employ norepinephrine and epinephrine as their transmitters. Other neurons, particularly in the central nervous system, employ dopamine as their transmitter. Dopamine is a particularly important transmitter for a variety of neuronal functions. Its loss is associated with Parkinson disease, and it is a critical agent in the mediation of pleasure and reward processes. Dopamine, due to its association
with pleasurable sensations, is widely implicated in the actions of a number of drugs of abuse, including cocaine, opiates, and methamphetamines.

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The International Language of Poppy (Opium)

Contrary to what its name suggests, opium is not a single chemical compound. Its chemical make-up is more like a salad, consisting of various substances including sugars, proteins, acids, water, and many alkaloids, among others. The people who grow opium for its narcotic value are primarily interested in the alkaloids.

An alkaloid is a complex organic chemical substance found in plants, which characteristically combines nitrogen with other elements, has a bitter taste, and typically has some toxic, stimulant, analgesic effects. There are many different alkaloids, 30 of which are found in the opium plant. While morphine is the most important alkaloid in opium—for its natural narcotic qualities as well as providing the chemical structure for heroin—another alkaloid, codeine, is also sought after for its medicinal attributes. Other alkaloids include papaverine, narcotine, nicotine, atropine, cocaine, and mescaline. While the concentration of morphine in opium varies depending on where and how the plant is cultivated, it typically ranges from 3 percent to 20 percent.

The International Language of Poppy
Bengali Afing-gach, Posto
Burmese Bhainzi
Dutch Papaver
English Poppy
French Pavot somnifere
German Mohnblume
Hindi Post, Khas-khas, Post dana
Hungarian Mak, Kerti mak
Italian Papavero
Japanese Hinageshi
Polish Mak lekarski
Portuguese Popoula
Romanian Mac
Sanskrit Ahiphena
Spanish Adormidera, Amapola
Swedish Vallmo
Thai Ton fin
Turkish Hashhash tohuma

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Peyote (Lophophora williamsii)

Pronunciation: pay-OH-tih (also pronounced peh-YOH-teh)
Chemical Abstracts Service Registry Number: 11006-96-5
Formal Names: Lophophora williamsii
Informal Names: Bad Seed, Big Chief, Black Button, Britton, Buttons, Cactus, Cactus
Head, Challote, Devil’s Root, Dry Whiskey, Dumpling Cactus, Half Moon, Hikori, Hikuli, Hyatari, Mescal, Mescal Beans, Mescal Buttons, Mescalito, Mescy, Nubs, P, Pellote, Peyotl, Seni, Shaman, Tops
Type: Hallucinogen.
Federal Schedule Listing: Schedule I (DEA no. 7415)
USA Availability: Illegal to possess
Pregnancy Category: None

Uses.
Peyote is part of a cactus plant. Native American folk medicine has used peyote cactus root for doctoring scalp afflictions. In folk medicine peyote has also been used against snake bite, influenza, and arthritis. Scientists have determined that peyote contains substances that might fight infections. Some Native Americans are reported to use light doses of peyote as a stimulant to maintain endurance when engaged in relentless activity permitting little nourishment
or water, a practice sounding much like traditional use of coca. Spaniards observed such peyote usage in the Aztec empire.

Peyote’s main active component is the hallucinogen mescaline. Some other varieties of cactus also contain mescaline, although generally in much smaller amounts. Researchers suspect the peyote cactus may additionally contain chemicals similar to those appearing in the brain upon use of alcohol. In addition to causing hallucinations, peyote can change perception of time.

Psychic effects can include feeling more peaceful and connected with life; craziness of the everyday world can recede. People can use the experience to work through their concerns and may be more open to suggestions. Physical senses may seem enhanced, and barriers between them may melt, such as allowing sounds to be seen.

Normally a Schedule I substance is illegal to possess except under special permission to do research with it, but for many years members of the Native American Church were allowed to possess and use peyote (but not the pure drug mescaline) for religious purposes. During the 1990s their legal situation became confused, and the issue was a matter of controversy when this book was written.

The religion of Peyotism (of which the Native American Church is but one variety) is a topic beyond the scope of this book, but drug-induced visions are only one part of the practitioners’ way of life. Observers have noted that Peyotism can be an effective way of dealing with addiction to alcohol and opiates. Traditional peyote use occurs in a group context, a social gathering
of persons sharing and furthering the same beliefs and goals. A solitary user estranged from such a setting is likely to have a far different peyote experience.

For instance, one element of a peyote session can be nervousness and fear, emotions that may have different impacts depending on whether a user is alone or is with a group of reassuring and supportive persons. A researcher with the Indian Health Service of the U.S. Public Health Service estimated that traditional peyote usage produced bad psychological experiences once in
70,000 doses, a safety record that the researcher attributed to the social context of traditional use. Physical damage has not been noted from traditional use.

Drawbacks.
Chills, muscle tension, nausea, and vomiting are typical unwanted peyote effects.

Abuse factors.
A study published in the 1950s concluded that peyote tolerance, dependence, and craving did not occur from traditional usage—a finding supported by other authorities as well. A canine experiment showed that tolerance to the vomiting effect occurred if dogs received daily peyote for a year.

Drug interactions.
Not enough scientific information to report.

Cancer.
Not enough scientific information to report.

Pregnancy.
Peyote has caused birth defects in hamsters. A study comparing peyote users to nonusers from the same Indian group found no increase in chromosome damage among the users.

Additional information.
Peyote is sometimes called “mescal,” which is also the name of an alcoholic beverage. The two substances are different, and the beverage has no connection with peyote. Likewise “mescal beans” are an alternative peyote name and also the name of a nonhallucinogenic food.

Additional scientific information may be found in:
Bergman, R.L. “Navajo Peyote Use: Its Apparent Safety.” American Journal of Psychiatry
128 (1971): 695–99.

Boyer, L.B., R.M. Boyer, and H.W. Basehart. “Shamanism and Peyote Use among the
Apaches of the Mescalero Indian Reservation.” In Hallucinogens and Shamanism,
ed. M.J. Harner, 53–66. New York: Oxford University Press, 1973.
Bruhn, J.G. “Mescaline Use for 5700 Years.” Lancet 359 (2002): 1866.
Ellis, H. “Mescal: A New Artificial Paradise.” The Contemporary Review 71 (1897). Reprinted
in Smithsonian Institution’s Annual Report 1897. Washington, DC: Author,
1898. 537–48.

Huttlinger, K.W., and D. Tanner. “The Peyote Way: Implications for Culture Care Theory.”
Journal of Transcultural Nursing 5, no. 2 (1994): 5–11.

Kapadia, G.J., and M.B.E. Fayez. “Peyote Constituents: Chemistry, Biogenesis, and Biological
Effects.” Journal of Pharmaceutical Sciences 59 (1970): 1699–1727.

La Barre, W. “Peyotl and Mescaline.” Journal of Psychedelic Drugs 11 (1979): 33–39.

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Pentobarbital (Cafergot, Nembutal, Pentobarbitone, Phenobarbitone )

Pronunciation: pen-toh-BAR-bi-tal
Chemical Abstracts Service Registry Number: 76-74-4
Formal Names: Cafergot, Nembutal, Pentobarbitone, Phenobarbitone
Informal Names: Nebbies, Nembies, Nemmies, Nimbies, Yellow Bullets, Yellow Dolls, Yellow Jackets, Yellows
Type: Depressant (barbiturate class).
Federal Schedule Listing: Schedule II (oral and parentral, DEA no. 2270), Schedule
III for suppositories (DEA no. 2271)
USA Availability: Prescription
Pregnancy Category: D

Uses.
This short-acting substance has sedative qualities but is considered ineffective in treating nervous apprehension. Because of the drug’s sleepinducing characteristics, it is used as a preliminary to administering anesthesia and as a short-term treatment for insomnia. Pentobarbital has been observed to lower blood pressure, body temperature, and muscle tone. The compound can be used as an emergency anticonvulsant when a person has seizures, and
has been used to treat alcohol addicts undergoing withdrawal. Pentobarbital has been found effective in reducing pressure that fluid creates in the brain after severe head injury. Pentobarbital reduces a type of nerve cell death called neuronal apoptosis, and this reduction may help prevent stroke. Animal studies indicate that pentobarbital can help protect brain tissue against radiation, which might have practical application during treatment of brain tumors. Veterinarians use the substance for euthanasia: An unusual demonstration of the drug’s strength occurred when a lion was poisoned by eating meat from a horse that had been killed with pentobarbital.

Drawbacks.
Although the drug is a sedative, it can cause hyperactivity in children. Sudden stoppage of combined pentobarbital and benzodiazepine therapy in an infant caused temporary chorea (involuntary jerking). A feline experiment showed that tremors reminiscent of Parkinson’s disease can occur when pentobarbital is administered with chlorpromazine (also called Thorazine, often used to treat psychotic behavior). Persons with porphyria, a body chemistry affliction that can provoke violence, are supposed to avoid pentobarbital. Examination of epileptic children receiving pentobarbital shows elevated readings for total cholesterol, though levels of high-density lipoprotein (so-called good cholesterol) and triglycerides (associated with heart attack and stroke) seem unaffected.

In a monkey experiment pentobarbital interfered with time perception, ability to learn, short-term memory, attention span, and interest in tasks. The substance impeded task performances in a human experiment, with performance getting worse as the amount of thinking necessary for a chore increased.

Such a drug is unlikely to be welcome in the workplace. Although children using the substance apparently have trouble with language skills, a study found language development to be normal two years after the medication ceased.

Abuse factors.
In a test, alcohol drinkers who were not alcoholics found pentobarbital less appealing than a placebo and experienced no euphoria from pentobarbital, a finding consistent with other studies of persons who do not abuse drugs. When given choices of assorted substances, monkeys chose pentobarbital less often than water, which indicates the compound has low addictive potential. In contrast, drug abusers participating in an experiment found effects of pentobarbital and diazepam to be similar. Those two drugs thus had comparable appeal even though scientists running the experiment found pentobarbital possessing only 10% of diazepam’s strength. A study testing various effects on former drug addicts found pentobarbital to be 15 times
stronger than meprobamate, but morphine acted 6 times stronger than pentobarbital.

Cross-tolerance among chlordiazepoxide, pentobarbital, and alcohol has been observed in rats. A study of sedative drug abusers found alcohol and pentobarbital to deliver similar effects, with pentobarbital possibly having more appeal. A monkey experiment indicates that alcohol increases the attractiveness of pentobarbital. Dependence can develop, and in humans the
pentobarbital withdrawal syndrome can duplicate the delirium tremens of alcohol withdrawal. A mice study found that tolerance to pentobarbital developed more rapidly if assorted drugs of abuse were also being administered (morphine, amphetamine, alcohol, or cocaine).

Drug interactions.
A case report notes that pentobarbital can almost double the speed with which theophylline (commonly used to treat asthma and other breathing difficulties) disappears from the bloodstream, requiring changes in normal theophylline dosage. In a mice experiment alcohol boosted pentobarbital’s potency. A human study found that chronic alcohol ingestion reduces
the effective length of a pentobarbital dose. Grapefruit juice extends the amount of sleep produced by pentobarbital in rats, and in mice the drug inhibits caffeine effects. At one time researchers suspected that taking pentobarbital along with MDMA would reduce organic brain damage caused by MDMA, but rat experiments indicate that any apparent benefit comes simply
from the lower body temperature produced by pentobarbital. Although cocaine is a stimulant, in a rat experiment it increased the sleep-inducing quality of pentobarbital.

Cancer.
In animal experimentation pentobarbital has caused cancer. In humans long-term usage is associated with cancer of the ovaries and bronchi, but that finding is weakened by the patients also smoking cigarettes. Pregnancy. A large survey of pregnancy outcomes found that pentobarbital does not appear to cause birth defects. Nonetheless pregnant women are supposed
to avoid the drug.

Additional information.
Some capsule formats of Nembutal (pentobarbital sodium CAS RN 57-33-0) contain FD&C Yellow No. 5 (tartrazine), which can cause asthma attacks or other allergic responses in sensitive persons, particularly if someone has adverse reactions to aspirin. Cafergot PB is a combination
of bellafoline, caffeine, and ergotamine tartrate. The combination was tested with and without pentobarbital sodium to determine effect on migraine headache. Presence of pentobarbital not only enhanced reduction of pain but also helped treat anxiety, nausea, vomiting, poor appetite, and low tolerance of light.

Additional scientific information may be found in:
Cole-Harding, S., and H. de Wit. “Self-Administration of Pentobarbital in Light and
Moderate Alcohol Drinkers.” Pharmacology, Biochemistry, and Behavior 43 (1992):
563–69.

Hambly, G., C. Frewin, and B. Dodd. “Effect of Anticonvulsant Medication in the Preschool
Years on Later Language Development.” Medical Journal of Australia 148
(1988): 658, 661–62.

Mintzer, M.Z., et al. “Ethanol and Pentobarbital: Comparison of Behavioral and Subjective
Effects in Sedative Drug Abusers.” Experimental and Clinical Psychopharmacology
5 (1997): 203–15.

Pickworth, W.B., M.S. Rohrer, and R.V. Fant. “Effects of Abused Drugs on Psychomotor
Performance.” Experimental and Clinical Psychopharmacology 5 (1997): 235–41.
Pierce, James I. “Drug-Withdrawal Psychoses.” American Journal of Psychiatry 119
(1963): 880–81.

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Pentazocine (Fortral, Fortralgesic, Fortralin, Fortwin, Liticon,Pentgin, Sosegon, Sosenyl, Talacen, Talwin, Talwin Nx)

Pronunciation: pen-TAZ-oh-seen
Chemical Abstracts Service Registry Number: 359-83-1. (Hydrochloride form 64024-15-3)
Formal Names: Fortral, Fortralgesic, Fortralin, Fortwin, Liticon, Pentgin, Sosegon, Sosenyl, Talacen, Talwin, Talwin Nx
Informal Names: 4 4s, Teacher, Ts, Yellow Footballs. Combination with methylphenidate:
Crackers, 1s & 1s, Poor Man’s Heroin, Ritz & Ts, Ts & Rits, Ts & Rs, Sets. Combination with tripelennamine: Ts & Blues, Ts & Bs
Type: Depressant.
Federal Schedule Listing: Schedule IV (DEA no. 9709)
USA Availability: Prescription
Pregnancy Category: C

Uses.
Pentazocine became available in the 1960s. Some authorities classify the drug as an opioid; some do not. Rather than having cross-tolerance with opiates and opioids, pentazocine can provoke a withdrawal syndrome from them. Volunteers who receive pentazocine have been uncertain about what sort of drug it is; some say it is a hallucinogen; some think they are receiving
alcohol.

Pentazocine has about the same pain relief strength as codeine. An experiment using oral surgery patients found pentazocine’s pain relief to be the same as aspirin’s. After drug abusers began grinding down Talwin tablets and injecting the powder to get morphine and heroin sensations, the manufacturer introduced Talwin Nx tablets, which include a chemical designed to block those sensations if the substance is injected. Dispute exists about whether the Nx version of Talwin actually prevents effects sought by illicit users.

Research indicates that women surgical patients tend to get better pain relief from pentazocine than male patients. Research also indicates that the drug’s surgical pain control is more effective for older patients and less effective for neurotics and for individuals with outgoing personalities.

The drug has been routinely used to ease cancer pain and has had success in reducing joint pain
caused by various afflictions, including arthritis. After noting that pentazocine does not prolong bleeding times, researchers called it suitable to fight pain from hemophilia, a blood disease that promotes bleeding. The substance has also been given as a treatment for stubborn cases of hiccups.

Investigators have documented that people can briefly experience euphoria after taking the drug. Some users feel more amiable and serene after a dose. Drawbacks. Unwanted pentazocine actions include rapid heartbeat, blood pressure changes (up or down), fainting, sweating, confusion, sleepiness, blurred vision, nausea, vomiting, and constipation. Studies have found that
1% to 10% of persons receiving the drug (especially an injectable pharmaceutical version) have odd psychological reactions such as hallucinations, delusions, or a sense of unreality about the world. The substance can interfere with decision making and physical movement. Research has shown that driving skills decline when a person uses the drug, and users should avoid operating
motor vehicles or other dangerous machinery. Because pentazocine has occasionally been associated with seizures, it should be used cautiously by persons prone to that affliction. The substance should also be used cautiously by people suffering from pancreas malfunction or breathing difficulty. The drug may be particularly hazardous for asthma sufferers who are overly sensitive to aspirin. Pentazocine is associated with skin hardening, which can result in
extensive surgical removal of affected areas, to be replaced with skin grafts.

Case reports tell of the drug provoking not only skin lesions but internal lesions in the digestive tract. Prolonged use of the substance can also cause muscle destruction that cripples a person’s ability to move arms and legs. The compound can dangerously reduce white blood cell levels. Rat experiments indicate the drug may provoke attacks of porphyria, a body chemistry disease
that can make people violent and sensitive to light.

One group of researchers documented that pentazocine increased the heart’s workload by 22% in cardiac disease patients. Another group found that after a heart attack the drug increases blood pressure and the heart’s need for oxygen and concluded that pentazocine is dangerous for heart attack patients.

Not all authorities agree with that conclusion, however; some say that such adverse cardiac effects can be avoided through careful dosage, and other opinion says the drug is preferable to morphine for heart attack patients.

Abuse factors.
Some abusers inject powder from oral pentazocine tablets.
Oral pentazocine tablets contain ingredients not intended for introduction into the bloodstream, and injection can be fatal even though the digestive system can handle the same ingredients without difficulty.

Pentazocine and the antihistamine-anesthetic tripelennamine are a common illicit drug combination called Ts & Blues, sometimes used as a substitute for heroin (“T” standing for Talwin and “Blues” for the antihistamine tablets’ color). The combination can create more euphoria than pentazocine alone produces and reduce the discontent caused by some doses of pentazocine. Users report development of memory trouble. Lung damage is a classic consequence of the combination, promoted by injecting oral formats of the drugs. Users
have been hospitalized with chest pain, anxiety, spasms, sweating, nausea, and lightheadedness. Fainting and seizures are less common problems. Kidney damage has been noted. Other antihistamines can also be dangerous to use with pentazocine.

Pentazocine tolerance and dependence can occur. After daily doses were given to monkeys for six weeks, mild withdrawal symptoms appeared when the animals received nalorphine, a substance that provokes withdrawal signs if someone has been using opioids. That result supports classifying pentazocine as an opioid, but in humans nalorphine does not cause pentazocine withdrawal— a result consistent with pentazocine not being an opioid. Pentazocine
withdrawal is normally likened to a light version of the opiate withdrawal syndrome, although case reports tell of some persons suffering intense physical discomfort for up to two weeks (cramping muscles, painful abdomen and back, nausea, itching, sweating, and general discomposure). Debate exists about whether pentazocine addiction should be treated by substituting other drugs such as methadone or whether treatment should avoid substitution
altogether. Some authorities have wondered if pentazocine addiction occurs in persons who are not polydrug abusers. Some authorities even question whether pentazocine addiction exists, noting cases in which body fluid testing contradicted drug users’ claims to be using the drug (while indicating they were using other substances). German researchers found that addiction reports are at least exaggerated; upon investigation, only 8 of 60 reports turned out to be authentic.

Drug interactions.
Persons who smoke or who live in a polluted air environment may need higher doses of pentazocine than persons who breathe clean air. Morphine and pentazocine boost each other’s pain-relieving action. Alcohol and possibly monoamine oxidase inhibitors (found in some antidepressants) may react badly with pentazocine.

Cancer.
Animal research has not shown pentazocine to cause cancer.

Pregnancy.
Normal production of litters has occurred when pentazocine was given to pregnant rats and rabbits, and no birth defects were apparent.

The drug is absorbed by the fetus if a pregnant woman takes a dose. Examination of one hospital’s records of all pregnant patients who used pentazocine illicitly in a two-year period showed that their infants tended to be premature and undersized, but no malformation was attributed to the drug. Newborns were occasionally dependent. Despite those disadvantages the children seemed to develop normally in their first year of life. When pentazocine was given simply as a pain reliever in childbirth, examination of the infants revealed no difference from children born to women who did not receive a medical dose of the drug during childbirth.
A study found Ts & Blues mothers to have an increased rate of assorted diseases that would not promote healthy fetal development: hepatitis, anemia, gonorrhea, syphilis. Such afflictions indicate a risk-taking lifestyle in which prenatal care is a small concern. A survey of maternity records at one hospital showed that pregnant women who used Ts & Blues tended to produce smaller infants, but no major birth defects were associated with the drug combination.

Another study found behavioral abnormalities in newborns that had fetal exposure to Ts & Blues, although the conduct may simply have been a temporary sign of drug withdrawal. Investigators running a rat experiment, however, noted long-term behavioral differences between a group of rats having fetal exposure to the drug combination and another group that was unexposed.

Additional scientific information may be found in:

Brogden, R.N., T.M. Speight, and G.S. Avery. “Pentazocine: A Review of Its Pharmacological
Properties, Therapeutic Efficacy and Dependence Liability.” Drugs 5
(1973): 6–91.

Debooy, V.D., et al. “Intravenous Pentazocine and Methylphenidate Abuse during
Pregnancy. Maternal Lifestyle and Infant Outcome.” American Journal of Diseases
of Children 147 (1993): 1062–65.

“Pentazocine.” British Medical Journal 2 (1970):409–10.

Saarialho-Kere, U., M.J. Mattila, and T. Seppala. “Parenteral Pentazocine: Effects on
Psychomotor Skills and Respiration, and Interactions with Amitriptyline.” European
Journal of Clinical Pharmacology 35 (1988): 483–89.

Showalter, C.V. “T’s and Blues: Abuse of Pentazocine and Tripelennamine.” Journal of
the American Medical Association 244 (1980): 1224–25.

Zacny, J.P., et al. “Comparing the Subjective, Psychomotor and Physiological Effects of
Intravenous Pentazocine and Morphine in Normal Volunteers.” Journal of Pharmacology
and Experimental Therapeutics 286 (1998): 1197–207.

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Opium (Papaver album, Papaver somniferum, Poppy)

Pronunciation: OH-pi-uhm
Chemical Abstracts Service Registry Number: 8008-60-4
Formal Names: Papaver album, Papaver somniferum, Poppy
Informal Names: Ah-pen-yen, Aunti, Aunti Emma, Big O, Black, Blackjack, Black Pill, Black Stuff, Chandoo, Chandu, Chinese, Chinese Molasses, Chinese Tobacco, Chocolate, Cruz, Dopium, Dover, Dover’s Deck, Dover’s Powder, Dreamer, Dream Gun, Dreams, Dream Stick, Easing Powder, Emma, Fi-Do-Nie, Garden-Poppy, Gee, God’s Medicine, Goma, Gondola, Gong, Goric, Great Tobacco, Gum, Guma, Hard Stuff, Hocus, Hop, Indonesian Bud, Joy, Joy Plant, Mawseed, Midnight Oil, Mira, Mud, O, Oil, OJ, OP, Ope, Pen Yan, Pen Yen, PG, Pin Gon, Pin Yen, Plant, PO, Pox, Skee, Tar, Tongs, Tox, Toxy, Toys, When- Shee, Winshee, Yen Shee Suey, Ze, Zero
Type: Depressant (opiate class).
Federal Schedule Listing: Schedule II (DEA no. 9600)
USA Availability: Prescription
Pregnancy Category: C

Uses.
Many opium products are discussed elsewhere in this book, but here we are dealing with the substance from which all those products originate. Opium has long been used to relieve pain, fight coughs, cure diarrhea, and control spasms. Traditionally, opium is dried sap harvested from the seedproducing portion of opium poppy plants. At harvest time fields of poppies can have a strong smell, and children in the fields can be overcome by those airborne chemicals. A modern opium variety is “poppy straw,” composed of dry or liquid extracts from the plant. The natural product can be used by itself or can be refined to produce various drugs known as “opiates,” valued for their medicinal effects.

Archaeologists have found evidence of opium poppy cultivation dating from 15,000 years ago, but examination of historical records has not proven that ancient peoples understood opium’s medicinal benefits; the product may have been used traditionally but without understanding how or even whether it worked. Opium may have been used in Roman Empire religious ceremonies, perhaps exploiting the drug’s effects to symbolize a process of death and reincarnation, and even older records imply that ancients may have believed that opium could produce happiness, although evidence of ancient recreational use is nonexistent.

The Opium War from 1840 to 1842 was the first drug war, followed by the second Opium War of 1856 to 1860. These military conflicts were fought against China by England and other European powers in order to force the Chinese government to legalize the opium trade (certainly a goal different from that of the “drug war” familiar to Americans as the twenty-first century
began).

Opium and its morphine component were widely used to treat wounded soldiers in the American Civil War, and later historians have routinely said that addiction became so common that it was called “the soldier’s disease.” Such illness may have existed, but an investigator who diligently examined medical writings from that time found none that attributed postwar addictions to war-related medical use. In that era the opium trade was legal, and someone who analyzed opium import statistics found no evidence that consumption rose due to Civil War addictions; a distinguished authority has noted that people of that era called dysentery “the soldier’s disease.”

Just before World War I an article in the Journal of the American Medical Association declared, “If the entire materia medica at our disposal were limited to the choice and use of only one drug, I am sure that a great many, if not the majority, of us would choose opium; and I am convinced that if we were to select, say half a dozen of the most important drugs in the Pharmacopeia,
we should all place opium in the first rank.”1 Although many useful drugs have been discovered since then, opium is still the basis for many standard medications. Because opium is a natural product, its morphine content can vary greatly from batch to batch. Opium commercially processed for medical use is adjusted so that 10% of any given amount of medical opium is composed of morphine.

Although medical opinion about opium has changed little, public opinion has changed a lot. Reasons for that shift go beyond the scope of this book, but in the nineteenth century, use of opium and its derivatives had wide social approval in America. Alcohol was considered more hazardous to health and home. One of the most telling measures of approval came from the life insurance industry in India, which freely granted policies to known opium users, as mortality statistics showed opium having no effect on life span. A life insurance official reported similar experience in China, although older users in China had higher mortality than older nonusers (probably many users took the drug for diseases that nonusers did not have, with the death rate
related more to those diseases than to opium). Some of those statistics would change as the twentieth century progressed because drug laws would change the kinds of people who used opium, thereby associating opium with populations having higher mortality for reasons unrelated to opium’s drug properties.

Although identified with China, opium has been grown in the United States. In the late eighteenth century Benjamin Franklin used laudanum (typically wine laced with opium) to treat himself for kidney stones. During the nineteenth century Americans used opium mainly as an ingredient in laudanum and paregoric. Paregoric is a liquid including anise, camphor, and opium. Paregoric was first produced in the eighteenth century as an asthma medicine.

The compound is no longer used for that purpose but can reduce lung congestion by helping people to cough up mucus. Paregoric is a standard diarrhea remedy and is used to help infants suffering from drug withdrawal syndromes. In the 1960s the compound had a flurry of popularity among opiate addicts who would process the product in hopes of isolating the opium, then inject the substance they produced. The outcomes were typical of what happens when oral medications are injected, resulting in lung damage and disfiguring injuries to injection sites.

Less familiar modern opium preparations include home remedy mixtures of the substance with caffeine, aspirin, and acetaminophen (Tylenol or other brands). In America opium preparations were once a standard method of quieting noisy infants and children, and that practice is still followed in some parts of the world. One hazard in that custom is the possibility of fatal overdose,
as people administering such concoctions do not always understand pediatric dosage.

Drawbacks.
Although some opium users have generally unhealthy lifestyles, few ailments have been attributed solely to the drug. Those ailments tend to be in the gastrointestinal tract, such as problems with the small intestine’s bile duct. “Cauliflower ear,” in which an ear thickens and becomes misshapen, was once associated with opium smoking. The affliction, however,
apparently came not from the drug but rather from the habit of lying down for hours in a comatose condition with an ear pressing against a hard surface.

Abuse factors.
Recreational use of opium is harder to define than we might think, because even if persons take the drug in a social setting, they can be seeking to reduce mental anxiety or physical pain, which is not the same as using a drug for fun. Some people swallow dry opium or drink tea made with
seed or with dried heads of poppy flowers. In the nineteenth century poppy tea was a common medicinal drink, but in the early twenty-first century the habit tends to be limited to opiate addicts. The traditional recreational way to use opium is to inhale its smoke. Heating opium enough to make it smoke can reduce the drug content, and opium is already far weaker than substances refined from it (such as morphine and heroin). One authority estimates that
the amount of active drug inhaled by someone who smokes a given weight of opium will typically be 300 to 400 times less than the drug content in the same weight of injected heroin. Moreover, while an entire dose of heroin might be ingested in a few seconds, a pipeful of opium is smoked over a much longer period to slowly savor its effects, further reducing the opium’s impact. The English poet Samuel Taylor Coleridge started out using opium for medical purposes, as did Thomas De Quincey, and both men produced classic accounts of hallucinations and creative inspiration occurring under opium’s influence. Those accounts and later ones may well be true, but for such results people need to be particularly sensitive to the drug and also be prone to such experiences regardless of pharmaceutical encouragement. Arsenic is sometimes added to opium to increase smokers’ interest in sexual activity, a practice generating reports of arsenic poisoning among users. Drug interactions. Not enough scientific information to report about the natural product, although many studies have examined drug interactions with opiates and opioids.

Cancer.
Laboratory tests find that opium smoke may cause cancer, as may opium dross (waste products, such as scrapings from the inside of an opium pipe, which some persons chew or suck). Opium is suspected of causing esophageal and bladder cancer.

Pregnancy.
A pregnant woman using paregoric can give birth to an infant having dependence with opium.

Additional information.
Seed from opium poppies is a food product commonly used in breads, cakes, and candies. Consumption of amounts found in a normal meal can cause a false opiate positive in drug screens; controversy exists about whether further analysis of results from such testing can show
that poppy seed was the cause. Poppy seed oil is a comparatively unfamiliar product, but animal tests indicate it has good potential for human nutrition. In some parts of the world iodized poppy seed oil has been used instead of iodized salt to treat goiter and has been suggested as a means of preventing nervous endemic cretinism caused by iodine deficiency in the diet of pregnant
women. Iodized poppy seed oil is taken up by cancerous portions of a liver, giving the substance clinical usefulness if anticancer drugs are blended into it, as the drugs then concentrate exactly where they are needed in the liver. Results from animal research have led investigators to speculate that consuming normal poppy seed oil may help prevent cancer.

Opium lettuce is not related to opium but can produce mild sensations similar to opium. Sedative and pain relief qualities of opium lettuce have been used for centuries. Lung and urinary tract afflictions have been treated with it. Opium lettuce is smoked for recreational purposes, but results have not caused the practice to gain popularity. A case report tells of individuals who
received medical care after injecting a preparation made from the plant. It has other names including Acrid Lettuce, Bitter Lettuce, Compass Plant, Great Lettuce, Green Endive, Lactucarium, Lactuca virosa, Poison Lettuce, Prickly Lettuce, Strong-Scented Lettuce, and Wild Lettuce.

Additional scientific information may be found in:
Aurin, M. “Chasing the Dragon: The Cultural Metamorphosis of Opium in the United
States, 1825–1935.” Medical Anthropology Quarterly 14 (2000): 414–41.

Gharagozlou, H., and M.T. Behin. “Frequency of Psychiatric Symptoms among 150
Opium Addicts in Shiraz, Iran.” International Journal of the Addictions 14 (1979):
1145–49.

Goodhand, J. “From Holy War to Opium War? A Case Study of the Opium Economy
in North-Eastern Afghanistan.” Disasters 24 (2000): 87–102.

Haller, J.S. “Opium Usage in Nineteenth Century Therapeutics.” Bulletin of the New
York Academy of Medicine 65 (1989): 591–607.

Kalant, H. “Opium Revisited: A Brief Review of Its Nature, Composition, Non-Medical
Use and Relative Risks.” Addiction 92 (1997): 267–77.

Lerner, A.M., and F.J. Oerther. “Characteristics and Sequelae of Paregoric Abuse.” Annals
of Internal Medicine 65 (1966): 1019–30.

Quinones, M.A. “Drug Abuse during the Civil War (1861–1865).” International Journal
of the Addictions 10 (1975): 1007–20.

Strang, J. “Lessons from an English Opium Eater: Thomas De Quincey Reconsidered.”
International Journal of the Addictions 25 (1990): 1455–65.
Note
1. 64 (February 6, 1915): 477.

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Nitrous Oxide (Dinitrogen Monoxide, Dinitrogen Oxide, Entonox)

Pronunciation: NIGH-truhs OX-eyed
Chemical Abstracts Service Registry Number: 10024-97-2
Formal Names: Dinitrogen Monoxide, Dinitrogen Oxide, Entonox
Informal Names: Fall Down, Gas, Hippie Crack, Hysteria, Laughing Gas, Nitro, Nitrous, Nitrous Acid, Noss, Pan, Shoot the Breeze, Tanks, Thrust, Whippets
Type: Inhalant.
Federal Schedule Listing: Unlisted
USA Availability: Nonprescription, but sales and usage are controlled in some
jurisdictions

Uses.
This drug has been known since the 1720s. Some authorities describe nitrous oxide as an opioid; some persons even use the gas to counteract effects from stimulants. Nitrous oxide actions and its recreational use are similar to those of other inhalants. Recreational use is illegal in some jurisdictions but has a venerable history. The writer Samuel Taylor Coleridge, thesaurus compiler Peter Mark Roget, and potter Josiah Wedgwood were all eighteenthcentury notables who relaxed with nitrous oxide.

Although this substance is a pharmaceutical product, it also occurs naturally. For instance, eating lettuce generates enough nitrous oxide that scientists can measure it in a person’s breath. Large quantities are produced by wild prairie grass. Humans do not receive enough nitrous oxide from such natural sources to be affected, however. The substance is also produced by the human
body. One study found the amount to increase as oral hygiene declined. As with the amounts produced by grass and lettuce, the level created by the body is too small to have any known effect on a person. From a global environmental perspective, however, nitrous oxide is a gas that promotes the greenhouse effect and ozone layer destruction, and concern exists about medical
usage affecting the world’s climate. Medical sources are estimated to create 2% of the atmosphere’s supply. Such usage may seem insignificant in that regard, but the gas is so durable in the atmosphere that any artificial source has been described as an environmental hazard.

Medically this drug is used as an anesthetic and to relieve pain ranging from dental work to migraine headache and cancer. In a medical context nitrous oxide is considered a reliable sedative. Experimental usage to treat anxiety has been successful, and one authority has noted a therapeutic antidepressant action. The substance has been used to help persons break entazocine addiction. Researchers report success in using the gas to ease alcohol,
nicotine, and opioid withdrawal and to reduce craving for alcohol, tobacco, and marijuana among addicts. The latter three substances are so different from one another that nitrous oxide’s ability to reduce craving for all of them is remarkable. Some medical practitioners claim that a single dose of the gas actually eliminates craving for those substances, but that claim sounds much
like those made for other “miracle cure” addiction treatments over the years but that turned out to be overly optimistic.

In former times, nitrous oxide was used to fight ear afflictions. For many years the substance was believed to make hearing more acute, but tests of hearing ability while using the compound show no improvement—and volunteers in those tests even felt they had lesser ability to detect soft sounds.

Nitrous oxide can increase pressure in the middle ear, and a case report tells of treatable hearing loss caused by the drug. Hearing defect has been reported from recreational use as well.

Typical nitrous oxide actions are tingling, numbness, dreaminess, euphoria, dysphoria (the opposite of euphoria), altered sensory perceptions, changed awareness of the body, and different experience of time flow. Although nitrous oxide is not classified as a hallucinogen, some descriptions of experiences are indistinguishable from hallucinations, particularly if a user is talented at creating internal imagery. Some persons claim to achieve mystical insight
while under the drug’s influence. Intoxication from a dose lasts only a few minutes.

Drawbacks.
The substance disrupts learning ability. That action has been exploited medically to promote amnesia of unpleasant procedures. In a typical experiment volunteers who inhaled a low dose of the drug showed worsened reaction time, worsened ability to do arithmetic, and general sedation accompanied by nervous system depression (as opposed to stimulation). Interference with driving ability has been noted one-half hour after a dose. In another experiment volunteers felt stimulated; in still another experiment some individuals were sedated, and others became stimulated. One group became weary, uneasy, and confused. Short-term exposure can cause dizziness, nausea, vomiting, and breathing difficulty. Some recreational users quickly inhale
as much nitrous oxide as possible and hold their breath. This technique causes a sudden change of pressure inside the lungs and can rupture small interior structures needed for breathing. Blood pressure can go up or down, depending on dosage. Users can lose consciousness, which may be hazardous in a recreational context due to falls or inability to shut off the gas source. The
substance deactivates vitamin B12, an effect that can cause numbness and difficulty in moving arms and legs. Other results can be impotence and involuntary discharge of urine and feces. Nitrous oxide interferes with blood clotting, and long-term exposure has caused blood abnormalities. Persons with chronic industrial exposure have more kidney and liver disease than usual.

Nitrous oxide can become very cold when released as a gas from a pressurized container, cold enough to cause frostbite upon meeting skin or throat.

Breathing nitrous oxide without an adequate supply of oxygen can be fatal; a little in a closed space or a lot from a face mask can suffocate a user. Although nitrous oxide is called nonflammable, when inhaled it can seep into the abdominal cavity and bowels, mixing with body gases to create a flammable combination. If ignited the result would be like setting off an explosive inside the body; the danger is real enough that surgical personnel administering
nitrous oxide as an anesthetic have been warned about it.

As with many other drugs, effects of nitrous oxide can be influenced by changes in setting. For example, volunteers who knew what to expect performed better on tests than persons who had no information about what nitrous oxide would do to them.

Abuse factors.
In tests of the drug’s appeal, people in general chose nitrous oxide no more often than placebo; such lack of preference is a classic sign of low addictive potential. One experiment revealed a catch to such findings, however: Volunteers who enjoyed nitrous oxide effects chose it more often than placebo, and volunteers who disliked the drug actions chose it less often
than placebo. Thus, overall in the general population the drug might be no more attractive than placebo, but nonetheless some persons may find it captivating.

Such a finding is consistent with drugs having high abuse potential, such as heroin; so the fact that persons typically find no attraction in nitrous oxide does not prove low abuse potential for nitrous oxide. Its nickname “hippie crack” suggests that users have recognized an abuse potential. Nonetheless, a medical practitioner who administered the gas as a drug addiction
treatment said that in 15,000 cases not a single addict indicated subsequent craving for nitrous oxide; such a patient population would be expected to show particular susceptibility if given a substance with abuse potential. The same practitioner notes that regardless of theoretical possibilities, 200 years of experience demonstrate that nitrous oxide is among the least abused drugs.

Tolerance develops in rats. Human experimentation documents tolerance developing to some effects (such as euphoria and pain relief) but not necessarily to all.

Drug interactions.
In an experiment comparing light drinkers of alcohol to moderate drinkers, the moderate drinkers found nitrous oxide more appealing. One group of researchers found that alcohol boosts nitrous oxide effects and that the drug combination creates effects produced by neither substance alone. Those researchers concluded, however, that the combination was not
potent enough to have more appeal than nitrous oxide alone. That conclusion assumes, of course, that drug abusers base their conduct on rational analysis of scientific findings. In a similar experiment comparing users and nonusers of marijuana, when given a choice neither group preferred nitrous oxide more than a placebo, but nitrous oxide effects felt stronger to marijuana users. In rats ketamine boosts effects from nitrous oxide. In a human medical context
that combination is routine and appears safe, but the combination causes brain damage in rats. Persons using morphine or other opiates can experience muscle rigidity when inhaling nitrous oxide, a situation that can interfere with breathing.

Cancer.
Studies do not indicate that nitrous oxide causes cancer in animals. Whether the drug causes cancer in humans is unknown. Genetic damage similar to the amount from daily smoking 10 to 20 cigarettes has been found in health care workers routinely exposed to minuscule amounts of nitrous oxide; such damage might have a potential for causing cancer.

Pregnancy.
Fertility is lower in female rats exposed to nitrous oxide than in rats having no exposure. Lower fertility has also been observed among female health care workers with occupational exposure to the gas, and reduced fertility is also reported for males. Offspring of male mice exposed to nitrous oxide have weighed less than normal and have not matured as fast as normal.

Birth defects resulted from an experiment exposing pregnant rats to the gas for 24 hours. When given to pregnant women during childbirth the drug builds up in the fetal blood and brain; one authority recommends administering oxygen to any newborn whose mother received nitrous oxide while giving birth. As the twenty-first century began researchers reported that the
gas might cause permanent fetal and newborn brain damage, a finding in contrast to previous understanding of the drug. Occupational exposure to nitrous oxide is associated with smaller infants and lower birth weight and may increase likelihood of spontaneous abortion. Pregnant and breast-feeding health workers are advised to avoid rooms where nitrous oxide residues may
contaminate the air. Sperm abnormalities and lower fertility have been noted in male rats exposed to nitrous oxide. Wives of men exposed to the gas have shown a higher spontaneous abortion rate, compared to wives of men with no exposure. The compound is not detected in milk of nursing mothers.

Additional information.
“Nitrous acid” is an unstable nitrite substance. The nickname “nitrous acid” is sometimes used for nitrous oxide, but they are different substances.

Additional scientific information may be found in:
Block, R.I., et al. “Psychedelic Effects of a Subanesthetic Concentration of Nitrous Oxide.”
Anesthesia Progress 37 (1990): 271–76.

Danto, B.L. “A Bag Full of Laughs.” American Journal of Psychiatry 121 (1964): 612–13.

Dohrn, C.S., et al. “Subjective and Psychomotor Effects of Nitrous Oxide in Healthy
Volunteers.” Behavioural Pharmacology 3 (1992): 19–30.

Linden, C.H. “Volatile Substances of Abuse.” Emergency Medicine Clinics of North America
8 (1990): 559–78.

Temple, W.A., D.M. Beasley, and D.J. Baker. “Nitrous Oxide Abuse from Whipped
Cream Dispenser Chargers.” New Zealand Medical Journal 110 (1997): 322–23.

Yagiela, J.A. “Health Hazards and Nitrous Oxide: A Time for Reappraisal.” Anesthesia
Progress 38 (1991): 1–11.

Zacny, J.P., et al. “Examining the Subjective, Psychomotor and Reinforcing Effects of
Nitrous Oxide in Healthy Volunteers: A Dose-Response Analysis.” Behavioural
Pharmacology 7 (1996): 194–99.

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