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Forensic Pharmacology

Page 10

by B Zedeck


  rences of certain aspects of a person’s LSD experience, without

  the user having taken the drug again. A flashback occurs sud-

  denly, often without warning, and may occur within a few days

  PiHKAL and TiHKAL

  Alexander “Sasha” Shulgin received his Ph.D. in biochemistry

  from the University of California, Berkeley. His research inter-

  ests are in psychiatry and pharmacology. A student aroused

  his interest in MDMA, and in the late 1970s and early 1980s,

  Shulgin introduced MDMA to psychologists for use in their

  patients. Shulgin synthesized and tested on himself, and on a

  small group of friends, hundreds of psychoactive chemicals.

  Shulgin and his wife Ann collected the entire chemical syn-

  thetic data and descriptions of effects, and published several

  books including PiHKAL (Phenethylamines I Have Known and

  Loved): A Chemical Love Story and TiHKAL (Tryptamines I Have

  Known and Loved): The Continuation.

  Hallucinogens

  95

  or even years after LSD use. Dysphoric effects following use of

  hallucinogens include sadness, anxiety, memory impairment,

  and depression.

  FORENSIC ISSUES

  Each dose of LSD (about 0.05 mg) is too small to be sold and

  administered separately. A solution of LSD is applied to a carrier,

  such as paper, which is then cut up into individual portions. A

  person convicted of distributing LSD is sentenced according to

  the entire weight of material seized, including the carrier. Since

  carriers may be of different weights, the same number of doses

  of LSD may carry different sentences. Although recognizing the

  unfairness of this law, the Supreme Court ruled that the weight

  of LSD does include carrier and that it is up to Congress to

  change the statute.

  In one actual case, a man used LSD and, within an hour there-

  after, killed a store owner. The defendant claims that he awoke

  one morning and took five to six Fioricet® tablets, went out and

  purchased two bags of heroin, and took cocaine hourly for five

  hours. Then, for the first time in six years, he took six “hits” of

  LSD. His memory afterward was vague, until he realized that

  he was in police custody. He apparently entered a store, had an

  argument with the owner, and killed him. People witnessing the

  events captured and held the defendant until the police arrived.

  The man was found guilty of murder.

  SUMMARY

  There are two main chemical categories of hallucinogens: the

  indolealkylamine derivatives, which are related to the neurotrans-

  mitter serotonin, and the phenethylamine derivatives, which

  96 Forensic Pharmacology

  are related to norepinephrine and dopamine. Hallucinogens

  alter the senses affecting sight, sound, touch, taste, and smell.

  They induce vivid images and sounds, profound emotional epi-

  sodes, altered perceptions of time and space, out-of-body expe-

  riences, and, if doses are high enough, convulsions. Tolerance

  does develop. There is some evidence that ecstasy can cause

  irreversible damage to serotonin neurons. Effects usually begin

  within minutes and can last for many hours. With LSD, flash-

  backs of prior experiences can occur without the user having

  taken more of the drug.

  Dissociative

  Anesthetics

  10

  Dissociative anesthetics induce analgesia in patients who are

  conscious but feel removed from their surrounding environment.

  The two prominent dissociative anesthetics are phencyclidine

  (PCP) and ketamine. PCP is a synthetic drug first prepared in

  1926 and tested as a general anesthetic for surgical patients in the

  late 1950s under the trade name of Sernyl®. Although anesthe-

  tized, patients given phencyclidine remained conscious, staring,

  and rigid, without depression of respiration or cardiovascular

  function. Following surgery, however, patients became deliri-

  ous, disoriented, and unmanageable, and phencyclidine testing

  was discontinued. Until 1978, the drug was still used legally

  for veterinary anesthesia under the name Sernylan®. In the late

  1960s, PCP became popular as a street drug in San Francisco

  and was termed the “peace pill.” In spite of reports of “bad trips”

  and violent behavior, its popularity increased during the 1970s

  and 1980s. Though illicit use of PCP declined with the rise of

  cocaine use in the 1980s, it now appears to be increasing.

  Street names for PCP include angel dust, cadillac, CJ, crystal,

  dust, elephant tranquilizer, embalming fluid, hog, jet fuel, juice,

  killer weed, love boat, Peace, PeaCePill, rocket fuel, sherms

  97

  98 Forensic Pharmacology

  Figure 10.1 Drug enforcement agents in the Phillipines surround

  confiscated bags and vials of ketamine after an apartment raid in May

  2005. The drugs had an estimated street value of $150,000 U.S. dollars.

  In powdered form, ketamine has an appearance similar to cocaine but

  a vastly different pharmacology.

  Dissociative Anesthetics

  99

  (using cigarettes produced by Nat Sherman Tobacco Company

  for dipping into liquid PCP), whack, and zoom. When used in

  combination with embalming fluid (which contains formalde-

  hyde, methanol, and ethanol), it is known on the street as wets,

  illy, and fry. It is also used in combination with heroin, LSD, and

  marijuana. The combination with marijuana is termed killer

  joints, crystal supergrass, or, in Spanish, yerba mala. PCP is listed

  in Schedule II.

  Calvin Stevens developed ketamine while working at Parke-

  Davis in 1961. It is used as a veterinary and human anesthetic,

  and is a Schedule III drug. It was widely used as a field anesthetic

  in the Vietnam War, and it entered the rave scene in the early

  1990s. Ketamine has been used as a date rape drug. Street names

  include baby food, cat Valium, honey oil, jet, K, keets, ket, special

  K, super acid, super C, and vitamin K (Figure 10.1). Trade names

  are Ketalar®, Ketajet®, and Ketaset®.

  PHARMACOLOGY OF PCP AND KETAMINE

  Both PCP and ketamine can be used as a liquid or solid and can

  be injected, ingested, snorted, or smoked when sprinkled on

  marijuana or parsley leaves. Heat destroys much of the drug.

  Peak blood levels occur within 15 minutes after smoking.

  The effects last for approximately 4 hours, although it may take

  more than 24 hours for an individual to return to a normal state.

  The drugs are stored in fatty tissue and released slowly. PCP has

  a long half-life ranging from many hours to days, and the PCP

  glucuronide metabolite can be found in urine for several days or

  weeks. PCP is found in breast milk. The half-life of ketamine is

  three to four hours, and metabolites of ketamine are excreted in

  urine. PCP and ketamine cross the placental barrier, and infants

  of chronic abusers have been born with cerebral palsy, facial

  deformities, and behavioral abnormalities.

  100 Forensic Pharmacology

  PCP and ketamine bind to the NMDA receptor
and block

  the neurotransmitter glutamate. PCP also blocks reuptake of

  dopamine, norepinephrine, and serotonin. Because so many

  neurotransmitters are affected, the signs and symptoms of PCP

  intoxication are numerous and varied.

  The acute behavioral effects of PCP and ketamine include

  euphoria, distortion of the senses and of time, impaired judg-

  ment, anxiety, sedation, analgesia, dizziness, dissociation from

  surroundings, amnesia, psychosis, panic attacks, paranoia, vio-

  lent behavior, hallucinations, catatonia (a condition character-

  ized by bizarre rigid positions and unresponsiveness), coma,

  and seizure. People may have thoughts of death and dying,

  and are susceptible to suggestion and manipulation. Under the

  influence of PCP, individuals have shown very bizarre behavior,

  including lying down in traffic, suddenly murdering or raping

  family members, and robbing a bank using a broom. Often the

  individual cannot recall any of the events.

  The physiological effects include an increase in blood pres-

  sure and body temperature, nystagmus, slurred speech, ataxia,

  blurred vision, excessive sweating and salivation, fast heart rate,

  nausea, vomiting, and extraordinary strength. Deaths have been

  recorded from heart or respiratory failure.

  Tolerance to dissociative anesthetics does develop. Psychologi-

  cal dependence is greater than physical dependence, although

  withdrawal symptoms may last for several weeks and include

  diarrhea, chills, tremor, anxiety, depression, and irritability. Pro-

  longed use of PCP may induce permanent learning disabilities,

  amnesia, depression, and antisocial behavior.

  FORENSIC ISSUES

  Examples of actual cases involving PCP include driving while

  impaired, murder, kidnapping, robbery, rape, and burglary. In

  Dissociative Anesthetics 101

  one particular case, a young woman driver struck another car,

  and the two occupants were killed. The driver was apprehended

  Drug Effects:

  Animals Versus Humans

  All medication needs to be approved by the Food and Drug

  Administration (FDA) before it can be released to the public

  in the United States. Many of the pharmacology studies of a

  drug’s efficacy and safety are first done on laboratory ani-

  mals. This is because there is much similarity in the anatomy,

  physiology, and biochemistry of animals and humans, and

  there is much experimental evidence showing similarity in

  response to many different drugs. Arguments in a lawsuit that

  a specific chemical is causal y linked to an individual’s injury

  or behavior often use data from animal studies.

  However, occasional y there are responses in humans that

  are unexpected based upon results from animal studies. The

  response to dissociative anesthetics is a good example of one

  such difference. Whereas humans exhibit delirium following

  treatment with PCP, animals exhibit sedation. Different meta-

  bolic pathways or rates of metabolism, and differences in mode

  of elimination between animals and humans, might account for

  the variation in responses. For example, rats do not have a gall

  bladder and dogs sweat minimal y. It is easy to see that choos-

  ing the wrong species in animal tests could result in inaccurate

  data relevant to humans. Nevertheless, preclinical testing is

  necessary, and there is much research today to develop in vitro

  in the laboratory) procedures that can predict human in vivo (in

  the body) responses. As more of these tests prove to be reli-

  able, fewer animals wil be used in research.

  102 Forensic Pharmacology

  five hours later, and a blood test revealed a significant amount

  of PCP. She admitted to smoking PCP about 20 minutes before

  the accident. Testimony for the prosecution at both a grand jury

  hearing and at the subsequent trial explained PCP pharmacoki-

  netics and the effects of PCP on mental functions and coordina-

  tion. The defendant was found guilty of vehicular manslaughter

  and sentenced to two to six years.

  SUMMARY

  PCP and ketamine are dissociative anesthetics. They can induce

  analgesia without loss of consciousness. The individual appears

  awake but will not remember the experience, and vital signs

  such as respiration and heart rate are not impaired. The drugs

  distort perceptions of sight and sound, and produce feelings of

  detachment and dissociation from the environment and self.

  Persons abusing PCP exhibit very bizarre behavior and may

  become violent.

  Inhalants

  11

  Inhalants of abuse are substances whose volatile vapors can

  be inhaled either through the nose or the mouth into the lungs

  and then travel to the brain, where they induce euphoria and

  mind-altering effects. In the late 1700s, an English chemist,

  Joseph Priestley, discovered that nitrous oxide gas has mind-

  altering and anesthetic effects, and, in the 1830s, chloroform

  was discovered to have anesthetic effects as well. Many of the

  volatile solvents, paint thinners, gasoline degreasers, and glues

  were abused during World War I and subsequently, but it was

  not until 1959 that inhalant abuse was first documented in

  the media, in Denver, Colorado, and then use spread to other

  cities. Inhalants are common among adolescents and are often

  the first drugs of abuse because they are inexpensive, difficult

  to detect, and easily available. During 2004, 9.6% of 8th grad-

  ers, 5.9% of 10th graders, and 4.2% of 12th graders had used

  inhalants.17

  Inhalants are found in many commercial products and are

  not listed as controlled substances. They can be solvents such as

  toluene, found in paint thinner, degreaser, nail polish remover,

  gasoline, and glue; propellants such as butane and propane,

  103

  104 Forensic Pharmacology

  Figure 11.1 The blood-brain barrier prevents the passage of large

  molecules, such as proteins, into the brain. Small molecules, such

  as glucose and molecules found in drugs of abuse, are able to pass

  through the barrier.

  Inhalants 105

  used in hair sprays and cooking sprays; gases, including

  medical anesthetics such as chloroform and nitrous oxide

  (laughing gas, also used as propellant for whipped cream and

  inhaled from balloons); and nitrites, including amyl nitrite

  and isobutyl nitrite. Many of the inhalants are flammable, and

  people who use them can suffer serious burns.

  Some street names for inhalants include air blast, hippie

  crack, moon gas, poor man’s pot, rush, and snappers. Amyl

  nitrite is known as amies, pearls, and poppers. Nitrous oxide

  is known as hysteria, laughing gas, NOZ, shoot the breeze, and

  whippets.

  PHARMACOLOGY OF INHALANTS

  Vapors can be inhaled directly from a can, a bag (called “bag-

  ging”), a balloon, or an inhalant-soaked cloth (called “huff-

  ing”). Inhalants enter the bloodstream through the capillaries

  on lung alveoli and, being highly lipid soluble,
easily pass the

  blood-brain barrier (Figure 11.1). They interfere with ion

  movement in the cell membrane at the glutamate or GABA

  receptor, resulting in an inhibition of transmission.

  Depending on the dose, inhalants can cause effects ranging

  from intoxication to anesthesia. Intoxication can last only a

  few minutes or several hours, if inhalants are taken repeat-

  edly. Initially, users may feel slightly stimulated, euphoric, and

  light-headed. With repeated inhalations, users may feel less

  inhibited and less in control, and can hallucinate. Other effects

  include headache, muscle weakness, abdominal pain, severe

  mood swings and violent behavior, numbness and tingling of

  the hands and feet, nausea, and lack of coordination. Inhaling

  highly concentrated amounts of chemicals can quickly lead to

  arrhythmia, heart failure, and death. This is known as “sud-

  den sniffing death.” The nitrites relax smooth muscle causing

  106 Forensic Pharmacology

  vasodilation and induce flushing, warmth, hypotension, and

  dizziness. For example, amyl nitrite is used as a medication

  to relieve angina (chest pain caused by lack of blood flow and

  oxygen to the heart) by dilating the coronary vessels.

  Signs of inhalant abuse are unusual breath odor or chemical

  odor on clothing; paint or stain marks on the face, fingers, or

  clothing; spots or sores around the mouth; and red or runny eyes

  or nose. Other clues include hidden rags or clothing, or empty

  containers.

  Chronic abuse of inhalants can cause severe, irreversible effects

  on the brain, heart, liver, lungs, kidneys, and blood, and can

  result in hearing loss, limb spasms, cognitive impairment, and

  various psychological and social problems. Inhalants damage

  the peripheral nerves, leading to muscle weakness and paralysis,

  and damage the nerve fibers in the CNS. Inhalant abuse during

  pregnancy can cause spontaneous abortion, premature delivery,

  and fetal abnormalities such as low birth weight, small head size,

  facial abnormalities, and muscle tone abnormalities similar to

  those occurring in fetal alcohol syndrome.

  Nitrous oxide can react with vitamin B12, preventing its use

  in red blood cell development and resulting in anemia. Use of

  nitrites can rapidly result in fatal methemoglobinemia, a condi-

  tion that reduces the ability of the blood to transport oxygen. In

  1944, 11 men were admitted to a New York hospital with bluish

 

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