Controlled Substances Unit 2

Drug

substance capable of a physiological change

Medicine

mixture of drugs and inert ingredients used to prevent or treat symptoms of disease

Forensic Toxicology

detecting and IDing the presence of drugs and poisons in body fluids, tissues, and organs in relation to the law

Drug Classification Methods

1. Origin

2. Effect

3. Chemistry

4. Use

5. Scheduling (potential for abuse)

Origin Drug Classification

1) Natural Product

• opiate alkaloids = derived from opium poppy

2) Semi-Synthetic

• heroin made by soaking morphine in vinegar

3) Synthetic

• pharmaceuticals, valium, dronabinol (delta-9 THC)

Categories of Drug Classification Effects

1. CNS Depressants

2. CNS Stimulants

3. Hallucinogenics

4. Dissociative Anesthetics

5. Narcoctic Analgesics

6. Inhalants

7. Cannabis

Central Nervous System (CNS) Depressants

“downers”

• slows down the operation of the brain and body

• slowed heartbeat, lower blood pressure, reduced anxiety

• alch, barbituates, anti-anxiety tranquilizers (Valium, Xanax, Prozac

• antidepressants (ex. Zoloft)

CNS Stimulants

“uppers”

• speed up and overstimulate the body

• accelerated heart rate and elevated blood pressure

• cocaine, amphetamine, meth

• can be hallucinogenic in high doses

Hallucinogens

cause the user to have altered perception of reality

• alter mental perception of time/space/feeling

• LSD, MDMA (ecstacy), psilocybin (magic mushrooms), peyote

Dissociative Anesthetics

inhibit pain by dissociating the brain’s perception of the pain

• PCP and dextromethorphan

Narcotic Analgesics

relieve pain, induce euphoria, and create mood changes in the user

• Opium, codeine, heroin, morphine, methadone, vicodin, and oxycontin

Inhalants

breathable substances that produce mind-altering results and effects

• toulene, rubber cement, paint, gasoline, paint thinners, hair sprays, and various anesthetic gases

Cannabis

majijuana

• delta-9-tetrahydrocannabinol (THC)

• includes all cannabinoids

Predator Drugs (USE)

• Date-rape drugs, drug-facilitated sexual assault (DFSA) 

• Alcohol, ketamine, Rohypnol, GHB (Gamma-Hydroxybutyrate) 

• Lack of memory often leads to delayed testing 

Club Drugs (USE)

• Used to create “highs” and energy at parties and in clubs 

• Ecstasy (MDMA, methylenedioxymethamphetamine), LSD (lysergic acid diethylamide), psilocybin, PCP (phencyclidine) 

Performance-Enhancing Drugs (USE)

• Anabolic steroids, human growth hormones (HGH) 

• Horses too (gambling) 

Controlled Substances Act

1970

• placed regulated substances into 1 of 5 schedules

• based on

  • accepted medical use

  • potential for abuse

  • safety or dependence libability (addition potential)

• HIGHEST = SCHEDULE I

• LOWEST = SCHEDULE V

Schedule I

no accepted medical use with a lack of accepted safety and high abuse potential; medications within this schedule may not be prescribed, dispensed, or administered for medical use

• ex) heroin, peyote, ecstasy, LSD

Schedule II

high abuse potential with severe psychological or physical dependence; however, these medications have an accepted medical use and may be prescribed, dispensed, or administered

• ex) morphine, codeine, hydromorphone, methadone, oxycodone, fentanyl, amphetamine, etc

Schedule III

abuse potential less than Schedules I or II but more than Schedule IV medications; abuse may lead to moderate or low physical dependence or high psychological dependence

• ex) Tylenol with codeine, anabolic steroids, ketamine

Schedule IV

abuse potential less than Schedule III but more than Schedule V medications

• ex) various benzodiazepines

Schedule V

medications with the least potential for abuse among the controlled substances

• ex) phenergan with codeine, Robitussin AC, etc.

Drug Enforcement Administration (DEA)

primarily responsible for enforcement of Controlled Substances Act

• updated implementation

  • gets confusing with weed

• temporary control on emergency basis

  • in case there’s influx of drug associated deaths (need to see if something can be released back to public or permanently controlled)

• can’t control everything because medicinal use

• goal is to protect public health from dangerous controlled substances but ensure patients have access to pharmaceuticals for legitimate medicinal purposes

• DEA registration required to work with controlled substances

  • pharmacies, academies, retailers

Cannabis

all products derived from the Cannabis Sativa L.

• multiuse plant: stem (fiber), seeds (oil), resin (cannabinoids)

Cannabis Sativa

light green, narrow leaves, tall in stature, long-flowering cycle

Cannabis Indica

dark green, broad leaves, shorter in stature, long-flowering cycle

Cannabis Ruderalis

hybrid of cannabis sativa and cannabis indica

Dioecious plant

male and female components on separate plants

Male Cannabis sativa L.

harvested for hemp

Female Cannabis sativa L.

harvest for THC content

• flowers contain ~4-24% THC

• Leaves ~1-5% THC

delta9-tetrahydrocannabinol (THC)

main psychoactive component

• Schedule 1 controlled substance

• comes from resin

• other cannabinoids are also present

Hand rubbing

collecting resin on hands

shaking

shake plant over plastic to collect resin

sieving

rub plant on mesh sieve to filter the small resin particles

Water Extraction

put plant in water and agitate

• plant material floats and the resin sinks

Tumbling

plant material is tumbled in a vessel with small holes

Soaking

soak plant material in a solvent that will dissolve resin, and evaporate the solvent

Percolating

heat solvent in a container with marijuana suspended above liquid and allow vapors to condense on the plant material, dissolve resin, and drop back into the solvent

Effects of weed = ventral striatum

sense of euphoria/relaxation

Effects of weed = neocortex

distortions of sensory perceptions

Effects of weed = hypothalamus

increase in appetite

Effects of weed = amygdala

anxiety, fear, and panic

Effects of weed = hippocampus

impaired learning

Effects of weed = cerebelum

decreased motor control

Hemp

grown specifically for industrial use

• hardy plant

• easy to cultivate

• used in fiber, clothing, rope, cosmetics, etc

Marijuana

grown specifically for psychoactive properties

• delta9-THC typically 1-5% from leaves

• higher from oily resin from flowering tops

• selective breeding to increase delta9-THC content

2018 Federal Farm Bill

• Marijuana means the plant Cannabis sativa L, whether growing or not, the seeds of that plant, and every compound, manufacture, salt, derivative, mixture, or prep of that plant/seeds

• hemp = not more than 0.3% delta9-THC on a dry weight basis

• since both come from Cannabis sativa L must identify delta9-THC and demonstrate that the concentration is greater than 0.3%

• super confusing because what does “dry weight” mean?

Sinsemilla

Spanish for “no seed”

• cultivation technique to get the highest delta9-THC content

• female flower heads — “buds” that remain unfertilized throughout maturity

Trichomes

hair-like structures on the epidermis of the plant

Cystolithic Hairs

shape of a bear claw

• base contains calcium carbonate

• not unique to marijuana, but useful for identification

• type of trichome

Glandular Hairs

round structures on the top

• sometimes described as mushroom-shaped

• type of trichome

Cover Hairs

long and thin

• type of trichome

Delta9-THC

Cannabidiol (CBD)

non-psychoactive, medicinal target

Cannabinol (CBN)

mildy psychoactive, THC degredation product

Tetrahydrocannabinol Acid (THCA)

precursor to THC, decarboxylation to THC with heat

Cannabidolic Acid (CBDA)

precursor to CBD, decarboxylation to CBD

CNS Depressants

substance that slows down the operation of the brain and body

• reduce anxiety

• tranquilizers

• sedatives

• anti-depressants

• anti-histamines

• muscle relaxants

• most are abused pharmaceuticals

• ex) Xnanax, Valium, etc

CNS Depressant Types

1. Alcohol = social consumption

2. Barbiturates = sleep, sedative, anti-anxiety, prevent seizures (ex. phenobarbital)

3. Benzodiazepines = sleep sedative, anti-anxiety, depression (ex. Diazepine = Valium)

4. Nonbenzodiazepines = sleep sedative, anti-anxiety, depression (ex. Zolpidem = Ambien)

5. Miscellaneous = Gamma-Hydroxybutyric Acid (GHB)

Alcohol

most abused CNS depressant (Ethanol = intoxication, methanol = blindness = moonshine)

• drinking alters an individual’s mood, behavior, and neuropsychological functioning

• Commonly mixed with other CNS depressants (Benzodiazepines)

• forensic relevance is blood alch testing (legal limit = 0.08 g/dl)

Barbiturates

barbituric acid first synthesized in 1864

• German chemist Adolf von Baeyer

• no sedative or hypnotic properties

• nobel prize in 1905 for work with dyes (blue indigo dye)

• mods to barbituric acid led to active compounds → barbital synthesized in 1902 by German chemists Emil Fischer and Joseph Merring

Barbiturate Categories

1. Long acting = barbital, phenobarbital (treat seizures in young children/animals)

2. Intermediate/Short Acting = pentobarbital, secobarbital (physician-assisted suicide), butalbital

3. Very-Short acting = methohexital & thiopental

Barbiturate Dangers

• have one of the highest risks of overdose of all illegal drugs!

  • steep slope in dose-response curve

  • considerable overlap in therapeutic and toxic doses

• numerous celebs have overdosed = Elvis, Marilyn Monroe, Hendrix

• Physician-assisted suicides

• Reccommends barbiturates for suicide (controversial)

Medicinal Uses of Barbiturates

• migraine medications = fiorcet and fiorinal (barbital)

• anticonvulsants for seizures = mebaral (mephobarbital)

• surgical anesthetics = surital (thiamylal)

• treatment of insomnia = luminal (phenobarbital)

Rohypnol & Flunitrazepam

• 10x more potent than diazepam and rapid onset

• extreme muscle relaxation and memory loss

• used in drug-facilitated sexual assaults

• Schedule I controlled substance

Nonbenzodiazepines

lates 1980s & early 1900s

• Z-type drugs

• primarily sleep aids

• most common = Zolpidem (Ambien)

• somewhat forensically relevant

• same analysis techniques as benzodiazepines

Gamma-Hydroxybutyric Acid (GHB)

• Dr. Henri Laborit discovered GHB in 1960 while researching GABA-like inhibitors (investigating possible anesthetics)

• GHB sold as an anesthetic in Europe in 1964, but not widely adopted as it causes seizures

• 2022, sodium oxybate (Xyrem) released for narcolepsy

• colorless and odorless (easy to spike into drinks unnoticed)

• undetectable in urine after a few hours

• best analysis = hair

Gamma-AminoButyric Acid (GABA)

• GABA receptors are main target of almost all CNS depressants

• originally available through supplements for body builders

  • produce Human Growth Hormone (HGH)

• popular at raves

  • reduced inhibitions

• most well-known for drug-facilitated sexual assaults

• Schedule I in 2000

CNS Stimulant

compound that speeds up and overstimulates the body

• accelerated heart rate and elevated blood pressure

• can be hallucinogenic in high doses

• common examples: cocaine, amphetamine, methamphetamine, MDMA

Cocaine

derived from coca leaves

• Cocaine HCl = white crystalline powder that comes from coca leaves

• Cocaine Base = “crack” → irregularly shaped white rocks

• Street Names: Coke, Crack, Rock, Snow

• Schedule II controlled substance → accepted medicinal use for it’s anesthetic properties (eye surgery)

• increases energy levels by increasing synaptic dopamine levels → regulates movement and pleasure

• increases norepinephrine → stimulates the CNS for flight or fight → stimulates the brain for alertness, attention, and memory

• increases serotonin → promotes well-being and happiness

How much cocaine could be found in Coca-Cola?

Estimated 9 mg cocaine/glass

Harrison Act (1914)

banned non-medical use and imports of cocaine

• taxed medicinal use (not to support addicts)

What are the active and nonactive forms of cocaine?

ENANTIOMERS

L-Cocaine = active (coca leaves)

D-Cocaine = not active (synthesized)

• D-Cocaine is rarely seen without L-cocaine (1980s testimony)

GC-MS can’t differentiate

Amphetamine

comes from alpha-methylphenethylamine

• belongs to the phenethylamine class

• abuse is a relatively recent phenomenon → methamphetamine epidemic 1990s followed cocaine in 1980s

• increases the production of dopamine in the brain and blocks its metabolism → energy/strength/confidence but hallucinogenic in higher doses (delusions, paranoia)

• several current applications as prescription medications (ex. Aderall)

Methamphetamine

first synthesized in 1987 → structural analog of amphetamine (additional methyl group)

• ~5-10x more potent than amphetamine

• extensively used during WWII by both sides

• Schedule II controlled substance in 1970 CSA

Meth Mouth

severe tooth decay and gum disease

Meth Bugs

Formication → sensation that resembles that of small insects crawling on or under the skin when nothing is there

MDMA

3,4-Methylenedioxymethamphetamine = “ecstasy”

• Schedule I

• CNS stimulant and hallucinogen

• Desired: increased empathy, euphoria, and heightened sensations

• Adverse: memory problems, paranoia, difficulty sleeping, teeth grinding, blurred vision, sweating, and a rapid heartbeat

• when taken by mouth, effects begin after 30-45 min and last 3-6 hours

MDA

3,4-Methylenedioxyamphetamine

• synthesized in 1910

• investigated for treatment of Parkinson’s disease and as cough suppressant

Alexander Shulgin

chemist for Dow Chemical Company in 1967 → rediscovered MDMA from 1912

• experienced effects and changed his life forever

• developed a new synthetic method and provided it to a psychologist friend who used it for talk therapy

• “Cookbooks”

  • PiHKAL (Phenethylamines I Have Known And Loved): A Chemical Love Story (1991)

  • TiHKAL (Tryptamines I Have Known And Loved): The Continuation (1997)

  • Names, structures, active doses, effects, and synthetic routes

  • Over 250 hallucinogenic compounds between the two books

Hallucinogens

substances that cause the user to perceive things differently than reality

• alter mental perception of time/space/feeling

• very few hallucinogens cause true “hallucinations”

• sometimes referred to as psychadelics

• examples include: LSD, Psilocybin (magic shrooms), Peyote, MDMA (ecstacy)

Ayahuascas

South American psychadelic brew (hallucinogen)

Dr. Albert Hofmann

swiss chemist working for Sandoz

• synthesized LSD in 1938 as an intermediate to ergonovine (circulatory stimulant)

• in 1943, he began working with LSD again → this time, he was in search of a stimulant

• Accidental exposure on April 16th, 1943

• intentional ingestion of 250 micrograms 3 days later

  • became “Bicycle Day” → escorted home by an associate, thought he was going insane → 1st LSD trip

LSD Forms of Abuse

1. Sugar Cubes

2. Tablets/Capsules

3. Liquid Form (orally, intraveneously)

4. Blotter Paper → more distinguishable, light, and easy to transport/use'; put a logo on it

LSD Effects

Physical = dilated pupils, high body temperature, inceased heart rate/blood pressure, sweating/chills, sleeplessness

Physiological = depersonalization, distorted perception of reality, mood swings, paranoia, depression

**highest trip = first trip

Long-Term = flashbacks can occur weeks, months, or years later

• most last a very short time (1-2 min)

• decreased motivation

• prolonged depression

• impaired memory/concentration

• possible severe mental disturbances

• psychosis

• increased delusions

LSD

• schedule I controlled substance → anxiety/depression medicinal use research ongoing

• powerful hallucinogen (easily absorbed through skin)

• often abused as a club drug

• abuse has declined since 1999

• basic drug (multiple basic site [amines]) → base-base amphoteric molecule (complicated) and bulky

Dissociative Anesthetics

inhibits pain by cutting off or dissociating the brain’s perception of pain → not at all trying to solve the pain, just trying to ignore it

• interferes with glutamate and NMDA receptors in brain to cut off the pain signal

• important in cognition, emotion, and perception of pain

• examples: PCP, Ketamine

PCP

1-(1-Phenylcyclohexyl) Piperidine

• phencyclidine

• Schedule II synthetic drug

• recreationally used for hallucnogenic effects

• much more common in TX than in other states

• “angel dust” = PCP on marijuana

PCP Forms of Abuse

1. Smoked → most common (dipped cigarette, vaporizer, easily soluble in water, angel dust onto weed that’s smoked)

2. Injected

3. Snorted

4. Ingested orally (pills & capsules)

PCP Effects

Short-Term = hallucinations, sedation, amnesia, immobility

• effects felt within 2-5 min after smoking and 30-60 min after swallowing

• intoxination may last from 4-8 hours

Long-Term = addition leads to physiological dependence

• memory loss, mood swings, speech difficulty, and depression

• if abused during a developmental stage, people may forget how to speak, etc

PCP Analogs

approx 30 PCP analogs

• many Schedule I controlled substances

• examples: Rolicyclidine, Eticyclidine, Tenocyclidine

• similar chemical structur to other dissociative anesthetics (Ketamine)

• Core is the exact same (“Chemical scaffold”), we just change functional groups

Narcotic Analgesics

used to relieve moderate-to-severe acute or chronic painj

• can also induce euphoria and create mood changes in the user

• overused, overprescribed, and misused

• opium, morphine, heroin, hydrocodone, oxycodone, methadone, fentanyl (+ its analogs)

Opiates

alkaloids found naturally in opium

Opiods

natural, semisynthetic, or synthetic with opium— or morphine —like pharmacological action

• can be chemically different from any components in opium

Opium Poppy

beautiful flower capable of growing nearly everywhere

• hundred of rellated species, but only two capable of producing “opium”

• approx 90 days for maturation

• a golf-sized bulb, or pod, remains after the petals fall off

• fully developed bulb full of small, blackish poppy seeds

• must be harvested from the bulbs after the petals fall off but before the seeds fully develop

Harvesting Opium from Poppy

• have to harvest the opium pod

• each pod is carefully scored so the white milky latex oozes out

• cannot cut too deeply

• after several hours of air drying, latex becomes a discolored/gummy substance = raw opium

• repeated 3-4 times per pod

Morphine

first isolated and identified in 1803 by German chemist Friedrich Serturner

• 10x more potent than raw opium

• named after Morpheus, mythological son of sleep g-d Hypnos

• first active substance to be extracted, isolated, and identified from a plant

• first marketed by Serturner and Company as a pain med and treatment of opium/alch addition

Heroin

in search of a more powerful analgesic, scientists experiemented with morphine and made heroin

• marketed as a non-addictive alternative to morphine (addictive) and a cough suppressant

• found in southeast asia, southwest asia, south america, mexico

Harrison Tax Act (1923)

aims to curb drug abuse and addiction

• doctors and pharmacists are required to register and pay a tax for using heroin and other narcotics

Heroin Act (1923)

made manufacture and possession of heroin illegal