Substances of Abuse

Substances Of
Abuse
Law And Regulations , CNS Depressants , Stimulants
And Hallucinogens
Prepared And Presented By: Majd Al-Qudah, MD

Outline
Definition
Laws and regulations
statistics
Physical vs psychological dependence
Classes
Conclusion
References

Definition
One definition of the term ‘drug of abuse’ is any substance that,
because of some desirable effect, is used for some purpose
other than that intended. The intended use of the substance
could be for a therapeutic effect with, for example,
benzodiazepines, or a practical use in the case of the solvent
abuse by ‘glue-sniffing’.

Definition
Another definition of ‘drug of abuse’ is any substance whose
possession or supply is restricted by law because of its potential
harmful effect on the user. Such drugs are known as controlled
or scheduled substances.

Definition
Substance abuse refers to the harmful or hazardous use of
psychoactive substances, including alcohol and illicit drugs.
Psychoactive substance use can lead to dependence syndrome -
a cluster of behavioral, cognitive, and physiological
phenomena that develop after repeated substance use and that
typically include a strong desire to take the drug, difficulties in
controlling its use, persisting in its use despite harmful
consequences, a higher priority given to drug use than to other
activities and obligations, increased tolerance, and sometimes a
physical withdrawal state.
https://www.who.int/topics/substance_abuse/en/

Laws and regulations
National anti-drug institutions Among the institutions that work
against drugs, there is the Jordan Anti-Narcotics Department (AND),
which falls under the authority of the Public Security Directorate.
AND is in charge to maintain the minor internal drug distribution.
AND also co-ordinates the Jordanian fight against drug trafficking.
In 2009, Jordan adopted a National Strategy on drugs. It
encompasses law enforcement, prevention, harm-reduction and
rehabilitation components, as well as public awareness-raising
activities undertaken by the Anti-Narcotics Department of the Public
Security Department in cooperation with government bodies,
universities, schools, youth clubs, the media and Civil Society
Organizations.
DRUG SITUATION AND POLICY by Matthieu de La Rochefoucauld

Law enforcement and legislation
Criminal penalties listed in the Drug Abuse and Psychoactive
substances Act number 11, 1988. The government prohibits import,
export, transport, usage, production, and possession of banned drugs
unless it is for medical and research use and carried by authority.
According to the Jordanian Drug Abuse and Psychoactive substances
Act, the death penalty is applied if the crime is internationally linked.
Prison sentence of up to two years if caught taking drugs.

Condemnation
• According to AND, the number of people involved in drug cases fell
by almost four percent between 2011 and 2012. In 2012, 4,713
people were arrested for drug possession and 732 were arrested for
drug dealing. The majority of those arrested for drug-related crimes
are foreign nationals. In 2009, AND apprehended 944 people for
drug trafficking and 3,687 others for possessing and taking drugs
that included opium, hashish, heroin, marijuana and amphetamines.

The exact cause of substance abuse is not clear,
with the two predominant theories being: either a
genetic disposition which is learned from others,
or a habit which if addiction develops, manifests
itself as a chronic debilitating disease
https://en.wikipedia.org/wiki/Substance_abuse

Statistics
In 2010 about 5% of people (230 million) used an illicit
substance.
Of these 27 million have high-risk drug use otherwise known as
recurrent drug use causing harm to their health, psychological
problems, or social problems that put them at risk of those
dangers.
In 2015 substance use disorders resulted in 307,400 deaths, up
from 165,000 deaths in 1990.
Of these, the highest numbers are from alcohol use disorders at
137,500, opioid use disorders at 122,100 deaths, amphetamine
use disorders at 12,200 deaths, and cocaine use disorders at
11,100
https://en.wikipedia.org/wiki/Substance_abuse

Social Stigma ..
In most areas of the medical history, patients try to be truthful, since
it is obviously in the best interest of their health that they do so.
With substance abuse, however, there are strong pressures
from social stigma and possible legal consequences that may
lead to concealment.
Drug and alcohol addictions are often regarded as signs of weakness.
Many patients hesitate to admit anything for which they expect to be
criticized.
Chapter 206Substance Abuse John B. Griffin, JR.

What Is Physical Dependence?
People who are physically dependent on drugs and alcohol
will experience a set of withdrawal symptoms when
abruptly stopping or reducing their use. When someone
uses drugs regularly in high amounts, their bodies become
dependent on those drugs and rely on them to carry out
normal functions.
Physical drug dependence begins with tolerance, which is
when the body adapts to a certain amount of drugs and
alcohol and needs a higher amount to feel the effects.
https://www.legacytreatment.org/blog/physical-dependence-vs-psychological-dependence

What Is Psychological Dependence?
Psychological dependence is more commonly known as addiction.
Addiction is a chronic, relapsing brain disorder and mental illness
marked by compulsive drug seeking and repeated drug use despite
negative consequences.
People who suffer from psychological drug dependence generally
experience strong urges to use drugs and struggle with quitting
despite numerous, repeated attempts. These individuals tend to spend
lots of time obtaining and using drugs, and recovering from the
effects.

Key Differences Between Physical
and Psychological Dependence
The main difference between physical and psychological
dependence is that physical dependence is marked by
withdrawal symptoms that make you feel physically ill,
while psychological dependence is marked by a
persistent, strong urge to use drugs despite negative
consequences.

Classification
CNS Stimulants
CNC Depressants
Hallucinogens

CNS Stimulants
Stimulants are substances that cause physical and
psychological functions to speed up. Individuals that abuse
stimulants tend to experience a major boost in energy,
euphoria, and a powerful sense of grandiosity. And while some
stimulant substances can be effective for individuals battling
certain mental health issues, several stimulants offer no
medical or psychiatric benefit.
© 2020 JourneyPure |

CNS Stimulants
Historically, stimulants were used to treat asthma and other respiratory
problems, obesity, neurological disorders, and a variety of other
ailments. As their potential for abuse and addiction became apparent,
the use of stimulants began to wane. Now, stimulants are prescribed
for treating only a few health conditions, including narcolepsy,
attention-deficit hyperactivity disorder (ADHD), and depression that
has not responded to other treatments.
Central Nervous System (CNS) Depressants and Stimulants Prescription Drugs and Pain Medications: Part 2 of 3

The Effects Of Stimulants
Euphoria
Decreased appetite
Wakefulness
Talkativeness
Energy
Increased concentration
Difficulty sleeping
Nervousness
Increased pulse and blood pressure
https://www.addictioncenter.com/stimulants

The Effects Of Stimulants
Stimulants produce an overabundance of dopamine, the pleasure-
inducing chemical in the brain. After continued abuse of stimulants,
the brain no longer produces normal amounts of dopamine, as it has
been conditioned to receive it from taking the drug. When the
individual stops taking the medication, they experience withdrawal
symptoms. This creates physical dependency on the drug and requires
the individual to continue using the drug in order to feel normal. Over
time, this can develop into an addiction.
https://www.addictioncenter.com/stimulants

Cocaine
Cocaine is street-available in both acidic (salt) and basic forms.
Cocaine hydrochloride (aka, “coke,” “blow,” “snow,” “nose candy,”
“yayo”) is a water soluble powder with a high melting point.
As such it is bioavailable (~30–60%) through insufflation (i.e.,
snorting, or “tooting”), or easily dissolved for intravenous injection; it
is not usually smoked as the active ingredient is destroyed by the
temperatures required for vaporization.
Time to peak subjective effect averages 14.6 minutes after
insufflation compared to 3.1 minutes following injection. Nasal
absorption is limited due to the vasoconstrictive properties of cocaine.
Stimulant Abuse: Pharmacology, Cocaine, Methamphetamine, Treatment, Attempts at Pharmacotherapy
Daniel Ciccarone, MD, MPH, Associate Professor

Cocaine
Base cocaine, aka “crack,” or “rock” , can be vaporized and
inhaled due it is lower melting point. The term “crack” reportedly
comes from the sound the material makes while melting.
Crack cocaine has rapidly spread due to its low cost and rapid
action. The time to reach peak subjective effect is significantly faster
for smoked (1.4 min) than for intravenous or insufflated cocaine.
Crack cocaine largely replaced an outmoded base form called
“freebase,” which involved a complicated series of dangerous steps to
solubilize and extract base cocaine from its hydrochloride salt.

Cocaine
The average purity of cocaine available on US streets was 50–60% in
2007.
Diluents, i.e., fillers, or “cut,” include simple sugars, e.g., dextrose,
starch, or white inert powders, e.g., talc. Adulterants, which may have
some additive or mimicking active effects, include topical anesthetics,
e.g., procaine, and cheaper stimulants, e.g., caffeine or ephedrine.
Cocaine is frequently used by heroin dependent users in combination,
aka, “speedball.” Tobacco, alcohol and marijuana are frequently used
in conjunction with cocaine.

Amphetamine
Methamphetamine exists in two stereoisomer, i.e., l- and d-, forms.
L-methamphetamine has peripheral alpha-adrenergic activity and
has been used in the past as a nasal decongestant.
D-methamphetamine (aka “speed,” “crystal,” “meth,” or “crank”) is a
powerful stimulant with 3–5 times the CNS activity as the l-isomer
and a half-life of 10–12 hours (cocaine’s half life is 0.5–2 hours).
It can be insufflated, smoked, injected, or inserted per rectum.

Amphetamine
Its forms are powder (usually white, but may be of other
colors), or crystalline. “Ice” (aka “glass,” or “Tina”) is a highly
purified form of d-methamphetamine which is intended for
smoking; it vaporizes at an even lower temperature than
crack cocaine

Effects Of Stimulants On
Neurotransmitter Systems
Stimulants facilitate the activity of the monoamine neurotransmitters,
i.e., dopamine, norepinephrine and serotonin, in the central (CNS) and
peripheral nervous systems.
Both cocaine and amphetamines act on presynaptic monoamine
reuptake transporters, but each in unique ways.
Cocaine is a reuptake inhibitor, i.e., it blocks the action of the
reuptake transporter thus allowing more neurotransmitter to stay
active in the synapse.
Amphetamines are releasers, i.e., they are taken up by the
transporter in exchange for neurotransmitter release into the
synapse.

Effects Of Stimulants On
Neurotransmitter Systems
Cocaine and amphetamine intake transiently increases
extracellular dopamine concentrations in the reward circuit.
Stimulants also increase serotonin and norepinephrine
activity and have effects on a number of other
neurotransmitter systems.

Acute Use: Intoxication And Overdose
Acutely, use of stimulants leads to rapid neurotransmitter release
resulting in euphoria, increased energy and libido, reduced fatigue
and appetite, and behavioral responses, e.g., increased self-
confidence and alertness.
Acute adrenergic effects include dose-responsive tachycardia and
elevated blood pressure.
With escalating effective dose (i.e., by greater potency, amount or
more efficient route) there is greater euphoria at first, but also
increased likelihood of toxic and dysphoric effects including:
insomnia, anxiety, irritability, confusion, paranoia, panic attacks and
hallucinations; related behavioral consequences include impulsivity
and grandiosity.

Acute Use: Intoxication And Overdose
Acute adrenergic side-effects include
hyperpyrexia, hyperreflexia, tremor, diaphoresis, tachycardia,
hypertension and tachypnea.
Overdose may manifest in
convulsions, cerebral hemorrhage or infarct, cardiac arrhythmias or
ischemia, respiratory failure and muscle overactivity leading to
rhabdomyolysis

Chronic Use
Repeated phasic use of low-dose cocaine may lead to increased
sensitivity including startle reactions, repetitive and stereotyped
behaviors, and alteration of motor function.
Spectrum of psychotic features including, paranoia, delusions and
hallucinations. The latter include tactile hallucinations, or
formication, colloquially referred to as “tweaking,” in which users
will commonly pick at their skin, or perform other repetitive searching
behaviors .

Chronic Use-Withdrawal
Withdrawal from cocaine and amphetamine produces such a strong
backlash of psychological and behavioral symptoms that it is
frequently referred to as a “crash.”
Acute withdrawal symptoms include hypersomnolence, strong
cravings and depression. Following this may be a several week period
of dysphoria, lethargy and anhedonia.
Relapses are common

Medical Complications
Resulting from mechanisms leading to tissue ischemia
include vasoconstriction, vasospasm, endothelial damage and
clotting stimulation (e.g., increased platelet activation and
aggregation).
• Stimulant use is associated with cerebrovascular disease and injury, including
hemorrhagic and ischemic stroke; myocardial infarction (all aforementioned
reasons plus increased oxygen demand); renal failure (secondary to ischemia
or rhabdomyolysis), gastrointestinal disease (e.g., ulceration and intestinal
infarction); muscle damage; nasal and sinus damage; and reproductive
complications (e.g., abruption placenta, low birth weight and feeding
difficulties).

History And Exam
https://bestpractice.bmj.com/topics/en-us/341

Diagnostic Investigations
https://bestpractice.bmj.com/topics/en-us/341

Management
General resuscitative and subsequent supportive measures are
the most crucial aspects.
• Ensure adequate airway protection, facilitate breathing with supplemental
oxygen, and gain control of the circulation with intravenous crystalloid (e.g.
normal saline 0.9%). • Initiate cardiac monitoring and electrocardiographic
studies. Gastric decontamination should be attempted with gastric lavage and
activated charcoal if the agent was taken orally within the last 1 - 2 hours, or
if delayed gastric emptying is present.
Seizures should be actively managed with benzodiazepines (e.g.
diazepam 0.1 mg/ kg IV bolus).
Check blood glucose and manage accordingly.
Management of stimulant drug over dose. Charl J van Loggerenberg, MB BCh, Dip PEC (SA), MBA (Wits), DBM (DMS)

Management
Severe Hypertension (> 180/110 mmHg) needs to be controlled to avert
intracerebral catastrophes such as hemorrhage and encephalopathy. One
can use nifedipine 5 mg po stat. Nonspecific betablockers such as
propranolol are not recommended because the subsequently unopposed
alpha-stimulation with the blockade of beta2-mediated vasodilation may
in fact worsen the hypertension and its attendant complications.
Agitation (often with seizures) can be controlled with benzodiazepines
(e.g. diazepam or midazolam 0.1 mg/kg IV.
Hyperthermia can be life threatening and should be treated actively.
Minimize excessive activity with benzodiazepines and institute cooling
measures.
Management of stimulant drug over dose. Charl J van Loggerenberg, MB BCh, Dip PEC (SA), MBA (Wits), DBM (DMS)

Psychopathology Of Action Of CNS Stimulant Drugs
The following behavioral aberrations in humans were found:
oMotor stereotypies with bizarre movements; repetitive, aimless activities;
("pottering"= "knick-knacking"= "punding") with various objects, including
own body; repetition of single words, phrases or musical expressions;
stereotyped drawing and writing (phenomena which are examples of mental
stereotypy);
oSocial stereotypies: prolonged sexual intercourse without ejaculation;
collective monologues;
oSocial withdrawal: "autism", social isolation with no or inappropriate
responses to social stimuli;
oParanoia;
oHallucinations and illusions: auditory, visual, tactile (microhallucinations).
Psychopathology induced by "speed drugs". Schiørring E.

CNS Depressants
• central nervous system (CNS) depressants are drugs that slow down
brain activity, making them effective for treating many conditions.
• These drugs operate by affecting the neurotransmitter gamma-
aminobutyric acid (GABA), which leads to side effects such as
drowsiness, relaxation, and decreased inhibition.
• Central nervous system depressants are used to treat a number of
different disorders, including: insomnia, anxiety, panic attacks,
stress, sleep disorders, pain, and seizures.
https://www.addictioncenter.com/drugs/drug-classifications/central-nervous-system-depressants/

Examples
Alcohol
Barbiturates
Benzodiazepines
Opioids

CNS Depressants
Different classes of CNS depressants work in different ways,
but all have the ability to reduce activity in the central
nervous system and lower levels of awareness in the
brain.
it’s important to note that almost all depressants have the
potential to be addictive.

Effects of Central Nervous System
Depressants
• Central nervous system depressants
work by increasing the production
of the neurotransmitter GABA,
which in turn slows down brain
activity and produces feelings of
relaxation, drowsiness, and a
number of other effects, including:
o Lowered blood pressure
o Pinpoint pupils
o Confusion or disorientation
o Slowed pulse and breathing
o Sleepiness or fatigue
o Difficulty urinating
o Dizziness
o Difficulty concentrating
o Memory loss
o Slowed reaction time
o Relaxation and euphoria
o Slurred speech
o Reduced inhibitions
o Loss of coordination
o Impaired judgement
o Blacking out

CNS Depressants- Long-term Use
• Long-term use can also produce a variety of negative effects, which
depend on the type of depressant used and the severity of misuse. In
particular, chronic abusers of depressants may develop a tolerance and
require increasing doses to maintain the desired effects. Other potential
long-term effects include:
o Chronic fatigue
o Weight gain
o Hypersomnia
o Sexual dysfunction
o Breathing and sleep difficulties
o Depression
o Suicidal thoughts
o Physical dependence
o Addiction

Barbiturates
Barbiturates, or “downers,” are a type of CNS depressant
that are prescribed to treat anxiety, tension, and sleep
disorders. Common barbiturates include Amytal, Luminal
(Phenobarbital), Mebaral, Nembutal, and Seconal.
Barbiturates were previously regarded as a generally safe
depressant, but problems with abuse, addiction, and overdose
quickly became apparent after widespread prescription.

Barbiturates
These drugs can generate a sense of euphoria and relaxation even
when taken in small doses, which encourages abuse in some.
 Barbiturates have also shown to have a dramatic impact on sleep
patterns, resulting in suppressed REM sleep.
In response to particularly high abuse rates from the 1950s to the
1970s, benzodiazepines, which are generally regarded as less
addictive and less likely to cause overdose, were developed and
popularized. Because the potential for addiction and overdose is so
high, the drugs are no longer commonly used to treat anxiety and
sleep problems.

Barbiturates are controlled substances due
to the potential they pose for abuse,
physical dependence, and addiction.
https://drugabuse.com/barbiturates/

Barbiturates are a class of sedative-hypnotic
drugs. They are commonly used as
antiepileptics (phenobarbital) and for the
induction of general anesthesia (thiopental).
Barbiturate Toxicity, Jolee T. Suddock; Matthew D. Cain.

Barbiturates Abuse
Phenobarbital has a relatively narrow therapeutic range, which means the
dose needs to be just right for it to be safe and effective. Those who take it
to control seizures are regularly tested to see if the drug concentration in
their bodies is within the right range. For those abusing barbiturates like
phenobarbital, their likelihood of visiting a doctor to be tested for drug
levels is extremely low. These users are at high risk of quickly boosting
their concentration of the drug to toxic levels in their bodies if they
regularly misuse the drug.
Even in the short term, barbiturates, if taken in excess, can quickly reach
dangerous levels and exert potentially deadly effects. Also, because
barbiturates are often taken with other drugs of abuse such
as alcohol, narcotic painkillers, and even stimulants, the risk is even higher.

Barbiturates Abuse
Some people abuse barbiturates because they desire the pleasant
psychoactive effects of these drugs, which are similar to those of
alcohol. These effects include making the user feel happy, relaxed,
more talkative, and less inhibited.
Barbiturates can be swallowed in pill form, crushed and snorted, or
injected intravenously.
Abusing barbiturates is extremely dangerous and can lead to severe
short- and long-term physical and psychological symptoms, physical
dependence, and accidental death.

Barbiturates Abuse- Signs and
Symptoms
• Increased talkativeness.
• Elation.
• Reduced inhibition.
• Impaired judgment.
• Emotional fluctuations.
• Sedation (users may seem really relaxed or drowsy).
• Slurred speech.
• Lack of coordination (users may fall over frequently).
• Confusion.

Effects of Barbiturate Abuse
• People who are abusing barbiturates will exhibit signs that are similar in
presentation to someone who is intoxicated by alcohol. These effects include, but
certainly are not limited to the following:
• Physical Health
• Increased sensitivity to sound.
• Increased sensitivity to pain.
• Changes in blood pressure.
• Breathing difficulties.
• Increased risk of developing bronchitis and pneumonia.
• Irregular menses in women.
• Sexual dysfunction.
• Increased risk of kidney failure.
• Respiratory depression.
• Overdose.
• Death.

Effects of Barbiturate Abuse
• Mental Health
• Anxiety, restlessness, or panic.
• Impaired mental functioning.
• Emotional instability.
• Loss of short- or long-term
memory.
• Insomnia.
• Hallucinations.
• Depression.
• Occupational and Social
Functioning
• Occupational issues or job loss.
• Loss of interest in hobbies and
responsibilities.
• Strained relationships.
• Neglect of self-care, such as
exercise and diet.
• Fatalities.

Barbiturates- Pathophysiology
Barbiturates act on GABA-A receptors by increasing the amount
of time the chloride ion channel is opened, which increases the affinity
of the receptor for GABA.
GABA is the primary inhibitory neurotransmitter of the central
nervous system which acts to reduce neuronal activity.
In contrast to benzodiazepines, they also act to increase chloride
influx in the absence of GABA which accounts for their ability to
depress the central nervous system significantly and contributes to
their toxicity.

Barbiturates- Toxicity
• The toxic dose of barbiturates varies. However, an oral dose of one
gram for most barbiturates can cause significant poisoning in an
adult.
• Fatal cases of ingestion have occurred with doses ranging
between 2.0 and 10.0 grams; the usual lethal blood level
ranges from 40 to 80 mcg/mL.

Barbiturates- Evaluation
As with most drug and medication-related toxicities, evaluation
often includes a qualitative assessment of the amount of drug taken
with a plasma or urine screening test.
Plasma barbiturate concentration and ingested dose have been
implicated as the most important correlates of toxicity.
 Immunoassays (EIA) can provide a cost-effective and sensitive
method to detect barbiturates and other substances that may be in
the body. Another method often used is gas chromatography/mass
spectrometry (GC/MS) which can further identify and confirm the
presence of a particular barbiturate.

Barbiturate Toxicity- Management
• Supportive; as there is no specific antidote for overdose. The first step in
treatment, as with any overdose, is assessing the patient’s airway,
breathing, and circulation. With significant sedation and respiratory
depression, intubation and mechanical ventilation may become necessary.
• Early treatment with activated charcoal may be useful and can be given
via nasogastric tube.
• Management of long-term use involves restoring central nervous system
(CNS) inhibitory tone. Abrupt cessation can lead to severe symptoms of
withdrawal; therefore, discontinuance of barbiturates should be a gradual
taper using medications that demonstrate cross-tolerance, with the first
line being benzodiazepines.

Benzodiazepines
• Sometimes called “benzos,” benzodiazepines are central nervous
system depressants that are prescribed to treat anxiety, sleep
disorders, convulsions, and other acute stress reactions. Common
benzos include Valium, Xanax, and Ativan.
• Benzodiazepines are highly effective in treating anxiety and insomnia
due to the sleep-inducing, sedative, and muscle-relaxing properties.
• While considered safe for short-term treatment, long-term or illicit
use can lead to the development of a tolerance, addiction, and
withdrawal symptoms upon cessation or rapid reduction in use.

Benzodiazepines- Pathophysiology
BZDs promote the binding of gamma-aminobutyric acid, or
GABA, an inhibitory neurotransmitter, to the GABAA receptor,
ultimately increasing ionic currents through the ligand-gated
chloride channels.
Benzodiazepine use, misuse, and abuse: A review, Allison Schmitz, PharmD

Benzodiazepines Overdose Symptoms
Dizziness
Confusion
Drowsiness
Blurred vision
Unresponsiveness
Anxiety
Agitation
Benzodiazepine Toxicity, Updated: Jan 23, 2020 ,Author: Chip Gresham, MD, FACEM;

Benzodiazepines Overdose- Physical
Examination
Nystagmus
Hallucinations
Slurred speech
Ataxia
Coma
Hypotonia
Weakness
Altered mental
status, impairment
of cognition
Amnesia
Paradoxical
agitation
Respiratory
depression
Hypotension

Benzodiazepines Overdose- Diagnosis
Immunoassay screening techniques are performed most
commonly. These tests typically detect BZDs that are metabolized to
desmethyldiazepam or oxazepam; thus, a negative screening result does
not rule out the presence of a BZD.

Benzodiazepines Overdose-
Management
• As with any overdose, the first step is an assessment of the patient's airway,
breathing, and circulation, and these should be addressed rapidly as needed.
• In any patient with an altered mental status, a blood glucose level should be
obtained immediately.
• The cornerstone of treatment in BZD overdoses is good supportive care and
monitoring.
• Single-dose activated charcoal is not routinely recommended, as the risks far
outweigh the benefit; BZD overdoses are very rarely fatal, and the resulting
altered mental status greatly increases the risk of aspiration following oral
charcoal dose.
• Flumazenil (Romazicon) is a specific antidote for BZD poisoning, but its use in
acute BZD overdose is controversial and its risks usually outweigh any possible
benefit. In long-term BZD users, flumazenil may precipitate withdrawal and
seizures;

Psychopathology Of Action Of CNS Depressant Drugs
exposure to these substances causes significant, problematic
behavioral or psychological changes. Symptoms may include:
osudden changes in mood
oimpaired judgment
oinappropriate sexual or aggressive behavior
oslurred speech
olack of coordination
ounsteady walk
orepetitive, uncontrolled eye movements
oimpaired attention and memory
ostupor or coma

Opioids
• Opioids are the most commonly prescribed pain medications in the
United States and in much of the world. Some opioids, such
as methadone, are also used for other purposes such as opioid
addiction treatment. There are a number of different opioids,
including legal prescription medications such
as codeine and hydrocodone, and illegal street drugs, such as heroin.
• While opioids vary tremendously in strength, addictive potential, and
other aspects, they tend to be very chemically similar and typically
have similar effects.

Types of opioids
Opioids are defined by their ability to bind to and influence
opiate receptors on cell membranes.
Opioid Abuse, Updated: Jun 21, 2018, Author: David W Dixon, DO; Chief Editor: Glen L Xiong, MD

Types of opioids
Naturally occurring
opioids
Semi-synthetic opioids
Synthetic opioids
• morphine
• narcotine
• codeine
• heroin,
• oxycodone,
• oxymorphone, and
• hydrocodone
• methadone
• fentanyl
• alfentanil

Types of opioids
Opium is extracted from
the plant Papaver
somniferum (the opium
poppy), and morphine is
the primary active
component of opium.
Endogenous neural
polypeptides such as
endorphins and
enkephalins are also
natural opioids.

Opioids- Pathophysiology
• Opioids act by binding to opioid receptors on neurons distributed throughout the
nervous system and immune system. Four major types of opioid receptors have
been identified: mu, kappa, delta.
• These receptors are the binding sites for several families of endogenous peptides,
including enkephalins, dynorphins, and endorphins. These endogenous peptides
regulate and modulate several important functions, including the following:
o Pain
o Stress
o Temperature
o Respiration
o Endocrine activity
o Gastrointestinal activity
o Mood
o Motivation

Opioid Abuse- Signs and symptoms
Intoxication state
Patients with opioid use disorders frequently relapse and present
with intoxication. Symptoms vary according to level of intoxication.
For mild to moderate intoxication, individuals may present with
drowsiness, pupillary constriction, and slurred speech. For severe
overdose, patients may experience respiratory depression, stupor,
and coma. A severe overdose may be fatal.

Opioid Abuse- Withdrawal state
Autonomic symptoms - diarrhea, rhinorrhea, diaphoresis,
lacrimation, shivering, nausea, emesis, piloerection
Central nervous system arousal - sleeplessness, restlessness,
tremors
Pain - abdominal cramping, bone pains, and diffuse muscle
aching
Craving - for the medication

Opioids Abuse- Laboratory Studies
Abuse and dependence
Urine drug screen
Detection of drugs in sweat and hair is a recent addition to drug abuse
detection technology. However, it is not used widely.
Withdrawal
Electrolytes
CBC count
Urine drug screen is rarely useful.

Intoxication
• Comprehensive urine drug testing is performed when the drug abuse habit of the
patient is unknown but suspected. Some labs use the inexpensive thin-layer
chromatography (TLC) procedure. This test has low sensitivity for commonly used
drugs. TLC cannot detect fentanyl.
• Enzyme immunoassay and radioimmunoassay are more sensitive than TLC, but they
are less specific because molecules with similar functional groups cross-react with
antibodies. These are relatively inexpensive tests.
• Gas-liquid chromatography (GLC) and gas chromatography-mass spectrometry (GC-
MS) are very sensitive and specific tests, but they are time consuming, labor
intensive, and expensive.
Screening and confirmation cut-off concentration for heroin, methadone,
morphine, and codeine is 300 ng/mL and are detected in urine within 1-4
days.

Addiction
• In case of historical or clinical evidence of IV drug abuse, perform
the following:
• LFT
• Rapid plasma reagent (RPR)
• Hepatitis viral testing
• HIV testing
• Blood cultures (in appropriate clinical setting)

Opioids Abuse- Management
Opioid intoxication
• General supportive measures for opioid intoxication are as follows:
• Assess patient to clear airway.
• Provide support ventilation, if needed.
• Assess and support cardiac function.
• Provide IV fluids.
• Frequently monitor the vital signs and cardiopulmonary status until the
patient has cleared opioids from the system.
• Give IV naloxone if necessary.

Naloxone is a specific opiate antagonist with no agonist or
euphoriant properties. When administered intravenously or
subcutaneously, it rapidly reverses the respiratory depression and
sedation caused by heroin intoxication.

Opioid maintenance therapy
• Pharmacologic therapy for heroin addiction has focused on ameliorating
withdrawal symptoms and reducing cravings. By replacing heroin with
legally obtained opioid agonists, many risk factors of the drug-abusing
lifestyle can be mitigated.
• Methadone maintenance therapy (MMT) has been the standard of care for
more than 30 years.

Opiate withdrawal
• Opiate withdrawal is generally considered less likely to produce severe
morbidity or mortality compared with barbiturates and benzodiazepines.
• Lofexidine (Lucemyra) is an oral centrally-acting alpha2 agonist approved
by the FDA in May 2018 for mitigation of opioid withdrawal symptoms in
adults.

Hallucinogens
Hallucinogens comprise a unique collection of substances
that are used to induce hallucinations or alterations of
consciousness.
Hallucinogens are drugs that cause alteration of visual,
auditory, or tactile perceptions but are also referred to
classes of drugs that cause alteration of thought and
emotion.
Hallucinogen Toxicity, Updated: Aug 15, 2018, Author: Joseph L D'Orazio, MD, FAAEM; Chief Editor: Sage W Wiener, MD

Hallucinogens
Naturally occurring hallucinogenic substances have been used
worldwide for millennia to induce altered states for religious and
spiritual purposes. While these practices still exist, the use of
synthetic hallucinogens for recreational purposes is much more
common today.
Patients under the influence of hallucinogens may exhibit a wide
range of behaviors with the potential to rapidly fluctuate from a
relaxed, euphoric state to one of extreme agitation and aggression

Hallucinogens
There is no perfect method to categorize hallucinogenic substances
because many overlap in structure, pharmacology, and clinical
features. One system groups hallucinogens into the following
families :
oIndole alkaloids (tryptamines): lysergic acid diethylamide (LSD)
oPiperidines/piperazines: phencyclidine (PCP)
oPhenylethylamine derivatives
oMiscellaneous psychoactive substances

Hallucinogens
A number of naturally occurring hallucinogens can be found in plants
and mushrooms. Many of these substances have long been used in
ritualistic medicine, and some are emerging agents of recreational use.
Included in these naturally occurring substances are DMT, psilocybin
and psilocin, mescaline, salvinorin A, lysergic acid amide (LSA), and
atropine and scopolamine.

LSD
LSD was first synthesized in 1938 by Albert Hoffman in an attempt
to derive new analeptic agents from extracts of the ergot
fungus Claviceps purpurea.
It first appeared in the United States in 1949 when it was used as a
model to study schizophrenia due to its potent psychotomimetic
effects.
The applications of LSD quickly broadened to include numerous
other medical and clandestine uses, including interrogation and
mind-control experiments.

Phencyclidine
• PCP and ketamine are piperidine derivatives with potent anesthetic
and illusionogenic properties.
• PCP was developed at Parke-Davis and Company in the late 1950s as
a potent and effective dissociative anesthetic. Its use was short-lived,
as it produced strong adverse side effects, including emergence
reactions with extreme agitation, disorientation, and hallucinations.
• PCP enjoyed a short use in the veterinary world during the 1960s,
during which time it was diverted in pill form throughout the San
Francisco region and eventually spread to surrounding states in the
form of powder ("angel dust") added to plant substances for smoking.

Phencyclidine
• PCP is most commonly sold as a liquid solvent in which the user will
dip a cigarette or marijuana joint (a so-called wet, dip, dipper, or
sherm)and the product is smoked, producing rapid clinical effects.
• Because of PCP’s strong volatile solvent smell, it often been referred
to as "embalming fluid" or "formaldehyde." This had led to some users
to erroneously believe that the clinical effects from abusing
formaldehyde are similar.
• Currently, illicit PCP is not diverted from health-care sources, but
rather produced illegally in clandestine labs due to ease of synthesis
and readily available precursors.

Ketamine
Ketamine was synthesized in 1962 as a replacement for PCP, and it
remains a widely used anesthetic with increasing non-operative
usage, including in emergency departments and the pre-hospital
setting.
More recently, ketamine in subanesthetic doses has been studied for
use as an antidepressant, particularly in cases that are refractory to
standard treatment or accompanied by suicidality.

Ketamine
Ketamine is used recreationally primarily as an insufflated powder.
 Its effects are dose-dependent and wide-ranging, from mild
alteration of sensorium to complete dissociation of consciousness
with powerful and sometimes disturbing hallucinogenic experiences
known as the "K hole".
Hallucinations from ketamine and PCP are due to agonism at the
sigma-receptor (previously classified as an opioid
receptor). Ketamine is known for being more psychologically
addictive than most psychedelics. It is commonly used at large
concerts and clubs

Hallucinogens- Pathophysiology
Hallucinogenic substances primarily exert their effect on the central
nervous system by way of neurotransmitter level manipulation.
Stimulating secretion, inhibiting reuptake, delaying enzymatic
breakdown, or directly stimulating or inhibiting neurotransmitter
receptors are all mechanisms by which hallucinogens can increase the
synaptic concentration of the major neurotransmitters (ie,
norepinephrine, serotonin, and dopamine).
Small differences in structure affect neurotransmitter levels
differently, which leads to the wildly varied clinical effects.

Hallucinogens- Pathophysiology
Tryptamines (eg, LSD, psilocybin, DMT) are strong
partial agonists at the 5-hydroxytryptamin
(5HT) receptors
Hallucinations from ketamine and PCP are due to
agonism at the sigma-receptor

Hallucinogens- Presentation
Some patients may provide a history of consuming a specific drug,
but may in fact have used a different one, as surreptitious
substitution of one drug for another by the manufacturer is common;
the product in question may not even have contained an active
hallucinogenic agent at all.
The duration of effect may also provide helpful clues for the agent
ingested. DMT has the shortest duration of action, peaking in seconds
and lasting less than 60 minutes. MDMA may produce effects for 4-
8 hours, whereas LSD can be active for well beyond 12 hours. Novel
phenylethylamine derivatives have widely variable durations of
action, ranging from 90 minutes to 20 hours or more.

Hallucinogens- Physical Examination
Patients under the influence of hallucinogenic agents may have a
wide range of physical exam findings, depending on the agent.
General features of simple, uncomplicated hallucinogen effect
include altered sensorium, tachycardia, tachypnea and possibly mild
to moderate blood pressure elevations.
Physical exam findings may include marked mydriasis, especially in
the setting of tryptamine or lysergamide use, or with anticholinergics.
 Findings on a focused neurologic examination are often normal
except in the setting of phencyclidine or ketamine use, which can
produce marked horizontal, vertical, or rotatory nystagmus.

Hallucinogens- Laboratory Studies
Testing directed at confirming exposure to a hallucinogenic
substance is rarely useful. Treatment is symptom guided and results
of confirmatory testing are not rapidly available.
Laboratory tests such as basic metabolic profiles, blood gases,
hormonal concentrations (thyroid-stimulating hormone, cortisol), and
creatine kinase can be used to identify complications from
hallucinogens and exclude alternative causes of altered mental status
(eg, acid-base disturbances, metabolic and endocrine pathology,
electrolyte abnormalities, rhabdomyolysis, renal failure, or stroke).

Hallucinogens- Laboratory Studies
When exposure confirmation is necessary (ie, forensic cases, research
purposes) expanded drug testing can be performed using specialized
immunoassays, liquid chromatography and mass spectrometry.

Hallucinogens- Management
benzodiazepines should be the first-line agent
Phencyclidine, dextromethorphan, and the novel hallucinogenic
agents have various degrees of stimulant qualities, which may
produce marked hyperthermia due to temperature dysregulation
and diffuse muscle fasciculation. Rapid initiation of cooling measures
is mandatory.
Patients with extreme agitation should be given adequate hydration
and watched closely for the development of rhabdomyolysis.

Cannabinoids and Synthetic
Cannabinoids
Cannabis sativa is the scientific name for the plant commonly known
as marijuana. It is used recreationally and medicinally for many
conditions.
The Cannabis sativa plant contains high levels of
tetrahydrocannabinol (THC) and other psychoactive cannabinoids.
Although THC is the principal psychoactive component of cannabis,
this plant is chemically complex and contains many other
cannabinoids, including cannabidiols, cannabinol, and
tetrahydrocannabivarin (THCV).
The psychoactive effects seen with cannabis use include relaxation,
euphoria, and heightened mood.

Cannabinoids Pathophysiology
The main psychoactive component of cannabis is delta-9-
tetrahydrocannabinol (THC), which acts as a partial agonist at
cannabinoid CB1 and CB2 receptors.
CB1 receptors are shown on both excitatory glutamatergic (Glut.) and
inhibitory (GABA) axon terminals
Most cannabis preparations also contain cannabidiol (CBD) has been
shown to have antipsychotic, anticonvulsive, neuroprotective and anxiolytic
effects and is believed to offset some of the undesirable psychotropic
effects of THC.
Cannabinoid abuse and addiction: Clinical and preclinical findings, Leigh V. Panlilio, Steven R. Goldberg,† and Zuzana Justinova

Cannabinoids Pathophysiology
Cannabinoid abuse and addiction: Clinical and preclinical findings, Leigh V. Panlilio, Steven R. Goldberg,† and Zuzana Justinova

Common Forms of Cannabinoids
Marijuana
The Marijuana plant contains natural compounds of Cannabinoids. These
plants have a long history of being abused. You can consume the plant in the
form of “edibles;” however, it is typically smoked out of a paper “joint” or a
tobacco glass pipe.
Synthetic Marijuana
Synthetic Cannabinoids such as K2 or Spice are manmade chemicals that
coat plant material to imitate the effects of the THC high from a Marijuana
plant. Synthetic Marijuana is much more dangerous due to the unknown
chemicals made up within the drug and the critical side effects it brings.
https://www.rehabspot.com/drugs/cannabinoids/

Side Effects of Cannabinoids
Although there are studies that show potential benefits from
Cannabinoids, there are many side effects from taking the drug. This
shows that an addiction to this natural drug can be hazardous.
Some side effects include:
• Rapid heart beat
• Dizziness
• Depression
• Hallucination
• Low blood pressure
• Paranoia
• Panic attacks
• Food cravings

Can You Overdose on Cannabinoids?
There have been no recorded deaths from using these drugs, and it
is not possible to overdose. However, there have been many reported
incidents on injury due to the “high” of the drug. The drug causes
a high that slows motor function and causes lack of coordination thus
putting the user at risk for injury.

Conclusion
Trying a drug just because a friend says it’s “cool,” might cost
you much more than you bargained for. So every person in this
room has to decide for themselves: Is it worth the risk?

References
• https://en.wikipedia.org/wiki/Substance_abuse
• https://www.who.int/topics/substance_abuse/en/
• Chapter 206 Substance Abuse John B. Griffin, JR.
• https://www.legacytreatment.org/blog/physical-dependence-vs-psychological-
dependence
• Central Nervous System (CNS) Depressants and Stimulants Prescription Drugs and Pain
Medications: Part 2 of 3
• https://www.addictioncenter.com/stimulants
• Stimulant Abuse: Pharmacology, Cocaine, Methamphetamine, Treatment, Attempts at
Pharmacotherapy Daniel Ciccarone, MD, MPH, Associate Professor

References
• Management of stimulant drug over dose. Charl J van Loggerenberg, MB BCh,
Dip PEC (SA), MBA (Wits), DBM (DMS)
• https://bestpractice.bmj.com/topics/en-us/341
• https://www.addictioncenter.com/drugs/drug-classifications/central-nervous-
system-depressants/
• https://www.nhs.uk/conditions/alcohol-misuse/
• https://pubs.niaaa.nih.gov/publications/aa72/aa72.htm
• Alcohol Toxicity, Updated: Nov 01, 2018 , Author: Michael D Levine, MD; Chief
Editor: Jeter (Jay) Pritchard Taylor, III, MD
• https://drugabuse.com/barbiturates/
• Hallucinogen Toxicity, Updated: Aug 15, 2018, Author: Joseph L D'Orazio, MD,
FAAEM; Chief Editor: Sage W Wiener, MD

References
• Barbiturate Toxicity, Jolee T. Suddock; Matthew D. Cain.
• Benzodiazepine use, misuse, and abuse: A review, Allison Schmitz, PharmD
• https://americanaddictioncenters.org/benzodiazepine/symptoms-and-signs
• Addiction: Part I. Benzodiazepines—Side Effects, Abuse Risk and Alternatives, LANCE P.
LONGO, M.D., University of Wisconsin Medical School, Milwaukee, WisconsinM.D.
• Benzodiazepine Toxicity, Updated: Jan 23, 2020 ,Author: Chip Gresham, MD, FACEM;
• Opioid Abuse, Updated: Jun 21, 2018, Author: David W Dixon, DO; Chief Editor: Glen L
Xiong, MD
• DRUG SITUATION AND POLICY by Matthieu de La Rochefoucauld
• Cannabinoid abuse and addiction: Clinical and preclinical findings, Leigh V.
Panlilio, Steven R. Goldberg,† and Zuzana Justinova
• https://www.rehabspot.com/drugs/cannabinoids/
• Psychopathology induced by "speed drugs". Schiørring E.

Thank You
Prepared and presented by : Majd Al-Qudah, MD
Supervisor: Prof. Abdelkader Battah
Course title: Chemical Toxins . 2020

Substances of Abuse

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