PSYCHIATRY

MD, PhD, Full Professor

University Snezana
Marjanovic
Alcohol, Opioids, and other
Substance/Related Disorders
Substance use disorders or SUDs encompass a spectrum of conditions varying in
severity from problematic use, abuse and varying grades of mild to more

severe dependence.

Over the last half century, various drug use epidemics have

characterised different population groups worldwide

 As the knowledge base of clinical neuroscience has expanded, the
understanding of these disorders has developed from being viewed
as a moral weakness to being viewed as complex biomedical
disorders affecting the brain and manifesting clinically as chronic
relapsing disorders. In addition, research has demonstrated
equivalent rates of relapse for addictive disorders and non-
compliance to treatment for medical disorders such as hypertension
and diabetes.
Epidemiology

 Trends in substance use vary from

country to country and
fluctuations occur in the
prevalence rates across time
periods.
 Epidemiologists use various
 Epidemiology investigates the definitions for substance use and
distribution and determinants of substance use disorders
substance use disorders; as well
as patterns of drug use over time
and its association with age,
gender and associated risk
factors.
 Definitions of substance use can vary from substance use once in
past month or year, life time use or use characterised by the fully
developed syndrome of addiction.
 Life time prevalence refers to fulfilling the criteria for a specified
pattern of use(i.e., abuse or dependence) at least once in a person’s
lifetime.
 Depending on the nature of substance use disorders, the chronicity
and the related mortality rates, prevalence and incidence rates can
differ markedly
 For example, due to the chronic nature of drug dependence, the prevalence
rates of substance dependence can be significantly higher than incidence
rates.
 Period prevalence measures, such as past year prevalence, records the rate
of patients fulfilling diagnostic criteria over the past year form the total
population at risk.
Prevalence:
Total number of cases at time/period
Total population at risk at time/period
Incidence:
 Number of new cases over period of time
 Total population at risk (without the disease) over period of time
 Incidence measures refer to the occurrence of newly diagnosed cases over
a specified time period.
 Cumulative incidence or the incidence proportion is usually expressed as
the total number of new cases per 10 000 or 100 000 patients over a period
of time i.e., over a five year period. Alternatively, incidence rates or density
can also be expressed as the number of new cases occurring in the at risk
population, over the total number of person years of observation.
 Most large epidemiological samples across countries have found that men
are at least 2-3 times more likely than women to use illicit substances and
develop substance use disorders such as abuse or dependence
 In addition, whereas men start using drugs at a younger age and take longer
to develop full blown dependency syndromes; women tend to develop
problems with addiction later in life, but develop severe problems more
rapidly
 However, there is evidence of a trend toward lower differences in substance
misuse rates, particularly alcohol abuse, in younger age cohorts; and
between males and females in the context of more equal and less traditional
gender roles
 Substances abuse problems cause significant disabilities for a relatively
high persentage of the population

 About 40% of the U.S population have used an illicit drugs at one time

 More than 15% of persons over age of 18 are diagnosed with this disorder
 Pathogenesis
Biological Factors

 The syndrome of drug dependence occurs as a result of a complex interplay of a

variety biological mechanisms as well as psychological and social factors.
 Dependence is characterised by repeated use of a substance resulting that ultimately
results in state of neural adaptation in the brain.
 Various drugs of abuse act on different receptor subsystems with many of these
systems converging onto to the final common pathway involved in reward seeking
behaviours, the mesolimbic dopamenergic pathway
 Altogether a number of neuro-anatomical circuits are involved in the
pathophysiology of addiction

 These include:
 a) The Reward-Seeking system consisting primarily mesolimbic
dopaminergic pathway and its subcomponents. This pathway stretches from
the cell bodies of the dopaminergic neurons in the ventral tegmental area of
the brainstem (substantia nigra) which project their axons onto the nucleus
acumbens in the ventral striatum. Pulsatile stimulation of these dopaminergic
neurons result in highly a pleasurable sensations
 b) The prefrontal cortex subcomponents are thought to be involved in
impulse regulation and modulation of reward seeking behaviour.
 These components include the OFC orbitofrontal cortex, the DLPFC, and
the ventro-medial cortex (VMC) as well as the loop circuits that stretch
from the frontal cortex through the striatum to the thalamus and back to the
cortex (cortico-striatal-thalamo-cortical circuits or CSTCC).
 These circuits that traverse the dorsal aspects of the striatum are also
implicated in the compulsive aspects of drug addiction.
 c) The extended amygdala (consisting of the central nucleus of the
amygdala, the Bed Nucleus of the strie terminales and the shell of the nAcc)
and its connections with the VTA and Nu Acumbens, plays an important
role in learning and conditioning of behaviours related to drug use.
 The extended amygdala is sensitive to stress hormones such as cortisol, and
plays a potentially important role in the triggering of relapses into drug
taking bihaviour caused by environmental and intrapsychic stressors.
 ) The basolateral cortical amygdala.
 This structure represents the neocortical cellular layers of the amygdala and
is thought to play an important role in environmental cue detection.
 This structure is therefore potentially important in cue induced drug taking
behaviours. People, places and objects such as drug paraphranelia that has
become conditioned with drug taking can potentially lead to stimulation this
anatomical area to induce relapses
 e) Memory systems in the hippocampal formation, involved in the memory
consolidation of events associated with substance use. This system is
interconnected among others with the extended amygdala.
 Definition


Substance-related disorders are characterized by changes in mood,
behaviour and cognition


Result of continued and prolonged use of the drug or
toxin
 Classification

 Alcohol (ethanol)

 Amphetamine – MDMA (Extasy)

 Caffeine

 Cannabis (Marijuana)

 Cocaine – crack is a rock base form of cocaine

 Classification

 Hallucinogens – mescaline and LSD

 Inhalants – solvents

 Nicotine

 Opioids

 Phencyclidine (PCP)
 Classification

 Sedatives, hypnotics, and anxiolytics

 Anabolic-androgenic steroids - testosterone

 Terminology

 Dependence – repeated use of a drug, with or without physical dependence

 Physical dependence indicates an altered physiologic state due to

repeated administration of a drug, the cessation of which results in a
withdrawal syndrome

 Abuse – Use of any drug, in a manner that deviates from approved social or
medical patterns
 Terminology

 Intoxication – A reversible syndrome caused by a specific substance, that effects one or

more of the following mental functions: memory, orientation, mood, judgment, and
behavioral, social and occupational functioning

 Withdrawal – A substance – specific syndrome that occurs after stopping or

reducing the amount of the drug or substance that has been used regularly over a
prolonged period of time – abstinence syndrome or discontinuation syndrome
 Terminology

 Tolerance – After repeated administration, a given dose of a drug produces a reduced

effects

Or

Increasingly larger doses must be administreted to obtain

the effects observed with the original dose
 Evaluation

 Substance – abusing patients are often difficult to detect and evaluate

 They almost always underestimate the amount of substance used, are prone to use denial,
are often manipulative

 Such patients usually require a confrontational approach

 Toxicology

Urine or blood tests are useful in comfirming

suspected substance use

 Although most drugs are well detected in urine, some are best detected in
blood (e.g barbiturates and alcohol)


Urine toxicology is usually positive for up to 2 days after the
ingestion of most drugs
 Physical examination


Carefully consider wether concomitant medical
conditions are substance-related
 Subcutaneous or intravenous abusers: AIDS, scars from injections, absesses, infections,
bacterial endocarditis, hepatitis, thrombophlebitis
 Alcohol – related disorders

 1. Disorders related to the direct effects of alcohol on the brain (alcohol

withdrawal,delirium, intoxication, hallucinosis)

 2. Disorders related to behavior associated with alcohol (alcohol abuse and dependence)

 3. Disorders with persisting effects (dementia, amnestic disorders...)

 Alcohol dependence and abuse

 Dependence - compulsive alcohol use, presence of three or more major

areas of impairment related to alcohol occuring with the same 12 months
(spending a great deal time to use of substance, try to control alcohol...)

 Abuse - alcohol is used in physically hazardous situations (e.g driving)

(not include tolerance or withdrawal)
 Pharmokinetics

 Peak blood concetration - 30 to 90 min

 90 % is metabolized by hepatic oxidation

 The rest is excreted unchanged by the kidneys and lung

 Alcohol is depressant that produces somnolence and decreased neuronal activity

 Subtypes of alcohol dependence

 Type A – late onset, mild dependence, little psychopathology

 Type B – severe dependence, early onset, severe psychopatology, polysubstance use

 Schizoid-isolated drinkers – tend to drink alone and subject to binge drinking

 Affiliative drinkers – tend to drink daily in social settings

 Gamma alcohol dependence – unable to stop drinking once they start
 Treatment

 The goal is prolonged maintenance in total sobriety

 Relapses are common

 Initial treatment requires detoxification

 Coexisting mental disorders should be treated

 Psychopharmacotherapy

 Disulfiram – unpleasant effects as a result of accumulation of acethaldehyd

resulting from the inhibition of aldehyde dehydrogenase - flushing, headache,
dyspnea

 Naltrexon – decreases the craving for alcohol, probably by blocking the release of
endogenous opioids

 Akamprosat – helps remain in abstinence

 Alcohol-related disorders

 Alcohol intoxication

 Alcohol induced psychotic disorders, with hallucinations (alcohol

hallucinosis)

 Alcohol withdrawal

 Alcohol withdrawal delirium (DT)

 Alcohol- induced persisting amnestic disorder

 Substance induced dementia

 Alcohol intoxication

 Recent ingestion of a sufficient amount of alcohol to produce acute maladaptive

behavioral changes

 Mild intoxication produces relaxed, talkative, euphoric person

 Severe intoxication produce more maladaptive changes – aggressiveness, irritability,

labile mood
 Alcohol intoxication - treatment

 Usually only suportative

 May give nutritients (thiamine, vitamin B12, folate)

 Observation for complications (e.g head injury)

 If patients tend to harm others or themself – Lorazepam per os or im or haloperidol per

os or im – for agitation
 Alcohol induced psychotic disorder,
with hallucinations

 Vivid, persistent hallucinations (often visual and auditory), without delirium, following
(usually within 2 days) a decrease in alcohol consumption in dependent person

 Usually requires at least 10 years of alcohol dependence

 Treatment: lorazeam, diazepam and haloperidol

 Alcohol withdrawal

 Begins within several hours after cessation or reduction in prolonged

heavy alcohol consumption

 Autonomic hyperactivity, hand tremor, insomnia, nausea or vomiting,

illusions or hallucinations, anxiety, grand mal seizures, agitation
 Alcohol withdrawal delirium
(Delirium tremens)

 After recent cesation of or reduction in severe, heavy alcohol use in medically

compromised patients with a long history of dependence

 Occurs in 1-3% of patients

 Marked authonomic hyperactivity- tachycardia, sweating, fever, anxiety or insomia

 Vivid hallucinations, paranoid delusions

 Delirium tremens typically develops 48 to 72 hours following cessation of
drinking and is characterised by clouding of consciousness, severe tremor,
visual and tactile hallucinations often in the form of small animal figures or
insects, agitation and fidgetiness as well as nausea and vomiting.
 Withdrawal seizures can also develop 48 to 72 hours following the last
drink. Delirium tremens is considered a medical emergency and treatment
in a facility geared towards the management of medical ill patients is
essential.
 Alcohol withdrawal delirium
(Delirium tremens) - treatment

 Take vital signs every 6 hours

 Observe the patient constantly

 Decrease stimulation

 Correct electrolyte imbalances

 Treat coexisting medical problems (e.g infection, head trauma)

 Alcohol withdrawal delirium
(Delirium tremens)

 If the patient is dehydrated - hydrate

 Chlordiazepoxide (Librium): 25-100 mg orally every 6 hours

 Lorazepam (Ativan):1-2 mg by mouth, iv or im every 4 hours

 Thiamine: 100 mg orally 1-3 times a day

 Alcohol withdrawal delirium
(Delirium tremens)

 Folic acid: 1 mg orally daily

 One multivitamin daily

 Mg sulfate: 1 mg im every 6 hours for 2 days in patients who have had postwithdrawal
seizures

 After the patient is stabilized, taper chlodiazepoxide by 20 % every 5 – 7 days

 Alcohol withdrawal delirium
(Delirium tremens)

 Provide medication for adequate sleep

 Treat malnutrition

 Antipsychotic should be used cautiously because they can precipitate seizures. If the
patient is agitated and psychotic and shows signs of benzodiazepine toxicity (ataxia,
slurred speech), use an AP such as haloperidol
 Alcohol induced amnestic disorder

 Disturbances in short memory resulting from prolonged heavy use of alcohol

 Wernike encephalopathy

 Korsakoff”s syndrome

 Amnesia, confabulation, disorientation

 Treatment: thiamine, clonidine and propranolol

 Wernicke’s encephalopathy is a further potential complication of alcohol
withdrawal. This condition can arise due to nutritional depletion of thiamine
leading to a cluster of neurological symptoms on the background of a
delirium. Physical signs of Wernicke’s encephalopathy include
opthalmoplegia with cranial nerve III and VI palsies as well as ataxia. Only
10% of patients with Wernicke's will have the classical triad of confusion,
ataxia, and nystagmus. Cranial nerve signs also only occur in about 25% of
patients.
 . Therefore, a diagnosis of Wernicke's should always be considered in
patients’ who present with alterations in level of consciousness in the
context of alcohol withdrawal. Untreated Wernicke's can result in death in
up to 20%, and as many as 20% of patients go on to develop neuronal
damage in the diencaephalic brain regions such as the mediodorsal
thalamus, periaquadauctal grey and mammilary bodies of the
hypothalamus.
 Damage in these neuroanatomical regions can result in anterograde
amnesia, characterised by the inability to learn new information. Also
known as diencephalic amnesia, this form of memory loss is characteristic
of Korsakoff’s psychosis, which is diagnosed according to the DSM-IV as
"Alcohol induced persistent amnestic disorder."
 Alcohol – induced dementia

 Other causes of dementia are exluded

 History of a chronic heavy alcohol consumption

 Usually mild

 Treatment – similar with other dementia (different causes)

 OPIOIDS

 Natural drug opium and its derivates, in addition to synthetic drugs with similar actions

 The natural drugs derived from opium - morphine and codeine

 The synthetic opioids - methadone

 Heroin - a semisynthetic drug and the strongest euphoriant property, producing the most
craving
 OPIOIDS

 Opioids affects opioid receptors

 Opioid receptors mediate analgesia, respiratory depression, constipation and dependence

 Dopaminergic reward pathways mediate addiction

 Route of administration is injected (HIV risk)

 OPIOIDS- Intoxication

 Objective signs – CNS depression, respiratory depression, decreased GIT motility,

analgesia, hypotension, bradycardia, pupillary constriction

 Subjective signs – Euphoria, tranquility, decreased attention and memory and

psychomotor retardation
 OPIOIDS - Overdose

 Usually accidental


Result from incorrect estimation of dose or lost tolerance to drug
 Signs – pinpoint pupils, respiratory depression, CNS depression
 OPIOIDS - Treatment


Icu admission and support of vital signs functions (eg iv fluids)
 Immediately administer 0,8 mg naloxone, an opioid antagonist, iv, and wait 15 min

 If no response, give 1,6 mg and wait 15 min

 If still no response give 3,2 mg and suspect another diagnosis (polysubstance

overdose)
 OPIOIDS - detoxification

 If objective withdrawal signs are present, give 10 mg of methadone, repeat if nessesary,

max dose 40 mg

 Clonidine – centraly acting agent that effectively relieves the nausea, vomiting, and
diarrhea associated with opioid withdrawal

 After detoxification, oral naltrexone has been effective in helping to maintain abstinence
for up to 2 months
 Discontinuation of heroin and other opioid derivatives is characterised by a
pronounced withdrawal syndrome. Although highly unpleasant, unlike
alcohol withdrawal heroin withdrawal is rarely associated with life
threatening complications. The syndrome of withdrawal is characterised by
severe dysphoria, craving for heroin, agitation, yawning, diaphoresis,
lacrimation, piloerection (goose bumps) pupil dilatation, muscle and
abdominal cramps as well as diarrhoea
Sedatives, hypnotics and anxiolytics

 The drugs associated with this group are BDZ

 Drugs of this class are used to treat insomnia and anxiety

 Alcohol and all drugs of this class are cross tolerant and their effects are additive

 They all have agonist effects on the GABA receptor

Sedatives, hypnotics and anxiolytics

 Dependence develops after at least several months of daily use, but persons vary widely
in this respect

 The major complication is overdose, with associated CNS and respiratory depression

 The lethality is low and overdose has been reduced by the use of BDZ antagonist
flumazenil
Sedatives, hypnotics and anxiolytics

 Withrawal is dangerous and can lead to delirium or seizures

 Drugs with short half-life may induce a more rapid onest of withdrawal and a more
severe withdrawal then drugs with a long-life (e.g diazepam)
 Amphetamines and amphetamine-like
substances (stimulants)

releasing catecholamines,
 Exert their major effects by

primary dopamine, from presynaptic stores in the reward pathways of

dopaminergic neurons

 Legitimate indications include attention-deficit disorders, narcolepsy and depression

 Usually taken oraly, but can be injected, inhaled, or smoked

Amphetamines and amphetamine-like
substances (stimulants)

 Amphetamine, extasy, ice

 The clinical syndromes are similiar to those associated with cocaine

 Can induce paranoid psychosis similiar to paranoid SCH

 Treatment – symptomatic

 BDZ for agitation

 Cocaine

 One of the most addictive of the commonly abused substances referred to as coke, blow,
cane, or freebase

 The effect are pharmacoligicaly similiar to those of other stimulants

 Usually inhaled, but can be smoked or injected

 Cocaine

 Intoxication – can cause restlessness, agitation, anxiety, pressured speech, paranoid ideation,
grandiosity, hyperactivity and other manic symptoms

 Associated with sudden death from cardiac complication

 The most prominent sign is craving for cocaine

 Withdrawal symptoms - fatique, lethargy, quilt, anxiety

 Characteristic withdrawal syndromes have been described for stimulants
such as cocaine, amphetamines and methamphetamine. The acute
withdrawal syndrome usually has its onset within 12 to 24 hours of the last
dose. The acute withdrawal syndrome is sometimes described as a "crash"
after the period of a high. This syndrome is characterised by feelings of
intense sadness and depression, severe fatigue and a tendency to oversleep
and eat
 The acute withdrawal syndrome typically subsides after 10 to 14 days. This
is followed by a period from week 2 to week 8 post cessation that is
characterised by renewed energy and a newfound confidence in abstinence.
This period has also been described as the "honeymoon period" where
persons typically feel confident that they are able to quit using stimulants
on their own.
 In the treatment setting this can often be characterised by treatment drop-
outs. By 2 months post drug cessation a third phase sometimes described as
"the wall" is described. This phase is characterised by severe fatigue and a
loss of the ability to experience pleasure (anhedonia). Usual routes to
experience pleasure are often drug associated. Recovering addicts often
experiences this stage is profoundly isolating
 Cocaine

 Treatment – symptomatic

 Agitation – BDZ

 Delirium or psychosis – AP

 Somatic symptoms – beta blockators

 Cannabis (marijuana)

 Cannabis sativa is a plant from which cannabis or marijuana is derived

 All parts of the plant contain THC (Tetrahydrocannabinol)

 Intoxication – euphoric effects appear within minutes, peak in 30 min, and last 2-4 hours

 Symptoms – euphoria, dysphoria, anxiety, inceasred apetite, tachycardia

 Cannabis (marijuana)

 Treatment of intoxication usually not required

 Anxiety – BDZ

 Hallucinations and delusions - AP

 Hallucinogens

 Natural and synthetic substances, also known as psychedelics or psychomimetics

 They produce hallucinations

 The clasic, naturally hallucionogen are psylocibin and mescaline

 The classic substitute halucionegens is MDMA (3,4-Methyl​enedioxy​methamphetamine)

 Hallucinogens

 Usually are eaten or smoked

 Act as sympathomimetics – HTA, tachycardia, hypertermia, dilated pupils

 Psychological effects – perceptual disturbances – frank hallucinations

 Psysical dependence or withdrawal does not occur

 Treatment: BDZ and AP

 Phencyclidine (PCP)

 Angel dust

 Dissociative anesthetic with hallucinogenic effects

 Causes paranoia and violence

 Treatment: BDZ and AP

 Inhalants

 Substances which are inhalated for psychotropic effects

 Gasoline, enamels, rubber cements, aerosols, remover

 Symptoms: euphoria, ataxia, confusion, disorientation, delirium and seizures

 Anabolic steroids

 Family of drug comprising the natural male hormone testosterone and a group of 50 synthetic analogs of
testosterone

 Use has been among male

 These drugs include thyroid hormones and stimulants

 Produce euphoria and hyperactivity, anxiety, manic symptoms, depression

 Treatment: psychotherapy to cope with body image distortions
Substance withdrawal syndromes

 Depending on the severity of the dependency syndrome alcohol withdrawal

can range from mild and spontaneously resolving states to severe,
potentially life threatening states. Mild withdrawal is characterised by
gastrointestinal symptoms such as nausea, retching and vomiting,
sympathetic hyperactivity as manifested by sweatiness, tachycardia, tremor
and insomnia. In the majority of cases mild to moderate withdrawal states
can be managed with outpatient detoxification regimes
 Risk factors for complicated withdrawal include:
 a) Previous history of complicated withdrawal
 b) History of withdrawal seizures
 c) Severe nutritional deficiencies (Vit B and thiamine)
 d) Underlying medical complications such as pancreatitis, liver damage,
peptic ulceration or oesophageal varices.
Clinical assessment

 In the routine clinical setting a thorough substance history should include

the following:
 a) The various different substances used including the substance of
preference.
 b) Age at first use, the frequency and amount of use over time. c) Date of
last use.
 d) The amount of money spent on substances.
 e) The amount of time spent daily on drug taking.
 f) Attempts at trying to quit, as well as the duration of abstinent periods.
 g) History of medical/physical complications including overdoses. This
includes a history of risk taking behaviour placing the individual at risk of
contracting transmissible conditions such as HIV or Hepatitis B.
 h) An assessment of the social and relationship consequences of the
substance
 i) Screening for mood, anxiety, psychotic and other psychological
symptoms that may co-occur with drug use. j) Family history of drug
dependence and abuse.
 k) A thorough forensic history and history of any legal involvement.
 l) A detailed personal history and quality of relationship with important
attachment figures as well as important developmental tasks.
 KANABINOIDI
KANABINOIDI
Treatment

 The consequences of addictive disorders span across a wide array of

potential biopsychosocial complications. Consequently the treatment needs
of individuals with addictions span across medical, psychiatric,
psychological, legal, social occupational and financial domains. Due to this
multidimensional nature of treatment needs many health providers are
likely to be involved in the treatment process.
 Treatment providers can include medical services, specialized psychiatric
services, social services, the criminal justice system and psychological
services. As the treatment needs of patients are highly heterogeneous,
treatment intensity and treatment modalities needs to be matched to the
individual patients needs. This requires frequent and effective interaction
between various role players in the addiction treatment process.
 The type of care is further determined along six dimensions: acute
intoxication or withdrawal potential; biomedical conditions or
complications; emotional, behavioural or cognitive conditions and
complications; readiness to change; relapse, continued use or continued
problem potential and recovery environment.