1. Substance use disorder
Substance use disorder (SUD) is the persistent
use of drugs despite substantial harm and
adverse consequences to self and others.
2. Neurobiology of substance
abuse
• The neurobiological framework describes the substance use and why
some people transition from using or misusing alcohol or drugs to
substance use disorder including it’s most severe form, addiction.
• It also explains how these substances produce changes in the brain
structure and functions that promote and sustain addiction and
contribute to relapse
3. Regions of the brain involved
• Basal Ganglia
• Extended Amygdala:
• Prefrontal Cortex:
4. Addiction cycle
◦ Addiction can be described as a repeating
cycle with three stages.
• Binge/Intoxication.
• Withdrawal/Negative Affect.
• Preoccupation/Anticipation.
5. The four behaviours
◦ It is necessary to explain four behaviors that are central to the addiction cycle: impulsivity,
positive reinforcement, negative reinforcement, and compulsivity.
• Impulsivity. An inability to resist urges
• Positive reinforcement. The process by which presentation of a stimulus such as a drug
increases the probability of a response like drug taking.
• Negative reinforcement. The process by which removal of a stimulus such as negative
feelings or emotions increases the probability of a response like drug taking.
• Compulsivity. Repetitive behaviors in the face of adverse consequences, and repetitive
behaviors that are inappropriate to a particular situation. People suffering from compulsions
often recognize that the behaviors are harmful, but they nonetheless feel emotionally
compelled to perform them. Doing so reduces tension, stress, or anxiety.
6. Tolerance and withdrawal
◦ The positively reinforcing effects of substances tend to
diminish with repeated use. This is called tolerance and may
lead to use of the substance in greater amounts and/or more
frequently in an attempt to experience the initial level of
reinforcement.
◦ Eventually, in the absence of the substance, a person may
experience negative emotions such as stress, anxiety, or
depression, or feel physically ill. This is called withdrawal,
which often leads the person to use the substance again to
relieve the withdrawal symptoms.
7. Binge/Intoxication stage: Basal
Ganglia
• The binge/intoxication stage of the
addiction cycle is the stage at which an
individual consumes the substance of
choice.
• This stage heavily involves the basal
ganglia and its two key brain sub-regions,
the nucleus accumbens and the dorsal
striatum.
• The rewarding effects of substances involve
activity in the nucleus accumbens,
including activation of the brain's
dopamine and opioid signaling system.
8. • A person learns to associate the stimuli present while using a substance—including
people, places, drug paraphernalia, and even internal states, such as mood—with the
substance's rewarding effects. Over time, these stimuli can activate the dopamine system
on their own and trigger powerful urges to take the substance. These “wanting” urges are
called incentive salience and they can persist even after the rewarding effects of the
substance have diminished.
• As a result, exposure to people, places, or things previously associated with substance use
can serve as “triggers” or cues that promote substance seeking and taking, even in people
who are in recovery
• These findings help to explain why individuals with substance use disorders who are
trying to maintain abstinence are at increased risk of relapse if they continue to have
contact with the people they previously used drugs with or the places where they used
drugs*
9. Habit Formation
◦ A second sub-region of the basal ganglia, the dorsal striatum, is involved in
another critical component of the binge/intoxication stage: habit formation. The
release of dopamine (along with activation of brain opioid systems) and release of
glutamate (an excitatory neurotransmitter) can eventually trigger changes in the
dorsal striatum.
10. WITHDRAWAL / NEGATIVE AFFECT STAGE:
EXTENDED AMYGDALA
The withdrawal/negative affect stage of addiction
follows the binge/intoxication stage, and, in turn,
sets up future rounds of binge/intoxication.
During this stage, a person who has been using
alcohol or drugs experiences withdrawal
symptoms, which include negative emotions and,
sometimes, symptoms of physical illness, when
they stop taking the substance.
The negative feelings associated with withdrawal
are thought to come from two sources:
diminished activation in the reward circuitry of
the basal ganglia and activation of the brain's
stress systems in the extended amygdala
11. • When used over the long-term, all substances
of abuse cause dysfunction in the brain's
dopamine reward system. For example, brain
imaging studies in humans with addiction have
consistently shown long-lasting decreases in a
particular type of dopamine receptor, the D2
receptor, compared with non-addicted
individuals
• At the same time, a second process occurs
during the withdrawal stage: activation of
stress neurotransmitters in the extended
amygdala. These stress neurotransmitters
include corticotropin-releasing factor (CRF),
norepinephrine, and dynorphin.
• these neurotransmitters play a key role in the
negative feelings associated with withdrawal
and in stress-triggered substance use
• The desire to remove the negative feelings that
accompany withdrawal can be a strong
motivator of continued substance use.
12. PREOCCUPATION/ ANTICIPATION STAGE :
PREFRONTAL CORTEX
◦ The preoccupation/anticipation stage of the addiction cycle is
the stage in which a person may begin to seek substances
again after a period of abstinence. In people with severe
substance use disorders, that period of abstinence may be
quite short (hours). In this stage, an addicted person becomes
preoccupied with using substances again. This is commonly
called “craving.
To help explain how the prefrontal cortex is involved in addiction,
some scientists divide the functions of this brain region into a “Go
system” and an opposing “Stop system.”The Go system helps
people make decisions, particularly those that require significant
attention and those involved with planning. People also engage
the Go system when they begin behaviors that help them achieve
goals.
13. The Go system also engages habit-response systems in the dorsal striatum, and it contributes to the impulsivity
associated with substance seeking.
The Stop system inhibits the activity of the Go system. Especially relevant to its role in addiction, this system
controls the dorsal striatum and the nucleus accumbens, the areas of the basal ganglia that are involved in the
binge/intoxication stage of addiction.
The lower activity in the Stop component of the prefrontal cortex is associated with increased activity of stress
circuitry involving the extended amygdala, and this increased activity drives substance-taking behavior and
relapse.
◦ Studies also show that diminished prefrontal cortex control over the extended amygdala is particularly
prominent in humans with post-traumatic stress disorder (PTSD), a condition that is frequently accompanied
by drug and alcohol use disorders. These findings bolster support for the role of the prefrontal cortex-
extended amygdala circuit in stress-induced relapse, and suggest that strengthening prefrontal cortex
circuits could aid substance use disorder treatment.
15. Alcohol Use Disorder (AUD) is a chronic relapsing
condition characterized by impaired control over alcohol
consumption, compulsive alcohol use, and negative
emotional states when not using alcohol.
17. SPECIES OF ALCOHOL DEPENDENCE
According to Jellinek, there are five ‘species’ of alcohol dependence on
the basis of the patterns of use
• Alpha (α)
• Beta (β)
• Gamma (γ)
• Delta (δ)
• Epsilon (ε)
18. Withdrawal symptoms
• M/c withdrawal syndrome is hangover
next morning
• Common withdrawal symptoms: mild
tremors, nausea, vomiting,weakness,
irritability, insomnia and anxiety
• Severe withdrawal symptoms are
characterised by one of the following:
• Delirium tremens
• Alcoholic seizures
• Alcoholic hallucinosis
19. Complications of Chronic alcohol
use
• Wernicke’s encephalopathy:
- It This is an acute reaction to a severe
deficiency of thiamine, the commonest
cause being chronic alcohol use.
Characteristically, the onset occurs after a
period of persistent vomiting.
• Korsakoff’s psychosis
-Clinically, Korsakoff’s psychosis presents
as an organic amnestic syndrome,
characterised by gross memory
disturbances, with confabulation. Insight is
often impaired.
20. • Marchiafava-Bignami disease
- This is a rare disorder characterised by
disorientation, epilepsy, ataxia, dysarthria,
hallucinations, spastic limb paralysis, and
deterioration of personality and intellectual
functioning.
• Alcoholic dementia.
• Cerebellar degeneration.
• Peripheral neuropathy.
• Central pontine myelinosis.
21. Treatment
• Before starting the treatment rule out any physical and psychiatric
disorder ad we’ll as co-morbid substance use disorder
• Assess for motivation for treatment , social support system,
personality characteristics of the patient
• The treatment can be broadly divided into two categories which are
often interlinked. These are detoxification and treatment of alcohol
dependence.
22. Detoxification
• It is the treatment of alcohol withdrawal symptoms. It can be achieved
on an outpatient basis.
• The drugs of choice for detoxification are usually benzodiazepines.
Chlordiazepoxide (80-200 mg/day in divided doses) and diazepam (40-80
mg/day in divided doses) are the most frequently used benzodiazepines.
• In patients suffering from delirium tremens, peripheral neuropathy,
Wernicke- Korsakoff syndrome, or other signs of vitamin B deficiency a
preparation of vitamin B containing 100 mg of thiamine (vitamin B1)
should be administered parenterally, twice everyday for 3-5 days.
• Followed by oral administration of vitamin B1 for at least 6 months.
23. Treatment of Alcohol
Dependence
1. Behaviour therapy
2. Psychotherapy
3. Group therapy
-Of particular importance is the voluntary self-help group known as AA
(Alcoholics Anonymous)
24. 4. Deterrent agents
-Also known as Alcohol sensitising drugs
A. Disulfuram
The contraindications of disulfiram use are first trimester of pregnancy, coronary artery disease, liver failure, chronic renal failure, peripheral
neuropathy, muscle disease and psychotic symptoms presently or in the past.
B. Citrated calcium carbimide (CCC)
C. Metronidazole
D.Animal charcoal, a fungus (Coprinus atramentarius), sulfonylureas and certain cephalosporins also cause a
disulfiram like action.
E. Anti-craving agents :- Acamprosate, naltrexone and SSRIs (such as fluoxetine)
F. Other medications such as benzodiazepines, antidepressants, antipsychotics, lithium, carbamazepine, and even
narcotics have been tried.
G. Psychosocial rehabilitation
