Addiction Psychiatry I

Paper B Syllabic content 11.1

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1. Epidemiology of substance use

A. Alcohol Use:
Epidemiological feature Rates
Percentage of general population who drank alcohol in 67% men; 53% women
the last week in the UK
Percentage of adults who drank above the recommended 55% men (24% of general population); 53%
limits among those who drank alcohol in the last week women (18% of general population)
Percentage of school pupils (aged 11-15) who had drunk 43%
alcohol at least once
Patients presenting to primary care that consume alcohol 20%
at harmful or hazardous levels
Annual prevalence of hazardous drinking (AUDIT score 38% of men; 15% of women; 27% of White
>= 8) in UK households adults, 18% of Black adults, 8% South
Asian adults
Peak age of hazardous drinking 16 to 19 (women); 20-24 years (men)
Prevalence of alcohol dependence 74 per 1,000 overall; 119 per 1,000 men and
29 per 1,000 women.
Number of all hospital attendees/admissions that are 1 in 16 hospital admissions (Pirmohamed,
alcohol related 2000); 1 in 6 A&E attendees (this rises to 8
in 10 during peak hours) (HEA, 1998).
Age-specific use patterns in alcohol dependent people Age at first drink (13-15), age at first
intoxication (15-17) and age at first
problem related to alcohol -22) is
essentially the same as the general
population for alcohol dependent patients.
But the age at death is around 60 years –
very premature.
Alcohol use during pregnancy One in 10 pregnant women drank in the
last week

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 B. Drug Use:
Epidemiological feature Rates
Percentage of UK adults (16 to 59) who took an illicit 1 in 12 (8.3%); frequent users i.e.
drug in the last year >once/month = 2.8%. (Cannabis (6.4%)
followed by powder cocaine (1.9%) and
ecstasy (1.3%))
Percentage of young adults (16 to 24) taking any drug 1 in 6 (16.3%); frequent users = 5.1%
in the last year in the UK
Percentage of adults aged 16 – 59 had taken a Class A 2.6%
drug in the last year
Percentage of school pupils who took an illicit drug in 12% (raises to 17% if all past exposure s are
the last year in the UK considered)
Percentage of drug users in the last year who use 61% when alcohol is also included; 7% for
multiple substances other drugs (not alcohol)
The most commonly reported age for first taking Cannabis - 16 years; powder cocaine and
drugs. ecstasy - 18 years
Average duration of drug use among regular users. Cannabis - 6.2 years; powder cocaine (4.4
years) or ecstasy (3.9 years)

The above data were obtained from Health & Social Care Information Centre. Statistics on Drug Misuse: England
2013 and Statistics on Alcohol: England 2014 (www.hscic.gov.uk; published 29th May 2014)

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2. Typology & Classification
A. Legal categorization:

1971 MISUSE OF DRUGS ACT UK

Class A drugs
Include: Ecstasy, LSD, heroin, cocaine, crack, magic mushrooms
(whether prepared or fresh), methylamphetamine (crystal meth),
other amphetamines if prepared for injection
Class B drugs
Include: Amphetamines, Methylphenidate (Ritalin), Pholcodine.
Class C drugs
Include: Cannabis, tranquilisers, some painkillers, GHB (Gamma-
hydroxybutyrate), ketamine

B. Psychiatric nosology:
 Magnus Huss in 8 coined alcoholism’ which included dependence, acute alcohol-related
health issues and cumulative social problems.
 ICD has a diagnostic code for harmful use’ wherein the actual damage is caused to the
drinker physically or mentally, but he has no dependence pattern (yet).
 ICD-10 alcohol dependence requires at least 3 out of following list satisfied in last 12 months:
1. Intense desire to drink alcohol
2. Difficulty in controlling the onset, termination and the level of drinking
3. Experiencing withdrawal symptoms if alcohol is not taken
4. Use of alcohol to relieve from withdrawal symptoms
5. Tolerance as evidenced by the need to escalate dose over time tom achieves same effect
6. Salience – neglecting alternate forms of leisure or pleasure in life
7. The narrowing personal repertoire of alcohol use.
 DSM IV had a concept of abuse’ which refers to maladaptive use defined as below:
1. Despite problems in social, occupational, physical and psychological domains
2. In hazardous situations
3. At least one month, recurring over a longer period usually.
4. But not dependent on alcohol.
 DSM IV alcohol dependence requires at least 3 out of following list lasting for at least a
month:
1. Consuming alcohol for longer period and in larger amounts than intended
2. Unsuccessful attempts to cut down
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 3. Experiencing withdrawal symptoms if alcohol is not taken
4. Use of alcohol to relieve from withdrawal symptoms
5. Tolerance as evidenced by the need to escalate dose over time tom achieve same effect
(at least 50% increase from start)
6. Salience – most time of life spent on pursuing alcohol directly or indirectly
7. Failure in role obligations and physical health
8. Giving up alternate pleasures
9. Continued use despite knowing the harm caused

 Major changes in DSM 5

o DSM-5 combines the DSM-IV categories of substance abuse and substance dependence
into a single Substance Use Disorder (SUD) that is measured on a continuum from mild
(replacing abuse) to severe (replacing dependence). The same broad criteria are used for
the diagnosis of specific substance-related disorders.
o DSM-IV substance abuse required only one symptom for a diagnosis, but in DSM-5, mild
substance use disorder requires two to three symptoms from a list of 11.
o While drug craving has been added to the list of diagnostic features, the description of
legal problems has been removed to reduce cultural variations that preclude international
comparisons.
o Furthermore, the topic of Addictive Disorders in DSM-5 is much broader, encompassing
non-substance related addictions as well. The gambling disorder is the only condition
currently included in the new category of behavioural addictions. Note that in DSM-IV
pathological gambling was listed under impulse control disorders.
o Internet gaming disorder has been included in Section III (disorders requiring further
research before formal diagnostic description). Similarly, caffeine use disorder is included
in Section III of DSM-5.

C. The concept of dependence:

Dependence is not a moral, but a medical concept and its historical development predominantly
centered on the use of alcohol though it is now extended to be used for different illicit drugs. It
focuses of treatment and indicates intensity, and predicts the outcome to some extent. It also
indicates the need for abstinence compared to reduced drinking in some users.
Edwards & Gross criteria for alcohol dependence (1976) included the following criteria:
1. Narrowed repertoire
2. Salience of alcohol-seeking behaviour
3. Increased tolerance
4. Repeated withdrawals
5. Drinking to prevent or relieve withdrawals.
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 6. Subjective awareness of compulsion
7. Reinstatement after abstinence
Neuroadaptation is a term used to differentiate a certain state from dependence. In case of SSRIs,
for example, discontinuation, loss of effect, relief from discontinuation on taking the same drug,
etc. can be present but no active drug seeking behaviour develops. This is called neuroadaptation.
Remarkably this starts developing as soon as the first dose is taken.
 Narrowing of repertoire: A social drinker may drink in various situations at various places
and may have various drinks of his choice. A dependent drinker will settle into a fixed
setting, sticking to one beverage. This may help him maintain a steady level of alcohol in the
blood without much fluctuation. Note that some widening of repertoire is inevitable in the
career of an alcohol drinker – moving from weekends only to all days of the week, etc.
 Salience refers to the neglect of all leisure and alternate forms of pleasure apart from
alcohol. One s life revolves around getting alcohol, storing it, saving money to buy it,
making opportunities to drink, etc.
 Tolerance:
o It has behavioural, pharmacokinetic and pharmacodynamic cellular mechanisms.
o Tolerance may be due to increased excitability of neurons when using depressants; in this
case withdrawal reactions will inevitably co-occur. Tolerance may also occur when the
potency of alcohol taken reduces due to other reasons such as pharmacokinetic changes. In
this case, withdrawal may or may not be present.
o Tolerance must be differentiated from withdrawal. Intermittent use is unlikely to lead to
withdrawal.
o Tolerance may occur even in intermittent use.
o Note that regular use of benzodiazepines causes much withdrawal anxiety but not much
tolerance is seen for the anxiolytic effects (when compared to hypnotic effects); this is in
contrast to barbiturates.
o Diminished tolerance is also a notable phenomenon in drinkers. This may be due to
 When drinking alcohol after a period of abstinence, the tolerance may revert to
normal and might lead to quick intoxication.
 Older patients with brain damage may have curtailed neuroadaptation leading to
reversed tolerance.
 Metabolic problems such as liver disease may apparently look like diminished
tolerance.
 Idiosyncratic in certain individuals
Withdrawal:
o This refers to physical and psychological symptoms due to non-availability of alcohol in a
dependent user.
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 o The pharmacology of reward is different from the pharmacology of withdrawal. Cocaine
induces modest withdrawal features but has very high reward potential.
o A user in withdrawal gives a very important opportunity towards permanent behaviour
change.
Compulsion refers to repetitive intense drug seeking with an urge. This is different from craving
which is a motivational state occurring in withdrawal.
Craving is a motivational state where emotional valence can be positive or negative. Tiffany
identified the following components of craving;
1. Urge/compulsion
2. Intention/plan – readiness to yield
3. Expectation of a satisfying outcome
4. Anticipation of decrease in pain / relief from negative effects
5. Loss of control
Some alcohol dependent patients may have a cognitive set characterized by the fear of
craving.
Reinstatement on relapse: This is a criterion stressed by Edward & Gross in their early
description of alcohol dependence. A patient, who is abstinent for a long time, may go back to the
original pattern of heavy drinking in a surprisingly rapid manner after having a priming dose of
alcohol (relapse). Various explanations for this include:
1. Abstinence violation effect – the cognition that I had a drink; so I am a drinker again
may force patients to reinstate full pattern of drinking
2. Propensity to experience withdrawal symptoms may be carried over even through the
period of abstinence in some individuals
3. Cues may trigger memory after a priming dose, making compulsive drinking a
behaviour.
Impaired control:
o Not in original Edwards & Gross criteria – but popularized in ICD and DSM.
o This is explained in two different ways
1. Within a single episode of drinking, one loses his control on the intended amount of
alcohol and ends up being often intoxicated.
2. Considering one s overall alcohol career it is evident that one tries to cut down
repeatedly but fails every time.
Cloninger’s classification:
Type 1 Type 2
Milieu limited Male limited
Males and females Males usually
Loss of control Inability to abstain

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 No strong family history Strong heritability
Not much criminality Antisocial traits high
Starts >25years Starts <25 years
Jellinek’s classification:
Type Description
Alpha Psychological dependence; undisciplined not progressive; no
withdrawal; major problems are in interpersonal domain only
Beta Physical damage but no dependence
Gamma Loss of control plus physical dependence. Withdrawal seen; earlier
stages are similar to alpha – most common among AngloSaxons
Delta No loss of control but unable to abstain e.g., in France this may be
socially accepted – no disapproval or interpersonal problems.
Epsilon Dipsomania – binges and bouts

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3. Pharmacological and physiological effects

A. Alcohol:
 Pharmacology: Intercalates into the fluid cell membrane; decreases NMDA sensitivity;
increases GABA sensitivity; down-
regulates calcium channels; up-
Time course of alcohol withdrawal
regulates nicotine receptor gated
sodium channels. •Onset of shakes (4-12 hours)
 Females have lower body water, a •Onset of perceptual disturbances (8-12 hours)
•Seizure onset (12-24 hours); peaks at 48 hours
higher alcohol absorption rate and
•Delirium onset (72 hours)
lesser alcohol dehydrogenase in
their gut mucosa compared to males. All of these lead to a higher oral availability in females
when compared to males.
 Features of alcohol withdrawal: Usually starts within 12 hours of last drink. Tremor,
diaphoresis, sleeplessness, GI distress and anxiety are prominent. Increased urge and
craving for alcohol may be seen. The severity of symptoms depends on the degree of pre-
existent drinking. If unattended symptoms may peak in 48 hours. In these cases, seizures
may occur. These are grand-mal seizures especially common in those who had previous
seizures (epilepsy or withdrawal seizures), head injury and electrolyte imbalance such as
hyponatraemia or hypokalemia. In around 5% patients, delirium tremens may set in.
Disturbed autonomic functions (pulse, temperature and blood pressure changes in either
direction), clouded consciousness with hallucinations (often Lilliputian) and agitation can
occur.
 Seizures: The incidence of seizures quoted as 8% in untreated alcohol-dependent patients.
This risk drops to 3% if withdrawal is being treated. This may be due to a kindling process
whereby episodic alcohol withdrawal sensitises the brain leading to increased likelihood of a
seizure with each future episode (true for all withdrawal symptoms – not just seizures).
 Delirium Tremens: 30% (not all) of the patients with withdrawal seizures later develop DTs.
Risk factors for DT and seizures include severe dependence, past history of DTs, being an
older patient and having an acute physical illness. 10% of those with DT may die if the
withdrawal is untreated. In patients experiencing polysubstance withdrawal that includes
alcohol, one must treat alcohol withdrawal DTs first, due to the significant mortality risk.

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 Opioids:
 The term opiate is often used interchangeably with an opioid, but opiate refers only to
natural opium alkaloids and the semi-synthetics derived from the alkaloids. Opioids have
potent analgesic, euphoriant and anxiolytic effects for which they are abused.
 Heroin is the most commonly used opioid and it is most commonly smoked (called chasing)
or injected IV/IM though it can be snorted or taken orally too. Street heroin is almost always
adulterated and impure; accidental injection of the pure form may result in death due to
toxicity.
 Once only use of heroin is quite rare – generally people progress from recreational exposure
to dependent pattern mostly. The current prevalence of heroin use in the UK is around 1%
(male-to-female ratio of 2:1), with most treatment seekers being in their 20s.
 receptors are important in opioid physiology. Mu μ , kappa κ and delta δ – all three are
G protein-coupled. Most abused opioids are Mu receptor agonists (morphine-like). This
mediates analgesia, respiratory depression, euphoria (only in some), drowsiness and
constipation. They increase dopamine release in VTA. Mu agonists induce tolerance for most
actions, but little or no tolerance is noted for constipation and miosis. Some cross-tolerance is
seen among different mu agonists. Kappa agonists produce dysphoria, no pupillary effect but
some analgesia. They decrease dopamine release in VTA (Kaplan & Sadock CTP, 2010).

Drug Routes Half life Strength

Morphine Multiple routes of intake; low 2-3 hours (both oral and Parenteral use 3 times
oral bioavailability (30%) iv) stronger than oral
Heroin Multiple routes of intake; poor <3 minutes 4-5 times stronger than
(diamorphine) oral bioavailability (30%) oral morphine
Methadone 80% oral bioavailability 15 to 60 hours 3-4 times stronger than
oral morphine
Buprenorphine Sublingual, transdermal or 30h if taken 40 times more potent at
injected sublingually (1-7h if receptor level, but a
taken orally) partial agonist
Oxymorphone, Oral 3 to 7 hours 5-7 times more potent
hydromorphone
Codeine, Oral (Pethidine – intravenous) 2-4 hours 0.1 to 0.2 times potent
dihydrocodeine, compared to morphine
pethidine
Adapted from Luty J. 2014 BJPsych Advances

 Intoxication effects
o Initial euphoria
o Apathy & dysphoria follows.

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 o Psychomotor agitation or retardation
o Pupillary constriction (if pupillary dilation is seen the overdose may be very severe and
anoxia has set in)
o Drowsiness or coma
o Slurred speech
o Impairment in attention or memory

 Withdrawal symptoms (cold turkey): Opioid withdrawal is rarely fatal in a healthy adult.
Morphine and heroin withdrawal syndrome begins 6 to 8 hours after the last dose, peaks in 2
days and reduces in a week usually.
o Dysphoric mood
o Nausea or vomiting
o Muscle aches
o Lacrimation or rhinorrhea
o Pupillary dilation, piloerection (gooseflesh), or sweating
o Diarrhea
o Yawning
o Fever
o Insomnia
Note that insomnia, bradycardia, temperature dysregulation, and a craving for opioids can
persist for months after an episode of withdrawal, necessitating maintenance methadone in
number of patients.

Cannabis:
 Pharmacology: Cannabis is obtained from the plant Cannabis sativa. The principal
component of cannabis is Δ 9-THC. The cannabinoid receptor is an inhibitory G protein (Gi)
linked receptor where endogenous cannabinoids called anandamides act. These receptors are
found in highest concentrations in the basal ganglia, the hippocampus, and the cerebellum,
and are sparse in the cerebral cortex and none in the brainstem; this may explain cannabis
minimal effects on respiratory and cardiac functions.

 Physiological effects: The euphoric effects appear within minutes after smoking, peak in
about 30 minutes, and last 2 to 4 hours. Tolerance to cannabis has been demonstrated in both
human and animal subjects. Psychological dependence has also been found. But the evidence
for physiological dependence is not strong.

 Withdrawal symptoms in humans are irritability, insomnia, anorexia and mild nausea. These
are very rare and occur only when very high doses are suddenly stopped.
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 Intoxication is characterised by impaired motor coordination, euphoria, a sensation of slowed
time, social withdrawal, conjunctival injection, increased appetite (munchies), dry mouth,
tachycardia. In some cases, cannabis intoxication is associated with heightened perceptual
sensitivity, depersonalization and derealization. Impairment in motor skills may remain long
after the euphoriant effects are gone.

Benzodiazepines (Sedatives/Hypnotics):
 Abusers include those who were prescribed at some point, but became dependent and use
supranormal doses obtained illegally, those who use benzodiazepines in combination with
other drugs, e.g. to boost methadone or come off stimulants and those dependent on
legitimate prescriptions, not able to stop them (non-abusers).
 Rates of dependence varies with duration of use – 15% of those using 1-5 months of
prescribed benzodiazepines develop dependence compared to nearly 40% of those using it
for nearly a year (De lasCuevas, 2003)
 Symptoms of intoxication includes slurred speech, incoordination, unsteady gait,
nystagmus , impairment in attention or memory, stupor or coma, behavioural changes
such as inappropriate sexual or aggressive behaviour, mood lability, and impaired
judgment.
 Symptoms of withdrawal includes prominent anxiety and autonomic hyperactivity,
increased tremor, insomnia, nausea or vomiting, transient visual, tactile, or auditory
hallucinations or illusions, psychomotor agitation, in some cases - grand mal seizures.
Kinaesthetic hallucinations are also reported in some individuals. Note that withdrawal
delirium can be fatal.
 Using prescribed benzodiazepines for 4 weeks or less rarely results in significant
withdrawal symptoms. If used for 4 months – 5-10% have withdrawals; 2 years – 25-45%;
6-8years – 75% (Law et al. 2004)
 The role of flumazenil: In contrast to barbiturates, the benzodiazepines have a larger
margin of safety in overdoses. The ratio of lethal dose to effective dose is about 200 to 1 or
higher. When benzodiazepines are taken in overdose with alcohol or other
antidepressants, this can be more serious. In such cases, death is usually due to respiratory
depression. Flumazenil is a specific benzodiazepine antagonist used in A&E/ICU to
reverse the effects of the benzodiazepines.
 Management of dependence in non-abusing patients with early/mild dependence,
minimal interventions such as advisory letters or short courses of relaxation. Where
dependence is established, graded discontinuation of prescribed benzodiazepine should
be tried; the goal must be cessation after safe withdrawal. Overall 66% may stop in the
short term though the long-term outcome is unknown. Additional psychological therapies

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 do not appear to increase the effectiveness of graded discontinuation but can be
considered. Additional pharmacological treatments such as buspirone, antidepressants
and anticonvulsants have been repeatedly shown to have no meaningful effect.
 Management of illicit drug users is less clear with no robust evidence to support
maintenance prescribing. Carbamazepine may be used instead of benzodiazepines to
control withdrawal symptoms from high doses of benzodiazepines

GHB: Gamma hydroxy butyrate

 GHB is a naturally occurring substance in the brain. It was synthesized as an anesthetic
initially but banned later due to rampant abuse by body builders, as it was thought to
boost growth hormone release. It is also abused as a date rape drug (being a colourless
liquid, it is easily concealed). It is sold as a powder that is reconstituted or in a
concentrated shampoo-like form.

 GHB is also abused for its euphoric effects that are short lived and is used as a substitute
for ecstasy in dance parties (raves). It goes by street names of Georgia Home Boy and
liquid ecstasy.

 Pharmacology: GHB has a GABA-like action; also inhibits dopamine release at a low dose
but boosts dopamine availability on chronic use. GHB can also induce the release of
noradrenaline in the hypothalamus. It causes respiratory depression and coma, especially
if mixed with alcohol. But the person may remain combative despite respiratory
depression. Can produce bradycardia in 1/3rd of users.

 A compound derived from GHB called sodium oxybate is licensed for named patient use
in USA for cataplexy associated with narcolepsy.

 In ICD and DSM, GHB abuse is described under the abuse of sedative-hypnotic drugs. A
withdrawal syndrome is reported in heavy users with features very similar to alcohol and
benzodiazepine withdrawal. In mild cases, it is limited to insomnia, tremors and anxiety.
But may extend to paranoia, hallucinations, psychotic behaviour and extreme agitation in
some. These effects start in 12 hours and can last up to 12 days.

 Routine toxicology screening does not detect GHB. Management of intoxication is

primarily supportive. Only anecdotal evidence exists in managing withdrawal syndrome –
lorazepam, diazepam or haloperidol could be used. Aspiration pneumonia is a common
cause of death among GHB users.

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 Stimulants:
A. Amphetamines:
 22% of 16-29 year old in UK have used amphetamines at least once. 10% of those who present
to addiction services have a primary amphetamine-related problem.
 Pharmacology: Amphetamines block catecholamine (DA & NEN especially) reuptake and
stimulate their release from vesicles. Typically amphetamines are used to stimulate
performance and induce a euphoric feeling by students, truck drivers, etc. Oral, IV and
insufflation (snorting) are the possible routes of use. Amphetamine is also called whiz or
speed.
 Many synthetic forms are now available. Some amphetamines such as phenylpropanolamine
(PPA) can exacerbate hypertension, toxic psychosis, and can cause intestinal infarction and
death. Methamphetamine is a potent form that can be inhaled, smoked, or injected
intravenously. Ice is a particularly strong purer form – smoked or injected.
 Intoxication effects include tachycardia or bradycardia (sometimes these arrythmias can be
fatal), pupillary dilation, elevated or lowered blood pressure, perspiration or chills , nausea or
vomiting , evidence of weight loss, psychomotor agitation or retardation, muscular weakness,
respiratory depression, chest pain, or cardiac arrhythmias, confusion, seizures, dyskinesias,
dystonias, or coma, psychological effects such as euphoria, changes in sociability, anxiety,
tension, stereotyped behaviours and impaired judgment.
 Withdrawal effects include dysphoric mood (crash) sometimes with suicidal ideation. fatigue,
vivid, unpleasant dreams, hypersomnia, increased appetite, psychomotor retardation and
small pupils.
 Tolerance develops over the due course of use; amounts several 100-fold greater than the
amount originally used may eventually be ingested or injected. Tolerance to various effects
develops unequally. Tachycardia, euphoria, anorexic effects and increased alertness diminish.
It is noted that acute tolerance develops to the subjective but not to the cardiopressor
(hypertensive) effects of d-amphetamine in healthy subjects. This finding implies that
individuals who repeatedly administer the drug to maintain certain levels of subjective effects
may increase plasma drug levels and physiologic effects to toxic levels.

B. MDMA (3, 4-methylene-dioxymethamphetamine):

 MDMA is a substituted amphetamine that produces subjective effects resembling those of
amphetamine and LSD (lysergic acid diethylamide). So it is partially hallucinogenic and
partially stimulant. It is often used for extended dance parties called raves among adolescents.
In the past several psychiatrists used it as an adjunct to psychotherapy as it can increase
empathizing ability albeit for a short while.

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 Pharmacology: It has two optical isomers: the R(-) isomers produce LSD-like effects, and the
S(+) isomers produce amphetamine-like effects. The LSD-like action is due to the capacity to
release serotonin from terminals – in the long term this damages the serotonin nerves
irreversibly and results in depression. Lower doses are more stimulant like; higher doses
produce more hallucinogenic or psychotomimetic effects. It can be consumed orally, injected
or snorted. Both tachyphylaxis (quick loss of activity after short repeated use) and some
tolerance are reported.
 MDMA abstinence-associated withdrawal symptoms include fatigue, loss of appetite,
depression, anxiety, and trouble concentrating. This happens on the same day or 2 days after
the last drug use, the most common mental or mood complaints are difficulty concentrating,
depression, anxiety and fatigue. These symptoms strongly resemble a miniature "crash" that is
seen as a withdrawal reaction after the use of stimulants.
 Harm reduction advice regarding maintaining hydration and avoiding overheating during
use

C. Khat (Cathinone):
 The fresh leaves of Catha edulis from East Africa (Somalia, Eritrea), and Yemen are used as a
stimulant for their amphetamine-like effects induced by the main ingredient cathinone.
 Cathinone has most of the CNS and peripheral actions of amphetamine. It is buccally
absorbed after chewing the leaf and being an alkaloid, gets metabolized rapidly with low
chances of toxicity.
 Synthetic methcathinone is also available for illicit use in many countries.

D. Cocaine:
 Cocaine is an alkaloid derived from the shrub Erythroxylon coca. It is a powerful positive
reinforcer and a strong dependence producer. It has a potent dopamine reuptake blockade
effect.
 It can be injected, smoked or snorted. Snorting can cause nasal septal perforation due to local
anaesthetic effect with repeated trauma, and vasoconstriction and ischemic necrosis.
 Pharmacology: Street cocaine can be freebased (released free from the base e.g. sodium
bicarbonate which is mixed with it) to produce a purer form called crack which when inhaled
acts as rapidly as IV use. The duration of cocaine s euphoric effects high depends upon the
route of administration. The faster the absorption, the more intense the high . Also, the faster
the absorption, the shorter the duration of action. The high from snorting is relatively slow in
onset, and may last 15 to 30 minutes while that from smoking or mainlining may last 5 to 10
minutes. Inhalation (smoking) or intravenous injections cause a very rapid onset of action.

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 At least 60% of cocaine users admit to mental health problems when surveyed. Among these
18% have psychotic experiences.
 Intoxication: There is increased energy, increased confidence, heightened self-esteem, and
perceived improvement on mental and physical tasks, euphoria, and diminished need for
sleep. With high doses agitation, irritability, impaired judgment, impulsive aggression, some
symptoms of mania with associated tachycardia, hypertension, and mydriasis are noted. In
some, a sensation of bugs crawling beneath the skin (formication) has been reported when
under the influence.
 Withdrawal: Effects of cocaine are short-lived - rapid cessation occurs due to rapid
metabolism resulting in withdrawal effects that can lead to repeated use. A characteristic
feature is intense cravings for cocaine with a striking lack of much physical withdrawal
symptoms. Dysphoria (crash), anhedonia, anxiety, irritability hypersomnolence, and
sometimes agitation are seen upon withdrawal. These effects usually end within 18 hours
though in heavy, dependent users this can last up to a week, peaking in 3 days.
 Physical adverse effects of cocaine includes
 Nasal perforation on snorting.
 Nonhemorrhagic cerebral infarctions.
 Subarachnoid, intraparenchymal, and intraventricular hemorrhages.
 TIAs
 Seizures (3 to 8% of A&E visits)
 Myocardial infarctions and arrhythmias

E. Caffeine:
 Pharmacology:
o Caffeine is a methylxanthine like theophylline. The half-life of caffeine in the human
body is 3 - 10 hours and the time of peak concentration is 30 to 60 minutes.
o Caffeine readily crosses the blood-brain barrier and acts as an antagonist of the
adenosine receptors, and so increase the intraneuronal cAMP. At high doses, it can affect
dopamine and noradrenergic neurons. Caffeine in nontolerant individuals may reduce
GABAergic activity in cerebral cortex and striatum, but tolerance to caffeine brings back
the GABAergic activity to the control value.
o A single cup has low to moderate doses of caffeine (i.e., 20 to 200 mg) that increases
alertness. 300 to 800 mg produces unpleasant anxiety and nervousness.
o Caffeine results in global cerebral vasoconstriction and a reduction in cerebral blood
flow; this may not occur in those over 65yrs. Tolerance does not develop to these
vasoconstrictive effects; blood flow shows a rebound increase after withdrawal.

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 Intoxication: Caffeine intake in excess of 250 mg (>2-3 cups at once) can produce restlessness,
nervousness, excitement, insomnia, flushed face, diuresis, gastrointestinal disturbance, muscle
twitching, rambling flow of thought and speech, tachycardia or cardiac arrhythmia, periods of
inexhaustibility and psychomotor agitation.

 Withdrawal is not recognized in DSM. But research criteria indicates that headache, marked
fatigue or drowsiness, marked anxiety or depression and nausea or vomiting can be seen even
at low doses from 100mg/day, beginning within 12 hours, peaking at 24-48 hours and lasting
up to 1 week.

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 Hallucinogens:
 Hallucinogens are also called psychedelics or psychotomimetics.

 Naturally occurring hallucinogens include psilocybin (from mushrooms) and mescaline.

Magic mushrooms especially the Liberty Cap (Psilocybe semilanceata) is popular in UK.
They may be eaten raw or cooked and prepared as a concoction. Small doses cause euphoria,
while larger doses (>25 mushrooms) act like LSD. They are not associated with dependence or
withdrawal; tolerance develops quite quickly.

 LSD is a classic synthetic hallucinogen, synthesized in 1938 by Albert Hoffman. LSD is a

synthetic base derived from the ergot alkaloids. It is also noted in rye fungus and was
responsible for lethal outbreaks of St. Anthony's fire in the middle Ages. The compounds are
also present in morning glory seeds in low concentrations. It is the most commonly used
hallucinogen in the UK. LSD has been commonly distributed as blotter acid. Sheets of paper
are soaked with LSD, dried and perforated into small squares. Popular designs are stamped
on the paper.

 LSD acts via sigma opioid and aspartate receptors as well as serotonergic effects. It can cause
acute confusion, visual sensory distortions, aggression, and sudden severe violence. Psychosis
can also result from its use. Tolerance to the sensory and other psychological effects is evident
as soon as the second or third day of successive LSD use. 4 - 6 days free of LSD is necessary to
lose significant tolerance. Cross-tolerance among mescaline, psilocybin, and LSD occurs, but
not between amphetamine and LSD. Both physical and psychological dependence on
hallucinogens are rare and not seen in present day clinical practice. This may be due to lack of
reliable euphoria from hallucinogen use.

 Phencyclidine (PCP) or angel dust is also a synthetic agent not commonly found in the UK
except as a contaminant of other drugs. PCP is usually smoked or snorted.

 Ketamine is structurally similar to phencyclidine and is used as a veterinary anaesthetic. It

does not depress the reticular activating system (thus does not knock of consciousness
completely) but reduces the cortical awareness of painful stimuli. It is taken as a sniffed
powder termed as K .

 Hallucinogen intoxication is characterized by marked anxiety or depression, ideas of

reference, fear of losing one's mind, paranoid ideation, perceptual changes e.g., subjective
intensification of perceptions, depersonalization, derealization, illusions, hallucinations,
synesthesias in a state of full alertness, pupillary dilation, tachycardia, sweating, palpitations,
blurring of vision, tremors, and incoordination. The usual sequence of changes follows a
pattern of somatic symptoms appearing first, then mood and perceptual changes, and, finally,
© SPMM Course 18
 psychological changes. In addition, PCP CLUB DRUGS
intoxication could cause the following
National Institute on Drug Abuse has listed some
additional features: vertical or horizontal drugs as club drugs according to their popularity
nystagmus, numbness or diminished in dance clubs and other party venues.
responsiveness to pain, ataxia and dysarthria These agents have diverse mechanisms of action, and
include MDMA, Ecstasy, Rohypnol, GHB,
with muscle rigidity. Pupil size is variable
Ketamine, LSD.
with PCP use, depending on the degree of
hypoxia and intoxication. GHB, flunitrazepam, rohypnol, and ketamine are
also called date rape drugs. These agents produce
sedation with strong amnesia. Thus they are
frequent culprits in drugging / spiking for the
Nicotine: purpose of theft or sexual assault.
 Nicotine is one of the most addictive and
widely used substances worldwide. Nicotine
dependence is recognized in ICD-10 and DSM-IV as a psychiatric disorder. 80% of cigarette
smokers are nicotine dependent.
 Pharmacology:
o Nicotine stimulates central nicotinic acetylcholine receptors and improves alertness.
o Polycyclic hydrocarbons in cigarette smoke are known to stimulate the hepatic
microsomal enzymes system, particularly CYP1A2. Smoking can lower the blood
levels of some drugs by up to 50%. This can affect both efficacy and side effects. The
drugs most likely to be affected are clozapine, olanzapine, chlorpromazine,
fluphenazine, haloperidol, tricyclic antidepressants, mirtazapine, fluvoxamine and
propranolol.
 Intoxication: Nicotine intoxication is not coded separately in classification systems. The most
important reason for therapeutic intervention in nicotine users is physical ill-health, especially
cardiovascular and respiratory diseases.
 Withdrawal symptoms: These are recognized in DSM. The features of withdrawal reaction
are dysphoric or depressed mood, insomnia, irritability, frustration, or anger, anxiety,
difficulty concentrating, restlessness, decreased heart rate and increased appetite or weight
gain. These symptoms begin a few hours after the last cigarette, peak 2 to 3 days after
quitting, and become less intense over 1 to 3 weeks. Smokers also report cravings for
cigarettes, which can last for a longer period of time. The mean weight gain after smoking
cessation is approximately 10 lb, and women and heavy smokers are at greatest risk for large
weight gains

© SPMM Course 19
 Inhalants:
 Inhalant substances are easily available, legal, and inexpensive – contributes to nearly 1%
of all substance related deaths. The most common profile is that of an adolescent who
skips classes at school.

 Often the substances inhaled are solvents for glues and adhesives; propellants for
aerosol paint sprays, hair sprays, thinners (e.g., paint products and typing correction
fluids); and fuels such as gasoline or petrol.

 Pharmacology: Inhalants generally act as CNS depressants; the concentrations of many

inhalant substances in the blood are increased when used in combination with alcohol.
The effects appear within 5 minutes of inhalation of vapours and can last for 30
minutes to several hours. Tolerance for inhalants has been reported.

 Signs of intoxication include dizziness, nystagmus, incoordination, slurred speech,

unsteady gait, lethargy, depressed reflexes, psychomotor retardation, tremor,
generalized muscle weakness, blurred vision or diplopia, stupor or coma and euphoria.
A recent inhalant user may have rashes around nose and mouth; unusual breath odours;
the residue of the inhalant substances on body or clothes; and signs of ocular and
oropharyngeal irritation.

 No dependence syndrome has been described; no reliable withdrawal syndrome has

been consistently recorded as per DSM.

© SPMM Course 20
4. Prescribing controlled drugs
The Misuse of Drugs Regulations 2001 define the authorised persons who can supply and possess
controlled drugs in their professional capacities. Accordingly, drugs are divided into five
schedules.

2001 MISUSE OF DRUGS REGULATIONS

Schedule Examples Regulations

1 Coca leaf, cannabis, LSD, mescaline No recognized medicinal use. Supply is limited to
research or other special purposes judged to be in the
public interest. Requires Home Office licence to
possess.

2 Diamorphine, dipipanone, Subject to special prescription requirements and safe

morphine, remifentanil, pethidine, custody requirements (with the exception of
secobarbital, glutethimide, secobarbital). Stock drugs must be recorded in a
amphetamine and cocaine register that meets the requirements of the 2001
Regulations, and drug stock must only be destroyed
in the presence of an appropriately authorized person.

3 The barbiturates (except These drugs are subject to the special prescription
secobarbital), buprenorphine, requirements (except for temazepam) but not to the
diethylpropion, mazindol, safe custody requirements (except for buprenorphine,
meprobamate, pentazocine, diethylpropion, flunitrazepam and temazepam) or to
phentermine, and temazepam the need to keep a register, although there are
requirements for the retention of invoices for 2 years

4 Part 1 Benzodiazepines (not temazepam) These drugs are not subject to the special prescription
and zolpidem requirements or to safe custody requirements. There
is no need to keep a register, although there are
Part 2 Androgenic and anabolic steroids, requirements for the retention of invoices for 2 years
clenbuterol, chorionic
gonadotrophin (HCG), non-human
chorionic gonadotrophin,
somatotropin, somatrem, and
somatropin

5 Weak preparations of drugs usually Exempt from all controlled drug regulations except
in other schedules, for example, the need to keep invoices for at least 2 years
morphine, codeine

All controlled drug prescriptions should have

© SPMM Course 21
  The patient s full name, address and age
 If a patient is homeless, no fixed abode is an acceptable address
 The name and form of the drug MUST be written
 The strength of the preparation, where appropriate
 The dose to be taken MUST be written
 The total quantity of the preparation, or the number of dose units, to be supplied in both
words and figures
 A patient identifier number (e.g. NHS number) should be included on prescriptions for
controlled drugs
 Prescriptions must be signed by the prescriber with their usual signature (this must be
handwritten) along with GMC number as a good practice
 The validity period of prescriptions for Schedule 1, 2, 3 and 4 controlled drugs have been
restricted to 28 days.
 Schedule 2 and 3 drugs cannot be prescribed on repeat prescriptions or under repeat
dispensing schemes.
 Patients ideally should collect the controlled drug in person after showing their
identification on the first occasion and signing the back of the prescription form.
 Substitute opioids should be prescribed in daily instalments whenever required.
Prescriptions of instalments must specify
o The number of instalments
o The interval between instalments,
o Instructions for supplies at weekends or bank holidays
o The total quantity to provide treatment for a period (this must not be exceeding 14
days generally)
o The quantity to be supplied in each instalment along with the duration of the
instalments to be set out on the prescription, for example dispense daily for
fourteen days starting on 3rd September .

© SPMM Course 22
 A quick review of addiction pharmacology
DRUG MECHANISM
Alcohol Intercalates into the fluid cell membrane; decreases NMDA sensitivity; increases
GABA sensitivity; down-regulates calcium channels; up-regulates nicotine receptor
gated sodium channels.
Amphetamine Acts via releasing stored monoamines especially noradrenaline and dopamine.
Hence a central sympathomimetic.
Buprenorphine Partial opioid agonist. Lower doses – mild agonism; higher doses – antagonistic
effects.
Cannabis Acts via cannabinoid receptors. CB1 is central and activated by 11OH tetra hydro
cannabinoid. This inhibits GABA tone in the substantia nigra and other areas. May
be related to increased dopamine activity at reward centres. CB2 is peripheral
immune-related and seen in spleen and thymus. (Endogenous cannabinoids called
anandamides are derived from arachidonic acid; their function is unclear)
Clonidine, Presynaptic alpha 2 agonist – reduces central sympathetic tone. Opioid receptors on
lofexidine locus coeruleus projections reduce noradrenergic tone on long-term use. The cellular
machinery compensates via up-regulation of adenylate cyclase and maintains
sympathetic tone in a chronic user. Sudden withdrawal leads to increased adrenergic
firing rate (withdrawal symptoms); hence alpha 2 autoreceptor stimulation which
reduces central sympathetic tone helps in opioid withdrawal.
Dexfenfluramine Produce massive serotonin release from nerve endings. [Fen-Phen was an off-label
& Fenfluramine combination of fenfluramine and phentermine used for promoting weight loss but
fenfluramine (and dexfenfluramine) was withdrawn due to irreversible serotonergic
damage, valvular regurgitation and pulmonary fibrosis].
Disulfiram Inhibits aldehyde dehydrogenase. Leads to accumulation of acetaldehyde if alcohol
is consumed producing unpleasant reactions.
Levomethadyl Long-acting opioid agonist; potentially similar use as methadone. Withdrawn due to
acetate (LAAM) prolonged QT and torsades de pointes. Pure mu agonist.
LSD 5HT2A partial agonism producing hallucinogenic effect
MDMA Has 2 isomers  R(-) isomers produce LSD-like effects and the S(+) isomers have
amphetamine-like properties LSD-like action is mediated via serotonin release from
presynaptic neurons. In the long term, this can damage serotonergic tracts
irreversibly.
Methadone Opioid receptor agonist. Longer acting than heroin and orally available. Pure mu
agonist.
Naloxone Short-acting opioid mu antagonist
Naltrexone Longer acting opioid mu antagonist
Phencyclidine Noncompetitive NMDA antagonist similar to ketamine; also binds to sigma
receptors
Varenicline Varenicline (Champix) is a partial agonist at the unit of nicotinic acetylcholine
receptor. It assists smoking cessation by relieving nicotine withdrawal symptoms
and reducing the rewarding properties of nicotine.

© SPMM Course 23
 Notes prepared using excerpts from
 Brauer, L. H., Ambre, J., & De Wit, H. (1996). Acute tolerance to subjective but not cardiovascular
effects of d-amphetamine in normal, healthy men. Journal of Clinical Psychopharmacology, 16(1), 72-
76
 http://www.aaem.org/statechapters/aprilcajem.pdf
 http://www.emedicine.com/emerg/topic848.htm
 Lyon et al. A Review of the effects of nicotine and schizophrenia antipsychotic medications.
Psychiatr serv 1999; 50; 1346-1350
 Mukhopadhyay, S & Poddar, MK (1998) Is GABA Involved in the Development of Caffeine
Tolerance? Neurochemical Reseaerch, 23: 63-68
 National Institute for Health and Clinical Excellence. Drug misuse: psychosocial interventions.
London: NICE, 2007. (www.nice.org.uk/CG051)
 National Institute for Health and Clinical Excellence. Drug misuse opioid detoxification:
www.nice.org.uk/CG052
 Rigotti NA. Clinical practice: Treatment of tobacco use and dependence. N Engl J Med.
2002;346:506.
 Rigotti, N. A 36 year old woman who smokes cigarettes. JAMA. 2000;284:741-749.
 Home Office UK: http://drugs.homeoffice.gov.uk/drugs-laws/misuse-of-drugs-act/

DISCLAIMER: This material is developed from various revision notes assembled while preparing
for MRCPsych exams. The content is periodically updated with excerpts from various published
sources including peer-reviewed journals, websites, patient information leaflets and books.
These sources are cited and acknowledged wherever possible; due to the structure of this
material, acknowledgements have not been possible for every passage/fact that is common
knowledge in psychiatry. We do not check the accuracy of drug-related information using
external sources; no part of these notes should be used as prescribing information

© SPMM Course 24