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CNS PHARMACOLOGY
The CNS [brain and spinal cord (SC)] can be divided into its
anatomical areas or its physiological functions, both of which our
knowledge base of the entire system is not
complete. The study of the drugs that can affect the brain and their varied
mechanisms of action (MOA) compounds the complexity of this system.
CENTRAL NEUROTRANSMITTERS
Neurotransmitters are chemical mediators which are released
from nerve endings into the synaptic cleft once an action potential has
been reached eliciting an influx of Ca++ ions (a voltage dependent
action). The neurotransmitter then reaches it target postsynaptic receptor
site with the result being either direct excitation or inhibition or
enhancing excitation or inhibition.
1. Biogenic amines:
a. dopamine-precursor of norepinephrine. Approximately ½ of CNS
content of catecholamines is dopamine with large amounts in the basal
ganglia (esp. caudate nucleus), olfactory tubercle, central nucleus of the
amygdala, limbic system, and certain areas of the frontal cortex. There
are 5 dopamine receptor subtypes: D1 (and D5) activate adenylyl
cylclase, D2 (and D3 & D4) inhibit adenylyl cyclase. Some D2 receptors
may also suppress Ca++ currents and activate K+ currents.
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b.norepinephrine-relatively large amounts are located in hypothalamus
and in certain zones of the limbic system (parts of amygdale &
hippocampus) but is present in most brain regions (cerebral cortex, brain
stem, cerebellum, and spinal cord) but in lower amounts. It is primarily
an excitatory neurotransmitter but in selected areas in the CNS & PNS it
has inhibitory effects.
c. epinephrine-epi containing neurons are found in medullary reticular
formation with some connections to the pontine region, diencephalic
nuclei, and paraventricular nucleus of the dorsal thalamus. Also found in
periaqueductal gray area and spinal cord.
d. serotonin (5-hydroxytryptamine or 5-HT)-is primarily an inhibitory
neurotransmitter. Is found in hypothalamus, limbic system, cerebellum,
piriform cortex, cerebral cortex, choroids plexus, and retina. It is found in
the highest concentration in platelets and the GI tract. There are 14
receptor subtypes each of which is composed of a further set of sybtypes.
e. histamine-most of histamine receptors are found in ventral posterior
hypothalamus and extends to ascending and descending tracts in the
brain. The histamine system is thought to function in regulating arousal,
body temperature, vascular dynamics, the reticular activating system.
There are 3 histamine receptor subtypes.
2. acetylcholine-seems to be an excitatory transmitter in the CNS vs. its
inhibitory effects in the PNS.
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3. amino acids-most common inhibitory and excitatory neurotransmitters
in CNS.
a. gamma-aminobutyric acid (GABA)-is major inhibitory mediator in
brain with cells containing GABA are some neurons in basal ganglia,
cerebellar Purkinje, cerebral cortex, and certain interneurons in spinal
cord. There are two subtypes of GABA: GABA-A (a
ligand-gated Cl- channel) and GABA-B (a G-protein coupled receptor).
b. glycine-inhibitory transmitter released by brainstem and interneurons
in spinal
cord.
c. glutamate-major excitatory neurotransmitter found in cerebral cortex
and brain stem.
d. aspartate-an excitatory neurotransmitter found in the visual cortex.
4. neuropeptides (polypeptides)
a. substance P
b. vasopressin
c. oxytocin
d. somatostatin
e. glucagons
f. angiotensin II
g. atrial natriuretic peptide
h. enkephalins
i. endorphins
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5. purine nucleotides
a. adenosine
b. ATP
ACTIONS OF DRUGS IN THE CNS
A. The structural and functional properties of neurons and their specific
receptors provides a means to modify CNS function, either specifically or
generally, by administering drugs that can act at defined receptor sites,
either causing inhibition or excitation at the receptor. Drugs that act
within the CNS include anticonvulsants, antiparkinsonian agents, opiod
& nonopiod analgesics, antiemetics, antipyretics, antidepressants,
anypsychotic & antimanic agents, and sedatives & hypnotics.
The drugs that selectively modify CNS function act either
specifically or nonspecifically according to its effect or response. For
example, the effect of the drug is specific when it binds to a target cell’s
receptors and affects an identifiable intracellular mechanism and imparts
a specific therapeutic action. (These include all the drug categories listed
above.) A drug is considered nonspecific if it produces effects on many
different target cells and results in diverse molecular mechanisms. The
nonspecific drugs are classified according to whether they produce
behavioral depression or stimulation.
Examples of nonspecific CNS depressants include the anesthetic gases,
ethanol, and some hypnoticssedatives.
Example of nonspecific CNS stimulants are caffeine and amphetamines.
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The specific drugs affecting the CNS include the psychotropic drugs
which are utilized to correct the “pathological”aspects of the CNS. The
four primary categories include the antidepressants, antipsychotics
(neuroleptic), antimanic drugs, and antianxiety
drugs.
It was previously recommended to discontinue certain classes of these
drugs, i.e.
TCAs and MAOIs, approximately two weeks before surgery; however it
is now recommended to continue these medications as the discontinuation
of these medications before surgery could possibly increases the risk of
the patient developing suicidal ideation or psychotic disturbances. As
well, it has been determined that the patient can safely undergo anesthesia
and surgery while currently taking these medications.
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CNS Stimulants
Central Nervous System Stimulation -primary action of a diverse
group of pharmacological agents -adverse effect associated with
many drugs.
Behavioral Manifestations of CNS Stimulation
-mild elevation in alertness, decrease in drowsiness and lessening of
fatigue (Analeptic Effect)
-increased nervousness and anxiety -convulsions.
Molecular Basis of CNS Stimulation
Imbalance between inhibitory and excitatory processes as in the
brain. This hyper-excitability of neurons results from:
* potentiation or enhancement of excitatory neurotransmission(e.g.
amphetamine)
* depression or antagonism of inhibitory transmission (e.g.
Strychnine)
presynaptic control of neurotransmitter release (e.g. picrotoxin)
Classification of CNS Stimulants
1-Analeptic Stimulants
2-Respiratory Stimulants
3-Convulsants
4-Psychomotor Stimulant
5-Sympathomimetics or Adrenergic CNS Stimulants
6-Methylxanthines
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Analeptic Stimulants
diverse chemical class of agents
majority can be absorbed orally
have a short duration of action –
primary expression of pharmacological effect is convulsions (tonicclonic) uncoordinated
pharmacological effect is terminated through hepatic metabolism
Possible Common Mechanism of Action -ability to alter movement of
chloride ions across neuronal membranes
Therapeutic Uses Group as a whole has limited therapeutic use.
Doxapram and Nikithamide - used to counteract postanesthetic
respiratory depression and for acute hypercapnia in chronic
pulmonary disease.
Pentylenetetrazole - used clinically as a tool for screening latent
epileptics and experimentally to screen compounds for anti-epileptic
activity.
Picrotoxin - used to study CNS mechanisms; it interferes with
pathways that are strychnine resistant.
Strychnine is a source of accidental poisoning. Also used to study
CNS mechanism because of its relatively specific action as a glycine
antagonist.
Adverse Reactions:
Convulsion is characterized by opisthotonos, i.e., tonic
extension of body and all limbs. Back is arched and only the back of
the head and the heels are touching the touching the surface. All
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sensory stimuli produce exaggerated response and slight sensory
stimulation may trigger convulsion.
Treatment of Strychnine Poisoning
(1) Remove/reduce external sensory stimuli
(2) Diazepam or Clonazepam I.V. or nitrous oxide by inhalation to
depress CNS and stop convulsions which can be fatal
PSYCHOMOTOR STIMULANTS
Drugs of Primary Importance
Amphetamine - prototype Methamphetamine
Methylphenidate
CHARACTERISTICS
all compounds are absorbed well orally
large portion of untransformed amphetamine is excreted unchanged
in the urine. Consequently, acidifying the urine with ammonium
chloride hastens its clearance, and thus reduces its reabsorption in
the renal tubules.
Overdose: hyperreflexia, tremors and convulsions
Fatalities: hyperthermia rather than cardiovascular effects
Pharmacological Actions
The primary effects of an oral dose are wakefulness, alertness,
decrease fatigue; mood elevation, increased ability to concentrate; an
increase in motor and speech activity. Amphetamines also diminish
the awareness of fatigue; person may push exertion to the point of
severe damage or even death.
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Stimulate the respiratory center, especially when respiration is
depressed by centrally acting drugs, (barbiturates and alcohol).
Amphetamine can reverse the marked sedation and behavioral
retardation resulting from reserpine-like drug.
Depresses appetite by their action on the lateral hypothalamus
rather than an effect on metabolic rate.
Mechanisms of Action
Releases monoamines at synapses in the brain and spinal cord.
Inhibits neuronal uptake of monoamine
Direct agonist of DA and 5-HT receptors
Antagonist at certain adrenreceptors
May inhibit monoamine oxidase.
Therapeutic Uses
Hyperkinesias - Methylphenidate
Narcolepsy - Amphetamine or methylphenidate
Obesity - Fenfluramine
Adverse Effects
CNS: Euphoria, dizziness, tremor, irritability, insomnia, Convulsion
(at higher doses), hyperthermia and coma
C.V. Cardiac stimulation leads to headache, palpitations, cardiac
arrhythmias, anginal pain
Other: Weight loss, Psychotic Reaction which are often misdiagnosed
as schizophrenia.
Addiction - including psychic dependence, tolerance and physical
dependence.
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Drug Interactions:
Tricyclic antidepressant
Antihypertensive Agents
Foods high in tyramine content
METHYLXANTINES
Caffeine:
Coffee (100-150 mg/cup)
Tea (30-40 mg/cups)
Cocoa (15-18mg/cup)
Theophylline: Tea and cocoa
Theobromine: Cocoa
Mechanisms of Action
Increase cyclic nucleotide concentration
Blocks adenosine receptors
Alters intracellular calcium distribution
Caffeine, the most widely used drug in the world, is a stimulant.
Commonly found in coffee, tea, soft drinks, chocolate and a wide
variety of over-the-counter medications, it is legal to buy and easily
accessible.
Caffeine is a physically addictive drug
Pharmacological
Activity/
Adverse Effects
Low Doses: 50-250mg/Caffeine (Oral Doses) Increase mental
alertness, decrease drowsiness Lessen fatigue
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Larger Doses: 250-600mg/Caffeine Irritability, restlessness, tremor,
insomnia, headache, palpitations and hyperesthesia GIT upset
Large Doses: > 1000 mg Overt excitement, delirium and clonic
seizures
Cardiovascular System: Increase rate and force of the heart by
directly stimulating myocardium (low doses) Tachycardia and
arrhythmias at higher doses. Peripheral vasodilation decease in blood
pressure (acute administration) Hypotension and cardiac arrest
(rapid i.v. theophyline)
Smooth Muscles: Relaxes vascular smooth muscle (Theophylline
»Caffeine)
Kidney: All xanthines are capable of producing some degree of
diuresis in humans (Theophylline > Caffeine)
Miscellaneous: Xanthines shorten clotting time by increasing tissue
prothrombin and factor V.
Adverse effects
Stimulate gastric secretions in patients with ulcer
Dehydration in children due to vomiting and transient diuretic action
(theophyline)
Allergic reaction (aminophylline)
Psychic Dependence (Caffeine)
Therapeutic Uses
Caffeine + plus ergot alkaloid (Ergotamine): used to treat migraine
headaches
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OTC preparations: Theophylline: Prophylaxis for chronic asthma
Respiratory Stimulant Bronchodilator for relief of asthmatic
symptoms
NICOTINE
CNS Effects:
Powerful CNS stimulant at lower doses; Large doses produce clonic
convulsion, then depress CNS, compounding postictal depression
Stimulates respiration
Produces emesis
Tolerance to central actions with chronic use
Cardiovascular Effects
Tachycardia
Increased blood pressure
Pupillary constriction
Cardiovascular collapse - due to CNS depression
Ganglionic blockade and arrhythmias Fatalities: Due to respiratory
failure
COCAINE
Psychomotor stimulant
local anesthetic
Chemistry- alkaloid from coca plant alkaloid is highly lipid-soluble
hydrochloride salt is water soluble
Routes of Administration
Chewing: with an-alkaloid material (South America)
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Sniffing: hydrochloride salt -absorption: nasal mucous membranes local vasoconstriction slows absorption and prolongs effect
Oral: large doses are needed for effect rapid onset
Smoking: cocaine is converted to alkaloid (freebase or "crack")
which is readily volatilized undegraded at lower temperature. I.V.
and smoking: reaches CNS in seconds in high concentration
produces more immediate and intense effects
Pharmacokinetics
large vol. of distribution
quickly metabolized: half-life 30-90 minutes
principal metabolites: a) Ecogonine methylester - inactive b)
Benzoylecogonine - inactive c) norcocaine - active
half lives of metabolites: 4 to 6 hrs. - metabolites: Excreted in urine
Drug Testing: BE - detectable for 1-3 days
for a few hours
Cocaine - detectable
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Drug addiction
Drug addiction is widely considered a pathological state. The disorder of
addiction involves the progression of acute drug use to the development
of drug-seeking behavior, the vulnerability to relapse, and the decreased,
slowed ability to respond to naturally rewarding stimuli. The Diagnostic
and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) has
categorized three stages of addiction: preoccupation/anticipation,
binge/intoxication, and withdrawal/negative affect. These stages are
characterized, respectively, everywhere by constant cravings and
preoccupation with obtaining the substance; using more of the substance
than necessary to experience the intoxicating effects; and experiencing
tolerance, withdrawal symptoms, and decreased motivation for normal
life activities.
By the American Society of Addiction Medicine
definition, drug addiction differs from drug dependence and drug
tolerance.
Drugs causing addiction
Drugs known to cause addiction include illegal drugs as well as
prescription or over-the-counter drugs, according to the definition of the
American Society of Addiction Medicine.


Stimulants:
o
Amphetamine and Methamphetamine
o
Caffeine
o
Cocaine
o
Nicotine
Sedatives and Hypnotics:
o
Alcohol
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o
Barbiturates
o
Benzodiazepines,
particularly
alprazolam,
clonazepam,
temazepam, and nimetazepam
o
Methaqualone and the related quinazolinone sedativehypnotics

Opiate and Opioid analgesics
o
Morphine and Codeine, the two naturally-occurring opiate
analgesics
o
Semi-synthetic opiates, such as Heroin (Diacetylmorphine),
Oxycodone, and Hydromorphone
o
Fully synthetic opioids, such as Fentanyl and its analogs,
Meperidine/Pethidine, and Methadone
Addictive drugs also include a large number of substrates that are
currently considered to have no medical value and are not available over
the counter or by prescription.
An article in the Lancet compared the harm and addiction of 20 drugs,
using a scale from 0 to 3 for physical addiction, psychological addiction,
and pleasure to create a mean score for addiction. Caffeine was not
included in the study. The results can be seen in the chart above.
Addictive potency
The addictive potency of drugs varies from substance to substance, and
from individual to individual
Drugs such as codeine or alcohol, for instance, typically require many
more exposures to addict their users than drugs such as heroin or cocaine.
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Likewise, a person who is psychologically or genetically predisposed to
addiction is much more likely to suffer from it.
Although dependency on hallucinogens like LSD ("acid") and psilocybin
(key hallucinogen in "magic mushrooms") is listed as Substance-Related
Disorder in the DSM-IV, most psychologists do not classify them as
addictive drugs.
The most common drug addictions are to legal substances such as:

Caffeine

Nicotine in the form of tobacco, particularly cigarettes

Alcohol
Individual mechanisms of effect
The basic mechanisms by which different substances activate the reward
system are as described above, but vary slightly among drug classes.
Depressants
Depressants such as alcohol and benzodiazepines work by increasing the
affinity of the GABA receptor for its ligand; GABA. Narcotics such as
morphine and methadone, work by mimicking endorphins—chemicals
produced naturally by the body which have effects similar to dopamine—
or by disabling the neurons that normally inhibit the release of dopamine
in the reward system. These substances (sometimes called "downers")
typically facilitate relaxation and pain-relief.
Stimulants
Stimulants such as amphetamines, nicotine, and cocaine, increase
dopamine signaling in the reward system either by directly stimulating its
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release, or by blocking its absorption (see "reuptake"). These substances
(sometimes called "uppers") typically cause heightened alertness and
energy. They cause a pleasant feeling in the body, and euphoria, known
as a high. This high wears off leaving the user feeling depressed. This
sometimes makes them want more of the drug, and can worsen the
addiction
Treatment
Treatments for drug addiction vary widely according to the types of drugs
involved, amount of drugs used, duration of the drug addiction, medical
complications and the social needs of the individual.
Determining the best type of recovery program for an addicted person
depends on a number of factors, including: personality, drug(s) of
addiction, concept of spirituality or religion, mental or physical illness,
and local availability and affordability of programs.
Many different ideas circulate regarding what is considered a
"successful" outcome in the recovery from addiction. It has widely been
established that abstinence from addictive substances is generally
accepted as a "successful" outcome, however differences of opinion exist
as to the extent of abstinence required.
In the USA and in many other countries, the goal of treatment for drug
dependence is generally total abstinence from all drugs, which while
theoretically the ideal outcome, is in practice often very difficult to
achieve. Other countries particularly in Europe argue the aims of
treatment for drug dependence to be more complex, with treatment aims
including reduction in use to the point that drug use no longer interferes
with normal activities such as work and family commitments, shifts away
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from more dangerous routes of drug administration such as injecting to
safer routes such as oral administration, reduction in crime committed by
drug addicts, and treatment of other comorbid conditions such as AIDS,
hepatitis and mental health disorders. These kind of outcomes can often
be achieved without necessarily eliminating drug use completely, and so
drug treatment programs in Europe often report more favourable
outcomes than those in the USA because the criteria for measuring
success can be met even though drug users on the programme may still be
using drugs to some extent. The supporters of programs with total
abstinence from drugs as a goal stress that enabling further drug use mean
prolonged drug use and a risk for an increase of total number of addicts;
the participants in the program can introduce new users in the habit.
Drug addiction is a complex but treatable brain disease. It is characterized
by compulsive drug craving, seeking, and use that persist even in the face
of severe adverse consequences. For many people, drug addiction
becomes chronic, with relapses possible even after long periods of
abstinence. In fact, relapse to drug abuse occurs at rates similar to those
for other well-characterized, chronic medical illnesses such as diabetes,
hypertension, and asthma. As a chronic, recurring illness, addiction may
require repeated treatments to increase the intervals between relapses and
diminish their intensity, until abstinence is achieved. Through treatment
tailored to individual needs, people with drug addiction can recover and
lead productive lives. The ultimate goal of drug addiction treatment is to
enable an individual to achieve lasting abstinence, but the immediate
goals are to reduce drug abuse, improve the patient's ability to function,
and minimize the medical and social complications of drug abuse and
addiction. Like people with diabetes or heart disease, people in treatment
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for drug addiction will need to change behavior to adopt a more healthful
lifestyle.
Anti-addictive drugs
Other forms of treatment include replacement drugs such as methadone or
buprenorphine, used as a substitute for illicit opiate drugs Although these
drugs are themselves addictive, opioid dependency is often so strong that
a way to stabilize levels of opioid needed and a way to gradually reduce
the levels of opioid needed are required. In some countries, other opioid
derivatives
such
as
levomethadyl
acetate,
dihydrocodeine,
dihydroetorphine and even heroin are used as substitute drugs for illegal
street opiates, with different drugs being used depending on the needs of
the individual patient.
Substitute drugs for other forms of drug dependence have historically
been less successful than opioid substitute treatment, but some limited
success has been seen with drugs such as dexamphetamine to treat
stimulant
addiction,
and
clomethiazole
to
treat
alcohol
addictionBromocriptine and desipramine have been reported to be
effective for treatment of cocaine but not amphetamine addiction.
Other pharmacological treatments for alcohol addiction include drugs like
disulfiram, acamprosate and topiramate, but rather than substituting for
alcohol, these drugs are intended to reduce the desire to drink, either by
directly reducing cravings as with acamprosate and topiramate, or by
producing unpleasant effects when alcohol is consumed, as with
disulfiram. These drugs can be effective if treatment is maintained, but
compliance can be an issue as alcoholic patients often forget to take their
medication, or discontinue use because of excessive side effects. [36][37]
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Additional drugs acting on glutamate neurotransmission such as
modafinil, lamotrigine, gabapentin and memantine have also been
proposed for use in treating addiction to alcohol and other drugs.
Opioid antagonists such as naltrexone and nalmefene have also been used
successfully in the treatment of alcohol addiction, which is often
particularly challenging to treat. These drugs have also been used to a
lesser extent for long-term maintenance treatment of former opiate
addicts, but cannot be started until the patient has been abstinent for an
extended period, otherwise they can trigger acute opioid withdrawal
symptoms.
Treatment of stimulant addiction can often be difficult, with substitute
drugs often being ineffective, although newer drugs such as nocaine,
vanoxerine and modafinil may have more promise in this area, as well as
the GABAB agonist baclofen. Another strategy that has recently been
successfully trialled used a combination of the benzodiazepine antagonist
flumazenil with hydroxyzine and gabapentin for the treatment of
methamphetamine addiction.
Another area in which drug treatment has been widely used is in the
treatment of nicotine addiction. Various drugs have been used for this
purpose such as bupropion, mecamylamine and the more recently
developed varenicline. The cannaboinoid antagonist rimonabant has also
been trialled for treatment of nicotine addiction but has not been widely
adopted for this purpose.
Ibogaine is a psychoactive drug that specifically interrupts the addictive
response, and is currently being studied for its effects upon cocaine,
heroin, nicotine, and SSRI addicts. Alternative medicine clinics offering
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ibogaine treatment have appeared along the U.S. border. Ibogaine
treatment for drug addiction can be reasonably effective, but potentially
dangerous side effects which have been linked to several deaths have
limited its adoption by conventional medical practice. A synthetic
analogue of ibogaine, 18-methoxycoronaridine has also been developed
which has similar efficacy but less side effects, however this drug is still
being tested in animals and human trials have not yet been carried out.
[edit] Alternative therapies
Alternative therapies, such as acupuncture, are used by some practitioners
to alleviate the symptoms of drug addiction. In 1997, the American
Medical Association (AMA) was adopted as policy following statement
after a report on a number of alternative therapies including acupuncture:
There is little evidence to confirm the safety or efficacy of most
alternative therapies. Much of the information currently known about
these therapies makes it clear that many have not been shown to be
efficacious. Well-designed, stringently controlled research should be
done to evaluate the efficacy of alternative therapies.
Accupuncture has been shown to be no more effective than control
treatments in the treatment of opiate dependence. Acupuncture,
acupressure, laser therapy and electrostimulation have no demonstrated
efficacy for smoking cessation.
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Medical definitions
The terms abuse and addiction have been defined and re-defined over the
years. The 1957 World Health Organization (WHO) Expert Committee
on Addiction-Producing Drugs defined addiction and habituation as
components of drug abuse:
Drug addiction is a state of periodic or chronic intoxication produced by
the repeated consumption of a drug (natural or synthetic). Its
characteristics include: (i) an overpowering desire or need (compulsion)
to continue taking the drug and to obtain it by any means; (ii) a tendency
to increase the dose; (iii) a psychic (psychological) and generally a
physical dependence on the effects of the drug; and (iv) detrimental
effects on the individual and on society.
Drug habituation (habit) is a condition resulting from the repeated
consumption of a drug. Its characteristics include (i) a desire (but not a
compulsion) to continue taking the drug for the sense of improved wellbeing which it engenders; (ii) little or no tendency to increase the dose;
(iii) some degree of psychic dependence on the effect of the drug, but
absence of physical dependence and hence of an abstinence syndrome
[withdrawal], and (iv) detrimental effects, if any, primarily on the
individual.
In 1964, a new WHO committee found these definitions to be inadequate,
and suggested using the blanket term "drug dependence":
The definition of addiction gained some acceptance, but confusion in the
use of the terms addiction and habituation and misuse of the former
continued. Further, the list of drugs abused increased in number and
diversity. These difficulties have become increasingly apparent and
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various attempts have been made to find a term that could be applied to
drug abuse generally. The component in common appears to be
dependence, whether psychic or physical or both. Hence, use of the term
'drug dependence', with a modifying phase linking it to a particular drug
type in order to differentiate one class of drugs from another, had been
given most careful consideration. The Expert Committee recommends
substitution of the term 'drug dependence' for the terms 'drug addiction'
and 'drug habituation'.
The committee did not clearly define dependence, but did go on to clarify
that there was a distinction between physical and psychological
("psychic") dependence. It said that drug abuse was "a state of psychic
dependence or physical dependence, or both, on a drug, arising in a
person following administration of that drug on a periodic or continued
basis." Psychic dependence was defined as a state in which "there is a
feeling of satisfaction and psychic drive that requires periodic or
continuous administration of the drug to produce pleasure or to avoid
discomfort" and all drugs were said to be capable of producing this state:
There is scarcely any agent which can be taken into the body to which
some individuals will not get a reaction satisfactory or pleasurable to
them, persuading them to continue its use even to the point of abuse —
that is, to excessive or persistent use beyond medical need.
The 1957 and 1964 definitions of addiction, dependence and abuse persist
to the present day in medical literature. It should be noted that at this time
(2006) the Diagnostic Statistical Manual (DSM IVR) now spells out
specific criteria for defining abuse and dependence. (DSM IVR) uses the
term substance dependence instead of addiction; a maladaptive pattern of
substance abuse, leading to clinically significant impairment or distress,
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as manifested by three (or more) specified criteria, occurring at any time
in the same 12-month period. This definition is also applicable on drugs
with smaller or nonexistent physical signs of withdrawal, for ex.
cannabis.
In 2001, the American Academy of Pain Medicine, the American Pain
Society, and the American Society of Addiction Medicine jointly issued
"Definitions Related to the Use of Opioids for the Treatment of Pain,"
which defined the following terms:[3]
Addiction is a primary, chronic, neurobiologic disease, with genetic,
psychosocial, and environmental factors influencing its development and
manifestations. It is characterized by behaviors that include one or more
of the following: impaired control over drug use, compulsive use,
continued use despite harm, and craving.
Physical dependence is a state of adaptation that is manifested by a drug
class specific withdrawal syndrome that can be produced by abrupt
cessation, rapid dose reduction, decreasing blood level of the drug,
and/or administration of an antagonist.
Tolerance is the body's physical adaptation to a drug: greater amounts of
the drug are required over time to achieve the initial effect as the body
"gets used to" and adapts to the intake.
Pseudo addiction is a term which has been used to describe patient
behaviors that may occur when pain is undertreated. Patients with
unrelieved pain may become focused on obtaining medications, may
“clock watch,” and may otherwise seem inappropriately “drug seeking.”
Even such behaviors as illicit drug use and deception can occur in the
patient's efforts to obtain relief. Pseudoaddiction can be distinguished
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from true addiction in that the behaviors resolve when pain is effectively
treated.
The Diagnostic and Statistical Manual of Mental Disorders, DSM-IV-TR
doesn’t use the word addiction at all. Instead it has a section about
Substance dependence
"When an individual persists in use of alcohol or other drugs despite
problems related to use of the substance, substance dependence may be
diagnosed. Compulsive and repetitive use may result in tolerance to the
effect of the drug and withdrawal symptoms when use is reduced or
stopped. This, along with Substance Abuse are considered Substance Use
Disorders...." [54]
A definition of addiction proposed by professor Nils Bejerot:
"An emotional fixation (sentiment) acquired through learning, which
intermittently or continually expresses itself in purposeful, stereotyped
behavior with the character and force of a natural drive, aiming at a
specific pleasure or the avoidance of a specific discomfort." [55]
[edit] Addiction and drug control legislation
Depending on the jurisdiction, addictive drugs may be legal only as part
of a government sponsored study, illegal to use for any purpose, illegal to
sell, or even illegal to merely possess.
Most countries have legislation which brings various drugs and drug-like
substances under the control of licensing systems. Typically this
legislation covers any or all of the opiates, amphetamines, cannabinoids,
cocaine, barbiturates, hallucinogenics and a variety of more modern
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synthetic drugs, and unlicensed production, supply or possession is a
criminal offence.
Usually, however, drug classification under such legislation is not related
simply to addictiveness. The substances covered often have very different
addictive properties. Some are highly prone to cause physical
dependency, whilst others rarely cause any form of compulsive need
whatsoever. Also, under legislation specifically about drugs, alcohol is
not usually included.
Although the legislation may be justifiable on moral or public health
grounds, it can make addiction or dependency a much more serious issue
for the individual: reliable supplies of a drug become difficult to secure,
and the individual becomes vulnerable to both criminal abuse and legal
punishment.
It is unclear whether laws against drugs do anything to stem usage and
dependency. In jurisdictions where addictive drugs are illegal, they are
generally supplied by drug dealers, who are often involved with
organized crime. Even though the cost of producing most illegal addictive
substances is very low, their illegality combined with the addict's need
permits the seller to command a premium price, often hundreds of times
the production cost. As a result, the addict sometimes turns to crime to
support their habit.