The Opiods

Opioid or Opiate?
Opiates are drugs of natural origin (derived from

opium)
Opioids are all opiate-like drugs (including
synthetic)
A technicality
I will use opioids

Opium
Morphine is the active ingredient

In use for thousands of years (since 4200 BC)

Primarily for diarrhea

Historically used at one time for almost all

diseases
Combined with alcohol, mixture called laudanum
Meaning something to be praised
The stone of immortality

Morphine isolated in early 1800s

Needle in 1856, by 1914, use of all opioid

products tightly controlled

Opiods
Use is widespread and impossible to stop
Pleasurable effects
Produce tolerance and physical dependence
Have potential for compulsive misuse

Agonists at highly specific receptor sites

Sites for endogenous opioids (eg, endorphins)
Mu, kappa, gamma
All strong opioids primarily act as agonists at the mu

receptor
Found in all brain structures and spinal cord
Pharmacological effects (analgesia, respiratory
depression, euphoria, reward, and constipation) all
follow from this action

Opioids
Pure Opioid Agonists
Morphine

Found in the opium poppy

Along with codeine (much less potent)
Usually administered by injection
Clinically superior for treating severe pain
Slow and incomplete absorption orally
Rapid onset from smoking opium
Crosses blood-brain barrier slowly
More water than lipid soluble
Heroin is faster
Only about 20% of administered drug reaches CNS

Opioids
Morphine
Reaches all body tissues
The liver metabolizes
One of its metabolites is 10-20x more potent
Accounts for much of the analgesic action
Difficult to urine test for morphine
Morphine and codeine and their metabolites are detectable,
but
Heroin is metabolized into morphine and codeine
Pharmacological Effects
Analgesia (altered perception of pain)
Euphoria
Sedation
Suppression of cough reflex
Reduced apprehension
Sense of tranquility

Opioids
Pharmacological effects
Mechanism of euphoria and positive reinforcing

effects involve DA and mu receptors

Opioids activate mu receptors in the mesolimbic (reward)

system by means of VTA

Same system involved in rewarding effects of cocaine and
alcohol

In the VTA, morphine inhibits GABA neurons via mu

receptors
Disinhibits DA neurons
Increasing DA output in the nucleus accumbens

Opioids
Development of tolerance and dependence is

characteristic feature of all opiods

Tolerance thought to involve NMDA receptor
Little with little use
Very marked with regular use
From 50 mg/day to 500 mg/day in 10 days!

Cross tolerance to all other opioids

Opioids
Codeine
Co-active ingredient in the poppy
Much less of it, much less potent, but.
Is metabolized into morphine!
Most commonly prescribed drug
Frequently sought drugs of abuse
Drugs that block conversion to morphine (SSRIs) block pain
relief of codeine

 Heroin (diacetylmorphine)
3x more potent than morphine
Produced from morphine
Increased lipid solubility
Faster more intense rush (inhalation or injection)

Metabolized into monoacetylmorphine and

morphine
Street heroin also contains acetylcodeine, which is
metabolizied into codeine, which is metabolized into
morphine

Why so heavily used for so long?

Positively reinforcing (euphoria)

Negatively reinforcing
Relieved pain, dependence developed
Relieve withdraw symptoms
Deficient endorphin systems?
Repeated use led to dysfunction and now is

required
Operant conditioning and the opponent-process