Opiates, opioids and cannabinoids in pain-relief


This is an updated version

Opiates

Opiates are a category of alkaloid drugs derived from opium, a product of opium poppies. At the present time opium itself is illegal in many areas of the world.

Opiates seem to work by simulating the action of endorphins, 'natural pain killer' compounds produced by the pituitary gland and the hypothalamus which affect the brain and produce analgesia - freedom from pain - and a sense of well-being.
Opium poppy and fruit
The poppy flower (left) grows into the fruit (right), which exudes sap containing a number of opiate compounds when it is cut.


Chemical compounds

3-D molecular structure

Click to stop/start molecules spinning
Other links below will highlight sections of molecules.

Opiates



Morphine is a purified opium extract, used medically for pain relief. As well as being highly effective, it is also highly addictive, and must only be used under strict supervision. It is more likely to be used for pain relief in terminally ill patients.

Morphine


Morphine is the most common active ingredient naturally found in opium.

The morphine molecule contains several ring structures, and so it is said to be an aromatic compound.


Heroin (diacetyl morphine, diamorphine) also has pain-killing properties but it has a very poor reputation as an illegal drug, which is very addictive.
Heroin


Heroin is a semi-synthetic opioid synthesized from morphine.

The two additional acetyl groups make the molecule more soluble, causing it to be more effective when injected. They are gradually removed from the molecule as it passes through the liver, reducing its effect.


Codeine (methyl morphine) is often used for pain relief, either on its own or in combination with other drugs such as paracetamol.
Codeine


Codeine is also found in lesser quantities in poppy extract.

The codeine molecule is the same as morphine but with a methyl group (-CH3).

Opioids


The term opioid means a (synthetic) compound that binds with opioid receptors, which are found principally in the central and peripheral nervous system and the gastrointestinal tract, as distinct from opiates which are chemically derived from opium itself.

Tramadol is an opioid pain medication used to treat 'moderate to moderately severe' pain.

Chemically it is 2-[(Dimethylamino)methyl]-1-(3-methoxyphenyl)cyclohexanol.

Tramadol interacts with µ opioid receptors (MOR) and it also functions as a Serotonin reuptake inhibitor (SRI) and norepinephrine reuptake inhibitor (NRI) so it may be called an SNRI.
Tramadol
In the human liver, Tramadol is usually converted into the much more active compound desmetramadol, by the removal of the single methyl group. This has different affinities so different users may experience different effects.

Tramadol is a Schedule IV controlled substance in the US and only available on prescription in the UK and many other countries.

Like opiates, it may be addictive. Primarily for this reason, it is banned in some countries, notably Egypt*, Dubai and Abu Dhabi. *See web reference below.

The World Anti-Doping Agency or WADA has officially banned Tramadol in a sports context.
Fentanyl is an opioid pain medication, widely used in the management of chronic pain.

Fentanyl was first made in 1960, but it has become the most widely used synthetic opioid in medicine It is available in several forms including skin patches, lozenges, 'lollipops', nasal spray and by injection.

Chemically, it is N-(1-(2-Phenylethyl)-4-piperidinyl)-N-phenylpropanamide

Fentanyl


Fentanyl is classified as a controlled Class A drug in the UK, under the Misuse of Drugs Act 1971. It is many times more active and harmful than other opiate drugs, and its recreational use has resulted in many deaths worldwide.
Oxycodone is an opioid, used in pain control following surgical procedures such as hip replacement.

Oxycodone


Oxycodone addiction is a cause for concern and so it is often given for no more than 5 days.

Overdose Prevention

Naloxone is a synthetic morphinan derivative, with a similar molecular structure to morphine.

It may also be known as N-allyl noroxymorphone

It may also be known by a more detailed chemical name:
17-allyl-4,5a-epoxy-3,14-dihydroxy morphinan-6-one

Conceivably, the ketone and allyl groups prevent this molecule from fully interacting with opioid receptors so that it does not have the same physiological effect as other opioids.
Naloxone


Naloxone is a non-selective and competitive opioid receptor antagonist, so it displaces opioids from the receptor sites where they attach. When administered by intravenous injection it reverses the effects of opioids on the central nervous system and respiratory system, and so it can restore normal breathing after a drugs overdose. It may also be given as a nasal spray.

Cannabinoids



Cannabis sativa - also known as hemp - has been cultivated in various parts of the world for the production of fibres for textiles.


Certain varieties contain chemicals which affect the brain and body function, and these are especially concentrated in the flowers. It is considered as an illegal drug in many parts of the world. However it has recently been legalised or de-criminalised in certain countries.


These chemicals derived from cannabis are called cannabinoids.

Tetrahydrocannabinol (THC) is the main psychoactive component of cannabis.

In some countries, a synthetic form has been made available for evalution as a medical drug.
Tetrahydrocannabinol (THC)


This molecule has 4 hydrogens which make it different from the basic compound cannabinol which does not have the same effects.

It also has a single -OH group which explains the ending of its name.


Cannabidiol (CBD) is a 'non-psychoactive' cannabinoid .
Cannabidiol (CBD)


This molecule has two -OH groups. This breaks open the middle aromatic ring, leaving the other two as distinct rings.

It is the principal compound in cannabis oil extracts. It is thought that Cannabinol has analgesic properties and shows potentially immunosuppressive and anti-inflammatory activities.

Cannabis oil has been used in the treatment of epilepsy** and cancer.

Some recent developments have been quite contentious and approval has sometimes varied in pace.

**See web references below.


Cannabinol (CBN) is a cannabinoid derived from THC as a result of 'storage and 'aging'. It has a much reduced psychoactive activity.
Cannabinol (CBN)


This molecule shows a double bond in the top ring.

It also has a single -OH group.
Cannabinoids interact with a variety of receptors in the brain to give the drug's main effects:

THC reacts with CB1 receptors. It is said to be a mild sedative (often causing a chilled out feeling or actual sleepiness) and also a mild hallucinogen (meaning that users may experience a state in which they see objects and reality in a distorted way).

There is also a second type of cannabinoid receptor CB2 which react more to CBD. These are only found in the immune system, and which are presumably responsible for other effects which are claimed.

Apparently beneficial effects relate to relief from pain and prevention of muscle spasms and tremors in certain conditions (multiple sclerosis, also some forms of arthritis) which are more or less untreatable with other drugs.
It is sometimes found to relieve the pain of menstrual cramps and childbirth.
As an anti-emetic, cannabinoids may relieve some of the side effects of anti-cancer treatments.
Glaucoma, a condition which may cause blindness due to buildup of pressure in the eye may also be reduced by treatment with cannabinoids.
It has been used in treating depression and other mood disorders, asthma, strokes, Parkinson's Disease, Alzheimer's Disease, alcoholism and insomnia.

Following on from this, some researchers are investigating other cannabinoid molecules, possibly with a similar structure which interact with the second receptors and which may be of use in the future.

External sites

Addiction Group is dedicated to help individuals suffering from substance abuse and prevent new cases through credible information and spreading awareness.
Drugs, Medications & Other Substances - quite a comprehensive list

An infographic explaining the impact the COVID-19 pandemic is having on the opioid epidemic.

Other molecule files on this website

The oxycodone molecule - rotatable in 3 dimensions

Web references

First six from Wikipedia, the free encyclopedia

Opiates

Hemp

Cannabinoids

Medical cannabis

Legality of cannabis by country

Fentanyl

Comparison of analgesic efficacy of oxycodone and fentanyl after total hip replacement surgery

About tramadol from the NHS

Tramadol from Frank

*Laura Plummer: British tourist jailed in Egypt likely to remain in prison despite reports of presidential pardon

Opioid addiction and death mail-ordered to your door

Why fentanyl is deadlier than heroin, in a single photo

Cannabis oil and cancer from Macmillan Cancer Support

**Family fight for six-year-old son to be allowed cannabis oil to treat his epilepsy

**Cannabis oil row: Billy Caldwell discharged from hospital

**Medicinal cannabis use to be reviewed by government

Is Cannabis oil legal in the UK? Where to buy CBD and the law as sales soar at Holland & Barrett

CBD Facts: What Most Consumers Don't Know
Author Dwight K. Blake was a Mental Health counselor but now works at AmericanMarijuana

Police expand use of overdose life-saver drug Naloxone - BBC news story