The Endocannabinoid System

Cannabinoids are compounds that are able to interact with the receptors found in the body’s endocannabinoid system (ECS). The ECS is made up of numerous receptors, cannabinoids and enzymes. The most well studied receptors are known as cannabinoid receptor 1 (CB1) and cannabinoid receptor 2 (CB2). CB1 is predominantly found in the brain and is acted upon by the body’s own cannabinoids (endocannabinoids) to regulate emotions, motor coordination and cognition. CB2 is predominantly found in immune cells and activation by endocannabinoids is thought to effect the immune system.

There are over 120 cannabinoids found in the Cannabis plant, the most common being THC and CBD. THC is similar to the endocannabinoids, by having stimulating effects at the CB1 and CB2 receptors. At sufficient doses THC can overstimulate CB1 receptors in the brain resulting in the ‘high’ typically associated with its recreational use. At low doses however, this is not typically experienced.

CBD on the other hand has a diverse role in the ECS. CBD’s main role is thought to be not through direct action at CB1 or CB2 receptors but by inhibiting an enzyme called fatty acid amide hydrolase (FAAH). This enzyme breaks down the body’s main endocannabinoids. By stopping this enzyme from working as it otherwise would it increases the amount of endocannabinoids available to stimulate cannabinoid receptors. However, CBD also works to change the shape of cannabinoid receptors reducing the effects of THC and endocannabinoids. This is thought to be the mechanism by which CBD can alter the effects THC, particularly reducing any associated euphoria or ‘high’.

In addition to their effects on the endocannabinoid system they have indirect and direct effects on receptors that are involved in pain pathways, mood and anxiety levels, inflammation, and movement.

The Endocannabinoid System

What is the Endocannabinoid System (ECS)

Facilitates the generation of new neurons and is involved in neuroprotection, regulation of motor activity, synaptic plasticity and control of certain memory processing.

Helps protect Gl tract from inflammation and abnormally high gastric and enteric secretions.

Plays a significant role in the hypothalamic function which regulates metabolism, reproduction and responses to stress.

Plays an important role in regulating bone mass and bone regrowth.

Regulates the immune system by suppressing proinflammatory cytokine production.

Maintains balance by controlling food intake and metabolic functions such as energy storage, nutrient transport and modulating insulin sensitivity.

Enhances stamina by regulating blood sugar and encourages ‘runner’s high’. Cannabinoid Receptors (CBr)

Cannabinoid receptors CBr, endocannabinoid, and enzymes form the endocannabinoid system (ECS).

The ECS is our body’s primary regulatory system and is spread out throughout the human body on nearly every organ. It helps regulate vital body functions, including: sleep, memory, mood, appetite, pain, reproduction, inflammation.

CB-1 is the most abundant in the nervous system (brain and spinal cord). You can also find GB-1 in vital and reproductive organs, connective tissues, various glands, gastrointestinal and urinary tract, and white blood cells.

Many tissues contain both CB-1 and CB-2.

CB-2 is found predominantly in the immune system. You can also find CB-2 in the gastrointestinal tract, tonsils, and thymus gland.

Many tissues contain both CB-1 and CB-2.

The Endocannabinoid System (ECS)

The endocannabinoid system (ECS) is a neuro-modulatory system expressed throughout the human central nervous system and the immune system. The ECS consists of neurotransmitters (known as endocannabinoids), receptors, and enzymes. Both endocannabinoids as well as cannabinoids derived from cannabis (phytocannabinoids) are able to interact with these receptors (CB1 and CB2). The endocannabinoid system has been found to play a role in a number physiological and cognitive functions including the regulation of mood, memory, appetite, temperature, and hormone levels as well pain signalling and inflammation.

Medical Cannabis May be Prescribed in a Number of Conditions

Medical cannabis products can currently be considered for use for a number of indications and can be prescribed by a specialist clinician, supported by a multi-disciplinary team, for diagnosed conditions where first-line therapies have failed. GPs can only prescribe medical cannabis under a shared care agreement with a specialist doctor. GPs can refuse to prescribe medical cannabis products if they believe that they do not have the necessary knowledge to do so.

Pain conditions

Chronic pain
Fibromyalgia
Migraine
Cluster Headache
Neuropathic pain
Cancer-Related Pain
Ehlers Danlos Syndromes
Palliative Care

Psychiatric Conditions

ADHD
Anxiety
Agoraphobia
Autistic Spectrum Disorder
Depression
Insomnia
OCD
PTSD
Tourette’s Syndrome

Neurological Conditions

Autistic Spectrum Disorder
Epilepsy
Migraine
Cluster headache
Multiple Sclerosis
Neuropathic pain
Parkinson’s Disease

Gastrointestinal

Crohn’s Disease
Ulcerative Colitis
Irritable Bowel Syndrome (IBS)

Cancer Related Conditions

Anxiety
Nausea and Vomiting
Appetite Loss
Depression
Palliative Care

Contraindications

Medical cannabis products are currently not recommended for use in patients who are/have:

Pregnancy/breast feeding

Ongoing or active psychosis
Unstable cardiovascular disease
Allergic reactions to ingredients or excipients

Caution
When prescribing medical cannabis, health professionals should be cautious of:

Children/adolescents
Interacting medicines

General Evidence for Medical Cannabis

Humans have been using cannabis for a number of indications for thousands of years, however, our scientific understanding of the active compounds within the plant has only developed in recent decades. Due to the interactions between cannabinoids and the human endocannabinoid system, medical cannabis may be prescribed for a large number of indications.

According to the UK Medical Cannabis Registry, chronic pain is the most common reason why people are prescribed medical cannabis. After this the next most common are psychiatric and neurological conditions.

Clinical research into medical cannabis is still in its infancy so there remains a general lack of high-quality clinical evidence to either support, or oppose, the use of CBMPs. However, there is a large base of real world evidence, such as that collected in databases and registries.

Common Side Effects

The side effects of medical cannabis can vary widely depending on the patient and the products used. The existing evidence suggests that side effects can differ from mild to serious and can include:

Very common side effects (more than one in 10 people)

feeling drowsy or sleepy
decreased appetite
diarrhoea
fever
feeling tired
vomiting or nausea

Common side effects (more than 1 in 100 people)

lack of energy or giddy
blurred vision
eating more than usual
difficulty speaking
change of taste or dry mouth
constipation/diarrhoea
cold, sore throat/mouth
respiratory tract infections (pneumonia, bronchitis)
blood tests showing increases in levels of certain liver enzymes or damage to the liver (signs include: abdominal pain, unexplained nausea and malaise, darkening of urine or jaundice)
shaking, of the body or parts of it
feeling bad-tempered (irritable, aggressive)
difficulty sleeping
cough
rash
increased appetite or weight loss
sialorrhea (drooling)
urinary tract infection
abnormal behaviours or agitation
loss of balance or falling over

Uncommon (affecting less than 1 in 100 people)

fainting
changes in pulse rate, heart rate or blood pressure
tummy pain
mouth or teeth changing colour