Doctors

Cannabis sativa is one of the oldest cultivated plants in human history. It’s use as a medicine was documented 5000 years ago in China and it’s use spread to ancient Japan, Mesopotamia, ancient Egypt, Greece and India as part of both medicine and spiritual tradition. In the 1600s it was introduced to Europe and the Americas. Until about 100 years ago it was used globally as a medicine to treat symptoms as diverse as epilepsy, fever, anxiety, pain, insomnia, digestive issues and skin disorders. As recently as 1971 it was included in the British Pharmacopoeia.
For a variety of political and economic reasons it went through a period of being demonised and classified as an illegal drug. 

 
In November 2018, the law in the UK changed to allow doctors on the Specialist Register to initiate prescriptions for cannabis-based products for medicinal use (CBPMs) to patients with certain medical conditions.  

This change was implemented via amendments to the Misuse of Drugs Regulations 2001 and was not a step towards legalising recreational cannabis, which remains a Class B controlled drug.  

Key Details of the Law Change 

• Rescheduling of Cannabis Products: Certain cannabis-based products that meet specific criteria were moved from Schedule 1 of the Misuse of Drugs Regulations (drugs with no therapeutic value) to Schedule 2 (drugs with therapeutic value, subject to strict control). 

• Prescribing Restrictions: Only doctors on the General Medical Council's (GMC) specialist register are permitted to initiate the prescription of these products. GPs cannot generally prescribe them, although they can refer patients to a specialist. 

• Conditions for Prescription: Prescriptions are limited to instances where a patient has an unmet clinical need and other licensed treatments have failed.  

The Endocannabinoid System (ECS): An Overview

The endocannabinoid system (ECS) was first identified in 1988 by a group of researchers funded by the U.S. government. They discovered a previously unknown type of receptor in the brain that responded to compounds in cannabis. This receptor was named the CB1 receptor.

Endocannabinoid Receptors

CB1 receptors are found primarily in the central nervous system (brain and spinal cord).

They help regulate:

• Digestive motility and gastric secretion

• Neurotransmitter and hormone release

• Intestinal permeability

• Appetite, mood, and sleep regulation

A few years later, a second receptor was identified, the CB2 receptor.

CB2 receptors are located mainly in the peripheral nervous system (nerve cells outside the brain and spinal cord), internal organs, and immune cells.

They play a key role in modulating inflammation and immune responses.

More recently, other related receptor types, including GPR55 (“Gamma”) and TRPV1 (“Vanilloid”), have also been recognised as interacting with endocannabinoid signalling pathways.

Endocannabinoid receptors are present in almost every organ and tissue in the body. They are particularly abundant in the brain, more so than any other neurotransmitter receptor type identified to date.

Endocannabinoids

In 1992, Raphael Mechoulam, William Devane, and Lumír Hanuš discovered the first naturally occurring endocannabinoid, anandamide (from the Sanskrit word ananda, meaning “bliss”). Anandamide acts as a messenger molecule, binding to CB1 and CB2 receptors to help regulate internal balance.

Three years later, a second major endocannabinoid, 2-arachidonoylglycerol (2-AG), was discovered. Both anandamide and 2-AG are produced on demand by the body (rather than stored), and their levels are carefully regulated by enzymes that synthesise and break them down.

How the ECS Works

The ECS is a complex cell-signalling network that helps maintain homeostasis, the body’s internal balance across all systems. It influences a wide range of physiological functions, including:

• Pain perception

• Immune response and inflammation

• Sleep and circadian rhythm

• Mood and stress response

• Hormone regulation

• Metabolism and body temperature

Because of its extensive role, the ECS has been described as the body’s “master regulatory system”, similar to an engine maintenance system in a modern car, constantly monitoring and fine-tuning other systems to keep the body running smoothly.

The Three Core Components of the ECS

1. Endocannabinoid receptors (CB1, CB2, and related receptors such as GPR55 and TRPV1)

2. Endocannabinoids (Anandamide and 2-AG)

3. Enzymes that synthesise and degrade these signalling molecules

Phytocannabinoids and the Endocannabinoid System

While the body produces its own cannabinoids (known as endocannabinoids), the cannabis plant synthesises its own class of similar compounds known as phytocannabinoids.

These plant-derived molecules can interact with the same receptors and pathways as our natural endocannabinoids, influencing physiological processes throughout the brain and body.

More than 140 distinct phytocannabinoids have been identified in Cannabis sativa, but the two most extensively studied and clinically relevant are Δ9-tetrahydrocannabinol (THC) and cannabidiol (CBD).

Δ9-Tetrahydrocannabinol (THC)

THC is the primary psychoactive compound in cannabis. It binds directly to CB1 receptors in the central nervous system and, to a lesser extent, CB2 receptors in peripheral tissues.

Through CB1 activation, THC influences:

• Pain modulation

• Mood, appetite, and sleep

• Nausea and vomiting (via effects on the chemoreceptor trigger zone)

• Muscle spasticity and motor control

At higher doses, THC’s psychoactive properties arise from its CB1 receptor activity in brain regions such as the hippocampus and prefrontal cortex. However, these same pathways can provide therapeutic benefit in conditions involving dysregulated neural signalling, for example, neuropathic pain or post-traumatic stress disorder (PTSD).

Clinically, THC acts as a partial agonist at CB1 and CB2 receptors, meaning its effects are dose-dependent and modulated by the presence of other cannabinoids, particularly CBD.

Cannabidiol (CBD)

CBD is non-intoxicating and exerts complex, multi-target effects.

It does not bind strongly to CB1 or CB2 receptors but influences them indirectly, enhancing the overall tone of the endocannabinoid system.

Mechanisms of action include:

• Inhibition of FAAH (fatty acid amide hydrolase), the enzyme that breaks down anandamide — leading to increased anandamide levels and prolonged activation of CB1 and CB2 receptors.

• Modulation of serotonin (5-HT1A) and TRPV1 (vanilloid) receptors, contributing to its anxiolytic and analgesic effects.

• Anti-inflammatory activity through suppression of cytokine production and microglial activation.

• Neuroprotective effects via antioxidant and anti-excitotoxic mechanisms.

CBD may also act as a negative allosteric modulator at the CB1 receptor; meaning it can subtly reduce the psychoactive intensity of THC when both are present. This synergistic modulation underlies what is known as the “entourage effect.”

Terpenes and Flavonoids

As well as the 147 known phytocannabinoids the plant also contains about 100 terpenes, these give the plants its smell, and about 100 flavonoids that give colour. They also have many medicinal properties.

The Entourage Effect

The “entourage effect” describes the synergistic interaction between multiple cannabinoids, terpenes, and other plant compounds that may enhance therapeutic benefit and reduce unwanted side effects.

Rather than acting as isolated compounds, these constituents work together to fine-tune receptor activity, producing a more balanced clinical response. It is why whole plant medications often work better than isolates.

For example:

• THC and CBD together can provide greater pain relief than either alone.

• CBD may counteract THC-induced anxiety or tachycardia.

• Certain terpenes (such as myrcene and beta-caryophyllene) may add sedative or anti-inflammatory effects through complementary pathways.

  
  

Clinical Implications

Understanding how phytocannabinoids interact with the ECS allows for targeted, personalised therapy to restore balance where dysregulation has occurred.

By modulating receptor activation and endocannabinoid tone, clinicians can influence key pathways involved in:

• Chronic pain and neuropathic pain

• Anxiety, depression, and sleep disorders

• Inflammatory and autoimmune conditions

• Spasticity (e.g., in multiple sclerosis)

• Appetite and nausea control (e.g., in cancer or HIV care)