chemistry of cannabinoids

PART 1: INTRODUCTION TO CANNABINOIDS

Section 1: Learning Outcomes (Page 2)

By the end of this lecture, students will be able to:

• Evaluate the chemistry of cannabinoids and their key compounds.

• Assess the formulation of cannabinoids in medicines and products.

• Explore the legality of cannabinoids in the UK.

• Discuss their use in epilepsy, pain management, and recreational settings.

Section 2: What Are Cannabinoids? (Page 3)

Cannabinoids are a diverse group of chemical compounds that act on cannabinoid receptors. They are broadly classified into three categories:

PART 2: THE ENDOCANNABINOID SYSTEM (ECS)

Section 3: Overview of the Endocannabinoid System (Pages 4-6)

3.1. Key Components (Pages 4-5):
The Endocannabinoid System (ECS) is a complex cell-signalling system composed of:

• Cannabinoid Receptors: Primarily CB1 and CB2 receptors.

  • CB1 receptors: Predominantly found in the central nervous system (brain, spinal cord). They mediate the psychoactive effects of THC.

  • CB2 receptors: Primarily found on immune cells and in peripheral tissues. They are involved in modulating inflammation and immune responses.

• Endocannabinoids: Endogenous lipid-based neurotransmitters (e.g., anandamide) that bind to these receptors.

• Metabolic Enzymes: Enzymes that synthesise and break down endocannabinoids (e.g., FAAH – fatty acid amide hydrolase).

3.2. Functions of the ECS (Page 6):
"The ECS regulates and controls many of our most critical bodily functions such as:

• Learning and memory

• Emotional processing

• Sleep

• Temperature control

• Pain control

• Inflammatory and immune responses

• Eating

The ECS is currently at the centre of renewed international research and drug development."

Image Description (Pages 4-5): Likely shows diagrams of the ECS, illustrating the location of CB1 receptors in the brain and CB2 receptors on immune cells, along with the molecular structures of endocannabinoids.

PART 3: CHEMISTRY OF CANNABINOIDS

Section 4: Key Phytocannabinoids – THC and CBD (Pages 7-8, 10-11)

4.1. Chemical Structures (Page 8):

Image Description (Page 8): Shows the chemical structures of THC and CBD side-by-side, highlighting the subtle but crucial differences in their ring structures.

4.2. Therapeutic Properties and Risks (Page 10):

• Key Message: Both THC and CBD exhibit promising therapeutic properties. However, THC carries risks of impairment and mental health issues, while high-dose, chronic CBD use can also have significant side effects.

Image Description (Page 10): A graph or diagram illustrating the dose-response or side-effect profile of THC versus CBD.

Image Description (Page 11): Likely a more detailed chemical diagram or a summary of cannabinoid biosynthesis pathways.

PART 4: FORMULATION OF CANNABINOIDS

Section 5: Medical and Recreational Formulations (Page 12)

Section 6: Examples of Licensed Cannabinoid-Based Medicines in the UK (Page 13)

Image Description (Page 13): Shows images of the product packaging or delivery devices for these medicines (e.g., Epidyolex bottle, Sativex spray, Dronabinol capsules).

PART 5: CANNABINOIDS IN SPECIFIC THERAPEUTIC AREAS

Section 7: Cannabinoids in Epilepsy Treatment (Page 14)

7.1. Epidyolex® – In-Depth:

• Active Ingredient: Botanically extracted cannabidiol (CBD).

• Formulation: Oral solution.

• Indication: Used as an adjunct (added to existing treatment) to clonazepam for the treatment of seizures associated with Lennox-Gastaut syndrome or Dravet syndrome. These are severe, treatment-resistant epilepsies that begin in childhood.

7.2. Side Effects of Epidyolex (CBD):

• Common or very common:

  • Aggression

  • Appetite decreased

  • Cough

  • Diarrhoea

  • Drowsiness

  • Fatigue

  • Fever

  • Increased risk of infection

  • Irritability

  • Nausea

  • Rash

  • Seizure (paradoxical, may occur)

  • Vomiting

  • Weight decreased

Section 8: Cannabinoids in Pain Management (Page 15)

8.1. Nabiximols (Sativex®) – In-Depth:

• Active Ingredients: Botanically extracted THC and CBD (approximately 1:1 ratio).

• Formulation: Oromucosal (oral-buccal) spray. The ethanol and polyethylene glycol vehicle facilitates absorption across the buccal mucosa.

• Indications (Specialist Use Only):

  1. As an adjunct treatment for moderate to severe spasticity in adults with multiple sclerosis (MS) .

  2. Treatment of intractable cancer pain (pain not relieved by strong opioids).

8.2. Side Effects of Nabiximols (THC + CBD):

• Common or very common:

  • Appetite abnormal

  • Balance impaired

  • Concentration impaired

  • Constipation

  • Depression

  • Diarrhoea

  • Disorientation

  • Dizziness

  • Drowsiness

  • Dry mouth

  • Dysarthria (slurred speech)

  • Euphoric mood

  • Feeling drunk

  • Malaise

  • Memory loss

  • Nausea

  • Oral disorders (e.g., mouth ulcers, pain)

  • Perception altered

  • Taste altered

  • Vertigo

  • Vision blurred

  • Vomiting

PART 6: CANNABINOIDS AS RECREATIONAL DRUGS

Section 9: Recreational Use and Associated Risks (Pages 16-17)

9.1. Common Recreational Products (Page 16):

• Cannabis: Typically THC-rich products sought for their euphoric effects ("high").

• Forms: Smoking (joints, pipes), edibles (cookies, gummies, drinks), oils, vaping.

9.2. Risks of Recreational Cannabis Use (Page 16):

• Psychological:

  • Paranoia, anxiety, panic attacks.

  • Impaired memory and concentration.

  • Increased risk of psychosis, particularly in individuals with a predisposition to mental illness.

• Physical:

  • Lung irritation and respiratory problems from smoking.

  • Increased heart rate.

  • Impaired coordination (accidents, injuries).

• Trends: Growing popularity of edibles and vapes. Also, the emergence of synthetic cannabinoids ("Spice") , which carry increased and unpredictable risks (severe toxicity, psychosis, death).

9.3. EVALI – A Specific Risk of Vaping (Page 17):

Image Description (Page 17): Likely shows images of lung damage from EVALI (e.g., chest X-rays or CT scans showing opacities) and a molecular structure of vitamin E acetate, highlighting its link to the condition.

PART 7: LEGALITY OF CANNABINOIDS IN THE UK

Section 10: The Legal Framework for Cannabis-Based Products for Medicinal Use (CBPMs) (Pages 18-19)

10.1. Key Legislation (Page 18):

• Cannabis-based products for medicinal use (CBPMs) are subject to strict control under the Misuse of Drugs Act 1971 and the Misuse of Drugs Regulations 2001 (MDR 2001) .

• Most CBPMs are classified as Schedule 2 controlled drugs.

10.2. Prescribing of CBPMs (Page 19):

• Specialist medical practitioners (doctors on the General Medical Council's Specialist Register) can prescribe CBPMs without requiring a Home Office licence.

• This is a significant change from previous law, allowing specialist-prescribed access for patients with specific clinical needs (e.g., spasticity in MS, severe epilepsy).

10.3. Licensing Requirements for Supply Chain (Page 19):

• However, as with other controlled drugs in Schedule 2, companies wishing to possess, supply, produce, manufacture, import, or export these products will require Home Office licences to lawfully undertake these activities.

• Exemptions: A limited licensing 'exemption' under the MDR 2001 applies to certain individuals acting in their professional capacities – e.g., a pharmacist or person conducting a retail pharmacy business. However, they must still comply with regulations and guidance (e.g., on wholesale dealing).

10.4. Additional Controls (Page 19):

• Regulation 16A of the MDR 2001 imposes additional controls on the order and supply of CBPMs for the purpose of administration (even if they are exempt products). This ensures robust governance and traceability.

Section 11: Ethical Considerations (Page 20)

The use of cannabinoids raises several ethical issues:

SUMMARY TABLE: KEY CANNABINOID-BASED MEDICINES IN THE UK