Unlocking CB₁ & CB₂: A Writer’s Take on Our Medical Cannabis Explained Series

In the mid-1960s, Raphael Mechoulam and colleagues isolated Δ⁹-tetrahydrocannabinol (THC), the molecule responsible for cannabis’s hallmark effects. Yet it wasn’t until 1990 that Herkenham et al. mapped the first cannabinoid receptor, CB₁, throughout the brain and spinal cord—and even in peripheral tissues like the heart, lungs and gastrointestinal tract¹. Three years later, Munro et al. identified CB₂ on immune cells, shedding light on how cannabinoids influence inflammation and immune responses².

Why Receptor Science Matters

Think of CB₁ and CB₂ as molecular “locks” on cell surfaces, each with its own distribution and function. CB₁ reigns in the central nervous system, where it helps fine-tune pain perception, memory formation, motor control and appetite. CB₂ lives mainly on macrophages and microglia, acting as a gatekeeper of inflammation. When these receptors engage with phytocannabinoids, they trigger the cascades that underpin therapeutic—and sometimes side—effects.

THC: Turning the Key

Δ⁹-THC behaves as a partial agonist at both CB₁ and CB₂, “flipping the switch” to produce analgesic and anti-emetic actions, along with the characteristic psychoactive effects³. In clinic, understanding THC’s receptor affinity helps prescribers anticipate both relief and intoxication, ensuring doses strike the right balance.

CBD: The Traffic Cop

Unlike THC, cannabidiol (CBD) doesn’t simply turn receptors on. Instead, it acts as a CB₁ antagonist and a CB₂ inverse agonist, subtly modulating receptor activity without causing intoxication⁴. This pharmacology underpins CBD’s ability to influence inflammation and may support symptom management without a “high.”

Bringing It to Practice

For UK prescribers, translating receptor science into compliant prescribing involves a few guiding principles:

1. Precision Symptom Targeting

   1. Pain or spasticity? CB₁-active formulations can be considered, with close monitoring for cognitive effects.

   2. Inflammatory conditions? CBD-rich oils may offer supportive modulation of immune responses.

2. Safety First

   1. High-CBD/low-THC ratios help minimise psych activity.

   2. Delivery route matters: topicals for local symptoms, orals for systemic needs.

3. Regulatory Alignment

   1. All licensed cannabis medicines in the UK are Schedule 2 and require specialist prescription under MHRA and Misuse of Drugs Act guidelines. Framing your choice around receptor profiles keeps every decision evidence-based and compliant.

      
      

As we kick off the Medical Cannabis Explained series with CB₁ and CB₂, our aim is simple: to turn complex receptor pharmacology into practical, compliance-friendly insights. Join us next time for real-world case studies, prescribing workflows and CPD-accredited discussions with Professor Mike Barnes.