A Pharmacologist Mapped Out the Full Therapeutic Landscape for Cannabinoid Drugs | Research

The takeaway

A 1999 review outlined clinical potential for CB1 agonists (spasticity, pain, glaucoma, asthma), CB1 antagonists (appetite suppression, schizophrenia, cognitive disorders), and drugs that boost endocannabinoid levels.

Read this if you want to understand the full range of therapeutic strategies being explored for cannabinoid-based medicines.

Both cannabinoid receptor agonists and antagonists have therapeutic potential

What the researchers found

This review provided a comprehensive pharmacological roadmap for cannabinoid therapeutics. Two CB1 agonists, THC and nabilone, were already in clinical use as antiemetics and appetite stimulants.

The review identified additional CB1 agonist applications: suppressing muscle spasm and spasticity in MS and spinal cord injury, relieving chronic pain, and managing glaucoma and asthma. But it also proposed the opposite approach: CB1 antagonists might serve as appetite suppressants, and could potentially help manage schizophrenia and cognitive or memory disorders.

CB2 receptor ligands and drugs that boost endocannabinoid levels indirectly represented another therapeutic avenue.

A practical concern was highlighted: oral THC had variable absorption and a narrow therapeutic window, making dosing unpredictable. This pointed to the need for better formulations and administration routes.

Why it matters

This review mapped a complete therapeutic strategy: agonists for some conditions, antagonists for others, and indirect approaches that boost endocannabinoids. This framework guided cannabinoid drug development for the following two decades.

The numbers in context

Two receptor types: CB1 and CB2. Two drugs in clinical use: THC and nabilone. Multiple proposed applications for agonists, antagonists, and indirect approaches.

How the study worked

Pharmacological review covering cannabinoid receptor subtypes, endocannabinoid system, clinical applications of agonists and antagonists, and formulation challenges.

What this study cannot tell us

A forward-looking review based on available evidence that was largely preclinical for many proposed applications. The therapeutic window problem remained unsolved for many applications.

How to read the evidence

A comprehensive pharmacological review. Authoritative perspective but many proposed applications were based on preclinical evidence.

When this study was published

Published in 1999. Several predicted applications have been explored clinically, with mixed results.

The bigger picture

Several predictions from this review materialized: rimonabant (a CB1 antagonist) was briefly approved as an appetite suppressant before being withdrawn for psychiatric side effects. Cannabinoid formulations improved with developments like nabiximols. The endocannabinoid-boosting approach led to FAAH inhibitor research.

Questions still open

Can CB1 antagonists be made safe for psychiatric applications? Will endocannabinoid-boosting drugs prove therapeutic? Can the narrow therapeutic window of THC be widened with better formulations?

Common questions

Why is oral THC difficult to dose?

Oral THC has variable absorption and a narrow therapeutic window, meaning the effective dose and the dose causing side effects are close together, making it hard to predict a dose that works without being uncomfortable.

Could blocking cannabinoid receptors be therapeutic?

Yes. This review proposed CB1 antagonists for appetite suppression and potentially schizophrenia. Rimonabant was later approved as an appetite suppressant but withdrawn due to psychiatric side effects.

Read the original research

Cannabis and cannabinoids: pharmacology and rationale for clinical use.

Forschende Komplementarmedizin, 6 Suppl 3, 12-5

View on PubMed ↗

Citation

Pertwee, R G. (1999). Cannabis and cannabinoids: pharmacology and rationale for clinical use.. Forschende Komplementarmedizin, 6 Suppl 3, 12-5.