A review outlined five pharmacological strategies for improving cannabinoid-based medicines, including targeting receptors outside the brain, focusing on specific tissues, and selectively activating CB2 receptors to reduce psychoactive effects.
Read this if you want to understand the future direction of cannabinoid-based pharmaceutical development.
5 strategies proposed for improving cannabinoid medicine safety profiles
What the researchers found
Three cannabinoid medicines were already in clinical use at the time: Cesamet (nabilone), Marinol (dronabinol), and Sativex (THC with CBD). The review identified numerous additional therapeutic targets including pain, epilepsy, anxiety, depression, neurodegenerative diseases, stroke, cancer, and cardiovascular disorders.
Five strategies were proposed to improve the benefit-to-risk ratio: targeting cannabinoid receptors outside the blood-brain barrier, targeting receptors in specific tissues, targeting upregulated receptors (which increase in disease states), selectively activating CB2 receptors (which are less psychoactive), and using adjunctive multi-targeting approaches.
Why it matters
The main barrier to broader cannabinoid medicine use is the psychoactive side effect profile. This review laid out concrete strategies for separating the therapeutic effects from the unwanted psychoactive effects, providing a roadmap for next-generation cannabinoid therapeutics.
The numbers in context
3 approved cannabinoid medicines reviewed. 5 strategies for improving benefit-to-risk ratio. Potential targets include 15+ disease categories ranging from pain to cancer to cardiovascular disorders.
How the study worked
Narrative review of preclinical and clinical evidence for cannabinoid receptor agonists, covering approved medicines, potential therapeutic targets, and pharmacological strategies for improving efficacy and tolerability.
What this study cannot tell us
Many of the proposed therapeutic targets were supported primarily by preclinical data at the time. The strategies are conceptual frameworks that still need to be validated through clinical trials. The review did not address regulatory or manufacturing challenges.
How to read the evidence
Comprehensive review by a leading cannabinoid pharmacologist; synthesizes preclinical and clinical evidence.
When this study was published
Published in 2012 by Roger Pertwee, a foundational figure in cannabinoid pharmacology. Several of these strategies have since been pursued in drug development.
The bigger picture
This review represents a pivotal moment in cannabinoid pharmacology where the field moved beyond simply using whole-plant cannabis or crude THC analogs toward rational drug design. The strategies outlined here have influenced subsequent drug development programs.
Questions still open
- Which of the five strategies has proven most successful in subsequent drug development? Can peripheral-only cannabinoid receptor targeting provide adequate pain relief? How many of the additional therapeutic targets have moved to clinical trials?
Common questions
What are the three approved cannabinoid medicines mentioned?
How can cannabinoid medicines avoid causing a high?
Read the original research
Targeting the endocannabinoid system with cannabinoid receptor agonists: pharmacological strategies and therapeutic possibilities.
Philosophical transactions of the Royal Society of London. Series B, Biological sciences, 367(1607), 3353-63
Citation
Pertwee, Roger G. (2012). Targeting the endocannabinoid system with cannabinoid receptor agonists: pharmacological strategies and therapeutic possibilities.. Philosophical transactions of the Royal Society of London. Series B, Biological sciences, 367(1607), 3353-63. https://doi.org/10.1098/rstb.2011.0381
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