Five Strategies for Making Cannabinoid Medicines More Effective With Fewer Side Effects
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.
Quick Facts
What This Study 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.
Key Numbers
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 They Did This
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.
Why This Research 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 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.
What This Study Doesn't 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.
Questions This Raises
- ?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?
Trust & Context
- Key Stat:
- 5 strategies proposed for improving cannabinoid medicine safety profiles
- Evidence Grade:
- Comprehensive review by a leading cannabinoid pharmacologist; synthesizes preclinical and clinical evidence.
- Study Age:
- Published in 2012 by Roger Pertwee, a foundational figure in cannabinoid pharmacology. Several of these strategies have since been pursued in drug development.
- Original Title:
- Targeting the endocannabinoid system with cannabinoid receptor agonists: pharmacological strategies and therapeutic possibilities.
- Published In:
- Philosophical transactions of the Royal Society of London. Series B, Biological sciences, 367(1607), 3353-63 (2012)
- Authors:
- Pertwee, Roger G(17)
- Database ID:
- RTHC-00604
Evidence Hierarchy
Summarizes existing research on a topic.
What do these levels mean? →Frequently Asked Questions
What are the three approved cannabinoid medicines mentioned?
Cesamet (nabilone) for chemotherapy nausea, Marinol (dronabinol/synthetic THC) for nausea and appetite stimulation, and Sativex (THC with CBD spray) for MS-related pain and spasticity. These were the approved cannabinoid medicines as of 2012.
How can cannabinoid medicines avoid causing a high?
The review outlines several approaches: targeting CB2 receptors instead of CB1 (CB2 activation is not psychoactive), targeting cannabinoid receptors outside the brain (peripheral only), and focusing on tissues where receptors are upregulated by disease. Each approach aims to provide therapeutic benefit without crossing the blood-brain barrier or activating the receptors responsible for psychoactive effects.
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Cite This Study
https://rethinkthc.com/research/RTHC-00604APA
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
MLA
Pertwee, Roger G. "Targeting the endocannabinoid system with cannabinoid receptor agonists: pharmacological strategies and therapeutic possibilities.." Philosophical transactions of the Royal Society of London. Series B, 2012. https://doi.org/10.1098/rstb.2011.0381
RethinkTHC
RethinkTHC Research Database. "Targeting the endocannabinoid system with cannabinoid recept..." RTHC-00604. Retrieved from https://rethinkthc.com/research/pertwee-2012-targeting-the-endocannabinoid-system
Access the Original Study
Study data sourced from PubMed, a service of the U.S. National Library of Medicine, National Institutes of Health.
This study breakdown was produced by the RethinkTHC research team. We analyze and report published research findings without making health recommendations. All interpretations are based solely on the published abstract and study data.