Multiple Breast Cancer Drug Classes Show Activity at Cannabinoid Receptors with Improved Properties
Fourteen drugs from five different classes of selective estrogen receptor modulators (SERMs) were screened at cannabinoid receptors, with four showing improved binding and selectivity compared to tamoxifen.
Quick Facts
What This Study Found
Building on the discovery that tamoxifen interacts with cannabinoid receptors, researchers screened 14 drugs from five structurally distinct classes of SERMs to find compounds with even better cannabinoid receptor properties.
Four of five SERM classes bound to cannabinoid receptors. Among the standout findings: ospemifene selectively bound to CB1 receptors, bazedoxifene selectively bound to CB2 receptors, while nafoxidine and raloxifene bound to both non-selectively. All four acted as inverse agonists, reducing baseline receptor activity.
These newer SERMs showed improved pharmacological characteristics compared to tamoxifen, including better receptor affinity and selectivity. The variety of selectivity profiles across different chemical scaffolds gives drug developers multiple options for targeting specific cannabinoid receptor subtypes.
Key Numbers
Fourteen SERMs from five classes screened. Four of five classes bound to cannabinoid receptors. Inverse agonist IC50 values ranged from nanomolar to low micromolar. Ospemifene was CB1-selective, bazedoxifene was CB2-selective.
How They Did This
Radioligand binding assays screened 14 SERMs at human CB1 and CB2 receptors. The four most promising compounds underwent full characterization including G-protein activation assays, intracellular cAMP measurements in intact cells, and antagonism studies using concentration-effect curves.
Why This Research Matters
The ability to selectively target CB1 or CB2 receptors is a major goal in cannabinoid drug development. CB2-selective compounds could potentially treat inflammation and pain without psychoactive effects. This study shows that multiple existing drug scaffolds can achieve this selectivity, expanding the toolkit for medicinal chemists.
The Bigger Picture
This study represents a broadening of the cannabinoid drug discovery pipeline. Rather than relying solely on cannabis-derived or traditional synthetic cannabinoids, researchers can now draw from multiple established drug families to develop new cannabinoid-targeting therapies with potentially fewer side effects.
What This Study Doesn't Tell Us
All data are from cell-based assays. Whether these SERM-derived compounds could be developed into practical cannabinoid drugs remains unknown. The concentrations needed for cannabinoid effects may be higher than typical therapeutic doses for their estrogen-related uses.
Questions This Raises
- ?Could bazedoxifene's CB2 selectivity be optimized further for anti-inflammatory applications?
- ?Do patients taking raloxifene for osteoporosis experience any cannabinoid-mediated effects?
Trust & Context
- Key Stat:
- Bazedoxifene selectively targets CB2 receptors; ospemifene selectively targets CB1
- Evidence Grade:
- Systematic cell-based screening with functional validation, but entirely preclinical with no in vivo data.
- Study Age:
- Published in 2016. Follow-up development of these scaffolds into optimized cannabinoid drugs would require years of additional research.
- Original Title:
- Selective Estrogen Receptor Modulators: Cannabinoid Receptor Inverse Agonists with Differential CB1 and CB2 Selectivity.
- Published In:
- Frontiers in pharmacology, 7, 503 (2016)
- Authors:
- Franks, Lirit N(2), Ford, Benjamin M(2), Prather, Paul L(3)
- Database ID:
- RTHC-01157
Evidence Hierarchy
Tests effects in animals (usually mice or rats), not humans.
What do these levels mean? →Frequently Asked Questions
Why does CB1 vs CB2 selectivity matter?
CB1 receptors are concentrated in the brain and mediate psychoactive effects, while CB2 receptors are primarily in the immune system. Drugs that selectively target CB2 could potentially treat inflammation and pain without causing a high.
Are these drugs being used for cannabinoid purposes now?
No. This is early-stage drug discovery identifying starting points for developing new cannabinoid-targeting compounds. The SERMs themselves are used for breast cancer and osteoporosis.
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Cite This Study
https://rethinkthc.com/research/RTHC-01157APA
Franks, Lirit N; Ford, Benjamin M; Prather, Paul L. (2016). Selective Estrogen Receptor Modulators: Cannabinoid Receptor Inverse Agonists with Differential CB1 and CB2 Selectivity.. Frontiers in pharmacology, 7, 503. https://doi.org/10.3389/fphar.2016.00503
MLA
Franks, Lirit N, et al. "Selective Estrogen Receptor Modulators: Cannabinoid Receptor Inverse Agonists with Differential CB1 and CB2 Selectivity.." Frontiers in pharmacology, 2016. https://doi.org/10.3389/fphar.2016.00503
RethinkTHC
RethinkTHC Research Database. "Selective Estrogen Receptor Modulators: Cannabinoid Receptor..." RTHC-01157. Retrieved from https://rethinkthc.com/research/franks-2016-selective-estrogen-receptor-modulators
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.