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Assessment of Morphine-induced Hyperalgesia and Analgesic Tolerance in Mice Using Thermal and Mechanical Nociceptive Modalities
Published on: July 29, 2014
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Mechanisms of cannabinoid tolerance
Mary K Piscura1, Angela N Henderson-Redmond2, Robert C Barnes3
1Department of Biomedical Sciences, Marshall University, Huntington, WV 25755, USA; Department of Biomedical Sciences, Edward Via College of Osteopathic Medicine, Auburn, AL 36832, USA.
Biochemical Pharmacology
|June 22, 2023
Summary
Cannabinoid tolerance, a significant issue in medical cannabis use, involves changes at the cannabinoid type 1 receptor (CB1R). Research highlights receptor downregulation and desensitization as key mechanisms.
Area of Science:
- Neuroscience
- Pharmacology
- Cannabinoid Science
Background:
- Cannabis and cannabinoids have historical therapeutic uses, but understanding their mechanisms remains limited.
- Therapeutic applications include chronic pain, spasticity, nausea, cachexia, and sleep disorders.
- Cannabis use disorder and tolerance are significant drawbacks to cannabinoid therapies.
Purpose of the Study:
- To review evidence of cannabinoid tolerance in various models (rodents, primates, humans).
- To elucidate neuroadaptations at the cannabinoid type 1 receptor (CB1R) underlying tolerance.
- To discuss potential strategies for mitigating cannabinoid tolerance.
Main Methods:
- Review of existing scientific literature on cannabinoid tolerance.
- Analysis of neuroadaptations at the CB1R, including expression levels and desensitization.
- Examination of intracellular signaling pathways involved in CB1R regulation.
Main Results:
- Cannabinoid tolerance is demonstrated across species, with prominent sex differences.
- CB1R expression is downregulated, and CB1R is desensitized in tolerant individuals.
- Intracellular pathways involving G protein-coupled receptor kinases and β-arrestin2 mediate CB1R desensitization.
Conclusions:
- Cannabinoid tolerance is linked to CB1R downregulation and desensitization.
- Understanding these neuroadaptations is crucial for developing strategies to reduce tolerance.
- Further research, including neuroimaging probes for human CB1R assessment, is needed.
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