Podcast 1006: Cannabinoid Pharmacology

Contributor: Travis Barlock, MD

Educational Pearls:

Endocannabinoid System: THC binds CB1 and CB2 receptors in neurons and immune cells

• Δ9-Tetrahydrocannabinol (THC) is the main psychoactive compound in cannabis

• CB1 and CB2 receptors typically bind endogenously-produced 2-arachidonoylglycerol (2-AG) and anandamide (AEA) to regulate pain, stress, and inflammation

• THC similarly binds CB1 and CB2, leading to the cannabinoid high: euphoria, paranoia, anxiety, analgesia, anti-inflammation, and appetite, among a variety of others

• Ingestion via edibles, vice inhalation via smoking, leads to chemical modification of Δ9-THC to 11-hydroxy-Δ9-THC, which more easily crosses the blood-brain barrier and binds CB1 with higher affinity, leading to increased psychoactivity

Cannabinoid Hyperemesis Syndrome (CHS): Chronic THC use leading to the classic presentation of persistent nausea and intense, frequent vomiting

• Chronic activation of CB1 receptors in brain builds a tolerance and dependence on THC, in addition to chronic activation of the capsaicin and vanilloid receptor TRPV1, which binds capsaicin or is activated by heat

• Treatment by warm showers works due to TRPV1 activation by heat

• Treated with benzodiazepines, fluids, and gastro-intestinal or central nervous system agents according to patient presentation

Over 200 synthetic cannabinoids have been created (K2, spice, black mamba, mojo, etc), which are more dangerous and can lead to a variety of etiologies

Acetaminophen binds CB1 receptors to reduce inflammatory pain

References

1. Loganathan P, Gajendran M, Goyal H. A Comprehensive Review and Update on Cannabis Hyperemesis Syndrome. Pharmaceuticals (Basel). 2024;17(11):1549. Published 2024 Nov 18. doi:10.3390/ph17111549

2. Wall ME, Sadler BM, Brine D, Taylor H, Perez-Reyes M. Metabolism, disposition, and kinetics of delta-9-tetrahydrocannabinol in men and women. Clin Pharmacol Ther. 1983 Sep;34(3):352-63. doi: 10.1038/clpt.1983.179. PMID: 6309462.

3. Mills B, Yepes A, Nugent K. Synthetic Cannabinoids. Am J Med Sci. 2015 Jul;350(1):59-62. doi: 10.1097/MAJ.0000000000000466. PMID: 26132518.

4. Klinger-Gratz PP, Ralvenius WT, Neumann E, et al. Acetaminophen Relieves Inflammatory Pain through CB1 Cannabinoid Receptors in the Rostral Ventromedial Medulla. J Neurosci. 2018;38(2):322-334. doi:10.1523/JNEUROSCI.1945-17.2017

Summarized by Sam Pahl | Edited by Sam Pahl & Ahmed Abdel-Hafiz, NREMT-P

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