Tag: CB1 downregulation

Scientific illustration showing THC activation of the CB1 receptor and the Gq/11–PLC–PKC–NEDD4L pathway leading to CB1 ubiquitination, proteasomal degradation and cannabinoid tolerance, with ECS.education branding.

How Repeated THC Exposure Can Reduce CB1 Receptors

Posted on September 14, 2026September 14, 2026 By Stefan Broselid

A new PNAS study identifies a previously underappreciated Gq/11–PLC–PKC–NEDD4L pathway that marks CB1 receptors for proteasomal degradation. The findings help explain how repeated THC exposure can reduce receptor availability and contribute to cannabinoid tolerance.

Endocannabinoid System (ECS)

Minimalist illustration showing a central dial without markings, positioned over a faint brain outline. The dial balances two opposing arrows labeled ‘Symptom Control’ and ‘Cognitive Function,’ with a hand hovering uncertainly above it, symbolizing the trade-off between therapeutic efficacy and cognitive safety in medical cannabis use without knowledge of CB1 receptor availability.

The Medical Cannabis Paradox: How Tolerance Threatens Long-Term Therapeutic Success

Posted on January 24, 2026January 24, 2026 By Stefan Broselid

A follow-up to “CB1 Availability as a Non-Invasive Biomarker: Bridging Endocannabinoid System Dysfunction and Therapeutic Monitoring“ The Emerging Evidence: Tolerance is Real and Quantifiable A recent study published in Frontiers in Pharmacology (2025) provided the first systematic measurement of how tolerance accumulates during medical cannabis treatment (Stith et al., 2025). Using real-world…