How THC & CBD Work (2 of 2)

The Endocannabinoid System

Cannabis works on more than just CB1 & CB2
Three more receptors that cannabis hits – TRPV1, PPARgamma & PPARalpha
If you haven’t read up on part 1 of this two part series. You can find it here (click me).

TRPV1 (a capsaicin receptor)

  • Location: neuronal somata in hippocampus & cerebellum


  • Work on gabanergic (relax) & glutamatergic (excite) terminals
  • Regulation of mood, fear, memory, food intake, visual development & locomotion
  • Mediates long-term depression through upregulation of AMPA receptor reuptake

PPARgamma, PPARalpha (receptors that help regulate gene expression)

  • Location: expressed in neurons, astrocytes, microglia


  • Anti-inflammatory & neuroprotective effects during acute & chronic neuroinflammatory insults (i.e. trauma, ischemia, AD, MS)
  • PPARalpha – may reduce dependence of nicotine & appetite
  • Both compounds: impact alcohol dependence

Author: David Katz |
Reference:Cristino L, Bisogno T, Di Marzo V. Cannabinoids and the expanded endocannabinoid system in neurological disorders. Nat Rev Neurol. 2020;16(1):9-29. doi:10.1038/s41582-019-0284-zLink to reference (click here)

Figure 1: The expanded endocannabinoid system
Figure 2: Neurophysiological roles of the expanded endocannabinoid system
Figure 3: Endocannabinoidome receptors in acute or degenerative neurological disorders

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