How does Sativex work?
Delta-9-tetrahydrocannabinol (THC) acts as a partial agonist at both the CB1 and CB2 human cannabinoid receptors, which are found predominantly at nerve terminals, where they have a role in retrograde regulation of synaptic function which may modulate the effects of neurotransmitters (e.g. reduce effects of excitatory neurotransmitters such as glutamate) (1).
Cannabidiol (CBD) has a role in calcium homeostasis and is an inhibitor of adenosine uptake, acting largely independently of known cannabinoid receptors (2,3); it also has the potential to modulate the anxiogenic and psychoactive effects of THC (4,5).
- Sativex Summary of Product Characteristics.
- Ryan D, Drysdale AJ, Lafourcade C, Pertwee RG and Platt B. Cannabidiol targets mitochondria to regulate intracellular Ca2+ levels. J Neurosci 2009;29(7):2053–2063.
- Carrier E, Auchampach JA & Hillard CJ. Inhibition of an equilibrative nucleoside transporter by cannabidiol: A mechanism of cannabinoid immunosuppression. PNAS 2006;103(20):7895–7900.
- Karniol IG and Carlini EA. Pharmacological Interaction between Cannabidiol and Δ9-Tetrahydrocannabinol Psychopharmacologia 1973;33:53-70.
- Zuardi AW, Shirakawa I, Finkelfarb E and Karniol IG. Action of cannabidiol on the anxiety and other effects produced by Δ 9-THC in normal subjects. Psychopharmacology 1982;76:245-250.