Human osteoclasts in vitro are both inhibited and stimulated dose-dependently by cannabidiol (CBD) and Δ9-tetrahydrocannabinol (THC)

Simone SR Nielsen, Juliana AZ Pedersen, Neha Sharma*, Pernille Krogh Wasehuus, Anais M Møller, Teis Esben Sondergaard, Kent Søe


Publikation: Bidrag til tidsskriftKonferenceabstrakt i tidsskriftForskningpeer review


Background: Conditions such as chronic pain have shown great benefits from cannabis treatment. However, there is a lack of well-controlled clinical trials to provide clarity on side-effects of cannabidiol therapeutics. We studied the effect of CBD and THC on osteoclasts and osteoblasts in vitro.

Methods: CD14+ monocytes from anonymous blood donors were differentiated into osteoclasts in vitro over 9 days using 25 ng/ml of both, M-CSF and RANKL. CBD and THC were purified from cannabis extracts by HPLC-DAD-HRMS. Osteoblasts were cultured from outgrowths of human bone. CBD or THC were added during osteoclast differentiation (7 days) and in mono- or co-cultures on bone slices (3 days) (0.3 to 100 μM; ≥5 technical replicates/condition).

Results: CBD and THC stimulated bone resorption at doses ranging from 1 to 10 μM (n=6 experiments) (eroded surface/BS: CBD, p=0.003; THC, p=0.012). However, doses of 30 μM CBD and THC inhibited osteoclastic bone resorption (eroded surface/BS: CBD, p=0.03; THC, p=0.03 ) (Fig. 1 and 2). CBD and THC inhibited fusion at >10 μM (n=5) (osteoclasts/field: CBD, p=0.03; THC, p=0.03) (nuclei/osteoclast: - CBD, p=0.03; THC, p= 0.03). Western blotting confirmed expression of endocannabinoid receptor, CB1 in osteoclasts. CBD and THC, in co-culture settings (n=3 experiments) displayed dose dependent inhibition of osteoclastic bone resorption (representative values from 1 experiment CBD, p
Conclusion: Osteoclastic differentiation and bone resorption are directly affected by CBD and THC possibly through CB1. Considering all experiments, our study suggests that overall, both drugs enhance resorption at low doses and suppresses it at higher doses. Generally, our data suggests that both drugs may trigger bone loss and accelerate osteoporosis in vivo.
TidsskriftBone Reports
Udgave nummerSupplement
StatusUdgivet - 1 maj 2022