The Effects of THC on Brain Mitochondria of Zebrafish

Abstract

Tetrahydrocannabinol (THC) is a cannabis and is the primary psychoactive component of marijuana. Cannabinoids can exert various biological effects. It has been shown to have therapeutic applications in the medical field such as treating medical pathologies: pain, epilepsy, and movement disorders. However, there are additional studies showing the negative impacts of THC. In particular, cannabis might directly affect brain function with a special emphasis on mitochondrial function. Therefore, we hypothesize that THC will decrease mitochondrial function. The aim of this study was to analyze the effects of THC on brain mitochondrial function using the model organism Danio.rerio (zebrafish).MethodsZebrafish were exposed to 20 mg/ml of THC and brain mitochondria was isolated. Oxygen consumption in the presence of glutamate/malate was monitored to determine mitochondrial function, and results compared to control zebrafish. Basal mitochondrial respiration (State 3 and State 4) was measured using a Clark‐type oxygraph electrode system. The respiratory control ratio (RCR) was also calculated by taking the ratio of state 3 divided state 4.ResultsZebrafish exposed to THC had a significantly lower State 3 respiration compared to control (n=6, p <0.05). A decrease in state 3 respiration is notable because it indicates that THC decreases electron transport and subsequently the rate at which brain mitochondria may synthesize ATP. Moreover, the RCR was significantly lower in THC treated fish (n=6 p<0.05). A higher RCR indicates mitochondria that are more tightly coupled with better function (i.e., better quality of mitochondria), whereas a lower RCR indicates that mitochondria are more loosely coupled with poorer function (i.e., damaged mitochondria) in response to treatment.ConclusionThese data demonstrate that the bioenergetics of brain mitochondria are impaired and THC does appear to have an impact on mitochondrial function.