Developmental effects of cannabinoids on zebrafish larvae

Area of Science:

• Neuroscience
• Pharmacology
• Developmental Biology

Background:

• Cannabinoids are compounds found in hemp, with Δ(9)-THC being the primary psychoactive component.
• Understanding cannabinoid effects on developing organisms is crucial for assessing potential risks.

Purpose of the Study:

• To investigate the behavioral and developmental effects of various cannabinoids and a cannabinoid antagonist (AM 251) in zebrafish embryos.
• To compare zebrafish responses to known mammalian responses.

Main Methods:

• Zebrafish embryos were exposed to different cannabinoids (Δ(9)-THC, and two others) and AM 251 acutely (1-12h) or chronically (96h).
• Behavioral analysis using automated video-tracking assessed locomotor activity via a visual motor response test.
• LC50 (lethal concentration 50%) was determined, and malformations were examined at 5 days postfertilization.

Main Results:

• Acute cannabinoid exposure induced a biphasic locomotor response: stimulation at low concentrations and suppression at high concentrations.
• Chronic exposure resulted in habituation to cannabinoid effects, with co-administration of AM 251 ameliorating excitation.
• Only Δ(9)-THC exposure led to a significant increase in malformations, including edema and axis bending.

Conclusions:

• Cannabinoids elicit behavioral effects in zebrafish that are comparable to those observed in mammals, particularly adult rodents.
• These behavioral effects are likely mediated, at least in part, by the CB1 receptor.
• Δ(9)-THC poses developmental risks to zebrafish embryos, indicating potential teratogenic effects.