Table 4.

Behavioral studies with the use of cannabinoids in the zebrafish model.

Tested Substances	Tested Doses	Behavioral Test	Tested Subjects	Main Findings	Ref.
CBD	40 mg/L	Novel tank diving test	Adult fish (6 months)	A 30-min exposure to CDB decreased swimming speed and traveled distance.	[80]
CBD, WIN55,212-2	For both agents: 0.5, 1, 5, 10 µg/mL	Light/dark test	Larvae (4–5 dpf)	CBD at a dose of 10 µg/mL reduced the traveled distance and velocity of movement in the darkness. Both lower tested doses (0.5 and 1 µg/mL) of WIN55,212-2 reduced the traveled distance and moving duration, whereas higher doses of the agent (5 and 10 µg/mL) turned out to be lethal to zebrafish larvae within less than 24 h.	[81]
JWH-018	THC: 2 µM, JWH-018: 3 µM	Forced light/dark test, startle stimuli test, novel tank diving test	Larvae (5 dpf in the forced light/dark test; 6 dpf in the startle response), adult (4 months in the novel tank diving)	After the developmental exposure to THC and JWH-018, impaired locomotion was detected during baseline and dark periods in the forced light/dark test. In the startle stimuli test, no significant differences in the traveled distance before and during the stimuli were recorded for JWH-018, whereas reduced activity before the stimuli was detected for THC. In the novel tank diving test, adult zebrafish who had been subjected to developmental exposure to JWH-018 spent less time on the bottom of the tank, whereas developmental exposure to THC had no impact on animals’ behavior.	[82]
Whole-plant Cannabis extracts	0.25, 0.5, 1, 2 µg/mL	Light/dark test	Larvae (120 hpf)	Zebrafish larvae can be used to assess the bioactivity of Cannabis extracts. Cannabis extracts with various chemical profiles have a distinct impact on baseline larval activity and stress responses.	[83]
ACEA (CB1 receptor agonist)	1 mg/kg	Acute restraint stress, novel tank diving test	Adult	Treatment with ACEA prevented both the acute restraint stress-induced anxiety-like behavior and oxidative stress in the zebrafish brain.	[84]
THC	40 nM, 1, 2 µM	Swimming pattern	Adult	Animals exposed to THC presented abnormal swimming patterns, i.e., circular swimming (behavioral stereotypy).	[85]
THC, CBD, THC + CBD	THC: 0.05, 0.1, 0.5, 1.5, 2.0 µM CBD: 0.75, 1.0, 1.75, 2.5, 3.75 µM THC + CBD: 0.5 + 0.5, 1.5 + 0.5 µM	Locomotor activity in Zebrabox and the light/dark test	Larvae (120 hpf)	Exposure to THC (at all tested concentrations) decreased the locomotor activity of larvae, whereas exposure to CBD at concentrations above 1.75 µM increased locomotor activity.	[86]
9,10-dihydro-5-hydroxy-2, 3,6-trimethoxyphenanthrene-1,4-dione isolated from a commercial cannabis product	1, 2.5, 3.5 µM	Locomotor activity	Larvae (5 dpf)	Concentrations above 2.5 µM increased the locomotor activity of larvae	[87]