Behavioral effects induced by the cannabidiol analogs HU-502 and HU-556.
Débora A E Colodete, Nicole R Silva, João Francisco C Pedrazzi, Manoela V. Fogaça, Isadora Cortez, Elaine A Del-Bel, Aviva Breuer, Raphael Mechoulam, Felipe V. Gomes, Francisco S Guimarães
Behavioural Pharmacology June 1, 2023 DOI: 10.1097/fbp.0000000000000727 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Preclinical behavioral pharmacology study in mice Peer reviewed |
|---|---|
| Population | Male Swiss mice |
| Interventions | HU-556 HU-502 cannabidiol amphetamine |
| Dose | HU-556: 0.01-3 mg/kg and 10 mg/kg; HU-502: 0.01-3 mg/kg and 10 mg/kg; cannabidiol: 15-60 mg/kg; all intraperitoneal |
| Measures | elevated plus maze (EPM), forced swimming test (FST), amphetamine-induced prepulse inhibition (PPI) disruption, amphetamine-induced hyperlocomotion, cannabinoid tetrad (hypolocomotion, catalepsy, hypothermia, analgesia) |
| Topics | CBD |
| Key points | The authors suggest that HU-556 produced anxiolytic-, antidepressant-, and antipsychotic-like effects, while HU-502 showed antipsychotic-like effects, at doses lower than cannabidiol's effective range and without the cannabinoid tetrad at those doses. HU-556 at higher doses caused catalepsy and hypolocomotion, whereas HU-502 did not. |
Abstract
Cannabidiol is a phytocannabinoid that lacks the psychotomimetic properties of Δ9-tetrahydrocannabinol (THC), the main psychoactive Cannabis sativa component. Cannabidiol has several potential therapeutic properties, including anxiolytic, antidepressant, and antipsychotic; however, cannabidiol has low oral bioavailability, which can limit its clinical use. Here, we investigated if two cannabidiol analogs, HU-502 and HU-556, would be more potent than cannabidiol in behavioral tests predictive of anxiolytic, antidepressant, and antipsychotic effects. Different doses (0.01-3 mg/kg; intraperitoneally) of HU-556 and HU-502 were tested in male Swiss mice submitted to the elevated plus maze (EPM), forced swimming test (FST), and amphetamine-induced-prepulse inhibition (PPI) disruption and hyperlocomotion. Cannabidiol is effective in these tests at a dose range of 15-60 mg/kg in mice. We also investigated if higher doses of HU-556 (3 and 10 mg/kg) and HU-502 (10 mg/kg) produced the cannabinoid tetrad (hypolocomotion, catalepsy, hypothermia, and analgesia), which is induced by THC-like compounds. HU-556 (0.1 and 1 mg/kg) increased the percentage of open arm entries (but not time) in the EPM, decreased immobility time in the FST, and attenuated amphetamine-induced PPI disruption. HU-502 (1 and 3 mg/kg) decreased amphetamine-induced hyperlocomotion and PPI impairment. HU-556, at high doses, caused catalepsy and hypolocomotion, while HU-502 did not. These findings suggest that similar to cannabidiol, HU-556 could induce anxiolytic, antidepressant, and antipsychotic-like effects and that HU-502 has antipsychotic properties. These effects were found at a dose range devoid of cannabinoid tetrad effects.
Comparable studies
Other preclinical and animal studies on CBD, most cited first.
Citations in the library
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- THC and CBD: Similarities and differences between siblings. Neuron February 1, 2023
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