Single and combined effects of plant-derived (THC, CBD) and synthetic (WIN-55,212) cannabinoids on cognition and cannabinoid-associated withdrawal signs in mice.

BACKGROUND AND PURPOSE:

It has been suggested that the non-euphorogenic phytocannabinoid cannabidiol (CBD) can ameliorate adverse effects of delta-9-tetrahydrocannabinol (THC). We determined whether CBD ameliorates cognitive deficits and withdrawal signs induced by cannabinoid CB1/CB2 receptor agonists or produces these pharmacological effects on its own.

EXPERIMENTAL APPROACH:

The effects of THC or the CB1/CB2 receptor full agonist WIN55212 (WIN) alone, CBD alone, or their combination were tested across a range of doses. Cognitive effects were assessed in C57BL/6 mice in a conditional discrimination task and in the Barnes maze. Cannabinoid withdrawal signs were assessed following precipitated withdrawal by acute administration of the CB1 antagonist SR141716, the 5-HT1A receptor antagonist WAY100635, the TRPV1 receptor antagonist capsazepine, or the adenosine A2A receptor antagonist SCH58261.

KEY RESULTS:

THC produced significant motor and cognitive impairment in the Barnes maze task, and none of these deficits were attenuated by the addition of CBD. CBD alone did not impact cognitive performance. Precipitation of withdrawal signs by SR141716 occurred in mice chronically treated with THC or WIN, and these withdrawal signs were not attenuated by addition of chronic CBD. Chronic treatment with CBD alone did not induce withdrawal signs precipitated by SR141716 or WAY100635. Chronic CBD treatment also produced anxiolysis and this was not altered by attempting to precipitate withdrawal-induced anxiety with a range of antagonists.

CONCLUSIONS AND IMPLICATIONS:

These data suggest that CBD as a monotherapy may prove to be a safer pharmacological agent for the treatment of several disorders as compared with CB1 agonism alone or in combination with CBD.

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