Cannabidiol inhibits THC-elicited paranoid symptoms and hippocampal-dependent memory impairment

J Psychopharmacol. 2013 Jan;27(1):19-27. doi: 10.1177/0269881112460109. Epub 2012 Oct 5.


Community-based studies suggest that cannabis products that are high in Δ⁹-tetrahydrocannabinol (THC) but low in cannabidiol (CBD) are particularly hazardous for mental health. Laboratory-based studies are ideal for clarifying this issue because THC and CBD can be administered in pure form, under controlled conditions. In a between-subjects design, we tested the hypothesis that pre-treatment with CBD inhibited THC-elicited psychosis and cognitive impairment. Healthy participants were randomised to receive oral CBD 600 mg (n=22) or placebo (n=26), 210 min ahead of intravenous (IV) THC (1.5 mg). Post-THC, there were lower PANSS positive scores in the CBD group, but this did not reach statistical significance. However, clinically significant positive psychotic symptoms (defined a priori as increases ≥ 3 points) were less likely in the CBD group compared with the placebo group, odds ratio (OR)=0.22 (χ²=4.74, p<0.05). In agreement, post-THC paranoia, as rated with the State Social Paranoia Scale (SSPS), was less in the CBD group compared with the placebo group (t=2.28, p<0.05). Episodic memory, indexed by scores on the Hopkins Verbal Learning Task-revised (HVLT-R), was poorer, relative to baseline, in the placebo pre-treated group (-10.6 ± 18.9%) compared with the CBD group (-0.4% ± 9.7 %) (t=2.39, p<0.05). These findings support the idea that high-THC/low-CBD cannabis products are associated with increased risks for mental health.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Cannabidiol / adverse effects
  • Cannabidiol / pharmacology*
  • Cannabis / adverse effects*
  • Cognitive Dysfunction / chemically induced*
  • Cognitive Dysfunction / prevention & control
  • Double-Blind Method
  • Dronabinol / adverse effects*
  • Dronabinol / antagonists & inhibitors*
  • Drug Interactions
  • Female
  • Hippocampus / drug effects
  • Humans
  • Learning / drug effects
  • Male
  • Memory Disorders / chemically induced*
  • Memory Disorders / prevention & control
  • Paranoid Disorders / chemically induced*
  • Paranoid Disorders / prevention & control


  • Cannabidiol
  • Dronabinol