In this Beckley Foundation sponsored study, we hoped to investigate the possible protective effects of CBD against the cognitive deficiencies elicited by THC (increased paranoia, working memory impairment and episodic memory impairment). Previous work had hinted at a protective effect, but this study used an increased sample size and more advanced measures for cognition and positive psychotic symptoms.
48 participants were randomized to receive either oral CBD or placebo 210 minutes before THC administered intravenously.
Psychotic symptom measures:
- Positive and Negative Symptom scale -PANSS (clinician rated). Subject rated from 1-7 (absent to severe) on presence of e.g. hallucinations.
- State Social Paranoia Scale – SSPS (self rated) persecutory statements (e.g. someone wanted me to feel threatened) mixed with positive, negative and neutral statements, all rated 1-5 (do not agree-totally agree).
- digit span (forward and reverse) testing working memory
- verbal learning task (12 nouns) with both immediate and delayed (25 minutes) recall, testing episodic memory
Subjects that had CBD then THC (versus placebo then THC) had a lower PANSS score than placebo group – but this did not reach significance.
However, they did have a significantly lower SSPS score (the self-rated scale) in comparison to placebo group.
Moving onto the cognitive effects of THC, the group who were pre-administered CBD were less impaired at a delayed recall in the verbal learning task.
Yet they experienced the same impairment relative to baseline as the placebo-then-THC group in the digit span and immediate recall portion of the verbal learning task.
Therefore, these findings suggest that CBD inhibits THC elicited paranoid symptoms, and also THC elicited episodic memory impairment, but has no protective effect for working memory.
These findings allow us to draw some conclusions regarding the neural structures affected by CBD and THC. Episodic memory relies on the integrity of hippocampal circuitry, and working memory seems dependent on prefrontal cortex function. The neural basis of psychotic symptoms is unclear at the moment.
We already know that THC affects neurons by disrupting synchronicity, but not firing rates of individual neurons. It seems that CBD therefore helps reduce this effect in the hippocampus, but is not as successful in the prefrontal cortex.
Future studies could examine if higher CBD doses or extended dosing over several days could produce stronger hippocampal/episodic memory protective effects, or if the protective effects would even extend to prefrontal cortex/working memory with higher doses.
- Amir Englund1
- Paul D Morrison1
- Judith Nottage1
- Dominic Hague1
- Fergus Kane1
- Stefania Bonaccorso1
- James M Stone2
- Avi Reichenberg1
- Rudolf Brenneisen3
- David Holt4
- Amanda Feilding5
- Lucy Walker1
- Robin M Murray1
- Shitij Kapur1
1The Biomedical Research Centre, Institute of Psychiatry, King’s College London, London, UK
2Department of Experimental Medicine, Imperial College London, London, UK
3Department of Clinical Research, University of Bern, Bern, Switzerland
4Division of Clinical Sciences, The Analytic Unit, St George’s, University of London, London, UK
5The Beckley Foundation, Oxford, UK