Cannabinoids and Psychosis – Cause and Treatment

Student thesis: Doctoral ThesisDoctor of Philosophy


Epidemiological studies suggest that cannabis is a risk factor for psychotic illness. The main active ingredient is Δ-9-Tetrahydrocannabinol (THC). In healthy humans, the acute administration of THC can elicit transient psychotic symptoms and cognitive impairment. THC stimulates the endocanabinoid CB1 receptor (CB1R). However, beyond CB1Rs, the mechanism underlying the pro-psychotic effects of THC is unknown. The ecploration of candidate mechanisms was the first major theme in this thesis. In Study 1 the pro-psychotic properties of intravenous (IV) THC were confirmed. Thereafter, studies 2and 3 explored whether the pro-psychotic effects were related to excess striatal dopamine release or abnormal neural oscillations respectively.

The cannabis plant contains over sixty cannabinoid molecules, one of which, Cannabidiol (CBD) can antagonise some of the pharmacological effects of THC. It has been suggested that the absence of CBD in modern, 'high-potency' forms of cannabis (sinsemilla or 'skunk') underlies the risk of such preparations for mental health. However, the evidence for this is sparse. Characterising the effect of CBD on THC-elicited responses was the second major theme in this thesis. Studies 4 and 5 tested whether CBD inhibited acute THC elicited psychosis. 

In study 1 the psychotomimetic effects of acute IV THC were confirmed. THC-elicited positive symptoms were distinct from anxiety, and negative symptoms were distinct from sedation. Cognitive performance was impaired under THC conditions. In study 2, THC had no significant effect on striatal dopamine release despite inducing robust positive psychotic symptoms. In study 3, THC-elicited positive psychotic symptoms were related to reduced bi-frontal coherence in the theta (4-8Hz) band. Studies 4 and 5 both showed that CBD pre-treatment inhibits acute THC-elicited psychosis.

Overall two major findings emerged. 1. The pro-psychotic effects of THC were related to abnormal neural oscillations, but not to striatal dopamine release; 2. Cannabidiol inhibits acute THC psychosis. 

Date of Award2012
Original languageEnglish
Awarding Institution
  • King's College London
SupervisorDominic Ffytche (Supervisor), Shitij Kapur (Supervisor) & Robin Murray (Supervisor)

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