Delta-9-Tetrahydrocannabinol, Cannabidiol and Psychosis

Student thesis: Doctoral ThesisDoctor of Philosophy


Use of cannabis has been linked to an increased risk of psychotic disorders and to impairments in cognitive function. Both of these effects have been attributed to its main psychoactive constituent, delta-9-tetrahydrocannabinol (THC). However, much of the evidence for these effects comes from studies that involved retrospective estimates of cannabis use, which may introduce a recall bias, particularly in people with psychosis. One way to address this issue is to study the effects of cannabis use prospectively in people at clinical high risk (CHR) for psychosis, a proportion of whom will subsequently develop psychosis.
The second major constituent of cannabis is cannabidiol (CBD). CBD is non-intoxicating, and there is some evidence that it may attenuate the adverse effects of THC. This possibility can be investigated by assessing the effects of cannabis containing different doses of THC and CBD.

This thesis aims to address two key questions: i) What are the consequences of cannabis use on the clinical outcomes and cognitive performance of individuals at CHR? ii) What effect does CBD have on the effects of THC on endocannabinoid signalling?

Chapter 1 provides an overview of the current literature on cannabis, THC, CBD, and the endocannabinoid system, focussing on the impact of cannabis use on the risk of psychosis and on cognitive functioning. It also describes the CHR state and its potential utility in studies of cannabis in psychosis.

In Chapters 2 and 3, I use data from a large, multisite, naturalistic study of individuals at CHR to examine the relationship between cannabis use and i) clinical outcomes and ii) cognitive performance. I found no evidence that cannabis use was related to the later onset of psychosis, the persistence of symptoms, or level of functioning. Although cannabis use has been associated with cognitive deficits in the general population, I found that impairments in cognitive performance in CHR individuals who had used cannabis were less severe than in those who had never used cannabis.

In Chapter 4, I examine the effects of cannabis containing varying ratios of CBD:THC on the peripheral endocannabinoid system in healthy volunteers. I found that THC altered the plasma concentration of endocannabinoid signalling molecules and biologically related lipids, and that these effects were not influenced by the co-administration of CBD.

Finally, in Chapter 5, I bring together the findings from Chapters 2, 3 and 4. I discuss their collective implications, review the limitations of each study. I then consider key challenges to future research on cannabis in relation to psychosis.
Date of Award1 Aug 2023
Original languageEnglish
Awarding Institution
  • King's College London
SupervisorPhilip McGuire (Supervisor) & Matthew Kempton (Supervisor)

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