Psychosis is a symptom associated with a range of mental illnesses, such as schizophrenia, bipolar disorder, and depression. It has the tendency to alter an individual’s state of mind, and thus, distort their perception of reality (Kesby, et al., 2018). This may lead to the onset of positive symptoms. These are a subset of symptoms recognized to distort normal function by amplifying certain perceptions, compared to negative symptoms which diminish certain emotions or perceptions. These symptoms may manifest as delusions, hallucinations, and unpredictable behaviour (Kesby, et al., 2018).
In 1949, Henri Laborit discovered chlorpromazine, which later acted as a prototype of phenothiazines, a commonly used group of antipsychotic medications (Tost, Alam, and Meyer-Lindenberg, 2010). This introduced a branch of antipsychotic treatment outside of mere sedation. Dopamine is an inhibitory neurotransmitter, responsible for inducing feelings of pleasure as a part of the brain’s reward system. It was discovered that these drugs were inhibiting dopamine D2 receptors, allowing for its downregulation and leading to the mitigation of psychosis symptoms. This suggests that one of the key pathophysiological factors underlying psychosis is dopamine synthesis. The dopamine hypothesis states that patients exhibiting symptoms of psychosis tend to illustrate higher levels of dopamine production, specifically, of D2 receptors in the striatum, which is highly interconnected with the prefrontal cortex. Psychosis may be triggered due to changes in these cortico-striatal networks (Kesby, et al., 2018). These networks are responsible for creating behaviours in order to reach a specific goal, so delusions may shift this behaviour in an extreme and unpredictable manner (Haber, 2016). Figure 1 showcases these mechanisms (Howes and Kapur, 2009).
Figure 1: This diagram shows how various risk factors, such as genetics, recreational drug use, stress, and frontotemporal dysfunction can lead to enhanced striatal dopamine production. This can then lead to increased aberrant salience, meaning there are behavioural reactions to stimuli which would otherwise be considered irrelevant, resulting in psychosis. Antipsychotics target the D2 receptors, causing dopamine production to decrease, thus decreasing aberrant salience and allowing for the management of psychosis symptoms (Howes and Kapur, 2009).
The brain is a network of connections which are vital for normal function; therefore, when additional networks become disrupted, symptoms of psychosis may also be induced (Kesby, et al., 2018). Figure 2 represents the various brain regions affected by schizophrenia, which characterizes the positive symptoms of psychosis (Banks, et al., 2021).

Figure 2: Psychosis stems from impairments within various brain regions, as depicted above. For instance, impairments in the occipital lobe, striatum and thalamus, can result in visual hallucinations. However, impairments in the auditory system, such as the temporal lobe, amygdala, and thalamus, can cause auditory hallucinations. Emotional, and thus, behavioural changes may result from impairments within the limbic system, hippocampus, and frontal lobe. The basal ganglia also has a strong affect on creating paranoia and hallucinations, as it is responsible for managing and integrating emotions, sensory information, and movement (Banks, et al., 2021).
Although antipsychotic medications can be beneficial, they can also cause side effects such as, sedation, weight gain, sexual dysfunction, and extrapyramidal symptoms which refer to involuntary movements (Hoenders, et al., 2018). Extrapyramidial symptoms are a common side effect, as antipsychotic medications block D2 receptors found within the basal ganglia, which is also responsible for movement (Figure 2). Some patients may prefer to integrate alternative medication to potentially mitigate these side effects and further improve the positive effects of orthodox medication. Ginkgo biloba is an ancient Chinese seed plant, which has been shown to reduce the aforementioned positive symptoms of psychosis by inhibiting the uptake of dopamine (Brondino, et al., 2013). The antioxidant properties of this extract allows for the improvement of brain circulation, leading to stable connections between the aforementioned brain networks (Hoenders, et al., 2018). This further leads to the improvement of psychosis symptoms.
Furthermore, cannabidiol (CBD) may pose as a novel therapy for psychosis (Davies and Bhattacharyya, 2019). It has been found that individuals representing symptoms of psychosis tend to have elevated levels of endocannabinoid anandamide and a greater expression of the cannabinoid 1 receptor (CB1). Due to CBD’s non-psychoactive behaviour and mechanism to down-regulate the activity of the agonists of the CB1 receptor, it behaves in the opposite manner to Tetrahydrocannabinol (THC). This allows for brain function to be regulated, as CB1 receptors are abundant in the brain. CBD also increases the production of endocannabinoid anandamide, thus reducing psychosis symptoms (Davies and Bhattacharyya, 2019).
Overall, with further research, the viability of alternative medication as adjunctive or mono-therapy for psychosis may be better understood. Thus, potentially allowing for the improvement or mitigation of adverse side effects from antipsychotics, and therefore leading to a better management of symptoms.
References
Banks, L., Barth, B., Balogh, R., Cole, A., Nonoyama, M., Partosoedarso, E. and Sanchez, O., 2021. Ella and Olivia’s Health: Schizophrenia. [online] Available at: <https://ecampusontario.pressbooks.pub/casestudieshealthsciences/chapter/ella-and-olivias-health-schizophrenia/> [Accessed 21 November 2023].
Brondino, N., De Silvestri, A., Re, S., Lanati, N., Thiemann, P., Verna, A., Emanuele, E. and Politi, P., 2013. A systematic review and meta-analysis of Ginkgo biloba in neuropsychiatric disorders: From ancient tradition to modern-day medicine. Evidence-Based Complementary and Alternative Medicine, 2013, p.e915691. https://doi.org/10.1155/2013/915691.
Davies, C. and Bhattacharyya, S., 2019. Cannabidiol as a potential treatment for psychosis. Therapeutic Advances in Psychopharmacology, 9, p.2045125319881916. https://doi.org/10.1177/2045125319881916.
Haber, S.N., 2016. Corticostriatal circuitry. Dialogues in Clinical Neuroscience, 18(1), pp.7–21. https://doi.org/10.31887/DCNS.2016.18.1/shaber.
Hoenders, H.J.R., Bartels-Velthuis, A.A., Vollbehr, N.K., Bruggeman, R., Knegtering, H. and de Jong, J.T.V.M., 2018. Natural medicines for psychotic disorders. The Journal of Nervous and Mental Disease, 206(2), pp.81–101. https://doi.org/10.1097/NMD.0000000000000782.
Howes, O.D. and Kapur, S., 2009. The dopamine hypothesis of schizophrenia: Version III—The final common pathway. Schizophrenia Bulletin, 35(3), pp.549–562. https://doi.org/10.1093/schbul/sbp006.
Kesby, J.P., Eyles, D.W., McGrath, J.J. and Scott, J.G., 2018. Dopamine, psychosis and schizophrenia: The widening gap between basic and clinical neuroscience. Translational Psychiatry, 8(1), pp.1–12. https://doi.org/10.1038/s41398-017-0071-9.
Tost, H., Alam, T. and Meyer-Lindenberg, A., 2010. Dopamine and psychosis: Theory, pathomechanisms and intermediate phenotypes. Neuroscience & Biobehavioral Reviews, 34(5), pp.689–700. https://doi.org/10.1016/j.neubiorev.2009.06.005.