Schizophrenia is an incurable neurodegenerative disease known for affecting individuals of all ages and gender. It roughly affects 20 million people worldwide, and diagnosed patients are 2-3 times more likely to die early when compared to the general population.
One of the most common symptoms affecting schizophrenic patients is prepulse inhibition (PPI) deficit. It takes away their ability to react appropriately to a weak stimulus, causing them to react abruptly to the weakest auditory and/or tactile stimuli.
Treating PPI in a Schizophrenic person could significantly improve the quality of life of schizophrenic patients. Unfortunately, due to the limited understanding of the neurological disorder, current pharmacological options for the treatment of PPI deficit in Schizophrenia lack specificity and therefore are not effective.
As a result, most family members and loves ones of those affected by Schizophrenic disorder struggle with daily life. Raising awareness for this being an effective and viable treatment for
Endocannabinoid System: An effective target for PPI treatment in Schizophrenia?
The role of different neuromodulators (glutamate, dopamine, serotonin, etc.) in PPI deficit seen in Schizophrenia has been extensively studied, however, the mechanism of action of non-classic neuromodulators such as endocannabinoids are at the infancy stage of research and there’s still much to learn from this treatment.
Previous post-mortem studies (patient brain examinations after death) have shown that patients diagnosed with Schizophrenia displayed abnormal expression and density of cannabinoid receptor CB1.
Also, previous studies have shown the expression of CB1 and serotonergic receptors 5-HT1A and 5-HT2A in the same brain regions that modulate PPI. Moreover, CB1 receptors have been found in serotonin neurons, and activation of the 5-HT2A receptors triggers endocannabinoid synthesis.
Is Cannabis Consumption an Effective Treatment For Schizophrenia?
Not quite. Previous studies have shown that cannabinoid receptor agonists such as THC increases the levels of serotonin. This interaction tends to counteract the effects of antipsychotic drugs that modulate the activity of 5-HT receptors in serotonin neurons.
Moreover, genetic predispositions might increase the chances of developing a psychotic episode in schizophrenic patients.
Can Cannabis-based Therapies be Effective Against PPI?
A study led by the University of Rio de Janeiro in Brazil investigated the effects of combining cannabinoids and serotonergic therapies for the treatment of PPI deficit in mice.
Researchers in this study found that none of the drugs targeting only the endocannabinoid system had an effect on PPI. However, they found that co-modulation of cannabinoid and serotonergic receptors through Rimonabant (CB1 receptor antagonist) and Volinanserin (5-HT2A antagonist) were able to increase PPI in normal and impaired-PPI mice models of Schizophrenia.
As a result, researchers reported that given its therapeutic potential, future clinical trials should test whether co-administration of Rimonabant with Volinanserin is beneficial for patients suffering from Schizophrenia.
Beaudoin, M., Potvin, S., Giguère, CE. et al. Persistent cannabis use as an independent risk factor for violent behaviors in patients with schizophrenia. npj Schizophr 6, 14 (2020). https://doi.org/10.1038/s41537-020-0104-x
GBD 2017 Disease and Injury Incidence and Prevalence Collaborators (2018). Global, regional, and national incidence, prevalence, and years lived with disability for 354 diseases and injuries for 195 countries and territories, 1990-2017: a systematic analysis for the Global Burden of Disease Study 2017. Lancet (London, England), 392(10159), 1789–1858. https://doi.org/10.1016/S0140-6736(18)32279-7
Laursen, T. M., Nordentoft, M., & Mortensen, P. B. (2014). Excess early mortality in schizophrenia. Annual review of clinical psychology, 10, 425–448. https://doi.org/10.1146/annurev-clinpsy-032813-153657
Marques, A.M., Macena, M.V., Cardoso, A.R. et al. Effects of combined 5-HT2A and cannabinoid receptor modulation on a schizophrenia-related prepulse inhibition deficit in mice. Psychopharmacology 237, 1643–1655 (2020). https://doi.org/10.1007/s00213-020-05485-0
