Cannabinoids for the Treatment of Schizophrenia? A Balanced Neurochemical Framework for Both Adverse and Therapeutic Effects of Cannabis Use

Abstract

Recent studies have found that cannabinoids may improve neuropsychological performance, ameliorate negative symptoms, and have antipsychotic properties for a subgroup of the schizophrenia population. These findings are in contrast to the longstanding history of adverse consequences of cannabis use, predominantly on the positive symptoms, and a balanced neurochemical basis for these opposing views is lacking. This paper details a review of the neurobiological substrates of schizophrenia and the neurochemical effects of cannabis use in the normal population, in both cortical (in particular prefrontal) and subcortical brain regions. The aim of this paper is to provide a holistic neurochemical framework in which to understand how cannabinoids may impair, or indeed, serve to ameliorate the positive and negative symptoms as well as cognitive impairment. Directions in which future research can proceed to resolve the discrepancies are briefly discussed.

The Endocannabinoid System: A Potential Target for the Treatment of Various Diseases

“…While some studies suggest that C. sativa L. use may increase the risk of developing psychotic disorders and even worsen prognosis and disease burden, likely due to psychoactive compounds [134,137], others suggest non-psychoactive compounds in the plant may have therapeutic efficacy.…”

Effect of illegal substance use on cognitive function in individuals with a psychotic disorder, a review and meta-analysis.

“…It has been suggested that cannabis might have a cognitive enhancing effect due to stimulating prefrontal neurotransmission (Coulston et al, 2007). The cognitive deficits in schizophrenia have been associated with a decrement in prefrontal dopamine activity (Coulston, Perdices, Henderson, & Malhi, 2010). It is therefore hypothesized that low, infrequent doses of cannabis may result in an increase in activity in the frontal lobe and subsequent improvement in cognitive function in those with a psychotic disorder (Cohen, Solowij, & Carr, 2008).…”

Involvement of medial prefrontal cortex alpha-2 adrenoceptors on memory acquisition deficit induced by arachidonylcyclopropylamide, a cannabinoid CB1 receptor agonist, in rats; possible involvement of Ca2+ channels

“…Given the established role of CB 1 R in the acquisition, encoding, and retrieval of memories (Riedel and Davies, 2005), variations in this receptor population possibly mediate the detected effects of cannabis use on memory (Castillo et al, 2012; Montgomery and Fisk, 2007). The cannabinoid system interacts with several neurotransmitter systems (Coulston et al, 2011) such as acetylcholine, dopamine, serotonin, gamma-aminobutyric acid (GABA), glutamate, and noradrenaline by activation of CB 1 R (Al-Hayani and Davies, 2002; Schlicker and Kathmann, 2001).…”