Academic journal article Indian Journal of Psychiatry

Cannabis and Psychosis: Neurobiology

Academic journal article Indian Journal of Psychiatry

Cannabis and Psychosis: Neurobiology

Article excerpt

Byline: Amresh. Shrivastava, Megan. Johnston, Kristen. Terpstra, Yves. Bureau

Cannabis is a known risk factor for schizophrenia, although the exact neurobiological process through which the effects on psychosis occur is not well-understood. In this review, we attempt to develop and discuss a possible pathway for the development of psychosis. We examine the neurobiological changes due to cannabis to see if these changes are similar to those seen in schizophrenic patients the findings show similarities; however, these mere similarities cannot establish a 'cause-effect' relationship as a number of people with similar changes do not develop schizophrenia. Therefore, the 'transition-to-psychosis' due to cannabis, despite being a strong risk factor, remains uncertain based upon neurobiological changes. It appears that other multiple factors might be involved in

these processes which are beyond neurobiological factors. Major advances have been made in understanding the underpinning of marijuana dependence, and the role of the cannabinoid system, which is a major area for targeting medications to treat marijuana withdrawal and dependence, as well as other addictions is of now, it is clear that some of the similarities in the neurobiology of cannabis and schizophrenia may indicate a mechanism for the development of psychosis, but its trajectories are undetermined.

Transition to Psychosis and Cannabis

Cannabis is involved in approximately 50% of psychosis, schizophrenia, and schizophreniform psychosis cases. [sup][1],[2],[3],[4],[5] Cannabis is a known risk factor for schizophrenia, although the exact neurobiological process through which the effects on psychosis occur is not well understood. Cannabis is also of particular interest in both the first-episode psychosis (FEP) [sup][6],[7] and the ultra high risk (UHR) populations. This is mainly due to their increased susceptibility to cannabis abuse. [sup][8],[9] Amongst FEP patients, cannabis equally affects those who go on to develop schizophrenia and those who do not. [sup][10] In spite of significant advancements, the sequence of biological events and a valid model of neurobiological mechanisms are lacking. [sup][4],[11],[12] In this review, we attempt to develop and discuss a possible pathway for the development of psychosis.

Tetrahydrocannabinol

The biochemical mechanism by which cannabis exerts its effects on physiology and behavior remained a mystery until the components of cannabis were extracted, and Delta-9-tetrahydrocannabinol (THC) was found to be the main psychoactive constituent of cannabis. [sup][13] The isolation of THC resulted in the characterization of a G protein-coupled receptor to which THC exerted specific and saturable binding, [sup][14] indicating the presence of an endogenous receptor to which cannabinoids could exert their effects. "Cannabidols", have 64 active isomers, each having differing effects on health and behavior. [sup][15] THC is the only active metabolite which has few important neurochemical properties and stimulates cannabinoid receptors type-1 (CB1) in the brain that differentially affect patients with schizophrenia. It is a lipophilic compound, which disappears from extracellular spaces by dissolving in lipid-rich membranes, not by excretion from the body. THC is slowly released, leading to long-lasting effects originating from brain areas containing a large proportion of spare receptors (reserve receptors). This compound also induces withdrawal and tolerance as well as potentiates alcohol and heroin dependence. In utero exposure to THC hampers appropriate interneuron positioning during corticogenesis. With respect to psychosis, THC has been associated with independently causing positive symptoms and neurocognitive changes. [sup][16] THC exposure induces changes in the prefrontal cortex (PFC) characterized by less synaptic density and/or efficiency. [sup][17] Cannabis varies greatly in the amount of the major psychoactive constituent-THC, thus the psychoactive effects vary according to the nature of cannabis and its pattern of use which results in a dose-response relationship. …

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