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 Table of Contents  
REVIEW ARTICLE
Year : 2017  |  Volume : 31  |  Issue : 3  |  Page : 143-146

Cannabis and its associated psychopathology


1 Specialist Psychiatry, District Hospital, Bishnupur, Manipur, India
2 Department of Psychiatry, Central Institute of Psychiatry, Ranchi, Jharkhand, India
3 Department of Psychiatry, Regional Institute of Medical Sciences, Imphal, Manipur, India

Date of Web Publication17-Aug-2017

Correspondence Address:
Rakesh Mohanty
Room No 43, Central Institute of Psychiatry, Ranchi - 834 006, Jharkhand
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/jms.jms_110_16

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  Abstract 


Cannabis has been used by humanity since a long time ago and the common belief by general population is that it is an innocuous drug. The prevalence of its use has been increased in many countries. It has been observed that the use of cannabis has been associated with various psychopathologies since its origin. The study of cannabis use and its consequences remains an interesting area both from the academic and clinical point of view. The various psychopathological syndromes associated with cannabis use that have been researched extensively include cannabis and psychotic disorders, especially, schizophrenia and mood disorders and not uncommon anxiety disorders and cognitive impairment. The association between cannabis and schizophrenia has received much attention. Various epidemiological, clinical, and experimental evidence show an association between the effects of cannabis on the brain and psychopathological disorders including schizophrenia. However, the association is often not clear. Cannabis use might be casually related to the later development of schizophrenia in an indirect way in a few heavy users, but commonly, its use may increase the risk in a person with a preexisting vulnerable to developing psychosis and may worsen the course of the disorder.

Keywords: Anxiety, cannabis, cognition, psychopathology, psychosis, schizophrenia


How to cite this article:
Haobam M, Mohanty R, Senjam G, Heramani N. Cannabis and its associated psychopathology. J Med Soc 2017;31:143-6

How to cite this URL:
Haobam M, Mohanty R, Senjam G, Heramani N. Cannabis and its associated psychopathology. J Med Soc [serial online] 2017 [cited 2017 Dec 18];31:143-6. Available from: http://www.jmedsoc.org/text.asp?2017/31/3/143/207670




  Introduction Top


Cannabis is one of the most common widely illegal drugs of abuse and has been used by humanity since a long time ago. According to the World Drug Report released by the United Nations Office on Drug and Crime in 2016 reports that in 2014 about 183 million people have been estimated to use cannabis corresponding to 3.8% (prevalence) of the population aged 15–64 years worldwide. Tentative estimates suggest that cannabis is the most common illicit substance use in Asia, with an annual prevalence of use of 1.9% among those aged 15–64 years.[1],[2]

Cannabis is obtained from the plant Cannabis sativa and some other subspecies. The plant is known for its more than 61 identified cannabinoids, but most important is the metabolite tetrahydrocannabinol (THC) an active metabolite thought to be responsible for its psychoactive effects. After entering the blood stream, cannabinoids are distributed throughout the body, reaching earliest the tissues with highest blood flow (brain, lungs, and liver). Within the brain cannabinoids are differently distributed, reaching high concentrations in the neocortex, limbic system, visual and auditory area, motor area (basal ganglia and cerebellum), and pons. The half-life of THC is approximately 56 h in occasional users and 28 h in chronic users.[3] Some users use it as food or beverages while some smoke it as it is the fastest way to reach the brain and produce the desired effects. Use of cannabis is linked to deficits in tasks of executive functioning. It has been seen to cause negative effects on memory, along with that it hampers the ability to form new memories, and on attention and learning. In a laboratory setting, cannabis and THC usually produce dose-related deficits in reaction time, attention, motor performance and coordination, and information processing. These effects can last up to 28 days even after abstinence from the drug.[4]

Evidence obtained from both human studies and animal models suggests that exposure to cannabis during adolescent period increases the likelihood of developing psychopathology in adulthood. The endogenous cannabinoid ligands (endocannabinoids [eCBs]) anandamide and 2-arachidonoylglycerol and the naturally occurring cannabinoid receptor, cannabinoid type 1 receptors (CB1Rs), type 2 receptors are present and active during early brain development.[5] The eCBs system modulates the neurotransmission at both inhibitory and excitatory synapse in brain regions relevant to the regulation of pain, emotion, motivation, and cognition.[6] It is likely that disruption by THC to normal functioning of the eCBs system during adolescence can have profound long-term consequences on functioning in the adult brain.[7] The malfunctioning of the eCB system as well as perturbations in CB1R signaling have been linked to psychopathology and emotional dysregulation, including schizophrenia, anxiety, and depression. In spite of the current discrepancies regarding CB1R changes in animal models of schizophrenia, present findings point to the eCB system as an important neuromodulatory pathway that may have a critical role in the psychotic – related behaviors observed in these animals, that is, altered emotionality and social and cognitive deficits.[8]

Various evidence demonstrates a strong association between cannabis and psychopathology while some studies fail to find any association. The present review is to examine the relationship between use of cannabis and its associated psychosis, including schizophrenia, mania, depression, anxiety disorder, and cognitive impairment.


  Cannabis Use Disorders Top


Cannabis psychosis

Some evidence of the association between cannabis and psychosis have come from case reports, psychosis in community surveys of cannabis abusers, and observational studies of psychosis in cannabis users.[7] Studies have shown that cannabis psychosis to be short-lasting, often exhibited organic symptoms, such as confusion and amnesia, presence of more odd and bizarre behavior, violence, panicky affect but reactive and congruent affect.[8] However, the relationship has been criticized by various authors and the association is widely debated. It is suggested that cannabis in high doses may produce psychotic syndrome, but the evidence for a specific clinical syndrome that is identifiable as a cannabis psychosis is much less compelling.[9]


  Schizophrenia Top


Various studies have shown that regular cannabis use and psychotic disorders such as schizophrenia are likely associated in the general population.[10],[11] The Swedish conscript cohort was the first longitudinal study to demonstrate an association between cannabis use and schizophrenia in later life. The authors found that heavy cannabis use at the age of 18 led to increase risk of developing schizophrenia 15 years later and the authors after controlling for the confounding variables proposed that cannabis consumption is a life – event stressor for individuals vulnerable to schizophrenia and also found a dose – response relationship between schizophrenia and cannabis.[12] In a systematic review published in 2007 by Moore et al., seven longitudinal cohort studies were identified assessing psychotic outcomes in both users and nonusers of cannabis. The result of the studies shows an increased risk of psychosis (adjusted odds ratio = 1.41) persisting in six of the seven when confounders were controlled for and also indicative of dose-response relationship between cannabis and schizophrenia.[13]

In one meta-analysis, it was found that the age of onset of psychosis is about 2.7 years earlier in the cannabis use when compared to alcohol user.[14] The results from clinical studies suggest that THC can produce psychotic symptoms in a healthy patient and exacerbate those in schizophrenic patients.[15] However, only a small fraction of cannabis users develop schizophrenia, and hence it is likely that genetic vulnerability and environmental factors may have a role in the association.

Research in the recent years has identified some genetic alterations associated with increased vulnerability to schizophrenia following cannabis use. Notably is the one demonstrated by Caspi et al. who found that carrier of polymorphism in the catechol-O-methyltransferase (COMT) gene; Valene 158 alle were more prone to psychotic symptoms (including schizophrenia) later in life if they had used cannabis during adolescence.[16] A recent study also confirmed the role of AKT1 rs2494732 C/C genotype on the effect of cannabis use has shown increasing the risk of a psychotic disorder.[17] A systematic review of structural magnetic resonance imaging (MRI) studies by Lorenzetti et al. suggests that THC exposure can affect morphology, particularly regional changes (such as hippocampus and parahippocampus) in heavy cannabis users.[18]

Cannabis abuse may be a risk factor for psychotic disorders in vulnerable individuals; it can affect neurodevelopment during adolescent and a dysregulation of the eCB system can be a factor to psychosis including schizophrenia.[19]

Current consensus is that cannabis is considered as a component cause for schizophrenia including other environmental and genetic factors and when it is used early and heavy it increases the risk further.[10]


  Depression Top


Whether depression is a predisposing risk factor to substance abuse, with cannabis being used to mediate symptoms, or whether the use of cannabis directly exacerbates or induces depression is a matter of debate in the literature.[20] The studies have shown that lifetime use of cannabis increases the risk of depression in females, leads to greater suicidal ideations, and increases the level of depression with increasing involvement with cannabis use.[10] Another study by Feingold et al. concluded that there was no longitudinal association between cannabis use and increase the incidence of depression.[21] There are also opposing views about the nature of the causal relationship.[22] However, some researchers suggest that both environmental factors and genetic predisposition may play a role in the association.[5]

The experimental studies show that exposing adolescent rats with THC revealed a depressive behavior in the force – swim test, especially female rats. The findings suggest that adolescent cannabis exposure may affect the susceptibility to develop a mood disorder later in life and the gender differences may relate in those well documented among human patients with depression.[5]

The association between depression and cannabis dependence may be explained partially by a high degree of overlap in genetic factors predisposing to cannabis use and depressive disorders, supporting the hypothesis of shared risk factors.[10] Few negative studies do exist, a recent 3 year prospective study showed cannabis use did not increase the risk of depression.[20]


  Mania Top


There is limited evidence on cannabis and mania; however, population epidemiological studies suggest that cannabis use and mania may be related. A recent study by Gibbs et al. concluded that cannabis use may worsen the presence of manic symptoms in those diagnosed with bipolar disorder and may also act as a risk factor in the incidence of manic symptoms.[23] In bipolar disorder, cannabis use often precedes the onset of manic symptoms and cannabis use increases the duration of manic cycles, and most of the patients do not use cannabis after initial onset.[24] A study from India found that of the 244 patients with cannabis related diagnosis 12% received a diagnosis of bipolar disorder – mania with psychosis, the third common psychiatric condition after cannabis-induced psychosis (21%), and schizophrenia (14%).[10] However, a number of case studies implicate cannabis used for self-medication of manic symptoms.[25],[26]


  Anxiety Disorder Top


Anxiety disorder is one of the common complications that follows chronic heavy cannabis use. Panic attacks constitute the most frequent acute anxiety symptoms associated with cannabis use.[10] One meta-analysis shows that anxiety is significantly positively associated with the consumption and misuse of cannabis.[10] A recent study examined the relationship between cannabis use and mental health between the ages of 15 and 29 found that heavy cannabis use during adolescence was associated with an increased risk of developing an anxiety disorder later in life, even if the individual no more uses cannabis in adulthood.[6]

Treating rats chronically with cannabinoid agonist CP – 55,940 from PND28 to PND38 or with THC from PND28 to PND45 led to an increase in anxiety levels in adulthood, measured using the elevated pulse maze, or the open field test, respectively.[6]


  Cognitive Impairment Top


Many studies have supported the impression that cannabis has an effect on cognitive performance and eventual functioning, particularly with long-term usage. Using cannabis chronically before the age of 17 causes more severe cognitive decline compared to chronic use later in life. The most consistent findings are impairment of short-term memory, focused attention, basic oculomotor control, and executive functions.[7] One study showed prospective memory impairment associated with cannabis use in young adults, but the users were not aware of their deficits.[27] Cannabis-induced cognitive decline is mediated by the CB1 in the brain areas known to be associated with memory, attention, and other cognitive function.[10]

MRI and positron emission tomography studies have reported reduced overall cortical gray matter and increased white matter volume in adolescent cannabis users compared to users who began using cannabis in adulthood.[27] Functional MRI studies have revealed abnormal activation in the prefrontal cortex (PFC) and parietal brain regions of adolescent cannabis users. These structural changes have been associated with increased executive dysfunction and verbal memory deficits.[5] In addition, adolescent users of cannabis have reduced cerebral blood flow in the temporal, insular, and PFC regions, and these reductions in blood flow are associated with cognitive deficits.[28]

Some studies have reported complete recovery of impairments after 4 weeks of abstinence, whereas other studies describe persisting cognitive deficits, especially in the domains of attention, memory, and executive functions; one study suggests partial recovery.[10] In a meta-analysis, residual verbal memory impairments have been consistently demonstrated.[10]


  Conclusion Top


Evidence obtained from various studies including human and animal models suggest that the use of cannabis during adolescent may increase the risk of psychopathological disorders in adulthood. There has also been research in the field of genetic such as the polymorphism of the COMT gene to the development of schizophrenia following cannabis use. The role of cannabis in cognitive impairment has been investigated, but evidence for the reversibility of these dysfunction is mixed and its clinical importance needs to be demonstrated. Research shows that the use of cannabis may be a component cause in the later development of schizophrenia and it may precipitate disorders in persons who are vulnerable to develop psychosis. The role of eCB system as a neuromodulatory needs further research in this line following cannabis exposure. Since cannabis uses conventionally in India further research from our country is very much needed.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
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  In this article
Abstract
Introduction
Cannabis Use Dis...
Schizophrenia
Depression
Mania
Anxiety Disorder
Cognitive Impairment
Conclusion
References

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