Cannabis and mental illness in adolescents: a review

Abstract

This article reviews the literature on the association between cannabis exposure and mental illness in adolescents and provides the clinician with an evidence base to address cannabis use with teenagers. Traditionally cannabis was considered a benign recreational drug with low potential for long-term mental health problems and research on its potential therapeutic effects and recent developments to decriminalise cannabis in some American states has sent mixed messages to the public. Early initiation of cannabis use is a risk factor for developing psychosis and is associated with earlier age of onset of psychosis. Whilst the evidence is less robust, adolescent cannabis use is also associated with increased risk for bipolar mood disorders, suicide, anxiety, cognitive and depressive disorders. Early and frequent adolescent cannabis use can be considered as a predictor for mental illness later; and these young users may benefit from early screening and intervention.

Keywords:

• adolescents
• cannabis
• mental illness

View correction statement:

Cannabis and Mental Illness in adolescents

Introduction

Whilst substance use patterns differ regionally, globally, cannabis is the most commonly used illicit substance.¹ In a review of cannabis use trends in South Africa, cannabis use was associated with traumatic injuries in adults (29–59%), crime (39%) and HIV and seizures.² Cannabis use is associated with transient psychotic or affective symptoms during intoxication states; but the potential for more chronic symptoms that persist is of particular concern.³ There is now substantial evidence to suggest an association between early and frequent cannabis exposure in adolescence and the development of psychopathology later on.^4–6

Scope of cannabis use in South African adolescents

South Africa has been described in the lay press as the marijuana capital of the world. The South African Stress and Health study reported 8.3% prevalence for cannabis use in adults, with increasing prevalence in successive birth cohorts at a younger age.⁷ Based on national general population surveys, cannabis use is estimated to range from 2–9% in otherwise healthy adolescents in South Africa.⁸ Importantly, rates of use are much higher in the mentally ill population. For example, in a study in Durban, South Africa, 61.8% of adolescents (aged 10–18 years) admitted with psychotic symptoms reported lifetime cannabis use;⁹ while cannabis was the most common debut drug reported in adolescents with psychosis at Tygerberg Hospital in the Western Cape, South Africa.¹⁰

In view of the high prevalence of comorbid cannabis use in adolescents presenting to mental health care services, we examine this association in greater detail. Whilst we recognise that mental illness may render adolescents more vulnerable to substance use, there is growing evidence that primary substance use is associated with increased risk for development of mental disorders; and furthermore that comorbid cannabis use impacts negatively on the clinical features and prognosis of these mental disorders.¹¹

Method

A comprehensive literature review of the electronic data bases was conducted of cannabis and psychiatric disorders in adolescents.

Keywords included “cannabis”, “mental illness”, “psychiatric disorders” and “adolescents”.

The focus of this review was the association between cannabis use and psychiatric disorders in adolescents, including psychosis, mood, anxiety and cognitive disorders. Cannabis-related disorders such as cannabis use disorder, cannabis intoxication and cannabis withdrawal disorder are not discussed in this review.

Effect of cannabis on the adolescent brain

Cannabis is derived from the Cannabis Sativa plant, with Delta-9 tetrahydracannabinol (THC) being the primary psychoactive ingredient. Cannabis comprises more than 60 naturally occurring cannabinoids. Cannabinoid receptors are found in high density in the hippocampus, prefrontal cortex, anterior cingulate gyrus, basal ganglia and cerebellum. The endocannabinoid system is implicated, directly or through other neurotransmitters such as dopamine and glutamate, in the development of mental illness.¹² The endocannabinoid system has an inhibitory effect on neurotransmitter release, and exogenous cannabinoids such as THC disrupt this system, leading to excess glutamate release. Resultant excitotoxic effects influence post-synaptic pruning, which in turn may negatively influence adolescent experience-dependent maturation of neural circuitry within the prefrontal areas.^12–14

While the specific biological effects of cannabis on the developing adolescent brain remain the focus of extensive research, several factors have been proposed to explain differential sensitivity to the psychotropic effects of cannabis evident between individuals.¹⁴ These factors include: the amount, duration, and potency of cannabis; early exposure; and possible genetic and environmental factors.

Cannabis and psychosis

Cannabis use is an independent risk factor for the development of psychosis. Comorbid use in first episode psychosis (FEP) is associated with earlier age of onset, while persistent cannabis use in early-onset psychosis predicts poorer outcome.^15,16 Arseneault et al. (2004) showed that the association between adolescent cannabis use and adult psychosis persists even after controlling for other confounding variables. They concluded that early initiation of cannabis use confers a two-fold increased risk of later development of schizophrenia; and that the earlier the age of cannabis initiation, the greater this risk. Specifically, cannabis use before age 15 years is associated with a three-fold increased risk of schizophreniform disorder at age 26 years.^4,17 More recently, Estrada et al. (2011) reported that age of first cannabis use seems to modify age of onset of schizophrenic spectrum disorders and other psychiatric disorders; and that the use of cannabis before age 18 is associated with an increased risk of psychosis compared to that associated with initiation of cannabis in adulthood.^18,19

There are a number of clinical factors that are known to correlate with poorer course and outcome of psychosis. These include: early age of onset (AO) of psychosis; long duration of untreated psychosis (DUP); and predominance of negative psychotic symptoms, especially at psychosis onset. It is thus relevant to consider the relationship between cannabis and AO, DUP and symptoms at onset, as these factors are considered proxies for long-term outcome.

Cannabis and age of onset of psychosis

Cannabis use is associated with earlier age of onset of psychosis in adult studies.²⁰ This is supported by a study of first episode psychosis in 625 adolescents and young adults (age 14–29 years) where 87.6% of participants initiated cannabis use before onset of symptoms. In this study, age of onset of psychosis was earlier in those with early initiation of cannabis use (by age 14 years); however this phenomenon was not observed in those initiating cannabis at older ages.¹⁶ In contrast, the Child and Adolescent First Episode Psychosis Study (CAFEPS) of 110 adolescents with early onset psychosis, reported that cannabis users were on average older than non-users.²¹ However, a recent meta-analysis shows that age of onset in cannabis users is on average 2.70 years earlier than in non-cannabis users.²²

Cannabis and duration of untreated psychotic symptoms

Duration of untreated psychosis (DUP) is defined as the period between the first appearance of positive psychotic symptoms and the initiation of treatment and is measured in weeks. It is of interest as it has prognostic implications. Longer DUP is associated with a poorer outcome of psychosis at 2 years.²³ A meta-analysis of nine adolescent and adult studies found no association between cannabis use and DUP; however the author noted an association between the timing of cannabis use and DUP. While DUP was shorter in cannabis users in studies where cannabis use was defined in terms of current or recent use; DUP was longer in cannabis users in studies based on lifetime cannabis use.²⁴ This suggest that early, adolescent initiation of cannabis use may be associated with longer DUP and thus a poorer course and prognosis for the psychotic illness. Support for this comes from a study by Schimmelmann and colleagues who reported that cannabis use was associated with longer duration of psychotic symptoms in adolescents (cannabis users DUP = 6.1 weeks vs. non-cannabis users DUP = 3.0 weeks).²⁵

Cannabis use and psychotic symptoms at psychosis onset

FEP adolescent patients with a history of cannabis use are reported to have more positive psychotic symptoms and greater illness severity at onset.^21,25 In the CAFEPS study, adolescent cannabis users were older at baseline and had higher positive and negative syndrome scale (PANSS) positive scores and lower PANSS negative, PANSS general and PANNS total scores than non-users.²¹

Cannabis and prognosis in psychosis

Cannabis use is associated with poor medication adherence; and persistent use is associated with worse symptomatic and functional outcomes and greater service disengagement than those who cease cannabis use.²⁵

Cannabis and mood disorders

Bipolar mood disorder is associated with increased risk of substance use and misuse. Importantly, premorbid cannabis use has been associated with earlier age of onset and increased manic episodes in bipolar mood disorder.²⁶

The evidence for an association between cannabis and depressive psychopathology is weaker and inconclusive.²⁷ Rey et al. (2002) showed an association between cannabis use and depressive symptoms in a sample of adolescents but not in adults; and this was supported by an Australian study of frequent adolescent cannabis use increasing the risk of anxiety or depression at age 21 years.^28,29 This was also supported by a review by Degenhardt et al. (2003).⁶ It is important to note that Moore et al. reviewed 24 reports from 15 cohort studies (6 adult and 7 school-based cohorts) and found that while almost all studies reported increased risk of affective outcomes, effect sizes were small and many studies were underpowered. These authors stress the important fact that observed associations does not prove causality and that in many studies of cannabis use and depression, confounding factors were not adequately addressed.³

Cannabis and suicide

Suicide remains an important cause of mortality in adolescents and it is estimated that between 3.5% and 52.1% of adolescents have suicidal ideation. Intensive cannabis use, defined as several times per week, was associated with an increased transition rate into suicidal ideation for male youth aged 10–24 years old in an analysis of a 30-year longitudinal birth cohort.³⁰ Conversely, there was no evidence that suicidal ideation led to cannabis use in this population. These authors reported that the earlier the intense use of cannabis was initiated, and the greater the frequency of use, the faster vulnerable individuals developed suicidal ideation.³⁰

Cannabis and anxiety

It is suggested that cannabis at low doses may have anxiolytic effects; while at high doses it may be anxiogenic.³¹ There is limited evidence on the association between adolescent cannabis use and anxiety disorders.^27,28 However, in their 2012 review, Degenhardt et al. reported that regular adolescent cannabis use was significantly associated with anxiety in adolescence and early adulthood, even if the users ceased using cannabis.⁶

Cannabis and cognition

Adolescence is a period of brain development with normal re-organisation of grey matter, which may be associated with synaptic pruning or loss of glial cells and increased myelination of intra-cortical neurons. White matter also continues to increase in adolescence, more in males than in females.¹²

In a systematic review of the effects of cannabis on the adolescent brain, James et al. (2013) concluded that that there was possibly greater memory loss and hippocampal volume changes in healthy adolescent cannabis users compared with non-users.¹² Interestingly, functional neuroimaging studies show that when cognitive demand is low, cannabis users appear to function as well as healthy abstinent controls. However cannabis users recruit greater brain areas and drop performance when cognitive demand is increased.¹² Specifically, cannabis users show impairments in residual memory and attention, even following abstinence.³²

Somewhat unexpectedly, in a meta-analysis of patients with schizophrenia, it appears that those with a lifetime history of cannabis use perform better on cognitive tasks at onset of psychosis than those without a cannabis history.³³ Kumra et al. (2012) suggest that the effects of cannabis in adolescent psychosis are primarily related to functioning of the left parietal lobe and to a lesser extent the left thalamus.³⁴ Clearly, further research on the effects of cannabis on brain development in healthy and psychotic adolescents is still required.

Explaining cannabis use and mental illness

There are four main theoretical models postulated to explain the high prevalence of cannabis use in psychosis^35–37 and these theories could be extended to explain cannabis use in other psychopathologies also.

Firstly, substance misuse is secondary to primary mental illness and may be viewed as an attempt to self-medicate symptomatology. Similarly, it is suggested that individuals may use substances to self-medicate dysphoric symptoms. As this review shows, this cannot adequately explain the relationship between psychosis and cannabis; as cannabis has been shown to be casual in the pathways to several mental disorders including psychosis.²⁴

The second model proposes that substance misuse precipitates psychiatric illnesses such as substance-induced psychotic or mood disorders. Here one anticipates psychopathology manifesting during acute intoxication states, but remitting as systemic drug levels drop over time.

The third model suggests that mental illness and substance-related disorders share biological and psychosocial risk factors such as genetics, family history, childhood traumatic experiences, and cognitive impairment; and that the development of mental illness is due to an interaction of multiple factors, including in many cases the presence of substance use.

Finally, several risk factors such as personality traits, learning models, and coping styles should be considered, especially in relation to differential vulnerability to cannabis and mental disorder.

There is still debate on the most applicable model to mental illness and no single model may account for comorbidity in different groups, thus multiple models may be pertinent in an individual. These models may be useful to guide clinicians in understanding patients at an individual level and thus developing a more effective treatment plan.^35,36

Implications for treatment

Dual diagnosis of early and frequent cannabis use and mental illness in adolescents has multiple negative implications for social functioning, such as academic decline,³⁸ increased risk of physical injury³⁹ and risky behaviours such as unprotected sex⁴⁰ and other illicit substance use.⁵ There is thus a need for routine cannabis screening in adolescents with mental illness and for therapeutic programs for dual diagnosis patients.

Ideally we need more programs on substance use prevention and mental health promotion at school levels to increase awareness of the potential harms associated with early cannabis use. Consideration should be given to the introduction of routine cannabis screening at schools, with informed written parental consent and adolescents assent. This random screening may aid to deter cannabis use in this vulnerable age group.

Clinicians need to engage actively with their young patients on substance use issues. Screening high risk adolescents for common mental illnesses using brief questionnaires may also assist in early detection and treatment. A history of early cannabis use should alert the clinician to a potential increased vulnerability to develop psychopathology. There is no doubt that early intervention is critical to improving outcome. The treatment of adolescents with dual diagnosis of cannabis-related disorders and other psychopathology should be holistic and encompass integrated treatment for both problems.

Conclusion

There is a high prevalence of cannabis use in adolescents with mental illness in South Africa and globally. The risk for psychopathology appears to be greater with earlier age of first cannabis exposure and more frequent use. There is clearly an association between early cannabis use and increased risk for developing psychosis later in biologically vulnerable individuals. The evidence for a causal relationship between cannabis use and other mental illnesses remains inconclusive and this question requires further study.

From a public health perspective, there is a profound need for psycho-education of both the public and policy-makers on the substantial negative effects of cannabis on mental health, as exposure to this drug is very common in all communities. The recent calls for legalisation of cannabis need to consider the far reaching implications of sanctioning the use of a drug that is being increasingly recognised as a risk factor for psychiatric disorders.