Those with a recorded history of cannabis use in general practice records are at a much higher risk of developing mental ill health problems such as anxiety or depression as well as severe mental illnesses, new research shows.
The findings point to the need for a public health approach to the management of people misusing cannabis, including the need to emphasize the importance of general practitioners to continue enquiring about recreational drug use.
While the links between cannabis use and severe mental illnesses such as schizophrenia and psychosis are well researched, the associations are less clear between cannabis use as described in patient’s GP records and other, more common types of mental ill health such as depression and anxiety.
In a new study, published in Psychological Medicine, researchers in the University of Birmingham’s Institute for Mental Health and the Institute of Applied Health Research found a strong link between general practice recorded cannabis use and mental ill health in one of the largest cohorts ever explored.
Senior author Dr. Clara Humpston said: “Cannabis is often considered to be one of the ‘safer’ drugs and has also shown promise in medical therapies, leading to calls for it be legalized globally. Although we are unable to establish a direct causal relationship, our findings suggest we should continue to exercise caution since the notion of cannabis being a safe drug may well be mistaken.”
Dr. Joht Singh Chandan said: “The research reaffirms the need to ensure a public health approach to recreational drug use continues to be adopted across the UK. We must continue to progress measures to improve the prevention and detection of drug use as well as implement the appropriate supportive measures in an equitable manner to prevent the secondary negative health consequences.”
Using primary care data drawn from the IQVIA Medical Research Database (IMRD-UK), the researchers found following the first recorded use of cannabis, patients were three times more likely to develop common mental health problems such as depression and anxiety. In addition, they were almost seven times more likely to develop severe mental illnesses such as psychosis or schizophrenia.
The dataset included records from 787 GP practices around the UK gathered over a 23-year period between 1995 and 2018. The researchers were able to include data from 28,218 patients who had a recorded exposure to cannabis. These were matched to 56,208 patients who had not been using cannabis and controlled for sex, age, ethnicity, smoking status and other relevant characteristics.
A Review of the Effects of Cannabis in Mental Illness
Cannabis use has been described as one of many environmental influences associated with an individual’s increased vulnerability towards the development of psychotic illness [13, 35, 38, 61], with approximately one in every four individuals in this population presenting with a concurrent CUD diagnosis . Several studies have demonstrated negative effects of cannabis use in patients with schizophrenia.
Specifically, THC in cannabis has been associated with an increased risk of psychosis in a dose-dependent manner: regular cannabis users and heavy cannabis users are 2- and 4-times more likely to develop psychosis, respectively [39, 100]. Furthermore, increased risk for earlier psychotic symptom presentation has been observed in conjunction with cannabis use in the general population [70, 81].
Results from one of the largest longitudinal studies involving over 50,000 male participants indicates that those who smoked cannabis by the age of 18 had twice the risk for receiving a diagnosis of schizophrenia, while those who used chronically were at six times the risk compared to non-users .
Notably, the administration of intravenous THC in healthy individuals has been shown to directly induce psychotic symptoms, both self-reported and assessed by the Positive and Negatve Symptom Scale (PANSS) [32, 107]. Across multiple studies, cannabis use has been correlated with earlier onset of psychosis, increased symptom severity, higher rates of relapse and longer hospitalization time, as well as overall poorer illness and quality-of-life outcomes [33, 40, 54, 58, 79, 90, 99, 113, 145].
In one study, continued cannabis use following psychosis onset, when compared to discontinued use, was associated with higher rates of relapse, longer hospital admissions, enhanced positive and negative symptoms, as well as a variety of negative impacts on daily functioning . Importantly, cannabis abstinence has been shown to ameliorate cognitive impairments related to cannabis use, such as verbal memory and learning, as well as specific symptomology (e.g. depression), suggesting that cannabis may contribute to symptom exacerbation in schizophrenia [116–118].
Interestingly, however, a recent trial by McGuire and colleagues suggests the potential of administering 1000 mg of cannabidiol (CBD) daily for 6 weeks alongside current antipsychotics for reducing positive symptoms as rated by the PANSS, as well as for improving self-reported and clinician-reported functional outcomes in schizophrenia compared to placebo .
Moreover, a study by Leweke and colleagues compared the efficacy of CBD to a potent antipsychotic, amisulpride, in acute schizophrenia, describing similar efficacy in clinical symptomatic improvement as well as superior side effects, such as increased anandamide serum levels that were significantly associated with clinical improvements .
In a trial similar to McGuire et al.’s, conducted by Boggs and colleagues, 600 mg of CBD was administered daily for 6 weeks and, despite being well tolerated, was not associated with any improvement with symptoms using the PANSS, or with cognition compared to placebo in stable, treated patients with schizophrenia .
A systematic review of the therapeutic potential of CBD and higher CBD cannabis preparations for psychosis and schizophrenia describes a promising future with effective and tolerable results thus far . Moreover, published on the ClinicalTrials.gov database, there are currently two active, but not yet recruiting, clinical trials that will assess CBD in acute schizophrenia (NCT02088060), as well as in early psychosis (NCT02504151). There are also two completed trials that have assessed CBD in acute psychosis (NCT00628290) and in schizophrenia or schizophreniform disorder (NCT00309413), but have no published results. Randomized mulit-site clinical trials are needed to substantiate the external validity of these trials.
Major Depressive Disorder (MDD) and Bipolar Disorder (BD)
In MDD, much of the evidence suggests harmful consequences of cannabis use. In a 40-year study that analyzed a cohort of over 400 individuals across several time points, cannabis use was correlated with an increased risk of receiving a MDD diagnosis, and earlier onset of cannabis use was correlated with a shorter time to MDD presentation . Other studies have shown similar results, demonstrating a positive correlation between cannabis use and depression, of which chronic use further strengthens this association [75, 120].
One study found the association between MDD and cannabis only in those with CUD, rather than those who occasionally use cannabis, while other studies describe weekly cannabis use being sufficient [4, 75]. This warrants a deeper investigation towards the extent of cannabis use (e.g. frequency and CBD/THC potency) that is necessary to better understand this association. Not only has cannabis use been shown to potentially predict risk of developing MDD, but it has also been shown to promote depressive symptom progression [5, 106].
Despite a substantial collection for the harmful implications of cannabis on depressive outcomes, there are other studies that have found no correlation between cannabis use and later MDD diagnosis or symptom severity after controlling for multiple confounding factors, including other illicit drug use, education and childhood upbringing [34, 51, 111]. Nonetheless, there have been no randomized, clinical trials for the use of cannabinoids in depression.
There are, however, studies that have analyzed depression symptoms as secondary outcome measurements in participants with other disorders, such as chronic pain, but no significant therapeutic benefit has been found in association with the administered cannabinoids, including nabiximols and dronabinol . Thus far, the literature suggests more evidence for harms, rather than therapeutic effects, of cannabis in MDD (Table 1); research gaps need to be addressed in future research with prospective, controlled study designs.
Similarly, the majority of evidence suggests harmful effects of cannabis use in bipolar disorder (BD), another common mood disorder associated with CUD . Using a nationally representative sample of over 40,000 individuals, cannabis use has been associated with a greater risk of BD onset . This association has been found by others, with higher frequency cannabis use further potentiating the risk for developing BD and worsening BD symptomology, including sucide risk [111, 144].
One study highlights a positive association between BD and cannabis use, but with interactive effects of cannabis use and BD measures on gender and medication type , while other studies describe cannabis use as predictive of longer affective episode duration, more frequent rapid cycling between mood states, as well as lower remission rates and lower clinical and functional recovery [137, 155].
In contrast, another study suggests an improvement in BD symptoms 4 hours following cannabis use ; however, this only reflects an acute profile of cannabis use in BD. There are additional studies that suggest no statistically significant relationship between cannabis and BD outcomes [73, 121]. Moreover, there have been no studies to investigate any therapeutic relationship between cannabinoids and BD. Further research is necessary to better understand the nature of the relationship between cannabis and BD, but thus far the current literature indicates that there are more harmful consequences compared to benefits associated with long-term cannabis use in BD symptomatology and disease progression.
About 50% of respondents in a 2017 Canadian cannabis survey claimed that cannabis had a positive effect on anxiety . Despite this claim, much of the research to date suggests otherwise. For example, there is significant evidence for an association between cannabis use, agoraphobia and social anxiety disorder (SAD) [27, 140]; in a nationally representative study, a clear, statistically significant association was observed between daily cannabis use and SAD .
However, findings on this co-morbidity across disorders of anxiety remain mixed. For instance, regarding generalized anxiety disorder (GAD), research ranges from a two-fold increased risk of anxiety symptoms with cannabis use to no significant association between the two factors [37, 144]. One study supports the relationship between cannabis use and GAD, but not between cannabis use and SAD, further complicating the results , while others describe persistent reports of heightened anxiety symptoms in cannabis users compared to non-users .
Some studies have investigated the effects of cannabis use in early childhood and adolescent stages, demonstrating an increased risk of developing anxiety symptoms and anxiety disorder, which was strengthened with earlier onset of cannabis use [25, 36, 69]. Again, there are also studies that describe a lack of any significant correlation after controlling for significant confounds, such as cigarette use and childhood factors [34, 57, 130, 156].
A systematic review by Whiting et al. on the medical use of cannabinoids describes only one clinical trial conducted by Bergamaschi and colleagues in which a single 600 mg dose of CBD in individuals with SAD was associated with improved scores on a visual analogue scale after a simulated public speaking test in comparison to placebo; however, the authors note how this study holds high potential bias [7, 152].
Any other study assessing benefits of cannabis on anxiety are, however, only secondary analyses within pain populations [55, 108, 135, 152]. Nonetheless, the current literature does not suggest any robust therapeutic benefits of cannabis for anxiety, and therefore is inconsistent with claims of self-medication. Further research should focus on prospective designs that allow researchers to understand the directionality of the association between cannabis and anxiety.
Post-Traumatic Stress Disorder (PTSD)
Cannabis use has become increasingly common amongst patients with PTSD . Although there is mixed data regarding the use of cannabis as a treatment for PTSD, current research has shown a strong positive association between PTSD symptom severity and daily cannabis use . There is evidence that supports the notion that individuals with PTSD use cannabis as a means for coping with symptoms, primarily involving insomnia in contrast to anxiety-related symptoms [10, 56].
This finding, however, has been challenged as Metrik and colleagues found that, while individuals with PTSD report using cannabis to cope with sleep disturbances, patients later report significantly poorer sleep quality and physical health . In terms of PTSD symptom severity, most data supports the association of cannabis users having a higher likelihood of presenting with PTSD symptoms, experiencing heightened negative affect, and showing improvements in symptoms following cannabis abstinence [91, 98, 141, 153].
Moreover, when an individual meets PTSD criteria and concurrently uses cannabis, they typically experience increased withdrawal and craving . Other studies either show mixed support for both the potential harms [26, 62, 104, 148], the therapeutic benefits, of which mostly involves improvements in sleep-related outcomes [18, 45, 64, 124], or show lack of association between PTSD outcomes and cannabis use .
There is mixed data for the use of cannabis as a therapeutic treatment for PTSD. A randomized, double-blind, cross-over study describes therapeutic effects of nabilone (target dose of 3 mg daily for 7 weeks), a synthetic cannabinoid that mimics the effects of THC, for nightmares, global functioning and overall well-being in comparison to placebo . Another study showed similar improvements following nabilone administration; however, this was a retrospective design .
Another study examined the administration of THC in patients with PTSD, describing favourable results in a sample of 10 participants . To note, nearly half of the studies that assess cannabis use in PTSD, as well as its potential therapeutic effects, were conducted in U.S. military veterans, who exhibit high comorbidities of cannabis use and CUD, commonly reporting the use of cannabis to cope with one’s traumatic experiences [8, 45, 62, 78, 80, 98, 104, 105, 153].
This population may be the most benefited by research in this area based on the high prevalence of cannabis use, which may have positive or negative effects on recovery. Despite no association between cannabis use and PTSD development, there are reported harmful effects from cannabis use on psychiatric outcomes in PTSD. There are also, however, non-significant associations that have been concluded between cannabis use and PTSD symptomatology. Additionally, reported benefits are minimal and involve mixed findings across studies. Accordingly, further research is required using prospective, controlled clinical designs to understand the relationship between cannabis and PTSD.
Self-Report vs. Scientific Evidence
The majority of the empirical literature supports the argument that cannabis produces more harm than benefits insofar as psychiatric illness severity and progression (Table 1). Despite the current gaps that exist in research surrounding this topic, there seems to be a discrepancy that remains between evidence for cannabis’ therapeutic potential and self-reported motivation underlying cannabis use. For example, in a cross-sectional study across 1,429 participants from 18 different countries, individuals reported using cannabis “medically” rather than “recreationally”, and users described pain (61.2%), anxiety (58.1%) and depression (50.3%) as top reasons for using cannabis .
Other studies have found similar results, with sleep, pain and anxiety among the most common reasons for use [11, 50, 122, 151]. Individuals are also directly reporting the use of cannabis to self-medicate specific mental illnesses, such as anxiety and PTSD [26, 50, 142]. Additionally, some clinicians are directly prescribing cannabis for anxiety and depression [110, 122]. However, it is clear that there is limited evidence to make any strong conclusions about therapeutic effects of cannabis . Due to the anticipated increase in cannabis availability with legalization, and subsequent increased prevalence, it is important to resolve the paradox surrounding why cannabis users report self-medication for psychiatric symptoms when the science, to date, does not support this account.
Methodological Shortcomings in the Current Literature
In order to understand the discrepancy between self-reported reasons for cannabis use and the scientific evidence that currently exists, there are many areas of research that must be addressed, see Table 1. For schizophrenia, while initial results have been promising, more rigorous, controlled trials, as well as multi-site clinical trials, are necessary to confirm CBD’s therapeutic potential. The evidence, however, is strong surrounding the harms of recreational cannabis use in schizophrenia. Although, additional longitudinal, prospective studies are necessary in understanding what exact preparations of cannabis, frequency of cannabis use and age of onset of use promote this association.
For MDD, there are only secondary analyses of cannabinoids benefiting depressive symptoms. Future research addressing the direct relationship between specific cannabinoids and MDD using appropriate measures are necessary. Moreover, longitudinal, prospective designs as well as controlled, clinical trials must assess the relationship between cannabis use and potential harms, such as risk of MDD and worsening of depression symptoms and outcomes.
There is only minimal evidence in BD suggesting the harms of cannabis use, therefore, future controlled, prospective designs are necessary in furthering these primary findings. Considering anxiety disorders, additional longitudinal, prospective studies as well as controlled, clinical trials are necessary for determining any therapeutic potential of cannabinoids. Moreover, similarly as described in MDD and BD, future research is required to determine the specific harms that cannabis can induce in anxiety, as findings are currently mixed.
Finally in PTSD, current trials reporting benefits of cannabis involve specific populations, such as exclusively male participants or military veterans, and very small sample sizes. Future controlled studies addressing these limitations are warranted. To better understand potential cannabis harms, longitudinal, prospective studies must be conducted to determine the exact association between cannabis use overtime in PTSD of which also addresses frequency, preparation and onset of cannabis use.
Physical Harms of Cannabis
Apart from the current evidence that suggests both short- and long-term risks in psychiatric illness, cannabis involves other adverse effects that must not be overlooked. Cognition can be impaired with both acute use of cannabis as well as overtime in chronic users. This includes impaired short-term memory, motor coordination and control, executive functioning, as well as altered judgement [12, 28, 103, 136].
These deficits can put individuals at higher risk for injury and disease, for example, from motor vehicle accidents due to impaired motor control or from sexually transmitted disease due to impaired judgement in sexual encounters . Additionally, short-term cannabis use, if consumed at high doses and with high THC potency, can induce paranoia and even psychosis, as described in the ‘schizophrenia’ section [31, 149].
With respect to long-term effects, a major risk involved with cannabis use is addiction; roughly 8.9% of individuals who use cannabis develop an addiction following lifetime exposure . Moreover, almost half of chronic users experience robust withdrawal symptoms after cessation, which can include characteristics that range from sleep problems and nightmares to dysphoria and nausea .
Of note, cannabis use has also been associated with progression to other illicit drug use, which becomes strengthened with increased frequency and earlier onset of use , therefore placing individuals at risk for other substance use disorders and drug-related harms. A second long-term adverse effect that has been substantiated is risk of smoking cannabis is risk of developing symptoms of chronic bronchitis due to airway and lung inflammation .
Other adverse effects that are more strongly associated with cannabis use onset specifically in adolescence involves poorer education outcomes, cognitive impairment and hindrance to one’s overall success [31, 96, 149]. Finally, other forms of cannabis consumption can be associated with additional harms towards the user. Apart from smoking cannabis via joints, pipes, blunts or bongs, other methods for administering cannabinoids include butane hash oil (“dabs”) and oral consumption (“edibles”), which pose risks that are associated with stronger and slower delivery, respectively, as well as with the inaccuracy in product labelling [6, 94, 147].
Alternatively, one form of consumption that may pose less risk for users in comparison to smoking involves the method of vaporizing cannabis, which is associated with fewer respiratory problems [44, 46, 60]. Depending on the route of administration, physical harms may differ slightly; however, these outcomes must be acknowledged regardless of the focus (i.e. therpauetic benefits or potential harms) in discussions of cannabis and mental illness.
reference link : https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6397076/
More information: Keerthy et al (2021). The associations between primary care recorded cannabis use and mental ill health in the UK: A population-based retrospective cohort study using UK primary care data. Psychological Medicine.