A 21-year-old patient with a history of major depressive disorder (MDD) and CUD is brought to an outpatient crisis center for evaluation. The patient reports using cannabis once weekly until it became available recreationally 3 months earlier when the patient’s use increased to twice daily. Evaluation of the patient at the crisis center found that the patient had a Beck Depression Inventory (BDI) score of 29; the prior BDI score was from the patient’s last clinic visit 3 years ago, and the score was 5. The patient reports no regular psychiatry appointments over the last 3 years as depression symptoms had been controlled. The patient has a flat affect; reports decreased interest, motivation, or pleasure in any activities; denies any symptoms of psychosis; and admits to feeling hopeless. These symptoms seemed to have started within the last month. When directly questioned, the patient endorses suicidal thoughts with a plan of overdosing on prescription and over-the-counter medication.

The relationship between cannabis use and affective disorders, including depression, is not as clearly described as the relationship between cannabis and psychosis.15-17,19 Whereas psychosis tends to be seen following cannabis use in a dose-dependent manner,15-17,19 depressive symptoms have been reported both preceding and following cannabis use.20 The patient in Case 1 did not experience the psychotic symptoms despite the increase in cannabis use but has experienced worsening depressive symptoms. The National Epidemiologic Survey on Alcohol and Related Conditions data for individuals 18 years of age or older found that lifetime CUD and past year CUD were both associated with an increased risk of being diagnosed with MDD in the past year with an OR of 2.8 (95% confidence interval [CI] 2.33-3.41) for lifetime cannabis use and OR 2.6 (95% CI 2.26-2.95) for past year use cannabis use.21 A systematic review exploring the effect of cannabis use on depressive symptoms found an increased rate of depression in adolescents and young adults up to 32 years old who use cannabis compared with individuals that did not use cannabis with an OR of 1.37 (95% CI 1.16-1.62).22

The US Preventive Services Task Force recommends screening for depression in all adults, including pregnant, postpartum, and older adults.23 Depression screenings tools such as the Patient Health Questionnaire, the Center for Epidemiologic Studies Depression Scale, BDI, the Well-Being Index, or the Geriatric Depression Scale may be incorporated into electronic medical record platforms to ensure the data is captured and can be monitored for trends in depression symptoms.23-28 Incorporating depression screenings into primary care settings can expand the monitoring, resulting in prospective identification of patients who could benefit from early intervention. Early identification may reduce time from symptom onset to initiation of treatment interventions such as motivational interviewing and cognitive behavioral therapy. Nonpharmacologic approaches may be more beneficial than pharmacologic treatment as initial trials with fluoxetine, venlafaxine, and quetiapine have not demonstrated effectiveness for treating depression in patients with CUD.23,29-35 Depression screens in all adults is strongly encouraged; however, targeting cohorts at higher risk for depression with cannabis use, such as younger patients or those with an existing substance use disorder, would be an appropriate initial step prior to scaling to screen all adults.22,23

Determining the role of cannabis in this suicidality can be tricky. Suicidality includes suicidal ideation, suicide attempts, and/or general suicide behavior. Studies attempting to define the association between cannabis use and suicidality have been constrained by confounders. Difficulty quantifying the dose or frequency of cannabis, establishing the time frame of suicidal ideation in relation to cannabis use, and the complexities introduced with concomitant substance use and comorbid conditions have all been recognized as confounders. Estimates of suicidality in individuals who are using cannabis vary by cohort. A comparison of those who use cannabis with non–cannabis users from the general population found cannabis users that have epilepsy did not have an elevated suicidal ideation risk with an OR of 0.75 (95% CI 0.35-1.60) or suicide attempt risk OR 0.75 (95% CI 0.30-1.87).36 Individuals who were daily or near daily cannabis users did have an elevated suicidality risk compared to non–cannabis users with an OR of 3.2 (95% CI 1.72-5.94), and adolescents also carried a higher risk of suicide attempt with an OR of 3.46 (95% CI 1.53-7.84).22,37,38 Coroner toxicology results from individuals who died by suicide found cannabis present in an average of 9.5% of suicides.38 Similar findings were seen in an evaluation of more than 1400 autopsy reports in individuals 15 to 60 years old who died by suicide but did not overdose; cannabis was found to be the most common illicit substance detected in 10.5% of cases.39 It was found that the rates of those who died by suicide were higher for younger patients and those with a substance use disorder.38,40,41 In individuals who died by suicide whose age was up to 24 years old, 27.3% tested positive for cannabis, and 27% of individuals with a drug use history who died by suicide were positive for cannabis.38 The patient in Case 1 is 21 years old, which appears to increase the risk for suicidality, further supporting the need for evaluation and close monitoring of the patient.

It could be argued that cannabis was an anecdotal finding in those who died by suicide and that exploring the role of cannabis in those who attempt suicide or those with suicidal ideation would be more informative. A study evaluating self-reported cannabis use prior to a suicide attempt found that 10.2% of those who recently attempted suicide used cannabis within 24 hours of the attempt, and 13.2% used cannabis the day before the attempt.38 Drug Abuse Warning Network data from 2011, which included 228 366 emergency department visits of suicide attempts that involved medications found cannabis present in 15 615 (6.8%), and 45.7% of these individuals also had alcohol present.42 A meta-analysis evaluating 25 clinical trials investigating cannabis use and suicidal ideation or behavior found an OR of 3.2 (95% CI 1.72-5.94) for daily or near daily use, classified as heavy cannabis use, and suicide attempts compared with the general population and that those with psychotic and affective disorders using cannabis were 2.6 and 1.7 times, respectively, more likely to attempt suicide.37,38 This evidence suggests that patient 1’s increased frequency of cannabis use may have been a contributing factor in the current suicidal ideation the patient is experiencing.

The US Preventive Services Task Force does not recommend universal screening for suicide due to inadequate evidence.23 Whereas universal screenings are not recommended, screenings for patients with depressive signs and symptoms such as the patient in Case 1 are necessary. In this case, it was fortunate that the patient presented for help prior to acting on these suicidal thoughts. Clear messaging on how to access services may help enhance patient awareness of when and how to reach out for services should patients experience suicidal thoughts. Efforts such as advertising the suicide prevention hotline or the crisis text line along with signs about symptoms of suicidal behavior in public areas of health care centers is a suitable place to start. Additionally, educating the public at health events and encouraging health care professionals to consider screening high-risk populations, such as those using alcohol or patients with psychotic or affective disorders, for suicidality would be reasonable pilot cohorts.37,42 Establishing a library of resources and interprofessional partners, including crisis centers and medical and psychiatric care, can streamline care if patients are expressing suicidal thoughts in primary care settings, which are not always designed for this type of triage. Proactive implementation of these features creates a robust safety net for at-risk individuals.

A 69-year-old patient calls the community mental health center’s triage hotline complaining of severe chest pain, sweating, and shortness of breath. The patient has hypertension, hyperlipidemia, obesity, a prior myocardial infarction (MI) in 2002, schizoaffective disorder, and suspected CUD. After several years of abstinence from cannabis, a neighbor moved into the building a month earlier, and this individual is routinely using cannabis. The patient admits to joining the neighbor several times daily to smoke cannabis. Over the past week, the patient reports having felt short of breath when leaving the neighbor’s apartment and developing chest pain while walking the short distance back to the patient’s own apartment. Today these symptoms progressed in severity with the patient reporting breaking out in a sweat, having a sense of doom, and becoming too weak to walk back to the apartment and called for help.

Cannabis use has infrequently been associated with cardiovascular events.43 The cannabinoid receptor 1 (CB1), a main site of action for THC, can be found on heart and vascular smooth muscle.44,45 Activation of CB1 receptors in vitro has resulted in activation of the mitogen active protein kinase pathway, and this may interfere with normal vasodilation, increase reactive oxygen species, enhance proliferation of vascular smooth muscle, and promote cholesterol production.43 All of these actions can contribute to endothelial dysfunction and the development of atherosclerosis, which may ultimately lead to a cardiovascular event.43

In vitro pharmacologic actions do not always clearly translate into clinical effects. Clinically, cannabis has been observed to increase heart rate with changes ranging from 20% to 100% change from baseline that lasts for 2 to 3 hours.43,46-48 Changes in blood pressure have also been reported with alterations ranging from no apparent change in blood pressure to individuals experiencing hypotension and hypertension.44,46-48 These changes may not appear clinically significant alone, but in patients with preexisting conditions, they may contribute to the risk of developing a significant cardiac event. In a small study of patients with chronic, stable angina, exposure to 1 cannabis cigarette resulted in a decrease in time from exercise onset to angina by 50%.45 In addition to causing angina, a meta-analysis of 36 studies evaluating MI triggers ranked smoking cannabis as the third most common MI trigger after use of cocaine and heavy metal exposure.49 The effects of cannabis on cardiac tissue may be time-dependent as a multicentered study of 3882 patients presenting with an MI found an increased risk of MI within the first hour after cannabis inhalation compared with a period of not inhaling cannabis with a relative risk (RR) of 4.8 (95% CI 2.9-9.5).50 In the second hour after cannabis use, the risk reduced to RR 1.7 (95% CI 0.6-5.1).50 A retrospective analysis of 2097 patients followed for 11.2 years found cannabis use associated with increased all-cause mortality with a hazard ratio (HR) 2.09 (95% CI 1.25-3.5) and cardiovascular death HR 2.13 (95% CI 1.03-4.42).45 Additionally, a study evaluating the National Inpatient Sample of patients 15 to 54 years old from 2004 to 2011 found the RR of ischemic stroke in cannabis users compared to nonusers to range from 1.45 (95% CI 1.42-1.49) to 2.26 (95% CI 2.14-2.38) with those aged 45 to 54 years with the lowest risk and those 25 to 34 years with the highest risk.49

Patients may feel more comfortable reaching out to their psychiatric providers even with medical concerns. To accommodate this, interprofessional integrated care teams can address medical conditions in psychiatric settings in which patients are most comfortable. Psychiatric medications may contribute to the development of medical conditions; routine screening of weight, vital signs, and laboratory results may identify those patients at risk for cardiac events. Patients with hypertension and elevated low-density lipoproteins and tobacco and cannabis smokers may benefit from close follow-up and treatment to reduce cardiac events.45,50-53 Cardiovascular risk has been identified primarily with users who smoke cannabis; it is unclear at this time if the same risk is seen in patients who use different routes of administration, such as topically or oral ingestion. This risk should not be discounted, however, as the NSDUH survey found that 78.4% of cannabis users were smoking cannabis, and it was the most popular route of administration.1 Future research evaluating new cannabis formulations and different routes of administration would be quite valuable in defining cannabis’s effect on high-risk cardiovascular disease patients. Based on the existing information, there is an increased risk of cardiac events in high-risk patients; therefore, providing educational materials, such as signs of cardiac symptoms (ie, chest pain, shortness of breath, edema, weakness, blurred vision) and what to do should these symptoms occur, such as calling 911, may help reduce the time it takes to get a patient lifesaving care. Encouraging routine physical health assessments is important to prevent acute, life-threatening events, especially in populations with psychiatric conditions who may not routinely engage with primary care. Identifying interprofessional networks of specialists to assist medically high-risk patients can also help ensure that care is coordinated across all health care providers.