Psychiatric illness — There is evidence that marijuana use may increase the risk of schizophrenia and depression. Multiple prospective studies have demonstrated an increased risk of psychosis or psychotic symptoms with marijuana use (odds ratios ranging from 1.77 to 10.9), and several have also shown a dose-response relationship. A systematic review of longitudinal and case-control studies that excluded cohorts with identified mental illness, other substance-use problems, or acute marijuana intoxication, found a 40 percent increase in the risk of psychosis for those who had ever used cannabis (adjusted OR 1.41, 95% 1.20-1.65). Additionally, a dose-response relationship was demonstrated, with a twofold increase in risk for the group with the most frequent cannabis use (2.09, 1.54-2.84).

Evidence from the systematic review above was less strong that cannabis use is independently associated with affective disorders (anxiety or depression), after adjustment for confounders. Individual studies have come to different conclusions.

 
1. In a cohort study of 1601 students ages 14 to 15 who were followed for seven years, there was a dose-effect relationship between marijuana use and anxiety or depression. Daily use in young women was associated with an over five-fold increase in the odds of reporting depression and anxiety after adjustment for intercurrent use of other substances (odds ratio 5.6, 95% CI 2.6-12). In contrast, baseline depression and anxiety did not predict later marijuana use, suggesting that self medication was unlikely to explain the reported association.  
2. A twins study concluded that the association between marijuana use and major depression is likely due to shared genetic and environmental factors that predispose to both outcomes. However, the study also concluded that an association between marijuana use and suicide attempts may be causal, with early-onset marijuana use predisposing to suicide.

   Epidemiological studies cannot eliminate the possible influence of bias, confounding, and reverse causality (psychosocial problems leading to marijuana use) on the observed association. It is unlikely that a randomized study will be conducted, since cannabis is illegal in most countries and is associated with deleterious cognitive effects.

   Disputing the theory of reverse causality, a prospective study that followed 2437 young people (ages 14 to 24) for four years did not find that predisposition to psychosis (based on a psychological screening test) was a significant risk factor for marijuana use (OR 1.42, 95% CI 0.88-2.31) . This study found that in patients, marijuana use was associated with a small absolute increase in risk of psychotic symptoms at follow-up (21 versus 15 percent, adjusted risk difference 6 percent) for patients without a baseline predisposition for psychosis, while in patients with a baseline predisposition to psychosis the increase in risk was much greater (51 versus 26 percent, adjusted risk difference 24 percent).

   If the association between marijuana use and psychiatric illness is causal, it remains unclear whether marijuana acts to trigger the onset of these conditions only in vulnerable people, or whether it can provoke psychiatric illness in people who would otherwise not be predisposed to develop it. There is reasonable evidence that marijuana use exacerbates psychosis, and accumulating evidence that marijuana can precipitate schizophrenia in vulnerable individuals.

   Other effects — Tachycardia results from stimulation of the cardiac pacemaker by marijuana, which may worsen hypertension or underlying heart disease. One case-crossover study found that the risk of myocardial infarction onset was increased almost five times over baseline in the 60 minutes after marijuana use.

   Marijuana impairs the immune system by suppressing activity of natural killer cells and macrophages.

   Marijuana use also generally results in an increase in appetite.

   Marijuana use increases risk-taking behavior, and increases the risk of resumption of alcohol or cocaine dependence after hospital discharge for detoxification.

   Therapy — Patients who agree to therapy for marijuana abuse or dependence should be referred to a drug abuse treatment program. Marijuana dependence may require individualized treatment strategies which differ from those for other drugs of abuse; further research is indicated to determine appropriate treatment options. Trials of a number of agents drugs, including bupropion, divalproex, naltrexone, and nefazodone, have not demonstrated effectiveness in treating withdrawal symptoms, and there have been no pharmacological trials for prevention of recurrent marijuana use. A general overview of the treatment of patients with drug abuse problems is found separately.

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