Research in the past decade has focused on whether marijuana use actually causes other mental illnesses. The strongest evidence to date suggests a link between cannabis use and psychosis (Hall and Degenhardt 2009). For example, a series of large prospective studies that followed a group of people over time showed a relationship between marijuana use and later development of psychosis. Marijuana use also worsens the course of illness in patients with schizophrenia and can produce a brief psychotic reaction in some users that fades as the drug wears off. The amount of drug used, the age at first use, and genetic vulnerability can all influence this relationship. One example is a study  that found an increased risk of psychosis among adults who had used marijuana in adolescence and who also carried a specific variant of the gene for catechol-O-methyltransferase (COMT) (Caspi et al. 2005), an enzyme that degrades neurotransmitters such as dopamine and norepinephrine.

In addition to the observed links between marijuana use and schizophrenia, other less consistent associations have been reported between marijuana use and depression, anxiety, suicidal thoughts among adolescents, and personality disturbances. One of the most frequently cited, albeit still controversial, is an amotivational syndrome, defined as a diminished or absent drive to engage in typically rewarding activities. Because of the role of the endocannabinoid system in regulating mood, these associations make a certain amount of sense; however, more research is needed to confirm and better understand these linkages.

Adapted from Caspi et al., Biol Psychiatry, May 2005.
The influence of adolescent marijuana use on adult psychosis is affected by genetic variables. This figure shows that variations in a gene can affect the likelihood of developing psychosis in adulthood, following exposure to cannabis in adolescence. The COMT gene governs an enzyme that breaks down dopamine, a brain chemical involved in schizophrenia. It comes in two forms: "Met" and "Val." Individuals with one or two copies of the Val variant have a higher risk of developing schizophrenic-type disorders if they used cannabis during adolescence (dark bars). Those with only the Met variant were unaffected by cannabis use.