Evidence-Based Reviews

Does marijuana contribute to psychotic illness?

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Cannabis abuse is not benign, especially in adolescents.


 

References

Evidence grows that marijuana use can cause acute psychosis, bring forward in time a first schizophrenia episode, and worsen the prognosis of patients with psychotic disorders.

Roger, age 16, had been smoking marijuana on and off for about 2 years. His parents knew but believed this was a stage and not dangerous; they had tried marijuana in their youth without harm. Roger’s smoking had increased to several joints daily since he started a relationship with an older girl, who shared and encouraged his habit.

His parents became worried when Roger began making unusual comments, saying that food did not taste “right” and he thought someone was poisoning him. They brought Roger for psychiatric consultation at the recommendation of their family physician.

History and examination revealed that Roger had experienced vague persecutory ideas for several weeks but no systematized delusions or hallucinations. I told Roger and his parents he probably had a drug-induced psychosis and that symptoms would likely disappear without recurrence if he stopped using marijuana. At 2-weeks’ follow-up, he described no more psychotic experiences and said he now realized the danger for him of smoking marijuana. A review 1 month later showed Roger was doing well, and I discharged him after reinforcing the importance of abstinence. But his case didn’t end there.

Box 1

By what mechanisms does marijuana use cause psychosis?

The dopaminergic effect of cannabinoid receptors (such as CB1) may be one biologic mechanism, according to preliminary evidence. But the dopaminergic pathway might not be the most relevant mechanism, because the primary psychoactive constituent of marijuana—delta-9-tetrahydrocannabinol (delta-9-THC)—causes or increases psychotic symptoms in patients with schizophrenia despite treatment with dopamine receptor antagonists.2

Gene-environment interactions also appear to be relevant. A functional polymorphism in the catechol-O-methyltransferase (COMT) gene (COMT Val158 Met) moderates the influence of cannabis use on developing psychosis, according to a birth cohort study of 803 New Zealanders. COMT valine158 allele carriers were most likely to exhibit psychotic symptoms and develop schizophreniform disorder if they used cannabis during adolescence. This association did not apply to adult-onset cannabis use.3

Results were similar in a study in which 30 patients with a psychotic disorder, 12 relatives of patients with a psychotic disorder, and 32 healthy controls received delta-9-THC or placebo.4

Two years later, I received a request for information about Roger’s episode from an acute inpatient facility. Roger had been admitted after an incident at the local mall in which he screamed at people and accused bystanders of trying to harm him. Despite using marijuana only occasionally, his behavior had been deteriorating and was becoming increasingly bizarre. The attending psychiatrist believed Roger had schizophrenia.

Clinicians regularly deal with patients such as Roger who suffer from a psychotic disorder and use marijuana. This is hardly surprising because marijuana is the most widely used illicit drug. In 2006, 5% of 12th graders in the United States reported using marijuana daily during the previous month, and 42% had tried it at least once.1

Is psychotic patients’ use of marijuana a coincidence? Self-medication? Or could cannabis cause psychotic illness? This debate elicits strong views among community and professional groups. To help you provide up-to-date advice to patients and families, this review:

  • describes the growing body of evidence on the mental health consequences of marijuana use
  • seeks to help you detect and deal with the effects of marijuana use in clinical practice.

Marijuana and psychosis

Although the neurobiologic association is unclear (Box 1),2-4 up to 15% of users report psychotic phenomena after consuming marijuana.5 Naturalistic and experimental studies have confirmed that marijuana can induce short-lived psychotic experiences.

In two parallel trials, 22 healthy individuals6 and 13 stable, antipsychotic-treated schizophrenia patients7 were given 2.5 mg and 5 mg intravenously of delta-9-tetrahydrocannabinol (delta-9-THC)—the primary psychoactive constituent of marijuana. Both groups developed dose-related, transient, schizophrenia-like symptoms and altered perceptions:

  • Healthy volunteers showed the full range of psychotic symptoms. One individual said, “I thought you were giving me THC through the blood pressure machine and the sheets.”2
  • Schizophrenia patients tended to report increases in the symptoms of their specific conditions. Those with paranoid illnesses, for example, reported an escalation in persecutory ideas.
Transient psychotic phenomena are not equivalent to a psychotic illness, however. To meet diagnostic criteria for a psychotic disorder, symptoms must be persistent and impair psychosocial functioning.

Early reports. Anecdotal clinical reports that marijuana use could cause psychosis emerged in the 1960s but were largely ignored. Many clinicians assumed that psychotic individuals used marijuana to relieve troubling symptoms (self-medication).

A 15-year, longitudinal study examined the incidence of schizophrenia in >50,000 Swedish conscripts and concluded that marijuana use during adolescence increased the risk of schizophrenia.8 Skeptics questioned the validity of the diagnosis and the etiologic role of other drugs in this study and suggested that prodromal symptoms might have led to marijuana use, rather than marijuana triggering the psychosis.

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