For years it's been a classic chicken-or-egg riddle: Does smoking marijuana lead to schizophrenia, or are those with schizophrenia who use cannabis simply seeking the calming effects of the drug?
Researchers have suspected a link since the 1960s, and study after study has hinted that use of marijuana may trigger schizophrenia, a serious mental illness that affects one in 100 people.
Recent studies, however, provide evidence strong enough to give public health officials — not to mention parents and educators — pause, especially as legalization efforts pick up steam. The latest to weigh in is research to appear in the May issue of the Archives of General Psychiatry. Scientists in Australia followed nearly 4,000 young adults born between 1981 and 1984 at the 21-year mark, and found that the longer study participants had used marijuana, the higher the risk of psychosis-related outcomes. Those who had experienced hallucinations early were more likely to have smoked or used marijuana longer and more frequently.
The study's authors said there is significant complexity in the relationship: Essentially, those who were vulnerable to psychosis were more likely to use cannabis, which in turn could contribute to an increased risk of developing mental illness.
"The research is conflicting, but the preponderance of the evidence shows that something is there," said Ken Duckworth, the medical director of the National Alliance on Mental Illness.
If you are a teenager and you smoke marijuana, you put yourself at risk, he said, especially if you have the gene or genes suspected of predisposing one to schizophrenia.
Marijuana is the most used, and abused, illicit drug in the United States, with more than 4.2 million people over the age of 12 reporting substance abuse or dependence in 2008. That is more than twice the number of people who abuse or are dependent on pain relievers, (1.7 million) and cocaine, (1.4 million), the second and third most widely abused drugs in this country.
It is also the most widely used drug among those who have been diagnosed with schizophrenia. In the early 1970s, there was speculation cannabis helped dim the voices and other hallucinations typical with schizophrenia. But researchers started to look at it from the other direction, surmising that marijuana use, particularly heavy marijuana use, may contribute to the onset of schizophrenia symptoms.
In a large study reported in 1987, cannabis use in late adolescence was associated with an increased risk of a subsequent diagnosis of schizophrenia. Studies over the past five years have pinpointed direct connections between brain abnormalities and THC (tetrahydrolcannabinol), the primary psychoactive ingredient in marijuana.
In 2005, researchers at New York's Albert Einstein College of Medicine used a brain imaging technique called diffusion tensor imaging to study the brains of groups of adolescents for a year. They included healthy non-drug users, heavy marijuana users (daily use for at least a year) and schizophrenic patients. They found that repeated exposure to cannabis resulted in abnormalities in a critical fiber pathway in the brain related to higher aspects of language and auditory functions.
Two years later, in 2007, scientists at Cardiff University's School of Medicine in Wales found that regular cannabis use among young people increased their risk of developing a psychotic illness later in life by more than 40 percent. And the more they smoked marijuana, the higher the risk. Those who smoked most frequently were more than twice as likely to develop psychosis. Similar results were uncovered by Spanish researchers.
American researchers confirmed those findings in 2009. Emory University doctors reported that teenagers who progressed to daily marijuana consumption experienced psychotic and pre-psychotic symptoms of schizophrenia at earlier ages.
Scientists have known for years that schizophrenia runs in families. Now scientists can point to specific genes, including dysbindin-1, which affects glutamate synaptic function in the hippocampal function area of the brain. The genes neuregulin 1, G72, D-amino acid oxidase, and regulator of G protein signaling 4, or RGS4, have also been implicated.
David A. Lewis, director of the Translational Neuroscience Program at the University of Pittsburgh School of Medicine, and his research team were one of several groups to identify the RGS4 gene in studies of the prefrontal cortex as susceptible for schizophrenia.
In subsequent research Lewis and his colleagues found that gamma-aminobutyric acid, which is an important neurotransmitter required for cognitive processes such as working memory, is impaired by the cannabinoid 1 receptor, which is where THC is activated. In simpler terms, marijuana use impairs the brain's ability to perform intellectual tasks.
Both of these findings suggest a prefrontal cortex disruption that affects working memory, which is deficient in individuals with schizophrenia, according to Lewis. He hopes further study will ultimately result in drug therapies that will replace the loss of gamma-aminobutyric acid in schizophrenic patients and reduce hallucinations and other symptoms.
But here's the thing, NAMI's Duckworth said, once you develop symptoms of the disease, there's no going back. So why toss the dice by using marijuana?
"It's quite a chance to take. The uncertainty in the scientific knowledge should not be confused with the risk," Duckworth said.
Schizophrenia, characterized by serious hallucinations and delusions, is estimated to be the fourth most important cause of life-years lost through disability in the world. And it is irreversible, Duckworth said.
If marijuana consumption continues after a diagnosis, drug addiction is coupled with mental illness and is known in the mental health community as dual diagnosis.
Duckworth said the system is ill-prepared to deal with mentally ill people who are also drug abusers. The mental health system doesn't know how (or doesn't want) to treat the drug problem, and the substance abuse health system is ill-equipped to help the mentally ill. Duckworth said he has patients who have been told at drug counseling meetings to go off their psychiatric medications.
"Policymakers are realizing more and more that the [treatment] silos need to be blended," Duckworth said. But funding comes from varying places, and so coordination is difficult. Sadly, it is the patients who suffer more.
"The dually diagnosed have the worst outcomes," Duckworth said. They spend the most time in jail, they are the heaviest users of public health and social welfare services, and they die younger than any other cohort, he said.
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When it comes to marijuana use, his advice to teens and parents is simply: Don't chance it.