Cannabis and Schizophrenia: Which Users Are at Risk?

Many states are now making marijuana available for recreational use. Unfortunately, the popular literature and the internet are littered with misinformation and bias regarding the question of whether marijuana causes psychosis. Does cannabis cause schizophrenia? Some recent studies indicate that the answer depends on three factors. It depends upon your genes, it depends upon your age, and it depends upon how much THC, the principal active ingredient, is being taken into the body. Let’s consider each condition.

Who Are Your Parents?

Inheriting a genetic predisposition to psychosis makes one vulnerable to the consequences of long-term, high-dose cannabis use. Unfortunately, there are no genetic tests currently available to inform someone with certainty that they are at risk of developing psychosis. Your only option is to consider your siblings: Do any of them seem psychotic to you? If so, then you should seriously reconsider using marijuana.

Despite reports from observational studies of a dose-dependent correlation between cannabis use and the risk of psychosis, a causal link between cannabis use and psychotic disorders remains unproven. Why? Correlational results are frequently hindered by the possibility that another risk factor associated with cannabis use might be more closely associated with developing psychosis. Alternatively, people who are affected by the early symptoms of schizophrenia might be turning to marijuana to self-medicate themselves. Cannabis use by these nascent psychiatric patients might be reducing some of their symptoms long before they become part of their diagnosis.

A study recently published in the journal Molecular Psychiatry (Vol 23, 1287–1292) identified 10 different genetic variants, called single-nucleotide polymorphisms (SNPs), in almost 80,000 subjects. The risk of schizophrenia was increased if these variants were present in the marijuana users. A word of caution when considering your risk: Simply having an SNP that places you at risk is not sufficient to induce psychosis, should you decide to use marijuana. Reality is much more complicated than one gene = one disease.

The connection between marijuana and schizophrenia is also muddied by the fact that cannabis use is strongly associated with tobacco consumption. Conversely, tobacco use is strongly correlated with marijuana. Indeed, tobacco may act synergistically with marijuana to create addiction. Making matters worse, tobacco use increases the risk of becoming schizophrenic (we do not read as much about this link in the popular press).

Taken together, current genetic evidence indicates that the association between marijuana and psychosis is significantly influenced by tobacco use. This association essentially undermines any direct genetic link between marijuana use and schizophrenia, for example, if a person smokes, then it becomes impossible to establish a causal connection between cannabis and psychosis. Thus, marijuana users who also smoke cigarettes face a challenging dilemma: Do they feel genetically lucky?

How Old Are You?

The prenatal brain is very vulnerable to the presence of cannabis. Pregnant women should never use cannabis.

You’re an adolescent? The available evidence indicates that the adolescent brain is still vulnerable to exogenous cannabinoids. Essentially, cannabis alters the normal trajectory of brain maturation, although the consequences are less severe than those seen following prenatal exposure. The combined evidence from numerous human and animal studies suggests that exposure to cannabis during adolescence has the potential to produce subtle, but lasting, alterations in brain function and behavior. The severity differs according to the duration of use, age at first use, and underlying genetic vulnerabilities that are more likely to appear during adolescence, such as various psychopathologies.

If you’re beyond middle age, the use of whole-plant medical cannabis does not have a negative impact on cognition in older patients. Why are the effects of cannabis age-dependent? The answer to this question remains unknown but there is one fascinating potential mechanism that involves what is happening to the stem cells in your brain. Stem cells undergo neurogenesis and give birth to new neurons every day. Neurogenesis is obviously critical for the developing brain from prenatal to adolescence. Neurogenesis begins to decline at around middle age and is nearly absent by the time you are ready to retire.

Numerous PET imaging studies of humans suggest that the decline in neurogenesis is due to increased levels of brain inflammation that occurs naturally with advancing age. The decline in neurogenesis likely underlies age-related impairments in learning and memory and an increased incidence of depression. Research in my laboratory has demonstrated that a daily low dose of cannabis can significantly reduce brain inflammation. My lab’s research also demonstrated that stimulating cannabis receptors on surviving stem cells can restore neurogenesis.

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How Much Do You Smoke—and What Are You Smoking?

The cannabis products available today contain far higher concentrations of THC than ever before. Most of the available epidemiological data become moot when we try to compare data collected during the past few decades. Dosage matters.

How often someone uses marijuana each day also matters. Some of the original studies on the connection between marijuana and psychosis found that heavy users were more likely to develop symptoms of psychosis. Some of these “heavy users” reported smoking over 100 marijuana cigarettes every day. This is obviously not typical of most users. The problem is that the actual dose consumed is often difficult to determine in epidemiological studies.

Today, medical science lacks sufficient data to make a definitive claim regarding whether smoking cannabis induces psychosis. If you’re young, consume a lot of high-dose cannabis products every day, and possess a genetic predisposition to psychosis, then yes, you are at risk. Numerous studies during the past decade have demonstrated that people who use cannabis and who progress to schizophrenia have a significantly higher familial risk for psychosis as compared with people who use cannabis but do not progress to schizophrenia.

Thus, if you’re middle age, occasionally consume marijuana, and carry no known genetic predispositions, then no, you are not at risk. That last condition, your genetics, is the wild card in your genetic deck since science still lacks the ability to define the genetics of psychosis. In spite of the lack of certainty, it is very likely that many people will go ahead and spin the wheel of genetic roulette.

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