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Can Marijuana Cause Psychosis?

The question is not likely to go away soon.

Key points

  • The relationship between marijuana use and psychosis is not completely clear.
  • The association between marijuana and psychosis is likely influenced by tobacco use; tobacco use may increase the risk of psychosis.
  • Risk from marijuana depends on the genes, the age of use initiation, and how much is consumed.
Oleksandrum Shutterstock
Source: Oleksandrum Shutterstock

Given that so many states are now making marijuana available for medical and/or recreational use, the question of whether marijuana causes psychosis is not likely to go away soon. I am often asked by my students the following question: “If I smoke marijuana, will I become psychotic?” The answer depends on three factors: the genes of the person asking the question, the age of the person asking the question, and how much THC 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 marijuana. Unfortunately, there are no genetic tests currently available to inform someone with certainty that they are at risk of developing psychosis. Our 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 several high-profile observational studies of a dose-dependent association between cannabis use and risk of psychosis, a causal link between cannabis use and psychotic disorders remains controversial. Why? Observational 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. Marijuana use by these nascent psychiatric patients might be reducing some of their symptoms long before they become part of their diagnosis.

A recent study (Molecular Psychiatry 2018, Vol 23, 1287–1292) investigated 10 different genetic variants, called single-nucleotide polymorphisms (SNPs), in almost 80,000 subjects and found an increased risk of schizophrenia 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 actually 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 may increase the risk of becoming schizophrenic (we do not read as much about this in the popular press).

Taken together, current genetic evidence indicates that the association between marijuana and psychosis may be significantly influenced by tobacco use. This association complicates any direct genetic link between marijuana use and schizophrenia. Thus, marijuana users who also smoke cigarettes face a challenging dilemma: Do they feel genetically lucky?

How old are you? Why age matters

Still in the womb? The prenatal brain is very vulnerable to the presence of 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 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. If you would like to read more about this topic, click here.

How much do you smoke every day, and what are you smoking?

The marijuana available today contains 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. Dose 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 one hundred marijuana cigarettes every day. This is obviously not typical of most users. The problem is that the actual dose consumed is often difficult, or impossible, to determine in epidemiological studies. This is why most epidemiological studies are inconclusive about this topic.

Today, medical science lacks sufficient data to make a definitive claim regarding whether smoking marijuana induces psychosis. If you’re young, consume a lot of high-dose marijuana products every day, and possess a genetic predisposition to psychosis, then yes, you are at risk. 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.

The author serves on the Ohio Governor's Medical Marijuana Advisory Committee.

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