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Does Marijuana Use Cause Schizophrenia?

As the drug becomes more popular, concerns have been raised that its use can lead to psychotic disorders. Here’s what scientists know for sure, and what they don’t.

    Jan. 17, 2019

Nearly a century after the film “Reefer Madness” alarmed the nation, some policymakers and doctors are again becoming concerned about the dangers of marijuana, although the reefers are long gone.

Experts now distinguish between the “new cannabis” — legal, highly potent, available in tabs, edibles and vapes — and the old version, a far milder weed passed around in joints. Levels of T.H.C., the chemical that produces marijuana’s high, have been rising for at least three decades, and it’s now possible in some states to buy vape cartridges containing little but the active ingredient.

The concern is focused largely on the link between heavy usage and psychosis in young people. Doctors first suspected a link some 70 years ago, and the evidence has only accumulated since then. In a forthcoming book, “Tell Your Children,” Alex Berenson, a former Times reporter, argues that legalization is putting a generation at higher risk of schizophrenia and other psychotic syndromes. Critics, including leading researchers, have called the argument overblown, and unfaithful to the science.

Can cannabis use cause psychosis?

Yes, but so can overuse of caffeine, nicotine, alcohol, stimulants and hallucinogens. Psychosis is a symptom: a temporary disorientation that resembles a waking dream, with odd, imagined sights and sounds, often accompanied by paranoia or an ominous sensation. The vast majority of people who have this kind of psychotic experience do not go on to develop a persistent condition such as schizophrenia, which is characterized by episodes of psychosis that recur for years, as well as cognitive problems and social withdrawal.

Can heavy use cause schizophrenia or other syndromes?

That is the big question, and so far the evidence is not strong enough to answer one way or the other. Even top scientists who specialize in marijuana research are divided, drawing opposite conclusions from the same data.

“I’ve been doing this research for 25 years, and it’s polarizing even among academics,” said Margaret Haney, a professor of neurobiology at Columbia University Medical Center. “This is what the marijuana field is like.”

The debate centers on the distinction between correlation and causation. People with psychotic problems often use cannabis regularly; this is a solid correlation, backed by numerous studies. But it is unclear which came first, the cannabis habit or the psychoses. Children who later develop schizophrenia often seem to retreat into their own world, stalked periodically by bizarre fears and fantasies well outside the range of usual childhood imagination, and well before they are exposed to cannabis. Those who go on to become regular marijuana users often use other substances as well, including alcohol and cigarettes, making it more difficult for researchers to untangle causation.

Consider cigarettes, the least mind-altering of these substances. In a 2015 study, a team led by Dr. Kenneth S. Kendler of Virginia Commonwealth University analyzed medical data on nearly two million people in Sweden. The data followed the individuals over time, from young adulthood, when most schizophrenia diagnoses occur, to middle age. Smoking was a predictor for later development of the disorder, and in what doctors call a dose-response relationship: the more a person smoked, the higher the risk.

Yet nicotine attracts nowhere near the concern that cannabis does, in part because the two drugs are so different in their everyday effects: mildly stimulated versus stoned. Indeed, some scientists have studied nicotine as a partial treatment for schizophrenia, to blunt the disorders effects on thinking and memory.

Is it biologically plausible that cannabis could cause a psychotic disorder?

Yes. Brain scientists know very little about the underlying biology of psychotic conditions, other than that hundreds of common gene variants are likely involved. Schizophrenia, for instance, is not a uniform disorder but an umbrella term for an array of unexplained problems involving recurrent psychosis, and other common symptoms.

Even so, there is circumstantial evidence for a biological mechanism. Psychotic disorders tend to emerge in late adolescence or early adulthood, during or after a period of rapid brain development. In the teenage years, the brain strips away unneeded or redundant connections between brain cells, in a process called synaptic pruning. This editing is concentrated in the prefrontal cortex, the region behind the forehead where thinking and planning occur — and the region that is perturbed in psychotic conditions.

The region is rich with so-called CB1 receptors, which are involved in the pruning, and are engaged by cannabis use. And alterations to the pruning process may well increase schizophrenia risk, according to recent research at the Broad Institute of M.I.T. and Harvard. In a 2016 analysis, scientists there found that people with the disorder often have a gene variant that appears to accelerate the pruning process.

What does this mean for me?

Experts may debate whether cannabis use can lead to psychotic disorders, but they mostly agree on how to minimize one’s risk.

Psychotic conditions tend to run in families, which suggests there is an inherited genetic vulnerability. Indeed, according to some studies, people prone to or at heightened risk of psychosis seem to experience the effects of cannabis differently than peers without such a history. The users experience a more vivid high, but they also are more likely to experience psychosis-like effects such as paranoia.

The evidence so far indicates that one’s familial risk for psychotic disorders outweighs any added effect of cannabis use. In a 2014 study, a team led by Ashley C. Proal and Dr. Lynn E. DeLisi of Harvard Medical School recruited cannabis users with and without a family history of schizophrenia, as well as non-users with and without such a history. The researchers made sure the cannabis users did not use other drugs in addition, a factor that muddied earlier studies. The result: there was a heightened schizophrenia risk among people with a family history, regardless of cannabis use.

“My study clearly shows that cannabis does not cause schizophrenia by itself,” said Dr. DeLisi. “Rather, a genetic predisposition is necessary. It is highly likely, based on the results of this study and others, that cannabis use during adolescence through to age 25, when the brain is maturing and at its peak of growth in a genetically vulnerable individual, can initiate the onset of schizophrenia.”

Because marijuana has been illegal for so long, research that could settle the question has been sorely lacking, although that has begun to change. The National Institutes of Health have launched a $300 million project that will track thousands of children from the age of 9 or 10 through adolescence, and might help clarify causation.

For the near future, expert opinions likely will be mixed. “Usually it is the research types who are doing ‘the sky is falling’ bit, but here it is switched,” said Dr. Jay Geidd, a professor of psychiatry at the University of California, San Diego. “The researchers are wary of overselling the dangers, as was clearly done in the past. However, clinicians overwhelmingly endorse seeing many more adolescents with ‘paranoia’” of some kind.

In short: Regularly using the new, high-potency cannabis may indeed be a risk for young people who are related to someone with a psychotic condition. On that warning, at least, most experts seem to agree.

As the drug becomes more popular, concerns have been raised that its use can lead to psychotic disorders. Here’s what scientists know for sure, and what they don’t.

Cannabis

Terminology

Cannabis is a generic term used to denote the several psychoactive preparations of the plant Cannabis sativa. The major psychoactive consituent in cannabis is ∆-9 tetrahydrocannabinol (THC). Compounds which are structurally similar to THC are referred to as cannabinoids. In addition, a number of recently identified compounds that differ structurally from cannabinoids nevertheless share many of their pharmacological properties. The Mexican term ‘marijuana’ is frequently used in referring to cannabis leaves or other crude plant material in many countries. The unpollinated female plants are called hashish. Cannabis oil (hashish oil) is a concentrate of cannabinoids obtained by solvent extraction of the crude plant material or of the resin.

Epidemiology

Cannabis is by far the most widely cultivated, trafficked and abused illicit drug. Half of all drug seizures worldwide are cannabis seizures. The geographical spread of those seizures is also global, covering practically every country of the world. About 147 million people, 2.5% of the world population, consume cannabis (annual prevalence) compared with 0.2% consuming cocaine and 0.2% consuming opiates. In the present decade, cannabis abuse has grown more rapidly than cocaine and opiate abuse. The most rapid growth in cannabis abuse since the 1960s has been in developed countries in North America, Western Europe and Australia. Cannabis has become more closely linked to youth culture and the age of initiation is usually lower than for other drugs. An analysis of cannabis markets shows that low prices coincide with high levels of abuse, and vice versa. Cannabis appears to be price-inelastic in the short term, but fairly elastic over the longer term. Though the number of cannabis consumers is greater than opiate and cocaine consumers, the lower prices of cannabis mean that, in economic terms, the cannabis market is much smaller than the opiate or cocaine market.

Acute health effects of cannabis use

The acute effects of cannabis use has been recognized for many years, and recent studies have confirmed and extended earlier findings. These may be summarized as follows:

  • Cannabis impairs cognitive development (capabilities of learning), including associative processes; free recall of previously learned items is often impaired when cannabi is used both during learning and recall periods;
  • Cannabis impairs psychomotor performance in a wide variety of tasks, such as motor coordination, divided attention, and operative tasks of many types; human performance on complex machinery can be impaired for as long as 24 hours after smoking as little as 20 mg of THC in cannabis; there is an increased risk of motor vehicle accidents among persons who drive when intoxicated by cannabis.
Chronic health effects of cannabis use
  • selective impairment of cognitive functioning which include the organization and integration of complex information involving various mechanisms of attention and memory processes;
  • prolonged use may lead to greater impairment, which may not recover with cessation of use, and which could affect daily life functions;
  • development of a cannabis dependence syndrome characterized by a loss of control over cannabis use is likely in chronic users;
  • cannabis use can exacerbate schizophrenia in affected individuals;
  • epithetial injury of the trachea and major bronchi is caused by long-term cannabis smoking;
  • airway injury, lung inflammation, and impaired pulmonary defence against infection from persistent cannabis consumption over prolonged periods;
  • heavy cannabis consumption is associated with a higher prevalence of symptoms of chronic bronchitis and a higher incidence of acute bronchitis than in the non-smoking cohort;
  • cannabis used during pregnancy is associated with impairment in fetal development leading to a reduction in birth weight;
  • cannabis use during pregnancy may lead to postnatal risk of rare forms of cancer although more research is needed in this area.

The health consequences of cannabis use in developing countries are largely unknown beacuse of limited and non-systematic research, but there is no reason a priori to expect that biological effects on individuals in these populations would be substantially different to what has been observed in developed countries. However, other consequences might be different given the cultural and social differences between countries.

Therapeutic uses of cannabinoids

Several studies have demonstrated the therapeutic effects of cannabinoids for nausea and vomiting in the advanced stages of illnesses such as cancer and AIDS. Dronabinol (tetrahydrocannabinol) has been available by prescription for more than a decade in the USA. Other therapeutic uses of cannabinoids are being demonstrated by controlled studies, including treatment of asthma and glaucoma, as an antidepressant, appetite stimulant, anticonvulsant and anti-spasmodic, research in this area should continue. For example, more basic research on the central and peripheral mechanisms of the effects of cannabinoids on gastrointestinal function may improve the ability to alleviate nausea and emesis. More research is needed on the basic neuropharmacology of THC and other cannabinoids so that better therapeutic agents can be found.

Cannabis Terminology Cannabis is a generic term used to denote the several psychoactive preparations of the plant Cannabis sativa . The major psychoactive consituent in cannabis is ∆-9