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Cannabis, also called marijuana, pot, weed or hash, is a drug that comes from the plant Cannabis sativa (hemp plant).  Cannabis has been grown among cultures throughout history, due to the commercial, medicinal and spiritual value.  Both hemp and psychoactive marijuana were widely used in ancient China and Egypt and has been recorded its use throughout Asia, the Middle East, Southern Africa, America and Europe.

The plant contains more than 400 different chemicals, of which approximately 70 are considered cannabinoids. The major psychoactive component of the cannabis resin and flowers, tetrahydrocannabinol (THC), was first isolated in the 1960´s.

Nowadays, cannabis is, by far, the most commonly used illicit drug across the world.  It is estimated that 87.6 million adults in the European Union have tried cannabis during their lives.   The most recent survey results show most countries to be reporting either stability or increases in last year cannabis use among young adults.

The psychotomimetic effects of cannabis plant are known since thousands of years, but the first systematic work concerning psychotic-like experiences after acute cannabis use came in the 19th century, when the plethora of symptoms resembling those of schizophrenia, including delusions, disorganized speech, and other psychotic symptoms was described.

Schizophrenia is a severe, chronic and disabling mental disorder that affects approximately 1% of the population worldwide. Among psychiatric disorders, schizophrenia is the most disabling one and requires a disproportionate share of mental health services. The symptoms of schizophrenia are classified in three categories: positive symptoms, negative symptoms and cognitive deficits. Positive or psychotic symptoms mainly include delusions (false beliefs), hallucinations (hearing voices) and thought disorder. Negative symptoms comprise social withdrawal, loss of motivation and a reduced capacity to express emotional states. Cognitive impairments include disturbances in working memory or language comprehension.  The onset of the disease occurs in late adolescence and early adulthood.

Over the years, the question of whether cannabis is linked to schizophrenia development has frequently raised. Cannabis extracts can evoke transient psychotic states in healthy subjects and worsen symptoms in schizophrenic patients. The typical acute effects of cannabis resemble some of the symptoms of schizophrenia, in particular the sensory distortions and loss of motivation.

Moreover, the high amount of cannabinoid receptors (CB1), in the central nervous system, as well as the discovery that the psychoactive compound of cannabis, THC, actually binds to this receptor in the brain, seem sufficient reasons to consider cannabis and derivatives an interesting field of study in the context of schizophrenia.

To date, some epidemiological studies suggest that cannabis use increases the risk of developing schizophrenia but, across the population, the effect is relatively small. However, caution is required when interpreting cannabis abuse as a risk factor for developing schizophrenia. The most important evidence to support this view is that there is no major increase in the frequency of schizophrenia in the general population in spite of the fact that there is a significant growth in the number of cannabis abusers in young people. In fact, both the rate of incidence and the prevalence of schizophrenia fluctuate depending on decades, ethnicity, geographical location, economy, life style, migration and several other factors.

On the contrary, cannabis abuse is more frequent in the pre-schizophrenic stage of newly diagnosed schizophrenic patients than in age-matched controls. Moreover, schizophrenia patients have high rates of cannabis use and cannabis use disorders (cannabis abuse and cannabis dependence).

What seems clear is that cannabis consumption especially in early adolescence, a period of increased vulnerability to its effects, increases the risk of developing schizophrenia. Moreover, it is possible that cannabis will precipitate schizophrenia in vulnerable individuals who would otherwise have not developed it.

However, the neuronal and molecular mechanisms underlying psychotic symptoms elicited by cannabis abuse during adolescence is poorly understood. Some hypothesis point to the dopaminergic system, strongly involved in schizophrenia. Cannabinoid receptors CB1, the target of THC in the brain, appear to be important in modulating the activity of the neurotransmitter dopamine. Another hypothesis suggest that the amount of these cannabinoid receptors may be abnormal in those living with schizophrenia. A more recent study has found that frequent use of potent cannabis during adolescence may increase the activity of a type of serotonin receptors in the brain that are the main responsible for hallucinations. 

All these data suggest that there is a link between cannabis and schizophrenia.  Overall, a range of factors appears to play a part in the crossroads between psychiatric disorders and cannabis. These factors are, among others, the age at which marijuana is first used, how much and how often it is consumed, and genetic vulnerabilities.