Cannabis and psychosis: what do we
know and what should we do?
Marco Colizzi and Robin Murray
It is now incontrovertible that heavy use of cannabis increases
the risk of psychosis. There is a dose–response relationship and
high potency preparations and synthetic cannabinoids carry the
greatest risk. It would be wise to await the outcome of the dif-
ferent models of legalisation that are being introduced in North
America, before deciding whether or not to follow suit.
Declaration of interest
Copyright and usage
© The Royal College of Psychiatrists 2018.
Marco Colizzi (pictured) is a psychiatrist and clinical researcher interested in psychosis
and addiction. He is studying the neurocognitive and neurochemical effects of canna-
binoids on the human brain. Robin Murray is a professor of psychiatric research and has
spent much of his life studying the causes of psychosis.
Cannabis is used by approximately 200 million people across the
world. The current trend to popularise its medicinal properties,
real and imagined,
and to decriminalise or legalise it in many coun-
tries, is likely to be followed by greater use.
However, cannabis is
not as safe as was once thought.
Just as longitudinal studies of
tobacco smokers versus non-smokers nailed the link between cigar-
ettes and lung cancer, so similar prospective studies have shown that
heavy cannabis use carries with it an increased risk of psychosis.
Of 13 longitudinal studies in the general population, 10 have
shown that cannabis users are at significant increased risk of subse-
quently developing psychotic symptoms or schizophrenia-like
psychotic illness. The remaining three studies showed a trend in
the same direction; two had a short follow-up period and the
third limited power.
A recent meta-analysis
reported that the
odds ratio for developing psychotic symptoms or a psychotic dis-
order in individuals who had used cannabis over non-users
reached 3.9 (95% CI 2.84–5.34) among the heaviest users.
Of course, association does not prove causation. However, one
by one, alternative explanations have gradually been disproved.
Patients do not start using cannabis to self-medicate their psychotic
or prodromal symptoms or side-effects of drugs, but rather use it for
the same reasons as the rest of the population, principally for its
‘high’. The risk of psychosis remains after controlling for personality
disorder and use of other psychotogenic drugs. Some overlap
between genes carrying susceptibility to schizophrenia and to
drug use has been reported but insufficient to explain more than
a fraction of the relationship.
Of course, the vast majority of people using cannabis do not
develop a psychotic disorder. Not surprisingly, people with a para-
noid or ‘psychosis-prone’personality are especially vulnerable,
alongside people with other risk factors for psychosis such as child-
hood trauma. Starting use in adolescence and having a family
history of psychosis also carry more risk; some evidence points to
variants of genes involved in the dopamine system conveying
Neuroimaging studies have begun to clarify the neural under-
pinning of the psychotic symptoms induced by cannabinoids.
Unlike other drugs of misuse that have their maximum impact on
dopamine in the ventral striatum, long-term cannabis use induces
alterations in dopamine in the associative striatum, which recent
evidence pinpoints as the locus of abnormality underlying positive
The changing nature of recreational cannabinoids
Extract of Cannabis sativa contains over 80 different cannabinoids,
with delta-9-tetrahydrocannabinol (Δ9-THC) and cannabidiol
(CBD) the most important. Δ9-THC is the main psychoactive ingre-
dient, and administering it experimentally to healthy volunteers can
induce transient psychotic symptoms.
CBD appears to counteract
Δ9-THC-induced psychotic symptoms and cognitive impairment,
and may even have antipsychotic properties.
Most traditional forms of cannabis such as marijuana or hashish
used in the 1960s and 1970s contained less than 4% of THC and
often an equal proportion of the ameliorating CBD. However,
these have been displaced by stronger varieties in many countries.
In the UK, the type colloquially known as skunk now dominates the
market; it contains on average 16% THC; CBD is barely detectable
as the plant cannot produce high concentrations of both cannabi-
noids. In Holland forms of Nederwiet containing up to 60% THC
can be lawfully smoked in coffee shops. In Colorado, where canna-
bis has been legalised for recreational use, preparations such as wax
dabs containing up to 90% THC can be bought.
In the last 5 years, synthetic cannabinoids, often termed collect-
ively spice, have hit the market. In contrast to THC which is a partial
agonist at the cannabinoid CB
receptor, most synthetic cannabi-
noids are full agonists and consequently more powerful. Acute
anxiety and paranoid reactions are common but because new mole-
cules are constantly being produced and few have been tested in
animals, incidental toxic reactions can be dangerous.
detecting synthetic cannabinoids in urine has made them especially
popular in prisons.
Need for much more research
Little effort has been put into studying cannabis, compared with that
into alcohol or other recreational drugs. Effects of cannabis use on
other psychiatric disorders need to be further examined, with some
early reports claiming its use is beneficial for disorders such as post-
traumatic stress disorder and depression and others that it increases
The role of cannabis composition needs to be further
examined in such studies, as it is still unclear whether at specific
concentrations CBD might outweigh any harmful effects of Δ9-
The role of cannabis dependence in perpetuating use
The British Journal of Psychiatry (2018)
212, 195–196. doi: 10.1192/bjp.2018.1
deserves more study as does the possible synergistic effects of
tobacco and cannabis, a major issue as the two are commonly
Research into the numerous components of cannabis should be
encouraged since, like research into opiates, it may produce drugs
with important medical uses. Individual cannabinoid components
can then be subject to trials measuring their effectiveness for a
variety of ailments (for example pain, childhood epilepsy) in the
same way any other proposed drug is evaluated. When effective, it
should be introduced for prescription by doctors; several cannabin-
oid drugs already have become available in this manner.
What should we do now?
We psychiatrists need to be more alert to cannabis use by our
patients and take as detailed a history of drug use as we do of
alcohol consumption. Certain characteristics should give rise to par-
Patients who develop psychosis following misuse
of cannabis tend to have an earlier onset of illness and to have better
premorbid cognition and social function than other patients with
schizophrenia. We need to get better at detecting those patients
with established psychosis who continue to use cannabis, especially
high potency varieties, as this is associated with worse outcomes;
continued cannabis use and poor adherence to antipsychotics
tend to go together.
There is no strong evidence that any particular psychological
intervention is particularly helpful in aiding patients to stop using
cannabis. Nor have there been formal studies of which antipsychotic
is best although some evidence suggests that clozapine is less likely
to increase craving.
A curious divide has opened up between North America and the
UK. In the USA, cannabis use in young people has increased since
the mid-1990s as the number regarding use of cannabis as risky has
fallen; use and potency of the drug is greater in those states that have
legalised cannabis for medicinal or recreational purposes.
trast, use has fallen in England; in 1996, 25.8% of people aged 16–
24 admitted to having used cannabis in the previous year; by
2016, that number had declined to 16.4%.
This decline has occurred in spite of the fact that use of cannabis
has, in practice, been decriminalised in most parts of the UK. But,
should it be legalised? This was the policy of the Liberal
Democrats at the last election –although it did not turn out to be
a vote winner. Indeed, it is the case both in the USA and the UK
that much of the pressure to legalise is not coming from the
public but rather from investors keen to make a fast buck. Would
legalisation in the UK lead to an increase in consumption and can-
nabis tourism as evident in Amsterdam and Colorado, or could it be
combined with education so that consumption would actually fall?
The honest answer is that no one knows.
The sensible thing is to watch what happens in the next few
years as different models of legalisation are implemented in differ-
ent states in North America. The USA and Canada have embarked
on a major pharmaceutical experiment with the brains of their
youth, and we should wait and see the outcome of the experiment.
While we wait, we need public education to make the public aware
of the risks associated with heavy cannabis use. It would be a shame
when we are in sight of ridding the country of the scourge of tobacco
use, if it were to be replaced by use of a drug that, although less
harmful to the body, is more toxic to the mind.
Marco Colizzi, MD, National Institute for Health Research (NIHR) Biomedical Research
Centre (BRC), South London and Maudsley NHS Foundation Trust, UK; Department of
Psychosis Studies, Institute of Psychiatry, Psychology and Neuroscience, King’s College
London, UK; Robin Murray, FRS, FRCPsych, National Institute for Health Research (NIHR)
Biomedical Research Centre (BRC), South London and Maudsley NHS Foundation Trust;
Department of Psychosis Studies, Institute of Psychiatry, Psychology and Neuroscience,
King’s College London, UK; Department of Psychiatry, Experimental Biomedicine and
Clinical Neuroscience (BIONEC), University of Palermo, Italy
Correspondence: Marco Colizzi, Department of Psychosis Studies, Institute of
Psychiatry, Psychology and Neuroscience, King’s College London, London SE5 8AF, UK.
First received 12 Sep 2017, accepted 13 Dec 2017
We thank Professor Wayne Hall for his comments on a draft.
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Colizzi & Murray