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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 different models of legalisation that are being introduced in North America, before deciding whether or not to follow suit. Declaration of interest None.
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 doseresponse 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 2.845.34) 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-pronepersonality 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
psychotic symptoms.
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.
Difficulty in
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
their risk.
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, 195196. 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
smoked together.
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-
ticular suspicion.
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.
In con-
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, Kings 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,
Kings 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, Kings 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
... When contemplating the liberalisation of cannabis policy in North America, Colizzi and Murray (2018) urged caution regarding legislative change and advised that it seems best to observe how harms change there before embarking down the same path. They stated that "the USA and Canada have embarked on a major pharmaceutical experiment with the brains of their youth." ...
... They stated that "the USA and Canada have embarked on a major pharmaceutical experiment with the brains of their youth." The caution urged by Colizzi and Murray (2018) and the nuanced conclusions from Babor et al. (2018) contrasts with the confidence indicated by Hughes et al. (2018) that penalties seem relatively unimportant. Before dismissing any impact of penalties upon use rates, we decided to revisit the penalty change events examined by Hughes et al. (2018), but to focus upon adolescents. ...
... Our analysis focuses on past month use among 16-year-olds, indicating current use. This group constitute an extremely important group from a population health perspective, based upon the known hazards of adolescent cannabis use (Colizzi & Murray, 2018;Murray & Hall, 2020;Volkow et al. 2014;Wilson et al. 2019). There is emerging evidence that even minimal cannabis use around this vulnerable stage of brain development may result in measurable alterations in brain morphology (Orr et al. 2019;Albaugh et al. 2021). ...
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Objective: Penalties are used in an effort to curtail drug use by citizens in most societies. There are growing calls for a reduction or elimination of such penalties. Deterrence theory suggests that use should increase if penalties reduce and vice versa. We sought to examine the relationship between changes to penalties for drug possession and adolescent cannabis use. Method: Ten instances of penalty change occurred in Europe between 2000 and 2014, seven of which involved penalty reduction and three involved penalty increase. We conducted a secondary analysis of a series of cross-sectional surveys of 15-16-year-old school children, the ESPAD surveys, which are conducted every four years. We focused on past month cannabis use. We anticipated that an eight-year time span before and after each penalty change would yield two data points either side of the change. A simple trend line was fitted to the data points for each country. Results: In eight cases, the trend slope in past month cannabis use was in the direction predicted by deterrence theory, the two exceptions being the UK policy changes. Using the principals of binomial distributions, the likelihood of this happening by chance is 56/1024 = 0.05. The median change in the baseline prevalence rate was by 21%. Conclusions: The science seems far from settled on this issue. There remains a distinct possibility that reducing penalties could contribute to small increases in adolescent cannabis use and consequently increase cannabis-related harms. This possibility should be considered in any political decision-making influencing drug policy changes.
... However, in other countries, stronger varieties have been used, for example, a variety that is unable to produce high concentrations of both cannabinoids, the so-called Skunk, contains an average of 16% THC and a trace amount of CBD. Common in the Netherlands, Nederwiet contains up to 60% THC and is legally permitted for recreational use or fabrication of cannabis wax, which contains around 90% THC [4]. ...
... In recent years, synthetic cannabinoids, which are very popular among "designer drug" users, have been introduced to the market. Unlike THC, which is a partial agonist of the cannabinoid type 1 receptor (CB1R), most synthetic cannabinoids hold stronger psychomimetic properties due to being full agonists of CB1R [4]. ...
... Reports on the influence of cannabis with respect to the occurrence of a schizophrenic episode, secondary to cannabis use, have emerged over 30 years ago [27]. Further reports and studies appear regularly [4]. Cannabinoid intoxication may lead to the development of temporary psychosis-like symptoms. ...
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The rising popularity of medical marijuana and its potential therapeutic uses has resulted in passionate discussions that have mainly focused on its possible benefits and applications. Although the concept itself seems promising, the multitude of presented information has noticeable ramifications-terminological chaos being one. This work aimed to synthesize and critically analyze scientific evidence on the therapeutic uses of cannabinoids in the field of psychiatry. Emphasis was placed on the anxiolytic effects of cannabis constituents and their effects on post-traumatic stress disorder, anxiety disorders, schizophrenia spectrum, and other psychotic disorders. The review was carried out from an addictological perspective. A database search of interchangeably combined keywords resulted in the identification of subject-related records. The data were then analyzed in terms of relevance, contents, methodologies, and cited papers. The results were clear in supporting one common conclusion: while most findings provide support for beneficial applications of medical marijuana in psychiatry, no certain conclusions can be drawn until larger-scaled, more methodo-logically rigorous, and (preferably) controlled randomized trials verify these discoveries.
... skunk) is associated with mental health problems and physiological manifestations, including psychosis, dizziness, euphoria, drowsiness, dry mouth, confusion, somnolence and fatigue. 23,41,53 It is clear that more research is required with human participants (rather than animals) to examine the safety of different strains and components, dosage and routes of administration. 41 Advocates of medicinal cannabis suggest that it could reduce the rates of opioid dependence and deaths from overdose if patients switch from opioid-based pain relief to cannabis, as the risk of dependence is much lower and there are no reports of death from cannabis overdose. ...
... This includes impaired shortterm memory and motor coordination, altered judgement, paranoia, dependence disorder, psychosis, injuries, motor vehicle collisions and suicide. 53,56 Indeed, maternal suicide remains the leading cause of direct deaths occurring within a year after the end of pregnancy; 57 8% of the women who died during or up to a year after pregnancy in the UK between 2016 and 2018 were at severe and multiple disadvantages, also known as the 'toxic trio' of mental health diagnosis, substance misuse and domestic abuse. 57 Cannabis use in pregnancy has also been associated with still-birth, preterm labour, low birth weight, 'small for gestational age' and two-fold increased risk of admission to a neonatal intensive care unit. ...
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Aims and method As drug policies pertaining to cannabis use become more liberalised, the prevalence of cannabis use in pregnancy could increase. However, there is limited guidance available for clinicians. This paper presents a narrative review of literature published in the past 16 years (2006–2021) to (a) address the impact of legalisation and decriminalisation on the risks, ethics and support of women who use cannabis during pregnancy and (b) develop guidance for clinicians. Results Both national and international trends suggest increased use of cannabis over the past decade, while the risks of cannabis use for recreational or medicinal purposes in pregnancy remain unmitigated. Clinical implications This review confirmed that the recommendation of cannabinoid-based products for pregnant and breast-feeding women is currently premature. More research is needed to address safety concerns. We discussed navigating ethical concerns and suggest targeted management strategies for clinicians treating pregnant women who choose to use cannabis.
... Although only a small proportion of the estimated 192 million cannabis users will continue to use regularly (United Nations Office on Drugs and Crime 2020), a broad range of negative conditions can be described following prolonged and heavy cannabis use (Hall et al. 2019). Frequent and long-term exposure to cannabis has been associated with impaired cognition (Broyd et al. 2016b;Figueiredo et al. 2020;Solowij and Michie 2007), altered brain morphology (Lorenzetti et al. , 2016b and function (Bhattacharyya et al. 2009;Bloomfield et al. 2019;Martin-Santos et al. 2012), poorer psychosocial functioning (Ashton 2019;Hall and Degenhardt 2014), reduced quality of life (Goldenberg et al. 2017) and severe psychiatric illness including psychosis (Colizzi and Murray 2018;Di Forti et al. 2015;Moore et al. 2007;Murray et al. 2017). These cognitive functions are significantly affected during and beyond the period of acute cannabis intoxication (Broyd et al. 2016b). ...
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RationaleMismatch negativity (MMN) is a candidate endophenotype for schizophrenia subserved by N-methyl-D-aspartate receptor (NMDAR) function and there is increasing evidence that prolonged cannabis use adversely affects MMN generation. Few human studies have investigated the acute effects of cannabinoids on brain-based biomarkers of NMDAR function and synaptic plasticity.Objectives The current study investigated the acute effects of Δ9-tetrahydrocannabinol (THC) and cannabidiol (CBD) alone and in combination on the mismatch negativity (MMN).Methods In a randomised, double-blind, crossover placebo-controlled study, 18 frequent and 18 less-frequent cannabis users underwent 5 randomised drug sessions administered via vaporiser: (1) placebo; (2) THC 8 mg; (3) CBD 400 mg; (4) THC 8 mg + CBD 4 mg [THC + CBDlow]; (5) THC 12 mg + CBD 400 mg [THC + CBDhigh]. Participants completed a multifeature MMN auditory oddball paradigm with duration, frequency and intensity deviants (6% each).ResultsRelative to placebo, both THC and CBD were observed to increase duration and intensity MMN amplitude in less-frequent users, and THC also increased frequency MMN in this group. The addition of low-dose CBD added to THC attenuated the effect of THC on duration and intensity MMN amplitude in less-frequent users. The same pattern of effects was observed following high-dose CBD added to THC on duration and frequency MMN in frequent users.Conclusions The pattern of effects following CBD combined with THC on MMN may be subserved by different underlying neurobiological interactions within the endocannabinoid system that vary as a function of prior cannabis exposure. These results highlight the complex interplay between the acute effects of exogenous cannabinoids and NMDAR function. Further research is needed to determine how this process normalises after the acute effects dissipate and following repeated acute exposure.
... También daña el rendimiento psicomotor en una amplia variedad de tareas (coordinación motora y tareas operativas de muchos tipos); el rendimiento humano en el uso de maquinaria compleja se ve afectado hasta 24 horas después de fumar 20 mg de Δ9-THC; asimismo, existe un mayor riesgo de accidentes de coche entre las personas que conducen intoxicados por el CC, posiblemente relacionados con la calidad y su potencia. [24][25][26] ...
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The psychoactive properties of cannabis have been known forever. Since 1987, several prospective studies have suggested an increased risk of psychosis among cannabis users, with alternative explanations failing to account for such an effect. A cause-effect relationship has thus been implied. Further evidence has indicated that there is a dose-response relationship, and high-potency cannabis varieties confer the greatest risk of psychosis. As cannabis use has become more common over the last decades, one would expect a related increase in the number of schizophrenia cases. However, evidence in this regard remains equivocal for several reasons, including relying on databases that are not primarily designed to address such question and the issue that solid information regarding the incidence of schizophrenia is a relatively recent acquisition. Recent years have seen the development of online web publications, such as Google Trends and "Our World in Data", where data are explorable and interactable for tracking and comparing trends over specific periods and world regions. By using such databases, we believe that the question whether changes in cannabis use are associated with changes in schizophrenia rates can be answered, at least partly. Therefore, we tested these tools by evaluating trends in cannabis use and both cases and prevalence of schizophrenia in the United Kingdom, one of the countries where the incident rates for psychotic disorder have been suggested to be particularly increased by cannabis consumption. Crossing data from these tools revealed that interest in cannabis has been growing at the country level for over 10 years, with a parallel overlapping raise in psychosis cases and prevalence. Following up on this example, let us think of how many public health opportunities these public resources may offer. The question now is whether public health interventions for the benefit of the general population will follow suit.
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Objective: To compare the differential effectiveness of Cognitive Behavior Therapy (CBT) and Psycho-Education Therapy (PET) on minimizing Khat chewing behavior and associated mental health problems. Methodology: A randomized controlled trial was conducted on 40 regular Khat consumer men selected through consecutive sampling technique. The participants were randomly allocated to either CBT group or Psycho-education group by lottery method. The CBT group received seven sessions of manualized CBT for substance abuse and the psycho-education group received three sessions on addiction-related educations. Both therapies were carried out in group format. Depression and Anxiety Stress Scale (DASS) was used for assessing both groups before and after the administration of the therapies. Chi square and t-test were used to calculate the difference between the groups. Results: The age of participants of CBT and PET groups ranged from 18-25 years (mean 22.15 ±2.32 and 22.30 ±2.20 years respectively). A significant decrease was found in the Khat chewing behavior in CBT group as compared to the psycho-education group. Similarly other mental health problems in the CBT group were significantly reduced. Conclusion: CBT was effective in decreasing Khat chewing behavior and associated mental health problems.
Sleep disturbances are often cited as a primary reason for medicinal cannabis use and there is increasing clinical interest in the therapeutic potential of cannabinoids in treating sleep disorders. Burgeoning evidence suggests a role of the endocannabinoid system in regulating the circadian sleep-wake cycle, highlighting a potential avenue for developing novel therapeutics. Despite widespread use of cannabis products as sleep aids globally, robustly designed studies verifying efficacy in sleep-disordered populations are limited. While some study outcomes have suggested cannabinoid utility in insomnia disorder and sleep apnea, most studies to date are limited by small sample sizes, lack of rigorously controlled study designs, and high risk of bias. This critical review summarises the current evidence for the use of cannabinoids as a treatment for sleep disorders, and provides an overview of endocannabinoid modulation of sleep-wake cycles, and the sleep-modulating effects of plant-derived cannabinoids such as Δ⁹-tetrahydrocannabinol (THC), cannabidiol (CBD), and cannabinol (CBN). The review also discusses practical considerations for clinicians regarding cannabinoid formulations, routes of administration, respiratory concerns, dosing, potential side effects, drug interactions, and effects relevant to driving, tolerance, and withdrawal. While current interest in, and uptake of, medicinal cannabis use for sleep disorders may have surpassed the evidence-base, there is a strong rationale for continued investigation into the therapeutic potential of cannabinoids.
Background Research has yielded evidence for genetic and environmental factors influencing the risk of schizophrenia. Numerous environmental factors have been identified; however, the individual effects are small. The additive and interactive effects of multiple risk factors are not well elucidated. Twin pairs discordant for schizophrenia offer a unique opportunity to identify factors that differ between patients and unaffected co-twins, who are perfectly matched for age, sex and genetic background. Methods Register data were combined with clinical data for 216 twins including monozygotic (MZ) and dizygotic (DZ) proband pairs (one or both twins having a schizophrenia spectrum diagnosis) and MZ/DZ healthy control (HC) pairs. Logistic regression models were applied to predict (1) illness vulnerability (being a proband v. HC pair) and (2) illness status (being the patient v. unaffected co-twin). Risk factors included: A polygenic risk score (PRS) for schizophrenia, birth complications, birth weight, Apgar scores, paternal age, maternal smoking, season of birth, parental socioeconomic status, urbanicity, childhood trauma, estimated premorbid intelligence and cannabis. Results The PRS [odds ratio (OR) 1.6 (1.1–2.3)], childhood trauma [OR 4.5 (2.3–8.8)], and regular cannabis use [OR 8.3 (2.1–32.7)] independently predicted illness vulnerability as did an interaction between childhood trauma and cannabis use [OR 0.17 (0.03–0.9)]. Only regular cannabis use predicted having a schizophrenia spectrum diagnosis between patients and unaffected co-twins [OR 3.3 (1.1–10.4)]. Conclusion The findings suggest that several risk factors contribute to increasing schizophrenia spectrum vulnerability. Moreover, cannabis, a potentially completely avoidable environmental risk factor, seems to play a substantial role in schizophrenia pathology.
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Background Although cannabis use after a fi rst episode of psychosis has been associated with relapse, little is known about the determinants of this most preventable risk factor for relapse of psychosis. Here we aimed to study whether the eff ects on outcome vary depending on the type of cannabis consumed and usage pattern. Methods In this observational study, we prospectively recruited and followed up patients aged 18–65 years who presented with their first episode of psychosis to psychiatric services in south London, London, UK. Relapse of psychosis within 2 years after onset of psychosis was defined as risk of subsequent admission to hospital. We classified patients into different patterns of cannabis use based on continuity of use after onset of psychosis, potency of cannabis consumed, and frequency of use after the onset of their illness. We used multiple regression analyses (logistic or binominal) to compare the different cannabis use groups and propensity score analysis to validate the results. Findings Between April 12, 2002, and July 26, 2013, 256 patients presented with a first episode of psychosis. We did follow-up assessments for these patients until September, 2015. Simple analyses showed that former regular users of cannabis who stopped after the onset of psychosis had the most favourable illness course with regards to relapse. In multiple analysis, continued high-frequency users (ie, daily use in all 24 months) of high-potency (skunk-like) cannabis had the worst outcome, indexed as an increased risk for a subsequent relapse (odds ratio [OR] 3·28; 95% CI 1·22–9·18), more relapses (incidence rate ratio 1·77; 95% CI 0·96–3·25), fewer months until a relapse occurred (b –0·22; 95% CI –0·40 to –0·04), and more intense psychiatric care (OR 3·16; 95% CI 1·26–8·09) after the onset of psychosis. Interpretation Adverse effects associated with continued use of cannabis after the onset of a first episode of psychosis depend on the specific patterns of use. Possible interventions could focus on persuading cannabis-using patients with psychosis to reduce use or shift to less potent forms of cannabis. Funding National Institute for Health Research (NIHR).
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Background This study aimed to evaluate synthetic cannabinoid (SC)-induced psychosis in terms of patient profile and clinical characteristics with reference to concurrently hospitalized schizophrenic patients. Methods A total of 81 male patients diagnosed with psychotic disorder induced by the use of SCs (n=50; mean (standard deviation [SD]) age: 25.9 (5.5) years) or with schizophrenia (n=31, mean (SD) age: 42.9 (11.6) years) based on the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition, diagnosis criteria who were concurrently hospitalized at Erenköy Mental and Neurological Diseases Training and Research Hospital were included in this cross-sectional study. Data on sociodemographic characteristics, Brief Psychiatric Rating Scale (BPRS), Positive and Negative Syndrome Scale (PANSS), Frontal Assessment Battery (FAB), Hamilton Rating Scale for Depression (HRSD), and Hamilton Anxiety Rating Scale (HAM-A) were recorded in all the patients. Results Mean (SD) age at disease onset in SC-induced psychosis patients was 22.3 (5.6) years; 26.0% had suicidal ideation and 58.4% were hospitalized involuntarily. Marijuana was the most common first used substance (72.0%), and solitary use of SC was noted in 38.0% of patients. SC-induced psychosis patients had similar PANSS positive, BPRS, HRSD, and FAB scores and significantly lower PANSS negative scores (18.0 [6.5] vs 22.3 [6.0], P=0.004) than patients with schizophrenia, while they had similar HAM-A scores (17.8 [10.3] vs 21.6 [5.5], P=0.085) as young schizophrenics. Age at onset for SC (r=0.364, P=0.05) or substance (r=0.395, P=0.01) use was correlated positively with total FAB scores. Conclusion In conclusion, our findings revealed SC-induced psychosis to influence young individuals and be associated with remarkable rates of suicidal ideation and involuntary hospitalization as well as similar clinical picture with schizophrenia in terms of PANSS positive, BPRS, HRSD, HAM-A, and FAB scores. Younger age at onset was associated with poorer frontal lobe functions overall, regardless of the type of substance, and with poorer inhibitory control and programming performance in case of SC use.
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Cannabis use has been reported to induce long-lasting psychotic disorders and a dose-response relationship has been observed. We performed a systematic review of studies that investigate the association between the degree of cannabis consumption and psychosis and a meta-analysis to quantify the magnitude of effect. Published studies were identified through search of electronic databases, supplemented by manual searches of bibliographies. Studies were considered if they provided data on cannabis consumption prior to the onset of psychosis using a dose criterion (frequency/amount used) and reported psychosis-related outcomes. We performed random effects meta-analysis of individual data points generated with a simulation method from the summary data of the original studies. From 571 references, 18 studies fulfilled inclusion criteria for the systematic review and 10 were inserted in the meta-analysis, enrolling a total of 66 816 individuals. Higher levels of cannabis use were associated with increased risk for psychosis in all the included studies. A logistic regression model gave an OR of 3.90 (95% CI 2.84 to 5.34) for the risk of schizophrenia and other psychosis-related outcomes among the heaviest cannabis users compared to the nonusers. Current evidence shows that high levels of cannabis use increase the risk of psychotic outcomes and confirms a dose-response relationship between the level of use and the risk for psychosis. Although a causal link cannot be unequivocally established, there is sufficient evidence to justify harm reduction prevention programs.
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Genetic factors may explain the differences in individual sensitivity to the psychosis-inducing effects of cannabis.1,2 In view of the converging data from candidate gene and genome-wide association studies that the D2-AKT1 signaling pathway is relevant for the pathophysiology and outcome of schizophrenia,3 and on the basis of previous association between cannabis-related psychosis and both DRD2 (rs1076560)1 and AKT1 (rs2494732),2 we hypothesized that these polymorphisms interact in increasing the risk of psychosis in cannabis users. We expected the genetic pathway × cannabis use interaction model to better predict the individual’s odds of psychotic disorder than the single candidate gene×cannabis use interaction model.
Prospective epidemiological studies have consistently demonstrated that cannabis use is associated with an increased subsequent risk of both psychotic symptoms and schizophrenia-like psychoses. Early onset of use, daily use of high-potency cannabis, and synthetic cannabinoids carry the greatest risk. The risk-increasing effects are not explained by shared genetic predisposition between schizophrenia and cannabis use. Experimental studies in healthy humans show that cannabis and its active ingredient, delta-9-tetrahydrocannabinol (THC), can produce transient, dose-dependent, psychotic symptoms, as well as an array of psychosis-relevant behavioral, cognitive and psychophysiological effects; the psychotogenic effects can be ameliorated by cannabidiol (CBD). Findings from structural imaging studies in cannabis users have been inconsistent but functional MRI studies have linked the psychotomimetic and cognitive effects of THC to activation in brain regions implicated in psychosis. Human PET studies have shown that acute administration of THC weakly releases dopamine in the striatum but that chronic users are characterised by low striatal dopamine. We are beginning to understand how cannabis use impacts on the endocannabinoid system but there is much still to learn about the biological mechanisms underlying how cannabis increases risk of psychosis. This article is part of the Special Issue entitled “A New Dawn in Cannabinoid Neurobiology”.
Importance Over the last 25 years, illicit cannabis use and cannabis use disorders have increased among US adults, and 28 states have passed medical marijuana laws (MML). Little is known about MML and adult illicit cannabis use or cannabis use disorders considered over time. Objective To present national data on state MML and degree of change in the prevalence of cannabis use and disorders. Design, Participants, and Setting Differences in the degree of change between those living in MML states and other states were examined using 3 cross-sectional US adult surveys: the National Longitudinal Alcohol Epidemiologic Survey (NLAES; 1991-1992), the National Epidemiologic Survey on Alcohol and Related Conditions (NESARC; 2001-2002), and the National Epidemiologic Survey on Alcohol and Related Conditions–III (NESARC-III; 2012-2013). Early-MML states passed MML between NLAES and NESARC (“earlier period”). Late-MML states passed MML between NESARC and NESARC-III (“later period”). Main Outcomes and Measures Past-year illicit cannabis use and DSM-IV cannabis use disorder. Results Overall, from 1991-1992 to 2012-2013, illicit cannabis use increased significantly more in states that passed MML than in other states (1.4–percentage point more; SE, 0.5; P = .004), as did cannabis use disorders (0.7–percentage point more; SE, 0.3; P = .03). In the earlier period, illicit cannabis use and disorders decreased similarly in non-MML states and in California (where prevalence was much higher to start with). In contrast, in remaining early-MML states, the prevalence of use and disorders increased. Remaining early-MML and non-MML states differed significantly for use (by 2.5 percentage points; SE, 0.9; P = .004) and disorder (1.1 percentage points; SE, 0.5; P = .02). In the later period, illicit use increased by the following percentage points: never-MML states, 3.5 (SE, 0.5); California, 5.3 (SE, 1.0); Colorado, 7.0 (SE, 1.6); other early-MML states, 2.6 (SE, 0.9); and late-MML states, 5.1 (SE, 0.8). Compared with never-MML states, increases in use were significantly greater in late-MML states (1.6–percentage point more; SE, 0.6; P = .01), California (1.8–percentage point more; SE, 0.9; P = .04), and Colorado (3.5–percentage point more; SE, 1.5; P = .03). Increases in cannabis use disorder, which was less prevalent, were smaller but followed similar patterns descriptively, with change greater than never-MML states in California (1.0–percentage point more; SE, 0.5; P = .06) and Colorado (1.6–percentage point more; SE, 0.8; P = .04). Conclusions and Relevance Medical marijuana laws appear to have contributed to increased prevalence of illicit cannabis use and cannabis use disorders. State-specific policy changes may also have played a role. While medical marijuana may help some, cannabis-related health consequences associated with changes in state marijuana laws should receive consideration by health care professionals and the public.
Cannabis use and related problems are on the rise globally alongside an increase in the potency of cannabis sold on both black and legal markets. Additionally, there has been a shift towards abandoning prohibition for a less punitive and more permissive legal stance on cannabis, such as decriminalisation and legalisation. It is therefore crucial that we explore new and innovative ways to reduce harm. Research has found cannabis with high concentrations of its main active ingredient, δ-9-tetrahydrocannabinol (THC), to be more harmful (in terms of causing the main risks associated with cannabis use, such as addiction, psychosis, and cognitive impairment) than cannabis with lower concentrations of THC. By contrast, cannabidiol, which is a non-intoxicating and potentially therapeutic component of cannabis, has been found to reduce the negative effects of cannabis use. Here, we briefly review findings from studies investigating various types of cannabis and discuss how future research can help to better understand and reduce the risks of cannabis use.
Background and aims: Since 2012 four US states have legalized the retail sale of cannabis for recreational use by adults, and more are likely to follow. This report aimed to (1) briefly describe the regulatory regimes so far implemented; (2) outline their plausible effects on cannabis use and cannabis-related harm; and (3) suggest what research is needed to evaluate the public health impact of these policy changes. Method: We reviewed the drug policy literature to identify: (1) plausible effects of legalizing adult recreational use on cannabis price and availability; (2) factors that may increase or limit these effects; (3) pointers from studies of the effects of legalizing medical cannabis use; and (4) indicators of cannabis use and cannabis-related harm that can be monitored to assess the effects of these policy changes. Results: Legalization of recreational use will probably increase use in the long term, but the magnitude and timing of any increase is uncertain. It will be critical to monitor: cannabis use in household and high school surveys; cannabis sales; the number of cannabis plants legally produced; and the tetrahydrocannabinol (THC) content of cannabis. Indicators of cannabis-related harms that should be monitored include: car crash fatalities and injuries; emergency department presentations; presentations to addiction treatment services; and the prevalence of regular cannabis use among young people in mental health services and the criminal justice system. Conclusions: Plausible effects of legalizing recreational cannabis use in the United States include substantially reducing the price of cannabis and increasing heavy use and some types of cannabis-related harm among existing users. In the longer term it may also increase the number of new users.