What has research over the past two decades revealed about the adverse health effects of recreational cannabis use

TL;DR: The epidemiological literature in the past 20 years shows that cannabis use increases the risk of accidents and can produce dependence, and that there are consistent associations between regular cannabis use and poor psychosocial outcomes and mental health in adulthood.

Abstract: Aims To examine changes in the evidence on the adverse health effects of cannabis since 1993 Methods A comparison of the evidence in 1993 with the evidence and interpretation of the same health outcomes in 2013 Results Research in the past 20 years has shown that driving while cannabis-impaired approximately doubles car crash risk and that around one in 10 regular cannabis users develop dependence Regular cannabis use in adolescence approximately doubles the risks of early school-leaving and of cognitive impairment and psychoses in adulthood Regular cannabis use in adolescence is also associated strongly with the use of other illicit drugs These associations persist after controlling for plausible confounding variables in longitudinal studies This suggests that cannabis use is a contributory cause of these outcomes but some researchers still argue that these relationships are explained by shared causes or risk factors Cannabis smoking probably increases cardiovascular disease risk in middle-aged adults but its effects on respiratory function and respiratory cancer remain unclear, because most cannabis smokers have smoked or still smoke tobacco Conclusions The epidemiological literature in the past 20 years shows that cannabis use increases the risk of accidents and can produce dependence, and that there are consistent associations between regular cannabis use and poor psychosocial outcomes and mental health in adulthood

Summary

Conclusions:

• The epidemiological literature in the past 20 years has confirmed that cannabis use increases the risk of accidents, can produce dependence and that there are consistent associations between regular cannabis use and poor psychosocial outcomes and mental health in adulthood that warrant efforts to discourage adolescent cannabis use.
• The effects sought by cannabis users -euphoria and increased sociability -seem to be primarily produced by delta-9-tetrahydrocannabinol (THC) [3] .
• THC content has also increased in the Netherlands and probably in other developed countries [5].
• Cannabis is usually smoked in a "joint" or with a water pipe (sometimes with tobacco added) because smoking is the most efficient way to achieve the desired psychoactive effects [3] .
• This pattern, when continued over years and decades, predicts increased risks of many of the adverse health effects attributed to cannabis that are reviewed below [6] .

Figures

Table 1: summary of major adverse health outcomes of recreational cannabis use

Full text

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Author postprint of Hall, W. What has research over the past two decades revealed about the
adverse health effects of recreational cannabis use? Addiction 110, 19-35. 10.1111/add.12703
What has research over the past two decades revealed about the adverse
health effects of recreational cannabis use?
Wayne Hall
1,2,3
1. The University of Queensland Centre for Youth Substance Abuse Research,
The University of Queensland Centre for Clinical Research,
2. The National Addiction Centre, Kings College London
3. National Drug and Alcohol Research Centre, University of New South Wales
Paper presented at Through the Maze: Cannabis and Health International Drug Policy
Symposium Auckland, New Zealand, November 2013
Word count: 14,926 total; 9558 text

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Author postprint of Hall, W. What has research over the past two decades revealed about the
adverse health effects of recreational cannabis use? Addiction 110, 19-35. 10.1111/add.12703
Abstract
Background and Aims: To examine changes in the evidence on the adverse health effects of
cannabis since publishing an influential review of the literature in 1993.
Method: A comparison of the epidemiological evidence and conclusions reached in a 1993
literature review with the evidence and interpretation of the same health outcomes in 2013.
Results: Epidemiological research in the past 20 years has clearly shown that driving while
cannabis-impaired approximately doubles car crash risk and that around in 10 regular
cannabis users develop a dependence syndrome. Regular cannabis use in adolescence and
young adulthood predicts approximately double the risks of: early school leaving and welfare
dependence in adulthood, and of cognitive impairment, psychoses, depression and anxiety
disorders in adulthood. Regular cannabis use in adolescence is strongly associated with the
use of other illicit drugs (50 fold in better controlled studies). These associations between
regular use and poor outcomes have persisted after controlling for plausible confounding
variables in longitudinal studies. This suggests that cannabis use plays a contributory cause in
producing these outcomes but some researchers still argue that these relationships are
explained by the effects of shared causes or risk factors. Cannabis smoking probably
increases cardiovascular disease risk in middle aged adults but its effects on respiratory
function and respiratory cancer remain unclear because most cannabis smokers have smoked
or still smoke tobacco. More research is needed to understand the effects that increases in the
THC content of cannabis products may have had on their adverse health effects.
Conclusions: The epidemiological literature in the past 20 years has confirmed that cannabis
use increases the risk of accidents, can produce dependence and that there are consistent
associations between regular cannabis use and poor psychosocial outcomes and mental health
in adulthood that warrant efforts to discourage adolescent cannabis use.

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Author postprint of Hall, W. What has research over the past two decades revealed about the
adverse health effects of recreational cannabis use? Addiction 110, 19-35. 10.1111/add.12703
Why are we concerned about recreational cannabis use?
Over the past half century recreational cannabis use has become almost as common as
tobacco use among adolescents and young adults. Since its use was first reported over 40
years ago in the US, recreational cannabis use has spread globally to other developed
countries, and more recently, low and middle income countries [1,2].
The effects sought by cannabis users – euphoria and increased sociability - seem to be
primarily produced by delta-9-tetrahydrocannabinol (THC) [3]. These effects may be
modulated by cannabidiol (CBD), a nonpsychoactive cannabinoid found in many cannabis
products [3]. The THC content is highest in the flowering tops of the female cannabis plant.
The THC content of cannabis has increased over the past 30 years, in the USA from < 2% in
1980 to 8·5% in 2006 [4]. THC content has also increased in the Netherlands and probably in
other developed countries [5]
Cannabis is usually smoked in a “joint” or with a water pipe (sometimes with tobacco added)
because smoking is the most efficient way to achieve the desired psychoactive effects [3]. A
dose of 2 to 3 mg of THC will produce a “high” in occasional users who typically share a
single joint with others. Regular users may smoke up to three to five joints of potent cannabis
a day [6].
In epidemiological studies “heavy” or “regular” cannabis use is usually defined as daily or
near daily use [6]. This pattern, when continued over years and decades, predicts increased
risks of many of the adverse health effects attributed to cannabis that are reviewed below [6].
Unless otherwise stated, the remainder of this article deals with the adverse effects of
cannabis smoking, especially the adverse health effects of regular, typically daily, cannabis
smoking.
Our approach to the literature in 1993
In 1993 there were very few epidemiological studies of the health effects of cannabis. The
literature was dominated by (1) animal studies from the 1970s on the toxicity, teratogenicity
and carcinogenicity of cannabis and THC; and (2) human laboratory studies from the late
1970s and early 1980s on the effects of sustained cannabis use over 7 to 35 days on the health

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Author postprint of Hall, W. What has research over the past two decades revealed about the
adverse health effects of recreational cannabis use? Addiction 110, 19-35. 10.1111/add.12703
of college students. There were a small number of clinical studies of adverse health effects in
heavy cannabis users from the same period [7,8].
In the early 1990s in Australia (as elsewhere) there were strongly polarised views on the
health effects of cannabis. The published appraisals of the limited evidence were refracted
through the prism of the appraisers’ preferred policies towards cannabis (decriminalisation or
legalisation of personal use vs. intensified public education and law enforcement campaigns
to discourage use). We adopted the following approaches to maximise the chances that our
review would be seen as credible by advocates of these very different competing public
policies towards cannabis use.
First, Nadia Solowij, Jim Lemon and I applied the standard rules for making causal
inferences about the health effects of any drug to cannabis. That is, we looked for: (1)
epidemiological evidence of an association between cannabis use and the health outcome in
case-control and prospective studies; (2) evidence that reverse causation was an implausible
explanation (e.g. evidence from prospective studies that cannabis use preceded the outcome);
(3) evidence from prospective studies that had controlled for potential confounding variables
(such as other drug use and characteristics on which cannabis users differed from non-users);
and (4) clinical and experimental evidence which supported the biological plausibility of a
causal relationship [9].
Second, we specified the standard of proof that we would use in inferring that cannabis was a
probable cause of an adverse health effect, namely, evidence that made it more likely than not
that cannabis was a cause of the adverse health effect. As we pointed out, very few
conclusions could be drawn if we demanded proof beyond reasonable doubt. We also
identified possible adverse health effects that required further investigation e.g. if animal
and/or human evidence indicated an association between cannabis use and an adverse health
effect which was biologically plausible.
Third, we were prepared to infer that cannabis could have adverse health effects when it:
shared a route of administration with cigarette smoking e.g. respiratory disease, or produced
similar acute effects to those of alcohol e.g. on driving and crash risk; and had similar
pharmacological effects to other long-acting CNS depressant drugs e.g. benzodiazepines.

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Author postprint of Hall, W. What has research over the past two decades revealed about the
adverse health effects of recreational cannabis use? Addiction 110, 19-35. 10.1111/add.12703
Fourth, we compared the probable adverse health effects of cannabis with the known adverse
health effects of alcohol and tobacco. We aimed to do so in a way that used the same
evidential standards in drawing causal inferences about the probable adverse health effects of
all three drugs.
In the following analysis I apply these criteria to the more substantial research evidence that
has accumulated over the past 20 years on the adverse health effects of cannabis. For each
type of adverse health effect, I (1) briefly summarise the conclusions drawn in 1993; (2)
explain the reasons given for these conclusions; and (3) compare the conclusions reached in
1993 with the inferences that may reasonably be drawn in 2013. The review begins with
acute adverse health effects, those that may arise from a single episode of intoxication. It then
considers the adverse health and psychological effects of regular cannabis use over periods of
years and decades.
1. Adverse acute health effects
In 1993 the evidence indicated that the risk of a fatal overdose from using cannabis was
extremely small. This remains an uncontroversial conclusion because the dose of THC that
kills rodents is extremely high. The estimated fatal dose in humans derived from animal
studies is between 15 g [10] and 70 g [3]. This is far greater amount of cannabis that even a
very heavy cannabis user could use in a day [10]. There are also no reports of fatal overdoses
in the epidemiological literature [11]. There have been case reports of cardiovascular
fatalities in seemingly otherwise healthy young men after smoking cannabis [12] that are
discussed below under cardiovascular effects of cannabis smoking.
In 1993 we identified the following adverse acute effects of cannabis use: (i) unpleasant
experiences such as anxiety, dysphoria, and paranoia, especially among naive users; (ii)
cognitive impairment, especially of attention and memory; (iii) psychomotor impairment that
could impair a person’s ability to drive a motor vehicle while intoxicated; (iv) an increased risk
of psychotic symptoms in high doses, especially among those with a personal or family history
of psychosis; and (v) an increased risk of low birth weight babies, if cannabis was used during
pregnancy.

Frequently asked questions

Q1. What are the contributions in "What has research over the past two decades revealed about the adverse health effects of recreational cannabis use?" ?

This suggests that cannabis use plays a contributory cause in producing these outcomes but some researchers still argue that these relationships are explained by the effects of shared causes or risk factors. 

Q2. How many times did a person who tried cannabis use a diagnosis of schizophrenia?

After statistical adjustment for a personal history of psychiatric disorder by age 18 and parental divorce, those who had used cannabis 10 or more times by age 18 were 2.3 times more likely to receive a diagnosis of schizophrenia than those who had not used cannabis. 

Q3. What is the consistent finding in epidemiological studies of drug use in young adults?

The order of involvement with cannabis and other illicit drugs, and the increased likelihood of using other illicit drugs, are the most consistent findings in epidemiological studies of drug use in young adults. 

Q4. What is the effect of cannabis on the risk of a car crash?

In summary, the epidemiological and laboratory evidence on the acute effects of cannabis strongly suggests that cannabis users who drive while intoxicated increase their risk of motor vehicle crashes 2-3 times [20] as against 6-15 times for comparable intoxicating doses of alcohol. 

Q5. How much of the risk of failing to complete high school or post-secondary training was ?

The authors estimated that early use of cannabis contributed to 17% of the risk of failing to complete high school or post-secondary training. 

Q6. How many times did conscripts who tried cannabis have schizophrenia?

Conscripts who had tried cannabis by age 18 were 2.4 times more likely to be diagnosed with schizophrenia over the next 15 years than those who had not [91]. 

Q7. What was the main reason for the lack of studies that reported increased rates of birth defects?

It was also difficult to interpret the few studies that did reported increased rates of birth defects (e.g [22]) because cannabis users were more likely to smoke tobacco, and use alcohol and other illicit drugs during pregnancy [23]. 

Q8. How many low income women have reported lower scores on the Stanford-Binet Intelligence?

In the past 20 years another cohort of low income women with higher rates of regular cannabis use [31] has reported lower scores on memory and verbal scales of the Stanford-Binet Intelligence Scale at age 3 in children born to 655 low income women (half African-American and half Caucasian) in Pittsburgh between 1990 and 1995. 

Q9. What did the authors conclude that the studies were too varied to quantify risk?

An attempted meta-analysis of similar studies [97] concluded that the designs of these studies and measures used were too varied to meaningfully quantify risk and most of the studies had not excluded reverse causation or adequately controlled for confounding. 

Q10. What is the reason for the decline in cognitive performance of cannabis users?

Cognitive impairmentIn 1993 case-control studies reported that regular cannabis users had poorer cognitive performance than non-cannabis-using controls but it was unclear whether this was because cannabis use impaired cognitive performance, persons with poorer cognitive functioning were more likely to become regular cannabis users, or some combination of the two [9].