ArticlePDF AvailableLiterature Review
new england journal
n engl j med 370;23 june 5, 2014
Dan L. Longo, M.D., Editor
review article
Adverse Health Effects of Marijuana Use
Nora D. Volkow, M.D., Ruben D. Baler, Ph.D., Wilson M. Compton, M.D.,
and Susan R.B. Weiss, Ph.D.
From the National Institute on Drug
Abuse, National Institutes of Health,
Bethesda, MD. Address reprint requests
to Dr. Volkow at the National Institute
on Drug Abuse, 6001 Executive Blvd.,
Rm. 5274, Bethesda, MD 20892, or at
N Engl J Med 2014;370:2219-27.
DOI: 10.1056/NEJMra1402309
Copyright © 2014 Massachusetts Medical Society.
n light of the rapidly shifting landscape regarding the legaliza-
tion of marijuana for medical and recreational purposes, patients may be more
likely to ask physicians about its potential adverse and beneficial effects on
health. The popular notion seems to be that marijuana is a harmless pleasure, ac-
cess to which should not be regulated or considered illegal. Currently, marijuana is
the most commonly used “illicit” drug in the United States, with about 12% of
people 12 years of age or older reporting use in the past year and particularly high
rates of use among young people.
The most common route of administration is
inhalation. The greenish-gray shredded leaves and flowers of the Cannabis sativa
plant are smoked (along with stems and seeds) in cigarettes, cigars, pipes, water
pipes, or “blunts” (marijuana rolled in the tobacco-leaf wrapper from a cigar).
Hashish is a related product created from the resin of marijuana flowers and is
usually smoked (by itself or in a mixture with tobacco) but can be ingested orally.
Marijuana can also be used to brew tea, and its oil-based extract can be mixed into
food products.
The regular use of marijuana during adolescence is of particular concern, since
use by this age group is associated with an increased likelihood of deleterious
(Table 1). Although multiple studies have reported detrimental ef-
fects, others have not, and the question of whether marijuana is harmful remains
the subject of heated debate. Here we review the current state of the science re-
lated to the adverse health effects of the recreational use of marijuana, focusing
on those areas for which the evidence is strongest.
Adverse Effects
Risk of Addiction
Despite some contentious discussions regarding the addictiveness of marijuana,
the evidence clearly indicates that long-term marijuana use can lead to addiction.
Indeed, approximately 9% of those who experiment with marijuana will become
addicted3 (according to the criteria for dependence in the Diagnostic and Statistical
Manual of Mental Disorders, 4th edition [DSM-IV]). The number goes up to about 1 in
6 among those who start using marijuana as teenagers and to 25 to 50% among
those who smoke marijuana daily.4 According to the 2012 National Survey on Drug
Use and Health, an estimated 2.7 million people 12 years of age and older met the
DSM-IV criteria for dependence on marijuana, and 5.1 million people met the crite-
ria for dependence on any illicit drug1 (8.6 million met the criteria for dependence
on alcohol1). There is also recognition of a bona fide cannabis withdrawal syn-
drome5 (with symptoms that include irritability, sleeping difficulties, dysphoria,
craving, and anxiety), which makes cessation difficult and contributes to relapse.
Marijuana use by adolescents is particularly troublesome. Adolescents’ increased
vulnerability to adverse long-term outcomes from marijuana use is probably related
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new england journal
n engl j med 370;23 june 5, 2014
to the fact that the brain, including the endocan-
nabinoid system, undergoes active development
during adolescence.6 Indeed, early and regular
marijuana use predicts an increased risk of mar-
ijuana addiction, which in turn predicts an in-
creased risk of the use of other illicit drugs.7 As
compared with persons who begin to use mari-
juana in adulthood, those who begin in adoles-
cence are approximately 2 to 4 times as likely to
have symptoms of cannabis dependence within
2 years after first use.8
Effect on Brain Development
The brain remains in a state of active, experi-
ence-guided development from the prenatal pe-
riod through childhood and adolescence until
the age of approximately 21 years.9 During these
developmental periods, it is intrinsically more
vulnerable than a mature brain to the adverse
long-term effects of environmental insults, such
as exposure to tetrahydrocannabinol, or THC,
the primary active ingredient in marijuana. This
view has received considerable support from
studies in animals, which have shown, for ex-
ample, that prenatal or adolescent exposure to
THC can recalibrate the sensitivity of the reward
system to other drugs10 and that prenatal expo-
sure interferes with cytoskeletal dynamics, which
are critical for the establishment of axonal con-
nections between neurons.11
As compared with unexposed controls, adults
who smoked marijuana regularly during adoles-
cence have impaired neural connectivity (fewer
fibers) in specific brain regions. These include
the precuneus, a key node that is involved in
functions that require a high degree of integra-
tion (e.g., alertness and self-conscious awareness),
and the fimbria, an area of the hippocampus
that is important in learning and memory.
Reduced functional connectivity has also been
reported in the prefrontal networks responsible
for executive function (including inhibitory con-
trol) and the subcortical networks, which pro-
cess habits and routines.
In addition, imaging
studies in persons who use cannabis have revealed
decreased activity in prefrontal regions and re-
duced volumes in the hippocampus.
Thus, cer-
tain brain regions may be more vulnerable than
others to the long-term effects of marijuana.
One study showed that selective down-regula-
tion of cannabinoid-1 (CB1) receptors in several
cortical brain regions in long-term marijuana
smokers was correlated with years of cannabis
smoking and was reversible after 4 weeks of
Changes in CB1 receptors were not
seen in subcortical regions.
The negative effect of marijuana use on the
functional connectivity of the brain is particu-
larly prominent if use starts in adolescence or
young adulthood,
which may help to explain
the finding of an association between frequent
use of marijuana from adolescence into adult-
hood and significant declines in IQ.
The im-
pairments in brain connectivity associated with
exposure to marijuana in adolescence are consis-
tent with preclinical findings indicating that the
cannabinoid system plays a prominent role in
synapse formation during brain development.
Possible Role as Gateway Drug
Epidemiologic and preclinical data suggest that
the use of marijuana in adolescence could inf lu-
ence multiple addictive behaviors in adulthood.
In rodents exposed to cannabinoids during ado-
lescence, there is decreased reactivity of the do-
pamine neurons that modulate the brain’s re-
ward regions.18 The exposure of rodents to
Table 1. Adverse Effects of Short-Term Use and Long-Term or Heavy Use
of Marijuana.
Effects of short-term use
Impaired short-term memory, making it difficult to learn and to retain infor-
Impaired motor coordination, interfering with driving skills and increasing
the risk of injuries
Altered judgment, increasing the risk of sexual behaviors that facilitate the
transmission of sexually transmitted diseases
In high doses, paranoia and psychosis
Effects of long-term or heavy use
Addiction (in about 9% of users overall, 17% of those who begin use in ado-
lescence, and 25 to 50% of those who are daily users)*
Altered brain development*
Poor educational outcome, with increased likelihood of dropping out of school*
Cognitive impairment, with lower IQ among those who were frequent users
during adolescence*
Diminished life satisfaction and achievement (determined on the basis of
subjective and objective measures as compared with such ratings in the
general population)*
Symptoms of chronic bronchitis
Increased risk of chronic psychosis disorders (including schizophrenia) in
persons with a predisposition to such disorders
* The effect is strongly associated with initial marijuana use early in adolescence.
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Adverse Health Effects of Marijuana Use
n engl j med 370;23 june 5, 2014
cannabis in utero alters the developmental regu-
lation of the mesolimbic dopamine system of af-
fected offspring.19 If reduced dopamine reactivity
in the brain’s reward regions does follow early
exposure to marijuana, this effect could help to
explain the increased susceptibility to drug abuse
and addiction to several drugs later in life, which
has been reported in most epidemiologic stud-
ies.20 This theory is also consistent with animal
models showing that THC can prime the brain
for enhanced responses to other drugs.21 Al-
though these findings support the idea that mar-
ijuana is a gateway drug, other drugs, such as
alcohol and nicotine, can also be categorized as
gateway drugs, since they also prime the brain
for a heightened response to other drugs.22 How-
ever, an alternative explanation is that people
who are more susceptible to drug-taking behav-
ior are simply more likely to start with marijuana
because of its accessibility and that their subse-
quent social interactions with other drug users
would increase the probability that they would
try other drugs.
Relation to Mental Illness
Regular marijuana use is associated with an in-
creased risk of anxiety and depression,23 but cau-
sality has not been established. Marijuana is also
linked with psychoses (including those associat-
ed with schizophrenia), especially among people
with a preexisting genetic vulnerability,24 and
exacerbates the course of illness in patients with
schizophrenia. Heavier marijuana use, greater
drug potency, and exposure at a younger age can
all negatively affect the disease trajectory (e.g., by
advancing the time of a first psychotic episode by
2 to 6 years).25
However, it is inherently difficult to establish
causality in these types of studies because factors
other than marijuana use may be directly associ-
ated with the risk of mental illness. In addition,
other factors could predispose a person to both
marijuana use and mental illness. This makes it
difficult to confidently attribute the increased
risk of mental illness to marijuana use.
Effect on School Performance and Lifetime
In the 2013 Monitoring the Future survey of
high-school students,26 6.5% of students in grade
12 reported daily or near-daily marijuana use,
and this figure probably represents an underesti-
mate of use, since young people who have
dropped out of school may have particularly high
rates of frequent marijuana use.27 Since marijua-
na use impairs critical cognitive functions, both
during acute intoxication and for days after use,28
many students could be functioning at a cogni-
tive level that is below their natural capability for
considerable periods of time. Although acute ef-
fects may subside after THC is cleared from the
brain, it nonetheless poses serious risks to health
that can be expected to accumulate with long-
term or heavy use. The evidence suggests that
such use results in measurable and long-lasting
cognitive impairments,16 particularly among
those who started to use marijuana in early ado-
lescence. Moreover, failure to learn at school,
even for short or sporadic periods (a secondary
effect of acute intoxication), will interfere with
the subsequent capacity to achieve increasingly
challenging educational goals, a finding that
may also explain the association between regular
marijuana use and poor grades.29
The relationship between cannabis use by
young people and psychosocial harm is likely to
be multifaceted, which may explain the incon-
sistencies among studies. For example, some
studies suggest that long-term deficits may be
reversible and remain subtle rather than dis-
abling once a person abstains from use.
studies show that long-term, heavy use of mari-
juana results in impairments in memory and
attention that persist and worsen with increas-
ing years of regular use
and with the initiation
of use during adolescence.
As noted above,
early marijuana use is associated with impaired
school performance and an increased risk of
dropping out of school,
although reports of
shared environmental factors that inf luence the
risks of using cannabis at a young age and drop-
ping out of school
suggest that the relationship
may be more complex. Heavy marijuana use has
been linked to lower income, greater need for
socioeconomic assistance, unemployment, crim-
inal behavior, and lower satisfaction with life.
Risk of motor-vehicle Accidents
Both immediate exposure and long-term expo-
sure to marijuana impair driving ability; mari-
juana is the illicit drug most frequently reported
in connection with impaired driving and acci-
dents, including fatal accidents.35 There is a rela-
tionship between the blood THC concentration
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new england journal
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and performance in controlled driving-simula-
tion studies,36 which are a good predictor of real-
world driving ability. Recent marijuana smoking
and blood THC levels of 2 to 5 ng per milliliter
are associated with substantial driving impair-
ment.37 According to a meta-analysis, the overall
risk of involvement in an accident increases by a
factor of about 2 when a person drives soon after
using marijuana.37 In an accident culpability
analysis, persons testing positive for THC (typi-
cal minimum level of detection, 1 ng per milli-
liter), and particularly those with higher blood
levels, were 3 to 7 times as likely to be responsi-
ble for a motor-vehicle accident as persons who
had not used drugs or alcohol before driving.38
In comparison, the overall risk of a vehicular ac-
cident increases by a factor of almost 5 for drivers
with a blood alcohol level above 0.08%, the legal
limit in most countries, and increases by a factor
of 27 for persons younger than 21 years of age.39
Not surprisingly, the risk associated with the use
of alcohol in combination with marijuana ap-
pears to be greater than that associated with the
use of either drug alone.37
Risk of Cancer and Other Effects on Health
The effects of long-term marijuana smoking on
the risk of lung cancer are unclear. For example,
the use of marijuana for the equivalent of 30 or
more joint-years (with 1 joint-year of marijuana
use equal to 1 cigarette [joint] of marijuana
smoked per day for 1 year) was associated with
an increased incidence of lung cancer and several
cancers of the upper aerodigestive tract; however,
the association disappeared after adjustment for
potential confounders such as cigarette smok-
ing.40 Although the possibility of a positive asso-
ciation between marijuana smoking and cancer
cannot be ruled out,41 the evidence suggests that
the risk is lower with marijuana than with tobac-
co.40 However, the smoking of cigarettes that con-
tain both marijuana and tobacco products is a
potential confounding factor with a prevalence
that varies dramatically among countries.
Marijuana smoking is also associated with
inflammation of the large airways, increased
airway resistance, and lung hyperinflation, as-
sociations that are consistent with the fact that
regular marijuana smokers are more likely to
report symptoms of chronic bronchitis than are
; however, the long-term effect of
low levels of marijuana exposure does not ap-
pear to be significant.
The immunologic com-
petence of the respiratory system in marijuana
smokers may also be compromised, as indicated
by increased rates of respiratory infections and
Marijuana use has also been as-
sociated with vascular conditions that increase
the risks of myocardial infarction, stroke, and
transient ischemic attacks during marijuana in-
The actual mechanisms underlying
the effects of marijuana on the cardiovascular
and cerebrovascular systems are complex and
not fully understood. However, the direct effects
of cannabinoids on various target receptors (i.e.,
CB1 receptors in arterial blood vessels) and the
indirect effects on vasoactive compounds
help explain the detrimental effects of marijua-
na on vascular resistance and coronary microcir-
Limitations of the Evidence
and Gaps in Knowledge
Most of the long-term effects of marijuana use
that are summarized here have been observed
among heavy or long-term users, but multiple
(often hidden) confounding factors detract from
our ability to establish causality (including the
frequent use of marijuana in combination with
other drugs). These factors also complicate our
ability to assess the true effect of intrauterine
exposure to marijuana. Indeed, despite the use
of marijuana by pregnant women,48 and animal
models suggesting that cannabis exposure dur-
ing pregnancy may alter the normal processes
and trajectories of brain development,49 our un-
derstanding of the long-term effects of prenatal
exposure to marijuana in humans is very poor.
The THC content, or potency, of marijuana,
as detected in confiscated samples, has been
steadily increasing from about 3% in the 1980s
to 12% in 2012
(Fig. 1A). This increase in THC
content raises concerns that the consequences of
marijuana use may be worse now than in the
past and may account for the significant in-
creases in emergency department visits by per-
sons reporting marijuana use
(Fig. 1B) and the
increases in fatal motor-vehicle accidents.
increase in THC potency over time also raises
questions about the current relevance of the
findings in older studies on the effects of mari-
juana use, especially studies that assessed long-
term outcomes.
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Adverse Health Effects of Marijuana Use
n engl j med 370;23 june 5, 2014
There is also a need to improve our under-
standing of how to harness the potential medi-
cal benefits of the marijuana plant without ex-
posing people who are sick to its intrinsic risks.
The authoritative report by the Institute of
Medicine, Marijuana and Medicine,
the potential benefits of smoking marijuana in
stimulating appetite, particularly in patients
with the acquired immunodeficiency syndrome
(AIDS) and the related wasting syndrome, and in
combating chemotherapy-induced nausea and
vomiting, severe pain, and some forms of spas-
ticity. The report also indicates that there is
some evidence for the benefit of using marijuana
to decrease intraocular pressure in the treatment
of glaucoma. Nonetheless, the report stresses
the importance of focusing research efforts on
the therapeutic potential of synthetic or pharma-
ceutically pure cannabinoids.
Some physicians
continue to prescribe marijuana for medicinal
purposes despite limited evidence of a benefit
(see box). This practice raises particular con-
cerns with regard to long-term use by vulnerable
populations. For example, there is some evi-
dence to suggest that in patients with symptoms
of human immunodeficiency virus (HIV) infec-
tion or AIDS, marijuana use may actually exac-
erbate HIV-associated cognitive deficits.
THC in Marijuana Samples (%)
1995 1996 1997 1998 1999 2000 2001 2002 2003 2004 2005 2006 2007 2008 2009 2010 2011 2012
BDrug-Related Emergency Department Visits
APotency of THC
No. of Emergency Department
Visits (in thousands)
Marijuana Cocaine Heroin
In combination Alone
Figure 1. Increases over Time in the Potency of Tetrahydrocannabinol (THC) in Marijuana and the Number of Emer-
gency Department Visits Involving Marijuana, Cocaine, or Heroin.
Panel A shows the increasing potency of marijuana (i.e., the percentage of THC) in samples seized by the Drug En-
forcement Administration (DEA) between 1995 and 2012.
Panel B provides estimates of the number of emergency
department visits involving the use of selected illicit drugs (marijuana, cocaine, and heroin) either singly or in com-
bination with other drugs between 2004 and 2011.
Among these three drugs, only marijuana, used either in com-
bination with other drugs or alone, was associated with significant increases in the number of visits during this peri-
od (a 62% increase when used in combination with other drugs and a 100% increase when used alone, P<0.05 for
the two comparisons).
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larly, more research is needed to understand the
potential effects of marijuana use on age-related
cognitive decline in general and on memory
impairment in particular.
Research is needed on the ways in which
government policies on marijuana affect public
health outcomes. Our understanding of the ef-
fects of policy on market forces is quite limited
(e.g., the allure of new tax-revenue streams from
the legal sale of marijuana, pricing wars, youth-
targeted advertising, and the emergence of can-
nabis-based medicines approved by the Food and
Drug Administration), as is our understanding
of the interrelated variables of perceptions about
Clinical Conditions with Symptoms That May Be Relieved by Treatment with Marijuana or Other Cannabinoids.*
Early evidence of the benefits of marijuana in patients with glaucoma (a disease associated with increased pressure in
the eye) may be consistent with its ability to effect a transient decrease in intraocular pressure,
but other, stan-
dard treatments are currently more effective. THC, cannabinol, and nabilone (a synthetic cannabinoid similar to
THC), but not cannabidiol, were shown to lower intraocular pressure in rabbits.
More research is needed to es-
tablish whether molecules that modulate the endocannabinoid system may not only reduce intraocular pressure
but also provide a neuroprotective benefit in patients with glaucoma.
Treatment of the nausea and vomiting associated with chemotherapy was one of the first medical uses of THC and other
THC is an effective antiemetic agent in patients undergoing chemotherapy,
but patients often state
that marijuana is more effective in suppressing nausea. Other, unidentified compounds in marijuana may enhance
the effect of THC (as appears to be the case with THC and cannabidiol, which operate through different antiemetic
Paradoxically, increased vomiting (hyperemesis) has been reported with repeated marijuana use.
AIDS-associated anorexia and wasting syndrome
Reports have indicated that smoked or ingested cannabis improves appetite and leads to weight gain and improved mood
and quality of life among patients with AIDS.
However, there is no long-term or rigorous evidence of a sustained
effect of cannabis on AIDS-related morbidity and mortality, with an acceptable safety profile, that would justify its
incorporation into current clinical practice for patients who are receiving effective antiretroviral therapy.
Data from
the few studies that have explored the potential therapeutic value of cannabinoids for this patient population are
Chronic pain
Marijuana has been used to relieve pain for centuries. Studies have shown that cannabinoids acting through central
CB1 receptors, and possibly peripheral CB1 and CB2 receptors,
play important roles in modeling nociceptive re-
sponses in various models of pain. These findings are consistent with reports that marijuana may be effective in
ameliorating neuropathic pain,
even at very low levels of THC (1.29%).
Both marijuana and dronabinol, a
pharmaceutical formulation of THC, decrease pain, but dronabinol may lead to longer-lasting reductions in pain
sensitivity and lower ratings of rewarding effects.
Cannabinoids (e.g., THC and cannabidiol) have substantial antiinflammatory effects because of their ability to induce
apoptosis, inhibit cell proliferation, and suppress cytokine production.
Cannabidiol has attracted particular inter-
est as an antiinflammatory agent because of its lack of psychoactive effects.
Animal models have shown that can-
nabidiol is a promising candidate for the treatment of rheumatoid arthritis
and for inflammatory diseases of the
gastrointestinal tract (e.g., ulcerative colitis and Crohn’s disease).
Multiple sclerosis
Nabiximols (Sativex, GW Pharmaceuticals), an oromucosal spray that delivers a mix of THC and cannabidiol, appears
to be an effective treatment for neuropathic pain, disturbed sleep, and spasticity in patients with multiple sclerosis.
Sativex is available in the United Kingdom, Canada, and several other countries
and is currently being reviewed
in phase 3 trials in the United States in order to gain approval from the Food and Drug Administration.
In a recent small survey of parents who use marijuana with a high cannabidiol content to treat epileptic seizures in their
11% (2 families out of the 19 that met the inclusion criteria) reported complete freedom from seizures,
42% (8 families) reported a reduction of more than 80% in seizure frequency, and 32% (6 families) reported a re-
duction of 25 to 60% in seizure frequency. Although such reports are promising, insufficient safety and efficacy data
are available on the use of cannabis botanicals for the treatment of epilepsy.
However, there is increasing evidence
of the role of cannabidiol as an antiepileptic agent in animal models.
* AIDS denotes acquired immunodeficiency syndrome, CB1 cannabinoid-1 receptor, and CB2 cannabinoid-2 receptor,
HIV human immunodeficiency virus, and THC tetrahydrocannabinol.
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Adverse Health Effects of Marijuana Use
n engl j med 370;23 june 5, 2014
use, types of use, and outcomes. Historically,
there has been an inverse correlation between
marijuana use and the perception of its risks
among adolescents (Fig. 2A). Assuming that this
inverse relationship is causal, would greater per-
missiveness in culture and social policy lead to
an increase in the number of young people who
are exposed to cannabis on a regular basis?
Among students in grade 12, the reported preva-
lence of regular marijuana smoking has been
steadily increasing in recent years and may soon
intersect the trend line for regular tobacco
smoking (Fig. 2B). We also need information
about the effects of second-hand exposure to
cannabis smoke and cannabinoids. Second-hand
exposure is an important public health issue in
the context of tobacco smoking, but we do not
have a clear understanding of the effects of
second-hand exposure to marijuana smoking.
Studies in states (e.g., Colorado, California, and
Washington) and countries (e.g., Uruguay, Por-
tugal, and the Netherlands) where social and
legal policies are shifting may provide important
data for shaping future policies.
Marijuana use has been associated with substan-
tial adverse effects, some of which have been de-
termined with a high level of confidence (Table 2).
Marijuana, like other drugs of abuse, can result
in addiction. During intoxication, marijuana can
interfere with cognitive function (e.g., memory
and perception of time) and motor function (e.g.,
coordination), and these effects can have detri-
mental consequences (e.g., motor-vehicle acci-
dents). Repeated marijuana use during adoles-
cence may result in long-lasting changes in brain
function that can jeopardize educational, profes-
sional, and social achievements. However, the ef-
fects of a drug (legal or illegal) on individual
health are determined not only by its pharmaco-
logic properties but also by its availability and
social acceptability. In this respect, legal drugs
Grade 12 Students (%)
BReported Daily Use of Cigarettes or Marijuana
ACorrelation between Perceived Risk and Use
Past-yr use
of marijuana
Perceived risk
of marijuana
Grade 12 Students (%)
Daily cigarette use
in previous 30 days
Daily marijuana use
in previous 30 days
Table 2. Level of Confidence in the Evidence for Adverse Effects of Marijuana
on Health and Well-Being.
Effect Overall Level
of Confidence*
Addiction to marijuana and other substances High
Abnormal brain development Medium
Progression to use of other drugs Medium
Schizophrenia Medium
Depression or anxiety Medium
Diminished lifetime achievement High
Motor vehicle accidents High
Symptoms of chronic bronchitis High
Lung cancer Low
* The indicated overall level of confidence in the association between marijuana
use and the listed effects represents an attempt to rank the strength of the
current evidence, especially with regard to heavy or long-term use and use
that starts in adolescence.
Figure 2. Use of Marijuana in Relation to Perceived
Risk and Daily Use of Tobacco Cigarettes or Marijuana
among U.S. Students in Grade 12, 1975–2013.
Panel A shows the inverse correlation between the per-
ception of the risk associated with marijuana use and
actual use. Perceived risk corresponds to the percent-
age of teenagers who reported that the use of marijuana
is dangerous. Panel B shows the percentage of students
who reported daily use of tobacco cigarettes or mari-
juana in the previous 30 days.
Data for both graphs are
from Johnston et al.
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new england journal
n engl j med 370;23 june 5, 2014
(alcohol and tobacco) offer a sobering perspec-
tive, accounting for the greatest burden of dis-
ease associated with drugs77 not because they are
more dangerous than illegal drugs but because
their legal status allows for more widespread ex-
posure. As policy shifts toward legalization of
marijuana, it is reasonable and probably prudent
to hypothesize that its use will increase and that,
by extension, so will the number of persons for
whom there will be negative health consequences.
No potential conflict of interest relevant to this article was
Disclosure forms provided by the authors are available with
the full text of this article at
1. Center for Behavioral Health Statis-
tics and Quality. National survey on drug
use and health. Rockville, MD: Substance
Abuse & Mental Health Services Adminis-
tration, 2013.
2. Fergusson DM, Boden JM. Cannabis
use and later life outcomes. Addiction
3. Lopez-Quintero C, Pérez de los Cobos
J, Hasin DS, et al. Probability and predic-
tors of transition from first use to depen-
dence on nicotine, alcohol, cannabis, and
cocaine: results of the Nationa l Epidemio-
logic Survey on Alcohol and Related Con-
ditions (NESARC). Drug Alcohol Depend
4. Hall W, Degenhardt L. Adverse health
effects of non-medical cannabis use. Lan-
cet 2009;374:1383-91.
5. Gorelick DA, Levin KH, Copersino ML ,
et al. Diagnostic criteria for cannabis
withdrawal syndrome. Drug Alcohol De-
pend 2012;123:141-7.
6. Mechoulam R, Parker LA. The endo-
cannabinoid system and the brain. Annu
Rev Psychol 2013;64:21-47.
7. Hall W, Degenhardt L. Prevalence and
correlates of cannabis use in developed
and developing countries. Curr Opin Psy-
chiatry 2007;20:393-7.
8. Chen CY, Storr CL, Anthony JC. Early-
onset drug use and risk for drug depen-
dence problems. Addict Behav 2009;34:
319-2 2.
9. Gogtay N, Giedd JN, Lusk L, et al.
Dynamic mapping of human cortical de-
velopment during childhood through
early adulthood. Proc Natl Acad Sci U S A
10. Dinieri JA, Hurd YL. Rat models of
prenatal and adolescent cannabis expo-
sure. Methods Mol Biol 2012;829:231-42.
11. Tortoriello G, Morris CV, Alpar A,
et al. Miswiring the brain: Δ9-tetrahydro-
cannabinol disrupts cortical development
by inducing an SCG10/stathmin-2 degra-
dation pathway. EMBO J 2014;33:668-85.
12. Zalesky A, Solowij N, Yücel M, et al.
Effect of long-term cannabis use on axo-
nal fibre connectivity. Brain 2012;135:
13. Filbey F, Yezhuvath U. Functional con-
nectivity in inhibitory control networks
and severity of cannabis use disorder. Am
J Drug Alcohol Abuse 2013;39:382-91.
14. Batalla A, Bhattacharyya S, Yücel M,
et al. Structural and functional imaging
studies in chronic cannabis users: a sys-
tematic review of adolescent and adult
findings. PLoS One 2013;8(2):e55821.
15. Hirvonen J, Goodwin RS, Li C-T, et al.
Reversible and regionally selective down-
regulation of brain c annabinoid CB1 recep -
tors in chronic daily cannabis smokers.
Mol Psychiat ry 2012;17:642-9.
16. Meier MH, Caspi A, Ambler A, et al.
Persistent cannabis users show neuropsy-
chological decline from childhood to mid-
life. Proc Natl Acad Sci U S A 2012;109(40):
17. Gaffuri AL, Ladarre D, Lenkei Z.
Type-1 cannabinoid receptor signaling
in neuronal development. Pharmacology
18. Pistis M, Perra S, Pillolla G, Melis M,
Muntoni AL, Gessa GL. Adolescent expo-
sure to cannabinoids induces long-lasting
changes in the response to drugs of abuse
of rat midbrain dopamine neurons. Biol
Psychiatry 2004;56:86-94.
19. DiNieri JA, Wang X, Szutorisz H, et al.
Maternal cannabis use alters ventral stria-
tal dopamine D2 gene regulation in the
offspring. Biol Psychiatry 2011;70:763-9.
20. Agrawal A, Neale MC, Prescott CA,
Kendler KS. A twin study of early can-
nabis use and subsequent use and abuse/
dependence of other illicit drugs. Psychol
Med 2004;34:1227-37.
21. Panlilio LV, Zanettini C, Barnes C,
Solinas M, Goldberg SR. Prior exposure
to THC increases the addictive effects of
nicotine in rats. Neuropsychopharmacol-
ogy 2013;38:1198-208.
22. Levine A, Huang Y, Drisaldi B, et al.
Molecular mechanism for a gateway drug:
epigenetic changes initiated by nicotine
prime gene expression by cocaine. Sci
Transl Med 2011;3:107ra109.
23. Patton GC, Coffey C, Carlin JB, Degen-
hardt L, Lynskey M, Hall W. Cannabis use
and mental health in young people: cohort
study. BMJ 2002;325:1195-8.
24. Caspi A, Moffitt TE, Cannon M, et al.
Moderation of the effect of adolescent-
onset cannabis use on adult psychosis by
a functional polymorphism in the catechol-
O-methyltransferase gene: longitudinal
evidence of a gene X environment interac-
tion. Biol Psychiatry 2005;57:1117-27.
25. Di Forti M, Sallis H, Allegri F, et al.
Daily use, especially of high-potency can-
nabis, dr ives the earlier onset of psychosis
in cannabis users. Schizophr Bull 2014
March 19 (Epub ahead of print).
26. Johnston LD, O’Malley PM, Miech RA,
et al. Monitoring the Future: national sur-
vey results on drug use, 1975-2013 —
overview, key findings on adolescent drug
use. Ann Arbor: Institute for Social Re-
search, Universit y of Michigan, 2014 (http://
27. Bray JW, Zarkin GA, Ringwalt C, Qi J.
The relationship between marijuana ini-
tiation and dropping out of high school.
Health Econ 2000;9:9-18.
28. Crean RD, Crane NA, Mason BJ. An
evidence based review of acute and long-
term effects of cannabis use on executive
cognitive functions. J Addict Med 2011;
29. Lynskey M, Hall W. The effects of ad-
olescent cannabis use on educational at-
tainment: a review. Addiction 2000;95:
30. Macleod J, Oakes R, Copello A, et al.
Psychological and social sequelae of can-
nabis and other illicit drug use by young
people: a systematic review of longitudi-
nal, general population studies. Lancet
31. Solowij N, Stephens RS, Roffman RA,
et al. Cognitive functioning of long-term
heavy cannabis users seeking treatment.
JAMA 2002;287:1123-31. [Erratum, JAMA
32. Schweinsburg AD, Brown SA, Tapert
SF. The influence of marijuana use on
neurocognitive functioning in adolescents.
Curr Drug Abuse Rev 2008;1:99-111.
33. Verweij KJ, Huizink AC, Agrawal A,
Martin NG, Lynskey MT. Is the relation-
ship between early-onset cannabis use
and educational attainment causal or due
to common liability? Drug Alcohol De-
pend 2013;133:580-6.
34. Brook JS, Lee JY, Finch SJ, Seltzer N,
Brook DW. Adult work commitment, f i-
nancial stability, and social environment
as related to trajectories of marijuana use
beginning in adolescence. Subst Abus
35. Brady JE, Li G. Trends in alcohol and
other drugs detected in fatally injured
drivers in the United States, 1999-2010.
Am J Epidemiol 2014;179:692-9.
36. Lenné MG, Dietze PM, Triggs TJ,
The New England Journal of Medicine
Downloaded from at NIH on June 4, 2014. For personal use only. No other uses without permission.
Copyright © 2014 Massachusetts Medical Society. All rights reserved.
Adverse Health Effects of Marijuana Use
n engl j med 370;23 june 5, 2014
Walmsley S, Murphy B, Redman JR. The
effects of cannabis and alcohol on simu-
lated arterial driving: influences of driv-
ing experience and task demand. Accid
Anal Prev 2010;42:859-66.
37. Hartman RL, Huestis MA. Cannabis
effects on driving skills. Clin Chem 2013;
38. Ramaekers JG, Berghaus G, van Laar
M, Drummer OH. Dose related risk of
motor vehicle crashes after cannabis use.
Drug Alcohol Depend 2004;73:109-19.
39. Peck RC, Gebers MA, Voas RB, Ro-
mano E. The relationship bet ween blood
alcohol concentration (BAC), age, and
crash risk. J Safet y Res 2008;39:311-9.
40. Hashibe M, Morgenstern H, Cui Y, et
al. Marijuana use and the risk of lung and
upper aerodigestive tract cancers: results
of a population-based case-control study.
Cancer Epidemiol Biomarkers Prev 2006;
41. Callaghan RC, Allebeck P, Sidorchuk A.
Marijuana use and risk of lung cancer:
a 40-year cohort study. Cancer Causes
Control 2013;24:1811-20.
42. Tashkin DP. Effects of marijuana
smoking on the lung. Ann Am Thorac Soc
43. Pletcher MJ, Vittinghoff E, Kalhan R,
et al. Association between marijuana ex-
posure and pulmonary function over 20
years. JAMA 2012;307:173-81.
44. Owen KP, Sutter ME, Albertson TE.
Marijuana: respiratory tract effects. Clin
Rev Allergy Immunol 2014;46:65-81.
45. Thomas G, Kloner RA, Rezkalla S.
Adverse cardiovascular, cerebrovascular,
and peripheral vascular effects of mari-
juana inhalation: what cardiologists need
to know. Am J Cardiol 2014;113:187-90.
46. Stanley C, O’Sullivan SE. Vascular tar-
gets for cannabinoids: animal and human
studies. Br J Pharmacol 2014;171:1361-78.
47. Rezkalla SH, Sharma P, Kloner RA.
Coronar y no-f low and ventricular tachy-
cardia associated w ith habitual marijuana
use. Ann Emerg Med 2003;42:365-9.
48. Brown HL, Graves CR. Smoking and
marijuana use in pregnancy. Clin Obstet
Gynecol 2013;56:107-13.
49. Jutras-Aswad D, DiNieri JA, Harkany T,
Hurd YL. Neurobiological consequences
of maternal cannabis on human fetal de-
velopment and its neuropsychiatric out-
come. Eur Arch Psychiatry Clin Neurosci
50. ElSohly MA. Potency Monitoring Pro-
gram quarterly report no.123 — report-
ing period: 09/16/2013-12/15/2013. Oxford:
University of Mississippi, National Center
for Natural Products Research, 2014.
51. Drug Abuse Warning Network, 2011:
national estimates of drug-related emer-
gency department visits. Rockville, MD:
Substance Abuse and Mental Health Ser-
vices Administration, 2011 (http://www
52. Joy JE, Watson SJ Jr, Benson JA Jr, eds.
Marijuana and medicine: assessing the
science base. Washington, DC: National
Academy Press, 1999.
53. Merritt JC, Crawford WJ, Alexander
PC, Anduze AL, Gelbart SS. Effect of mari-
huana on intraocular and blood pressure in
glaucoma. Ophthalmology 1980;87:222-8.
54. Hepler RS, Frank IR. Marihuana
smoking and intraocular pressure. JAMA
55. Chen J, Mati as I, Dinh T, et al. Finding
of endocannabinoids in human eye tis-
sues: implications for glaucoma. Biochem
Biophys Res Commun 2005;330:1062-7.
56. Song ZH, Slowey CA. Involvement of
cannabinoid receptors in the intraocular
pressure-lowering effects of WIN55212-2.
J Pharmacol Exp Ther 2000;292:136-9.
57. Nucci C, Bari M, Spanò A, et al. Poten-
tial roles of (endo) cannabinoids in the
treatment of glaucoma: from intraocular
pressure control to neuroprotection. Prog
Brain Res 2008;173:451-64.
58. Zuardi AW. Cannabidiol: from an in-
active cannabinoid to a drug with wide
spectrum of action. Rev Bras Psiquiatr
59. Sallan SE, Zinberg NE, Frei E III. Anti-
emetic effect of delta-9-tetrahydrocanna-
binol in patients receiving cancer chemo-
therapy. N Engl J Med 1975;293:795-7.
60. Parker LA, Kwiatkowska M, Burton P,
Mechoulam R. Effect of cannabinoids on
lithium-induced vomiting in the Suncus
murinus (house musk shrew). Psycho-
pharmacology (Berl) 2004;171:156-61.
61. D’Souza G, Matson PA, Grady CD, et
al. Medicinal and recreational marijuana
use among HIV-infected women in the
Women’s Interagency HIV Study (WIHS)
cohort, 1994-2010. J Acquir Immune Defic
Syndr 2012;61:618-26.
62. Lutge EE, Gray A, Siegfried N. The
medical use of cannabis for reducing
morbidity and mortality in patients with
HIV/AIDS. Cochrane Database Syst Rev
63. Chiou LC, Hu SS, Ho YC. Targeting
the cannabinoid system for pain relief ?
Acta Anaesthesiol Taiwan 2013;51:161-70.
64. Wilsey B, Marcotte T, Tsodikov A,
et al. A randomized, placebo-controlled,
crossover trial of cannabis cigarettes in
neuropathic pain. J Pain 2008;9:506-21.
65. Wallace M, Schulteis G, Atkinson JH,
et al. Dose-dependent effects of smoked
cannabis on capsaicin-induced pain and
hyperalgesia in healthy volunteers. Anes-
the sio log y 2007;107:785-96.
66. Wilsey B, Marcotte T, Deutsch R,
Gouaux B, Sakai S, Donaghe H. Low-dose
vaporized cannabis significantly improves
neuropathic pain. J Pain 2013;14:136-48.
67. Cooper ZD, Comer SD, Haney M.
Comparison of the analgesic effects of
dronabinol and smoked marijuana in
daily marijuana smokers. Neuropsycho-
pharmacology 2013;38:1984-92.
68. Nagarkatti P, Pandey R, Rieder SA,
Hegde VL, Nagarkat ti M. Cannabinoids as
novel anti-inf lammatory drugs. Future
Med Chem 2009;1:1333-49.
69. Esposit o G, Filippis DD, Cirillo C, et a l.
Cannabidiol in inflammatory bowel dis-
eases: a brief overview. Phytother Res
70. Collin C, Davies P, Mutiboko IK, Rat-
cliffe S. Randomized controlled trial of
cannabis-based medicine in spasticity
caused by multiple sclerosis. Eur J 2007;
71. Cent onze D, Mori F, Koch G, et al. Lack
of effect of cannabis-based treatment on
clinical and laboratory measures in multi-
ple sclerosis. Neurol Sci 2009;30:531-4.
72. Porter BE, Jacobson C. Report of a par-
ent survey of cannabidiol-enriched canna-
bis use in pediat ric treatment-resista nt epi-
lepsy. Epilepsy Behav 2013;29:574-7.
73. Kogan NM, Mechoulam R. Cannabi-
noids in health and disease. Dialogues
Clin Neurosci 2007;9:413-30.
74. Hill TD, Cascio MG, Romano B, et al.
Cannabidivarin-rich cannabis ext racts are
anticonvulsant in mouse and rat via a
CB1 receptor-independent mechanism.
Br J Pharmacol 2013;170:679-92.
75. Cristiani SA, Pukay-Martin ND, Born-
stein RA. Marijuana use and cognitive
function in HIV-infected people. J Neuro-
psychiatry Clin Neurosci 2004;16:330-5.
76. Niedbala S, Kardos K, Salamone S,
Fritch D, Bronsgeest M, Cone EJ. Passive
cannabis smoke exposure and oral f luid
testing. J Anal Toxicol 2004;28:546-52.
77. Degenhardt L, Hall W. Extent of illicit
drug use and dependence, and their con-
tribution to the global burden of disease.
Lancet 2012;379:55-70.
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... Although most cannabis users primarily consume the substance for its relaxation and mild euphoric properties, cannabis has immediate undesired side effects such as decrease in short-term memory, dry mouth, impaired motor skills, reddening of the eyes, and feeling of paranoia or anxiety (Hall & Pacula, 2003). Studies (e.g., Forti et al., 2017;Volkow et al., 2014) continue to link cannabis use to the risk of suffering psychotic episodes, as well as numerous adverse effects that directly impact users and the wider society. Cannabis use has been linked to the risk of addiction, poor academic performance, and impeded lifetime achievement, adverse mental health, damaging brain development, vehicle accidents, and as gateways to other drugs (Forti et al., 2017;Volkow et al., 2014). ...
... Studies (e.g., Forti et al., 2017;Volkow et al., 2014) continue to link cannabis use to the risk of suffering psychotic episodes, as well as numerous adverse effects that directly impact users and the wider society. Cannabis use has been linked to the risk of addiction, poor academic performance, and impeded lifetime achievement, adverse mental health, damaging brain development, vehicle accidents, and as gateways to other drugs (Forti et al., 2017;Volkow et al., 2014). Cannabis use has also been associated with increases in antisocial behaviours and can spiral users into socio-economic challenges similar to people with alcohol abuse problems (Cerda et al., 2016). ...
... 36 , 37 Behaviorally and socially, marijuana may be a conduit to the use and eventual abuse of opioids and other addicting substances. [38][39][40][41][42][43][44] A national study of 43,093 cannabis user in the U.S. found that 10%, 20%, and 30% of them had progressed to illicit drug use within 3, 5 and 7 years, respectively, of first exposure to cannabis. 42 A study of 580 youth followed from ages 6 to 26 found that adolescent-onset marijuana use was associated with opioid misuse in young adulthood, including adjustment for socioecological factors associated with opioid misuse. ...
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Background: The hypothesis that marijuana availability reduces opioid mortality merits more complete testing, especially in a country with the world's highest opioid death rate and 2nd highest cannabis-use-disorder prevalence. Methods: The United States opioid mortality rate was compared in states and District of Columbia that had implemented marijuana legalization with states that had not, by applying joinpoint methodology to Centers for Disease Control and Prevention data. Variables included race/ethnicity and fentanyl-type opioids (fentanyls). Results: After the same rates during 2010-2012, the opioid mortality rate increased more rapidly in marijuana-legalizing than non-legalizing jurisdictions (2010-2020 annual pairwise comparison p = 0.003 for all opioids and p = 0.0004 for fentanyls). During the past decade, all four major race/ethnicities in the U.S. had evidence for a statistically-significant greater increase in opioid mortality rates in legalizing than non-legalizing jurisdictions. Among legalizing jurisdictions, the greatest mortality rate increase for all opioids was in non-Hispanic blacks (27%/year, p = 0.0001) and for fentanyls in Hispanics (45%/year, p = 0.0000008). The greatest annual opioid mortality increase occurred in 2020, the first year of the COVID-19 pandemic, with non-Hispanic blacks having the greatest increase in legalizing vs. non-legalizing opioid-death-rate difference, from 32% higher in legalizing jurisdictions in 2019 to more than double in 2020. Conclusions: Instead of supporting the marijuana protection hypothesis, ecologic associations at the national level suggest that marijuana legalization has contributed to the U.S.'s opioid epidemic in all major races/ethnicities, and especially in blacks. If so, the increased use of marijuana during the 2020-2022 pandemic may thereby worsen the country's opioid crisis.
... Likewise, heavy alcohol consumption is causally related to numerous acute and chronic diseases (Rehm et al., 2010). Moreover, the literature shows greater adverse health effects associated with the simultaneous use of alcohol and marijuana (Volkow et al., 2014;Yurasek et al., 2017). The literature also implies that the interaction of alcohol, marijuana, and nicotine may lead to more severe adverse effects (Roche et al., 2019). ...
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Objective This study explored the associations of heavy alcohol consumption with current e-cigarette, cigarette and dual use of e-cigarettes and cigarettes among a nationally representative sample of adults in the United States (US), and if these associations are modified by marijuana use. Methods Data from 157138 adults who participated in the 2020 Behavioral Risk Factor Surveillance System (BRFSS) were included in this cross-sectional analysis. Multinomial logistic regression was used to estimate the strength of the associations between heavy alcohol consumption (independent variable) and the tobacco use patterns (dependent variable, i.e., non-use, current e-cigarette use, current cigarette use and current dual use of e-cigarettes and cigarettes). We also assessed the interaction between past-month marijuana use and heavy alcohol consumption on the primary outcome. Results After the adjustment for potential confounders, heavy alcohol consumption (relative to no heavy alcohol consumption) was associated with higher odds of current e-cigarette (3.91 [2.25-6.78]), cigarette (3.02 [2.28-3.99]) and dual (4.78 [3.25-7.01]) use. The test for interaction showed that the associations of heavy alcohol consumption with the tobacco use patterns were modified by past-month marijuana use (p<0.05 for all groups), with associations being much stronger among past-month marijuana non-users. Conclusions Heavy alcohol consumption is positively associated with current e-cigarette, cigarette, and dual use among US adults. Further, the findings indicate that these relationships are modified by past-month marijuana use. Longitudinal research is needed to explore the role of marijuana in the association of heavy alcohol consumption with current e-cigarette, cigarette and dual use among adults.
... Additionally, it is thought that substance use behaviours cluster together, 40 or that some people are more prone to use drugs or engage in risky behaviours. [41][42] This study also found that adolescents in both age groups who had worked for money were more likely to vape than others who did not. It might be that the wages make vaping affordable for adolescents and that employed adolescents have more exposure to (often older) coworkers who vape. ...
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Background: Vaping is more prevalent among younger than older Canadians. While vaping is less harmful than combustible tobacco, it is not without health risk. Data and methods: Data from the 2019 Canadian Health Survey on Children and Youth were used to estimate vaping prevalence. Logistic regression models assessed the association of sociodemographic, youth, parenting and peer factors with vaping. The 2020 Canadian Community Health Survey identified adolescents who reported vaping before tobacco smoking. Data from the 2019 Canadian Tobacco and Nicotine Survey were used to examine vaping of e-liquids containing nicotine and flavours. Results: Vaping rates for 15- to 17-year-olds were nearly four times (21.3%) higher than those of 12- to 14-year-olds (5.4%). Two-thirds (66.1%) of 12- to 17-year-olds who had used both tobacco and e-cigarettes reported trying e-cigarettes first. E-liquids containing nicotine were used by 89.3% of 15- to 19-year-olds who reported vaping in the past 30 days; comparable with older adults. For both younger and older adolescents, having friends who engaged in negative behaviours, having been employed, and having consumed alcohol increased the odds. For 12- to 14-year-olds, attention deficit hyperactivity disorder was a risk factor, whereas having parents who usually knew who they were with and higher relatedness scores were protective. Among older adolescents, being male, being Canadian-born, having lower grades, and using tobacco or cannabis increased the odds of vaping. Interpretation: An adolescent's risk of vaping was most strongly correlated with other substance use, although other youth, parenting and peer characteristics also mattered. Because most of the data presented were collected before the COVID-19 pandemic and new vaping regulations, ongoing monitoring remains important.
Background To assess Hong Kong medical students’ knowledge, attitudes and beliefs on cannabis and its future legal reform. Methods A cross-sectional anonymous online survey were sent from 1st December 2018 to 31st August 2020 to all medical students from the Li Ka Shing Faculty of Medicine, the University of Hong Kong (HKU). Results 187 students (13.6%) responded the survey. Overall, students perceived cannabis possessed significant physical and mental health risks, but they were more neutral to its physical and mental benefits. They also supported legalizing cannabis more so for medical use than recreational use. Females perceived higher risks than males. Those who used cannabis before were more acceptable to recommend cannabis as medical treatments, perceived cannabis use with greater benefits and less risks, and were more likely to support legal reform for cannabis in Hong Kong than their counterparts. Students were also more likely to recommend medical cannabis than non-licensed cannabis to patients if they were legally available. Conclusion Medical students in Hong Kong supported legalization of cannabis for medical use despite perceiving significant risks from cannabis use. Future research should investigate public acceptance on medical cannabis in Hong Kong and other Asian countries.
Background There has been a lack of systematic exploration of remotely delivered intervention content and their effectiveness for behaviour change outcomes. This review provides a synthesis of the behaviour change techniques (BCT) contained in remotely delivered alcohol and/or substance misuse approaches and their association with intervention promise. Methods Searches in MEDLINE, Scopus, PsycINFO (ProQuest), and the Cochrane Library, included studies reporting remote interventions focusing on alcohol and/or substance misuse among adults, with a primary behaviour change outcome (e.g., alcohol levels consumed). Assessment of risk of bias, study promise, and BCT coding was conducted. Synthesis focussed on the association of BCTs with intervention effectiveness using promise ratios. Results Studies targeted alcohol misuse (52 studies) or substance misuse (10 studies), with predominantly randomised controlled trial designs and asynchronous digital approaches. For alcohol misuse studies, 16 were very promising, 17 were quite promising, and 13 were not promising. Of the 36 eligible BCTs, 28 showed potential promise, with seven of these only appearing in very or quite promising studies. Particularly promising BCTs were ‘Avoidance/reducing exposure to cues for behaviour’, ‘Pros and cons’ and ‘Self-monitoring of behaviour’. For substance misuse studies, three were very promising and six were quite promising, with all 12 BCTs showing potential promise. Conclusions This review showed remotely delivered alcohol and substance misuse interventions can be effective and highlighted a range of BCTs that showed promise for improving services. However, concerns with risk of bias and the potential of promise ratios to inflate effectiveness warrant caution in interpreting the evidence.
Despite decades of research, the precise etiology of schizophrenia is not fully understood. Ample evidence indicates that the disorder derives from a complex interplay of genetic and environmental factors during vulnerable stages of brain maturation. Among the plethora of risk factors investigated, stress, pre- and perinatal insults, and cannabis use have been repeatedly highlighted as crucial environmental risk factors for schizophrenia. Compelling findings from population-based longitudinal studies suggest low income as an additional risk factor for future schizophrenia diagnosis, but underlying mechanisms remain unclear. In this narrative review, we 1) summarize the literature in support of a relationship between low (parental) income and schizophrenia risk, and 2) explore the mediating role of chronic stress, pre- and perinatal factors, and cannabis use as established risk factors for schizophrenia. Our review describes how low income facilitates the occurrence and severity of these established risk factors and thus contributes to schizophrenia liability. The broadest influence of low income was identified for stress, as low income was found to be associated with exposure to a multitude of severe psychological and physiological stressors. This narrative review adds to the growing literature reporting a close relationship between income and mental health.
Marijuana use in the U.S. doubled between 2001 and 2013, largely due to increases in legalization laws. Little attention, however, is given to the type of marijuana user (e.g., recreational or medical), particularly with health outcomes. Our study used data from the 2017 Behavioral Risk Factor Surveillance System (N=5,349) to examine physical health, mental health, and demographic variables by marijuana user type (including non-marijuana users). In physical health, the non-marijuana group was generally healthier, getting the most sleep, lowest BMI, and lowest alcoholic consumption. Medical users self-reported the poorest physical health, BMI, and sleep. Similar results were found in the mental health category between non-marijuana and medical users. Future longitudinal research is needed to investigate whether medical users, over time, increase their marijuana use to include recreational use (i.e., become mixed users) as a method of coping with the combination of health, emotional, and quality of life problems. Although this is among the first nationally representative studies to examine unique marijuana user groups, future studies should track user groups over time to understand the implications of transitioning into medical or recreational user groups.
Background Cannabis is the illegal drug most frequently used by Minors in Austria. Due to the gradual decriminalization and legalization that has taken place in many European countries in recent years, the ÖGKJP would like to take a balanced and scientifically based stand on the complex issue of cannabis use and abuse among young people.Methods The authors searched the medline for current studies using searches tailored to each specific subtopic. Furthermore, recognized compendiums were quoted.ResultsWhile occasional recreational use of cannabis in adults with completed brain maturation and no risk profile for mental disorders is likely to be relatively harmless, early initiation of use with regular use and the increasingly available, highly potent cannabis varieties can lead to explicit and sometimes irreversible neurocognitive brain dysfunction.Conclusion Legalisation of cannabis consumption for minors needs to be objected to due to the risks of the expected damage in the area of brain development. At the same time, however, it is important to establish sensible legal regulations in order to be able to adequately counteract the fact that over 30% of all European young people occasionally consume cannabis. We are also clearly recommending to not criminalize cannabis users and provide necessary support to vulnerable and addicted cannabis users.
Objective Cannabis and alcohol co-use is highly prevalent and confers a host of risk factors that outweigh those related to the use of either substance alone; however, few studies have examined associations between varying levels of co-use intensity (i.e., frequency) and clinical variables. The present study characterizes the effects of co-use across varying levels of cannabis use frequency in a large sample of heavy drinkers. Methods Comparisons among co-use groups (i.e., no, light-to-moderate, and moderate-to-heavy cannabis use; N = 863; 33.95% female) on demographic and clinical variables consisted of one-way analyses of variance for continuous outcomes or Chi-Square tests for dichotomous outcomes. Multinomial logistic regression modeling was used to examine the relationship between demographic and clinical variables and co-use group membership. Multiple linear regression was used to explore associations among variables of interest and cannabis use days. Results Despite relatively low levels of cannabis use overall in the present sample, younger age, identification with male gender, treatment seeking for AUD, and concurrent tobacco use were robust predictors of co-use. Individuals reporting more frequent cannabis use also reported increased levels of alcohol craving and more heavy drinking days, as compared to those who reported fewer or no cannabis use days. Drinking days and treatment seeking for AUD significantly predicted increases in cannabis use days. Conclusion In clinical practice, younger age, male gender, and comorbid tobacco use represent identifiable risk factors for cannabis and alcohol co-use. While in treatment for AUD, reducing drinking days may be an intervention target to mitigate co-use.
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Drugged driving is a safety issue of increasing public concern. Using data from the Fatality Analysis Reporting System for 1999-2010, we assessed trends in alcohol and other drugs detected in drivers who were killed within 1 hour of a motor vehicle crash in 6 US states (California, Hawaii, Illinois, New Hampshire, Rhode Island, and West Virginia) that routinely performed toxicological testing on drivers involved in such crashes. Of the 23,591 drivers studied, 39.7% tested positive for alcohol and 24.8% for other drugs. During the study period, the prevalence of positive results for nonalcohol drugs rose from 16.6% in 1999 to 28.3% in 2010 (Z = -10.19, P < 0.0001), whereas the prevalence of positive results for alcohol remained stable. The most commonly detected nonalcohol drug was cannabinol, the prevalence of which increased from 4.2% in 1999 to 12.2% in 2010 (Z = -13.63, P < 0.0001). The increase in the prevalence of nonalcohol drugs was observed in all age groups and both sexes. These results indicate that nonalcohol drugs, particularly marijuana, are increasingly detected in fatally injured drivers.
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Unlabelled: Cannabis use is associated with an earlier age of onset of psychosis (AOP). However, the reasons for this remain debated. Methods: We applied a Cox proportional hazards model to 410 first-episode psychosis patients to investigate the association between gender, patterns of cannabis use, and AOP. Results: Patients with a history of cannabis use presented with their first episode of psychosis at a younger age (mean years = 28.2, SD = 8.0; median years = 27.1) than those who never used cannabis (mean years = 31.4, SD = 9.9; median years = 30.0; hazard ratio [HR] = 1.42; 95% CI: 1.16-1.74; P < .001). This association remained significant after controlling for gender (HR = 1.39; 95% CI: 1.11-1.68; P < .001). Those who had started cannabis at age 15 or younger had an earlier onset of psychosis (mean years = 27.0, SD = 6.2; median years = 26.9) than those who had started after 15 years (mean years = 29.1, SD = 8.5; median years = 27.8; HR = 1.40; 95% CI: 1.06-1.84; P = .050). Importantly, subjects who had been using high-potency cannabis (skunk-type) every day had the earliest onset (mean years = 25.2, SD = 6.3; median years = 24.6) compared to never users among all the groups tested (HR = 1.99; 95% CI: 1.50- 2.65; P < .0001); these daily users of high-potency cannabis had an onset an average of 6 years earlier than that of non-cannabis users. Conclusions: Daily use, especially of high-potency cannabis, drives the earlier onset of psychosis in cannabis users.
Children exposed in utero to cannabis present permanent neurobehavioral and cognitive impairments. Psychoactive constituents from Cannabis spp., particularly Δ(9)-tetrahydrocannabinol (THC), bind to cannabinoid receptors in the fetal brain. However, it is unknown whether THC can trigger a cannabinoid receptor-driven molecular cascade to disrupt neuronal specification. Here, we show that repeated THC exposure disrupts endocannabinoid signaling, particularly the temporal dynamics of CB1 cannabinoid receptor, to rewire the fetal cortical circuitry. By interrogating the THC-sensitive neuronal proteome we identify Superior Cervical Ganglion 10 (SCG10)/stathmin-2, a microtubule-binding protein in axons, as a substrate of altered neuronal connectivity. We find SCG10 mRNA and protein reduced in the hippocampus of midgestational human cannabis-exposed fetuses, defining SCG10 as the first cannabis-driven molecular effector in the developing cerebrum. CB1 cannabinoid receptor activation recruits c-Jun N-terminal kinases to phosphorylate SCG10, promoting its rapid degradation in situ in motile axons and microtubule stabilization. Thus, THC enables ectopic formation of filopodia and alters axon morphology. These data highlight the maintenance of cytoskeletal dynamics as a molecular target for cannabis, whose imbalance can limit the computational power of neuronal circuitries in affected offspring.
Marijuana has been used to relieve pain for centuries, but its analgesic mechanism has only been understood during the past two decades. It is mainly mediated by its constituents, cannabinoids, through activating central cannabinoid 1 (CB1) receptors, as well as peripheral CB1 and CB2 receptors. CB2-selective agonists have the benefit of lacking CB1 receptor-mediated CNS side effects. Anandamide and 2-arachidonoylglycerol (2-AG) are two intensively studied endogenous lipid ligands of cannabinoid receptors, termed endocannabinoids, which are synthesized on demand and rapidly degraded. Thus, inhibitors of their degradation enzymes, fatty acid amide hydrolase and monoacylglycerol lipase (MAGL), respectively, may be superior to direct cannabinoid receptor ligands as a promising strategy for pain relief. In addition to the antinociceptive properties of exogenous cannabinoids and endocannabinoids, involving their biosynthesis and degradation processes, we also review recent studies that revealed a novel analgesic mechanism, involving 2-AG in the periaqueductal gray (PAG), a midbrain region for initiating descending pain inhibition. It is initiated by Gq-protein-coupled receptor (GqPCR) activation of the phospholipase C (PLC)-diacylglycerol lipase (DAGL) enzymatic cascade, generating 2-AG that produces inhibition of GABAergic transmission (disinhibition) in the PAG, thereby leading to analgesia. This GqPCR-PLC-DAGL-2-AG retrograde disinhibition mechanism in the PAG can be initiated by activating type 5 metabotropic glutamate receptor (mGluR5), muscarinic acetylcholine (M1/M3), and orexin (OX1) receptors. mGluR5-mediated disinhibition can be initiated by glutamate transporter inhibitors, or indirectly by substance P, neurotensin, cholecystokinin, capsaicin, and AM404, the bioactive metabolite of acetaminophen in the brain. The putative role of 2-AG generated after activating the above neurotransmitter receptors in stress-induced analgesia is also discussed.
Unlabelled: Application of cannabinoids and endocannabinoids to perfused vascular beds or individual isolated arteries results in changes in vascular resistance. In most cases, the result is vasorelaxation, although vasoconstrictor responses are also observed. Cannabinoids also modulate the actions of vasoactive compounds including acetylcholine, methoxamine, angiotensin II and U46619 (thromboxane mimetic). Numerous mechanisms of action have been proposed including receptor activation, potassium channel activation, calcium channel inhibition and the production of vasoactive mediators such as calcitonin gene-related peptide, prostanoids, NO, endothelial-derived hyperpolarizing factor and hydrogen peroxide. The purpose of this review is to examine the evidence for the range of receptors now known to be activated by cannabinoids. Direct activation by cannabinoids of CB1 , CBe , TRPV1 (and potentially other TRP channels) and PPARs in the vasculature has been observed. A potential role for CB2, GPR55 and 5-HT1 A has also been identified in some studies. Indirectly, activation of prostanoid receptors (TP, IP, EP1 and EP4 ) and the CGRP receptor is involved in the vascular responses to cannabinoids. The majority of this evidence has been obtained through animal research, but recent work has confirmed some of these targets in human arteries. Vascular responses to cannabinoids are enhanced in hypertension and cirrhosis, but are reduced in obesity and diabetes, both due to changes in the target sites of action. Much further work is required to establish the extent of vascular actions of cannabinoids and the application of this research in physiological and pathophysiological situations. Linked articles: This article is part of a themed section on Cannabinoids 2013. To view the other articles in this section visit
Severe childhood epilepsies are characterized by frequent seizures, neurodevelopmental delays, and impaired quality of life. In these treatment-resistant epilepsies, families often seek alternative treatments. This survey explored the use of cannabidiol-enriched cannabis in children with treatment-resistant epilepsy. The survey was presented to parents belonging to a Facebook group dedicated to sharing information about the use of cannabidiol-enriched cannabis to treat their child's seizures. Nineteen responses met the following inclusion criteria for the study: a diagnosis of epilepsy and current use of cannabidiol-enriched cannabis. Thirteen children had Dravet syndrome, four had Doose syndrome, and one each had Lennox-Gastaut syndrome and idiopathic epilepsy. The average number of antiepileptic drugs (AEDs) tried before using cannabidiol-enriched cannabis was 12. Sixteen (84%) of the 19 parents reported a reduction in their child's seizure frequency while taking cannabidiol-enriched cannabis. Of these, two (11%) reported complete seizure freedom, eight (42%) reported a greater than 80% reduction in seizure frequency, and six (32%) reported a 25-60% seizure reduction. Other beneficial effects included increased alertness, better mood, and improved sleep. Side effects included drowsiness and fatigue. Our survey shows that parents are using cannabidiol-enriched cannabis as a treatment for their children with treatment-resistant epilepsy. Because of the increasing number of states that allow access to medical cannabis, its use will likely be a growing concern for the epilepsy community. Safety and tolerability data for cannabidiol-enriched cannabis use among children are not available. Objective measurements of a standardized preparation of pure cannabidiol are needed to determine whether it is safe, well tolerated, and efficacious at controlling seizures in this pediatric population with difficult-to-treat seizures.