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Marijuana is becoming legal in an increasing number of states for both medical and recreational use. Considerable controversy exists regarding the public health impact of these changes. The evidence for the legitimate medical use of marijuana or cannabinoids is limited to a few indications, notably HIV/AIDS cachexia, nausea/vomiting related to chemotherapy, neuropathic pain, and spasticity in multiple sclerosis. Although cannabinoids show therapeutic promise in other areas, robust clinical evidence is still lacking. The relationship between legalization and prevalence is still unknown. Although states where marijuana use is legal have higher rates of use than nonlegal states, these higher rates were generally found even prior to legalization. As states continue to proceed with legalization for both medical and recreational use, certain public health issues have become increasingly relevant, including the effects of acute marijuana intoxication on driving abilities, unintentional ingestion of marijuana products by children, the relationship between marijuana and opioid use, and whether there will be an increase in health problems related to marijuana use, such as dependence/addiction, psychosis, and pulmonary disorders. In light of this rapidly shifting legal landscape, more research is urgently needed to better understand the impact of legalization on public health. Expected final online publication date for the Annual Review of Medicine Volume 67 is January 14, 2016. Please see http://www.annualreviews.org/catalog/pubdates.aspx for revised estimates.
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Marijuana Legalization: Impact
on Physicians and Public Health
Samuel T. Wilkinson,
1
Stephanie Yarnell,
1
Rajiv Radhakrishnan,
1
Samuel A. Ball,
1,2,3
and Deepak Cyril D’Souza
1,2,4
1
Department of Psychiatry, Yale School of Medicine, New Haven, Connecticut 06511;
email: samuel.wilkinson@yale.edu
2
VA Connecticut Healthcare System, West Haven, Connecticut
3
The National Center on Addiction and Substance Abuse at Columbia University, New York,
NY 10027
4
Abraham Ribicoff Research Facilities, Connecticut Mental Health Center, New Haven,
Connecticut 06511
Annu. Rev. Med. 2016. 67:10.1–10.14
The Annual Review of Medicine is online at
med.annualreviews.org
This article’s doi:
10.1146/annurev-med-050214-013454
Copyright
c
2016 by Annual Reviews.
All rights reserved
Keywords
Abstract
Marijuana is becoming legal in an increasing number of states for both med-
ical and recreational use. Considerable controversy exists regarding the pub-
lic health impact of these changes. The evidence for the legitimate medi-
cal use of marijuana or cannabinoids is limited to a few indications, notably
HIV/AIDS cachexia, nausea/vomiting related to chemotherapy, neuropathic
pain, and spasticity in multiple sclerosis. Although cannabinoids show ther-
apeutic promise in other areas, robust clinical evidence is still lacking. The
relationship between legalization and prevalence is still unknown. Although
states where marijuana use is legal have higher rates of use than nonlegal
states, these higher rates were generally found even prior to legalization.
As states continue to proceed with legalization for both medical and recre-
ational use, certain public health issues have become increasingly relevant,
including the effects of acute marijuana intoxication on driving abilities,
unintentional ingestion of marijuana products by children, the relationship
between marijuana and opioid use, and whether there will be an increase
in health problems related to marijuana use, such as dependence/addiction,
psychosis, and pulmonary disorders. In light of this rapidly shifting legal
landscape, more research is urgently needed to better understand the impact
of legalization on public health.
10.1
ME67CH10-Wilkinson ARI 26 August 2015 14:36
INTRODUCTION
Marijuana is the most commonly used illicit drug in the United States, with 3.1 million individuals
reporting daily use in the last year and 8.1 million individuals reporting using marijuana most days
in the last month in 2013 (1). Marijuana has now been legalized for medical use in 23 states and
the District of Columbia. The process of legalization of marijuana for medical use is substantially
different from the approval of medications by the US Food and Drug Administration (FDA):
Approval occurs by popular vote or the action of a state legislature, and is thus not subject to
the higher standard of evidence required by the FDA for both efficacy and safety. As of April
2015, Colorado, Washington, Alaska, Oregon, and the District of Columbia have also legalized
marijuana for recreational use, with other states likely to follow. At the federal level, however,
marijuana remains illegal as a schedule I controlled substance, a category reserved for substances
with a high potential for abuse, lack of established safety, and no accepted medical use.
The public health impact of marijuana legalization remains a controversial issue. Advocates of
legalization contend that this policy change will provide for more stringent regulation and safer
use of marijuana, more efficient use of law enforcement resources, and possibly even a decline in
the prevalence of marijuana use among adolescents and of the use of “harder” drugs (e.g., cocaine
and heroin) (2, 3). Those opposing legalization cite the adverse effects of marijuana and worry that
legalization will lead to an increase in use, and thus an increase in health problems attributed to
marijuana. The latter view is reflected in the official position statements of prominent professional
medical associations such as the American Psychiatric Association, the American Society of Addic-
tion Medicine, and the American Medical Association, which have expressed concern regarding
the negative consequences of marijuana use. We review the potential impact of marijuana’s le-
galization on public health as well as conditions for which marijuana or its constituents may be a
legitimate treatment option.
OVERVIEW OF MARIJUANA
Unlike pharmaceutical medications, marijuana is not a single-agent compound but a complex
combination of more than 100 different chemicals, which include cannabinoids, flavonoids, and
terpinoids. The primary psychoactive component of marijuana is delta-9-tetrahydrocannabinol
(THC). However, other cannabinoid compounds—including cannabidiol (CBD), cannabinol,
cannabichromene, cannabidivarin, cannabigerol, and tetrahydrocannabivarin—have their own ac-
tions on the central nervous system and may modify the effects of THC (“entourage effects”). The
concentration of these compounds can vary substantially (4), making it difficult to characterize the
specific positive or negative health effects of marijuana, especially in uncontrolled and epidemio-
logical studies. In addition, the average content of THC in marijuana (as measured in confiscated
marijuana samples in the United States) has increased substantially from 1% in the 1980s to
9% in 2008 (5, 6). As THC is thought to be related to many of marijuana’s adverse effects,
this increase in potency means that relying on older studies for data about marijuana’s safety pro-
file may be problematic. Furthermore, given that individual cannabinoids present in whole-plant
marijuana have different pharmacological effects, data on individual cannabinoids cannot neces-
sarily be extrapolated to whole-plant marijuana and vice versa. More research is urgently needed
in light of the changing legal landscape and the increasing potency of marijuana.
ROUTES OF ADMINISTRATION
Marijuana is typically consumed via smoking of joints or blunts (dried marijuana leaves rolled
into cigarettes or cigars, respectively). More recently, in an effort to avoid the potentially harmful
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byproducts of burning marijuana, use of vaporizers has increased. Although this method of cannabis
consumption may theoretically avoid the inhalation of toxins, rigorous clinical studies confirming
its safety have not yet been done. When smoked or given intravenously, THC is rapidly absorbed,
producing physical effects within minutes. Oral doses delay the onset of effects by 30–120 min,
produce lower and irregular peak plasma levels compared to smoked THC, and prolong the
action of the drug (7). The inhaled route allows for real-time dose titration, whereas delayed onset
with oral consumption means that the individual cannot reduce the dose once effects, including
negative ones, emerge. Hence, individuals who are not familiar with the effects of THC or other
cannabinoids may become overwhelmed by the effects of oral consumption.
Although marijuana remains illegal at the federal level, individual components of marijuana
have been purified, tested, and approved by the FDA or similar regulatory agencies as medi-
cations for certain conditions. Oral THC is available as Dronabinol (Marinol
R
) and has been
approved by the FDA for the treatment of HIV/AIDS cachexia (8, 9) and nausea/vomiting related
to chemotherapy (10–12). Nabilone (Cesamet
R
) is an oral THC analog that is FDA-approved
for the treatment of nausea/vomiting related to chemotherapy (13). Nabiximols (Sativex
R
)isan
admixture of THC and CBD (approximately 1:1 ratio) in an oromucosal spray formulation; it has
been approved by regulatory agencies in Canada and many countries throughout Europe to treat
spasticity in multiple sclerosis (MS) (14, 15).
The list of qualifying conditions for which medical marijuana (most commonly consumed by
smoking) is legal on the state level varies substantially (Table 1), as does the level of evidence
for each condition (Table 2). Common conditions include pain, HIV/AIDS, cancer, glaucoma,
epilepsy/seizures, nausea/vomiting, spasticity/MS, agitation in Alzheimer’s disease, and posttrau-
matic stress disorder (PTSD). Although dronabinol and nabilone are both FDA-approved for
HIV/AIDS cachexia and chemotherapy-related nausea/vomiting, it is not known whether mari-
juana is also efficacious for the treatment of these conditions. The numerous other compounds
(i.e., cannabinoids, flavonoids, terpinoids) present in smoked or edible marijuana may interact with
the actions of THC. Large randomized controlled trials (RCTs) have shown efficacy of nabixi-
mols for MS-related spasticity, and at least two RCTs of smoked marijuana or an oral cannabis
extract also show efficacy in this condition (16, 17). At least three RCTs (total n = 101), designed
to test the efficacy of smoked marijuana for at least five days in treating neuropathic pain, have
been positive (18–20), with additional evidence from challenge studies. Additionally, large trials
testing the efficacy of nabiximols or an oral cannabis extract in neuropathic pain have also shown
benefit (17, 21, 22). Robust clinical evidence (i.e., largeRCTs) for other indications is generally
lacking (Table 2). Preclinical research, however, is promising: cannabinoids have demonstrated
anti-inflammatory (23) and anticonvulsant (24) properties. Furthermore, THC and CBD have
been shown to enhance extinction learning, a process critical in the treatment of PTSD (39, 40).
Evidence also suggests that cannabinoids may transiently lower intraocular pressure, suggest-
ing promise in the treatment of glaucoma (41). However, further research is needed to examine
whether these preclinical findings translate into clinical efficacy and to explore the potential risks
of smoked or edible marijuana compared to oral/nasal cannabis extracts.
RELATIONSHIP BETWEEN LEGALIZATION AND PREVALENCE
As marijuana has well-documented adverse health effects (discussed below), one of the principal
questions permeating the legalization debate is whether liberalized marijuana laws will lead to
increased prevalence of use. Generally, US states that have legalized medical or recreational
marijuana have higher rates of use than those where all forms of marijuana remain illegal (42–44).
However, it is difficult to ascertain whether this is attributable to legalization or is associated with
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Table 1 Common qualifying condition in states with medical marijuana laws
State (standard US postal abbreviations)
Qualifying
Condition
AK AZ CA
a
CO CT DC DE HI IL MA
a
MD ME MI MN MT NH NJ NM NV NY OR RI VT WA
Cancer X X X X X X X X X X X X X X X X X X X X X X X X
Glaucoma X X X X X X X X X X X X X X X X X X X X X
HIV/AIDS X X X X X X X X X X X X X X X X X X X X X X X X
Cachexia X X X X X X X X X X X X X X X X X X X X X
Pain X X X X X X X X X X X X X X X X X X X X X X X X
Nausea X X X X X X X X X X X X X X X X X X X X X X
Seizures/
epilepsy
X X X X X X X X X X X X X X X X X X X X X X X
Multiple
sclerosis
X X X X X X X X X X X X X X X X X X X X X X
Hepatitis C X X X X X X X X X X X X
Crohn’s
disease
X X X X X X X X X X X X X X
Agitation in
Alzheimer’s
X X X X X X X X X X X
Amyotrophic
lateral
sclerosis
X X X X X X X X X X X X X
Posttraumatic
stress
disorder
X X X X X X X X
Arthritis X X
Parkinson’s
disease
X X X X
a
Law allows physicians to recommend marijuana for any condition that they feel marijuana may help treat.
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Table 2 Evidence supporting the use of marijuana/cannabinoids for selected conditions
a
Agitation in Alzheimer’s
disease
Small RCT (N = 12) showed a decrease in agitation from dronabinol treatment, though sedation was a common
side effect, suggesting a nonspecific effect (25)
Long-term safety of psychoactive cannabinoids in demented patients is potentially problematic and has not been
thoroughly evaluated
Cachexia/anorexia Dronabinol is approved by the FDA for the treatment of cachexia in HIV/AIDS (8, 9)
Large RCT (N = 243) comparing oral THC, oral cannabis extract, and placebo for the treatment of
cancer-related cachexia showed no difference between treatment groups (26). Another large RCT (N = 469)
showed oral THC is inferior to megestrol in cancer-related cachexia (27)
Crohn’s disease Small RCT (N = 21) showed no difference in remission but suggested symptomatic improvement in the group
receiving active cannabis cigarettes; no objective measures (i.e., endoscopic biopsies) were evaluated (28)
Although preclinical evidence suggests a possible anti-inflammatory role of cannabinoids (23), large RCTs have not
established the efficacy of marijuana in Crohn’s disease
Epilepsy Three small RCTs (total N = 36) suggest cannabidiol may be useful in the treatment of epilepsy (29–31), but this
evidence is insufficient to draw definitive conclusions of cannabidiol’s long-term safety and efficacy (32). Larger
RCTs evaluating efficacy or safety of marijuana/cannabinoids in epilepsy have not been done
Nausea/vomiting Nausea and vomiting were among the first indications for which cannabinoids were approved for use. Dronabinol
(oral THC) and nabilone (an oral THC analog) are approved by the FDA for the treatment of chemotherapy-
induced nausea and vomiting (10–13)
Pain Large and moderately sized RCTs have demonstrated the efficacy of nabiximols or an oral cannabis extract to treat
neuropathic pain (21, 33, 34), although not all trials have been positive (NCT01606202; NCT00710424)
Smaller trials of limited duration (5 days) have suggested that smoked marijuana may be efficacious in treating
neuropathic pain (18–20)
Preliminary data exist for rheumatoid arthritis (35), although less evidence exists for non-neuropathic pain
Posttraumatic stress disorder
(PTSD)
A small RCT (N = 10) suggested that nabilone may improve nightmares in PTSD (36). Larger RCTs evaluating
efficacy and safety of marijuana/cannabinoids in PTSD have not been done
Spasticity Nabiximols is approved by regulatory agencies in Europe and Canada for the treatment of spasticity related to MS
(37, 38)
At least two RCTs show that smoked marijuana or an oral extract may be efficacious in the treatment of MS-related
spasticity (16, 17)
Abbreviations: FDA, US Food and Drug Administration; MS, multiple sclerosis; RCT, randomized controlled trial; THC, tetrahydrocannabinol.
a
Randomized controlled trials (placebo- or active-controlled), but not open-label or observational studies, are included as evidence.
regional variation in permissive attitudes or perceived risk with regard to marijuana (43). Indeed,
legal-marijuana states generally have higher rates of use even before legalization (42, 43).
The prevalence of marijuana use in adolescents is a point of particular interest in the policy
debate because many of the negative health effects of the drug (addiction/dependence, psychosis,
cognitive impairment) are heightened when use begins in adolescence (45–47). Evidence also sug-
gests that cannabis use in adolescence and early adulthood is associated with poor social outcomes,
including unemployment, lower income, and lower levels of life and relationship satisfaction (48).
Decades’ worth of data from the Monitoring the Future survey have shown a clear inverse rela-
tionship between risk perception and marijuana use among adolescents: the more risk attributed to
marijuana, the lower the percent of use among young people (49). This relationship has also been
seen among adults (50) and across age groups (51). It is feared that any decline in risk perception
resulting from legalization will be followed by an increase in prevalence of use.
Despite these concerns, several studies have failed to find a measurable effect of legalization for
medical use on adolescent prevalence using a pre–post analysis (43), a comparison with regionally
proximate states (42), or a difference-in-differences analysis (52). Two of these studies, however,
did not include data from marijuana-policy bellwether states such as Colorado, California, or
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Washington (42, 52). Data from the Youth Risk Behavior Survey (sponsored by the Centers for
Disease Control and Prevention) show an increase in youth rates of marijuana use (from 2011 to
2013) in New Mexico since medical marijuana was legalized in 2009, although this trend among
adolescents has thus far not been found in other states (53).
In 2009, the Obama administration issued a memorandum (the Ogden Memo) which instructed
prosecutors and law enforcement officials not to focus federal resources on individuals “whose
actions are in clear and unambiguous compliance with existing state laws providing for the medical
use of marijuana” (54), essentially decriminalizing medical marijuana use at the federal level. This
policy shift was associated with a drastic increase in medical marijuana registration applications in
Colorado (55); to our knowledge, this association has not been thoroughly evaluated in other states.
As noted above, most studies in adolescents have found no measurable effect of state-level policy
changes on marijuana prevalence (53); however, it is still too early to know the possible long-term
consequences of legalization for individuals and society. Furthermore, almost all studies evaluating
the policy effects of legalization have focused on the point in time when individual states legalized
marijuana; few have focused on the policy effects of the Ogden Memo (56). Three studies that
have compared pre- and post-2009 trends (in an effort to capture potential effects of the federal
shift in policy) have all found measurable differences in risk perception (51), an increased number
of drivers involved in motor vehicle fatalities who had positive toxicology tests for cannabis (55),
and an increase in unintentional pediatric ingestions of marijuana products (57). Further research
is needed to clarify the relationships among decriminalization, legalization, and prevalence.
DIVERSION OF LEGAL MARIJUANA TO MINORS
Another concern regarding adolescents and the legalization of marijuana is that of drug diversion,
or that adolescents will have access to cannabis from adults with legal access to medical or recre-
ational marijuana. In a cross-sectional survey (n = 80), almost half of adolescents participating in
outpatient substance-abuse treatment in Colorado reported using diverted marijuana. Compared
to those who had not used diverted medical marijuana, those who had were more likely to r eport
easy availability of marijuana, >20 times of use per month in the past year, and minimal peer
disapproval of regular use (58). Another study found a similarly high rate (74%) of adolescents
engaged in substance-abuse treatment who reported having used diverted medical marijuana (59).
In Colorado, the legalization of marijuana and its de facto decriminalization on the federal
level have led to the emergence of pediatric (nine years of age or younger) cases of unintentional
ingestion of marijuana products. From 2005 to October 2009 (prior to the Ogden Memo), there
were no marijuana-related emergency room (ER) visits for unintentional ingestions in Colorado.
From October 2009 through 2011 (following the Ogden Memo), there were 14 pediatric uninten-
tional ingestion ER visits that involved marijuana products, accounting for 2.4% of all ingestion
visits in the state (57). An analysis of national data from 2005–2011 found a 30% annual rate of
increase of such cases in states where medical marijuana was legal prior to 2005, whereas rates in
nonlegal states do not seem to be changing (60).
MARIJUANA AND OPIOID USE
Another important issue in the policy debate regarding marijuana legalization is the relationship
between marijuana and opioid use. Evidence suggests that marijuana and/or cannabinoids can
effectively mitigate some forms of pain or discomfort. It is an empirical question whether medical
marijuana would allow those prescribed opioid analgesics to taper off or at least reduce the dose of
their traditional pain medications (61). To our knowledge, no clinical trial evaluating the efficacy of
cannabis or cannabinoids for chronic pain has shown that cannabis use allows patients to lower their
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dose of opioid analgesics. Also, cannabis use has traditionally been associated with an increased
use of opioids (62). However, one recent study suggests that the passage of medical marijuana laws
may be associated with a decrease over time in opioid overdose mortality compared to estimates
of overdose mortality had these laws not been passed. Notably, states with medical marijuana laws
have higher rates of age-adjusted opioid overdose mortality than do states without such laws (63).
Further research is needed from epidemiological studies (to examine the relationship between
the passage of medical marijuana laws and prevalence of opioid use) and from clinical trials (to
investigate whether marijuana used to treat pain can allow patients to lower their opioid analgesic
doses and maintain similar rates of analgesia).
MARIJUANA AND DRIVING
With recent changes in its legal status, the impact of marijuana on driving ability is increasingly
relevant. Marijuana is the most common illicit drug reported in motor vehicle accidents (MVA)
(45). However, it is difficult to ascertain a causal contribution in many of these accidents as
marijuana has substantially varied effects on driving abilities due to factors such as tolerance,
differences in smoking techniques, and differences in absorptions of THC (64). Evidence has
shown that the potential negative effects of marijuana on driving may disappear after controlling
for other risky driving behaviors (65). Epidemiological studies attempting to characterize the
relationship between acute marijuana intoxication and MVA culpability have been mixed and are
not as strong as the relationship between alcohol intoxication and MVAs (66).
Experimental studies indicate that acute intoxication with marijuana affects a number of cog-
nitive and motor skills that are relevant to driving, including reaction time, attention, signal
detection, information processing speed, spatial working memory, verbal learning and recall, pro-
cedural memory, tracking accuracy, time and distance estimation, set shifting, motor coordination,
and danger perception (46). Results from driving simulator studies suggest that the effects of mar-
ijuana on driving may be dose dependent, with minimal to no impairment at low doses (67, 68)
and progressive impairment with increasing dose (64). Also, the effects of marijuana may be more
pronounced as the complexity of tasks increases (69). Notably, heavy users may exhibit minimal
functional impairment in selected driving tasks (64, 70), presumably due to tolerance.
Whereas alcohol intoxication leads drivers to underestimate their impairment (resulting in
speeding and other forms of increased risk taking), marijuana generally leads drivers to overesti-
mate their impairment (resulting in slower driving speeds despite explicit instructions to maintain
a particular speed). However, the combined effects on driving ability of marijuana and alcohol do
not nullify each other. Evidence suggests that impairment as a result of both substances is greater
than either alone (64) and may be more than additive (71).
The number of fatal cannabis-associated MVAs may be increasing. One Colorado study sug-
gests that the number of fatal MVAs in which the driver was cannabis positive has increased with
legalization, particularly with the change in federal policy in 2009; no such trend was seen in states
without medical marijuana laws (55). However, given that the number of fatal MVAs has been on
the decline in Colorado since 2004 (55), the perceived increase in marijuana-positive MVAs may
merely reflect the general increase in cannabis use in Colorado over the study period. Further,
as discussed above, the finding that a driver is marijuana positive at the time of a MVA does not
indicate that marijuana was the cause of the accident (64).
ADVERSE HEALTH EFFECTS
Marijuana use is linked to several adverse health outcomes, including addiction, impaired cogni-
tion, pulmonary effects, mental illness, and other problems (45).
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Addiction/Dependence
Approximately one in ten adult users of marijuana develops addiction, and this number is higher
among adolescents (72). The lifetime dependence rate of marijuana is generally lower than the
rates of other drugs, including alcohol, heroin, and cocaine (73). However, marijuana dependence
is the most prevalent substance-abuse diagnosis, excepting alcohol and tobacco dependence (1).
Impaired Cognitive Abilities
Acute effects. Among infrequent (nondaily) users, m arijuana causes impairment in the areas of
attention and concentration, impulse control, planning, decision making, and working memory
0–6 h after use (46, 74). Marijuana use results in slower response time in tasks of simple reaction
time, visuospatial selective attention, sustained attention, divided attention, and short-term mem-
ory, as well as impairment on a task of motor control (75). In chronic, daily users of cannabis,
acute abstinence results in greater cognitive impairment than acute use. In fact, marijuana may
normalize the cognitive dysfunction seen with cannabis withdrawal; however, this likely repre-
sents a lower level of cognitive function compared to that prior to onset of use(74). No significant
differences were observed for critical-tracking or divided-attention task performance in a cohort
of heavy, chronic cannabis smokers (76).
Persistent effects. Chronic marijuana use is associated with persistent impairment of attention,
verbal memory, working memory, decision making, and executive function (46, 74). Although
early evidence (using traditional neuropsychological assessments) showed that cognitive deficits
associated with marijuana use resolved by day 28 of abstinence (77), more recent data show subtle,
persistent cognitive deficits despite prolonged abstinence (78, 79). In support of these data is the
finding of a dose-dependent effect on cognition, such that early and greater quantity of marijuana
use results in greater cognitive deficits (80). This is particularly true for adolescents who begin
smoking marijuana in their early teens. In one study, adolescents who began smoking cannabis
early (14–22 years of age) and stopped by age 22 had significantly greater cognitive deficits at age
27 than nonusing peers (81). About 10% of cannabis-dependent adolescents report experiencing
a “serious problem” with memory loss (82). In a longitudinal birth cohort comprising 1,037
individuals followed through 38 years (the Dunedin study), persistent marijuana use was associated
with a six-point decline in intelligence quotient; these deficits were greater (eight points) when
use began in adolescence, and, importantly, these declines did not reverse after the cessation of
marijuana use (47).
Psychosis
Marijuana intoxication is associated with transient psychosis-like effects, including paranoia, ideas
of reference, flight of ideas, pressured thought, disorganized thinking, persecutory or grandiose
delusions, and auditory/visual hallucinations (46). Chronic daily use of marijuana has been associ-
ated with the emergence of a persistent psychotic disorder indistinguishable from schizophrenia
(46), although a causal link remains controversial. The current evidence suggests that marijuana
use may be a “component cause” in that it is neither necessary nor sufficient to cause schizophre-
nia (83). Like other negative effects of cannabis, the risk of psychosis appears to be heightened
by heavy and early use (84). Large epidemiological studies have shown a dose-dependent risk
for chronic psychosis as a result of marijuana exposure (83). Clearly, most people who consume
marijuana do not experience psychosis; the marijuana–psychosis link may be mediated through
genetic [COMT mutation (85)] and environmental [childhood maltreatment (86)] factors. With
the rising potency of marijuana strains, there is some evidence that rates of first-episode psychosis
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are also rising (87). Further, among persons with established psychotic disorders, marijuana use is
associated with a worse course of illness (88). Chronic, daily cannabis use is also associated with
the emergence of amotivational syndrome, characterized predominantly by a lack of motivation
and drive (46).
Pulmonary Effects
Although marijuana smokers generally consume their cigarettes (joints) at a fraction of the quan-
tity seen in tobacco smokers, legitimate concerns persist about the pulmonary effects of cannabis
smoke, especially given that some evidence suggests higher levels of carcinogens and tars in
cannabis cigarettes than in tobacco cigarettes (89). After adjusting for tobacco use and other
potential confounders, some (90, 91) but not all (92) studies implicate cannabis consumption as a
risk factor for lung cancer. Chronic cannabis use may lead to symptoms of bronchitis (93), although
moderate marijuana use does not seem to be associated with these symptoms (94). Cannabis va-
porizers are becoming increasingly popular and have been purported to decrease the amount of
toxins delivered; thorough research investigating the comparative safety of marijuana smoking
versus vaporization has not been done.
INTERACTIONS WITH OTHER DRUGS
In vitro studies have shown that cannabinoids can inhibit a number of hepatic enzymes that me-
tabolize common drugs, including CYP2D6 (95), CYP2C19 (96), CYP2C9 (97), and CYP3A4
(98). Other evidence in humans suggests that marijuana may also interfere with the drug concen-
trations of warfarin (99) and antiretroviral therapies (100). Further research is needed to explore
how components of marijuana might interact with other medications in a clinical setting.
SUMMARY
The legal status of marijuana is rapidly changing, with important implications for public health
and physician practice. The evidence for the legitimate medical use of marijuana or cannabi-
noids is limited to a few indications, notably HIV/AIDS cachexia, nausea/vomiting related to
chemotherapy, neuropathic pain, and spasticity in MS. Although cannabinoids show therapeutic
promise in other areas, robust clinical evidence is still lacking. The relationship between legaliza-
tion and prevalence is still unknown. States with legalized marijuana do have higher rates of use
than nonlegal states, but these higher rates are generally found even prior to legalization.
As states continue to proceed with legalization for both medical and recreational use, a number
of public health issues have become increasingly relevant, including the effects of acute marijuana
intoxication on driving abilities, unintentional ingestion of marijuana products by children, the
relationship between marijuana and opioid use, and whether there will be an increase in health
problems related to marijuana use, such as dependence/addiction, psychosis, and pulmonary prob-
lems. In light of the rapidly shifting legal landscape, more research is urgently needed to better
understand the impact of legalization on public health.
DISCLOSURE STATEMENT
The authors are not aware of any affiliations, memberships, funding, or financial holdings that
might be perceived as affecting the objectivity of this review.
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ACKNOWLEDGMENTS
This work was supported in part by NIMH grant 5R25MH071584-08 (S.T.W. and R.R.) and
5T32MH019961-18 (S.Y.).
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... Cannabis is also used as an antiemetic agent in various conditions. One of the side effects of the chronic and improper use of cannabis is hyperemesis syndrome (HES), which is becoming more common with increased use as a result of the legalization of marijuana [52][53][54][55]. Nausea and vomiting result from complex interactions between afferent and efferent pathways of the gastrointestinal tract, central nervous system, and autonomic nervous system [52,53]. ...
... Given the outcomes of recent legislation, it is likely that marijuana will be legalized in many states in the U.S. and in other parts of the world in the future [54,55]. Therefore, rigorous scientific research must be conducted so as to identify the specific targets, pharmacological effects, and the pharmacokinetic and pharmacovigilance profiles for the effective use of cannabis, and that should be supported by evidence-based clinical trials. ...
Article
Full-text available
The most common medicinal claims for cannabis are relief from chronic pain, stimulation of appetite, and as an antiemetic. However, the mechanisms by which cannabis reduces pain and prevents nausea and vomiting are not fully understood. Among more than 450 constituents in cannabis, the most abundant cannabinoids are Δ9-tetrahydrocannabinol (THC) and cannabidiol (CBD). Cannabinoids either directly or indirectly modulate ion channel function. Transient receptor potential vanilloid 1 (TRPV1) is an ion channel responsible for mediating several modalities of pain, and it is expressed in both the peripheral and the central pain pathways. Activation of TRPV1 in sensory neurons mediates nociception in the ascending pain pathway, while activation of TRPV1 in the central descending pain pathway, which involves the rostral ventral medulla (RVM) and the periaqueductal gray (PAG), mediates antinociception. TRPV1 channels are thought to be implicated in neuropathic/spontaneous pain perception in the setting of impaired descending antinociceptive control. Activation of TRPV1 also can cause the release of calcitonin gene-related peptide (CGRP) and other neuropeptides/neurotransmitters from the peripheral and central nerve terminals, including the vagal nerve terminal innervating the gut that forms central synapses at the nucleus tractus solitarius (NTS). One of the adverse effects of chronic cannabis use is the paradoxical cannabis-induced hyperemesis syndrome (HES), which is becoming more common, perhaps due to the wider availability of cannabis-containing products and the chronic use of products containing higher levels of cannabinoids. Although, the mechanism of HES is unknown, the effective treatment options include hot-water hydrotherapy and the topical application of capsaicin, both activate TRPV1 channels and may involve the vagal-NTS and area postrema (AP) nausea and vomiting pathway. In this review, we will delineate the activation of TRPV1 by cannabinoids and their role in the antinociceptive/nociceptive and antiemetic/emetic effects involving the peripheral, spinal, and supraspinal structures.
... 1 Fentanyl, tramadol, hydromorphone and morphine, the most commonly prescribed opioids, are used in acute and chronic pain management, and non-pain conditions such as multiple sclerosis. 2,3 Although the total number and rate of opioid prescription dispensed have declined in the last decade, the incidence of opioid use disorder (OUD) and rate of opioid overdose death are both increasing. 4,5 Over 40 million people suffer from opioid misuse or OUD globally. ...
Preprint
IMPORTANCE: Clinical epidemiological studies have found high rates of comorbidity between suicide attempts (SA) and opioid use disorder (OUD). However, the patterns of correlation and causation between them are still not clear due to psychiatric confounding. OBJECTIVE: To investigate the pairwise associations and interrogate the potential bidirectional relationship between OUD and SA using genetically based methods. DESIGN, SETTING, AND PARTICIPANTS: We utilized raw phenotypes and genotypes from UK Biobank, and summary statistics from Million Veteran Program, Psychiatric Genomic Consortium, iPSYCH, and International Suicide Genetics Consortium. Statistical genetics tools were used to perform epidemiological association, genetic correlation, polygenic risk score prediction, and Mendelian randomizations (MR). Analyses were conducted to examine the OUD-SA relationship with and without controlling for psychiatric disease status (e.g., major depressive disorder [MDD]). MAIN OUTCOMES AND MEASURES: OUD and SA with or without major psychiatric disorders (schizophrenia, bipolar disorder, major depressive disorder, and alcohol use disorder). RESULTS: Strong correlations between OUD and SA were observed at both phenotypic level (overall samples [OR=2.94, P =1.59e-14]; non-psychiatric subgroup [OR=2.15, P =1.07e-3]) and genetic level (r2=0.4 and 0.5 with or without conditioning on MDD). The higher genetic susceptibility to SA can increase the polygenic risk of OUD (OR=1.08, false discovery rate [FDR] =1.71e-3), while the higher susceptibility to OUD can also increase the risk of SA (OR=1.09, FDR =1.73e-6). However, predictive abilities for both were much weakened after controlling for influence of psychiatric diseases. A combination of different MR analyses suggested a possible causal association from SA to OUD (2-sample univariable MR: OR=1.14, P = 0.001; multivariable MR: OR=1.08, P = 0.001). CONCLUSIONS AND RELEVANCE: This study provided new genetic evidence underlying the strong OUD-SA comorbidity. While controlling for the influence of psychiatric diseases, there is still some clue on possible causal association between SA genetic liability and the risk for OUD. Future prevention strategy for each phenotype needs to take into consideration of screening for the other one.
... Phyto-and synthetic cannabinoid actions on neuronal excitability have become of increasing importance because of the widespread legalization of marijuana for medicinal and recreational use (Wilkinson et al., 2016). Our demonstration that VGSC inhibition by AEA occurs via CB1 provides an explanation for the antiepileptic and analgesic actions of exogenous cannabinoids (Benedetti et al., 2011;Holdcroft et al., 2006;Michalski et al., 2007;Perucca, 2017;Stockings et al., 2018). ...
Preprint
Endogenous cannabinoid signaling is vital for important brain functions and can be modified pharmacologically to treat pain, epilepsy, and posttraumatic stress disorder. Endocannabinoid mediated changes to excitability are predominantly attributed to 2-arachidonoylglycerol at synapses. Here we identify a pathway in the neocortex by which anandamide, the other major endocannabinoid, powerfully inhibits sodium conductances in the soma resulting in a loss of neuronal excitability. This pathway is mediated by the cannabinoid receptor, and its activation results in a decrease of recurrent action potential generation. The synthetic cannabinoid, WIN 55,212-2, also inhibits VGSC currents indicating this pathway is positioned to mediate the actions of exogenous cannabinoids. Highlights Anandamide (AEA), a major endocannabinoid, indirectly inhibits VGSC currents in neocortical neurons. This prevalent signaling pathway involves AEA activation of CB1 and other G-protein-coupled receptors localized to the intracellular compartment of neurons. CB1 activation by AEA reduces VGSC availability at the soma but not at the axonal compartment suggesting tighter functional coupling between VGSCs and CB1 at the cell body. Cannabinoid action on somatic CB1 inhibits VGSCs with high efficacy, providing a parallel pathway outside of nerve terminals, by which these ligands reduce neuronal excitability in the neocortex.
... Among the different ligands able to modulate the cannabinoid receptors, those present in the C. sativa plant exhibit a significant interest not only because of their role as possible therapeutic agents but also because of their increasing recreational use which may also pose a public health issue (Hall and Lynskey, 2016;Wilkinson et al., 2016). Knowing the details of the stimulation of different cannabinoid receptors by phytocannabinoid compounds may provide pharmacological tools to finely tune the endocannabinoid system. ...
Article
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Cannabidiol (CBD), the major non-psychoactive phytocannabinoid present in the plant Cannabis sativa, has displayed beneficial pharmacological effects in the treatment of several neurological disorders including, epilepsy, Parkinson’s disease, and Alzheimer’s disease. In particular, CBD is able to modulate different receptors in the endocannabinoid system, some of which belong to the family of G-protein-coupled receptors (GPCRs). Notably, while CBD is able to antagonize some GPCRs in the endocannabinoid system, it also seems to activate others. The details of this dual contrasting functional feature of CBD, that is, displaying antagonistic and (possible) agonistic ligand properties in related receptors, remain unknown. Here, using computational methods, we investigate the interacting determinants of CBD in two closely related endocannabinoid-activated GPCRs, the G-protein-coupled receptor 55 (GPR55) and the cannabinoid type 1 receptor (CB 1 ). While in the former, CBD has been demonstrated to function as an antagonist, the way by which CBD modulates the CB 1 receptor remains unclear. Namely, CBD has been suggested to directly trigger receptor’s activation, stabilize CB 1 inactive conformations or function as an allosteric modulator. From microsecond-length unbiased molecular dynamics simulations, we found that the presence of the CBD ligand in the GPR55 receptor elicit conformational changes associated with antagonist-bound GPCRs. In contrast, when the GPR55 receptor is simulated in complex with the selective agonist ML186, agonist-like conformations are sampled. These results are in agreement with the proposed modulatory function of each ligand, showing that the computational techniques utilized to characterize the GPR55 complexes correctly differentiate the agonist-bound and antagonist-bound systems. Prompted by these results, we investigated the role of the CBD compound on the CB 1 receptor using similar computational approaches. The all-atom MD simulations reveal that CBD induces conformational changes linked with agonist-bound GPCRs. To contextualize the results we looked into the CB 1 receptor in complex with a well-established antagonist. In contrast to the CBD/CB 1 complex, when the CB 1 receptor is simulated in complex with the ligand antagonist AM251, inactive conformations are explored, showing that the computational techniques utilized to characterize the CB 1 complexes correctly differentiate the agonist-bound and antagonist-bound systems. In addition, our results suggest a previously unknown sodium-binding site located in the extracellular domain of the CB 1 receptor. From our detailed characterization, we found particular interacting loci in the binding sites of the GPR55 and the CB 1 receptors that seem to be responsible for the differential functional features of CBD. Our work will pave the way for understanding the CBD pharmacology at a molecular level and aid in harnessing its potential therapeutic use.
... welche dieser Tätigkeiten kausal auf den Cannabiskonsum oder die Regulierung zurückzuführen sind. Da Cannabiskonsum als Risikofaktor für verschiedene negative soziale und gesundheitliche Auswirkungen gilt(Hall 2015;Levine et al. 2017; National Academies of Sciences 2017;Weiss et al. 2017;Wilkinson et al. 2016), aber selten der alleinige verursachende Faktor ist, ist diese Aufgabe von besonderer Bedeutung.Die umfassendsten und aktuellsten Bestandsaufnahmen der Beziehung zwischen Cannabiskonsum und gesundheitlichen Folgen wurde von den National Academies of Sciences(2017),Hall (2015) undLevine et al. (2017) zusammengefasst. Sie fassen den aktuellen Stand der Forschung zum Cannabiskonsum und einer Vielzahl von Gesundheitsfolgen wie Krebs, Atemwegserkrankungen, Verletzungen und Tod sowie psychosoziale und psychische Gesundheit zusammen. ...
... El cannabis, también conocido como marihuana, es la droga ilícita más usada a nivel mundial (1) , esta sustancia se obtiene a partir de la planta Cannabis sp, y su actividad psicotrópica ocurre principalmente por el componente delta 9-tetrahidrocannabinol (Δ9-THC) (2) . El consumo de esta sustancia varía a nivel mundial dependiendo de diversos factores, entre ellos el estatus legal de cannabis en cada país, donde su legalización en la salud pública continúa siendo tema de controversia ya sea por uso de manera recreacional o médica (3) . ...
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El uso de cannabis a nivel mundial ha tenido un auge en los últimos años, según datos de la Organización Mundial de la Salud, tendencia que de igual manera se ha manifestado en Costa Rica. Además, los diferentes componentes químicos de la marihuana se asocian a un uso variado de la misma tal como recreacional, medicinal, o cosméticamente. Lo anterior va a incidir directamente en que exista una mayor posibilidad de que los usuarios presenten un cuadro de intoxicación de marihuana por su uso inadecuado, por lo cual es primordial que los médicos y demás personal de salud logren identificar el cuadro clínico de un paciente intoxicado con cannabis, así como saber realizar un manejo integral y brindar el seguimiento adecuado de estas personas, para así minimizar el riesgo de posibles consecuencias nocivas atribuibles al consumo de cannabis.
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Prior studies have found an especially high prevalence of illicit substance use among adolescents and young adults in Brazil. The current study aimed to employ machine learning techniques to identify predictors of illicit substance abuse/dependence among a large community sample of young adults followed for 5 years. This prospective, population-based cohort study included a sample of young adults between the ages of 18–24 years from Pelotas, Brazil at baseline (T1). The Alcohol, Smoking and Substance Involvement Screening Test (ASSIST) was used to assess illicit substance use. A clinical interview was conducted to collect data on sociodemographic characteristics and psychopathology. Elastic net was used to generate a regularized linear model for the machine learning component of this study, which followed standard machine learning protocols. A total of 1560 young adults were assessed at T1, while 1244 were reassessed at the 5-year follow-up period (T2). The strongest predictors of illicit substance abuse/dependence at baseline (AUC of 0.83) were alcohol abuse/dependence, tobacco abuse/dependence, being in a current major depressive episode, history of a lifetime manic episode, current suicide risk, and male sex. The strongest predictors for illicit substance abuse/dependence at the 5-year follow-up (AUC: 0.79) were tobacco abuse/dependence at T1, history of a lifetime manic episode at T1, male sex, alcohol abuse/dependence at T1, and current suicide risk at T1. Our findings indicate that machine learning techniques hold the potential to predict illicit substance abuse/dependence among young adults using sociodemographic/clinical characteristics, with relatively high accuracy.
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Introduction: There are health implications with the statewide legalization of recreational marijuana that are still not fully understood and require further examination. This study evaluates the prevalence of marijuana use in patients being treated for a variety of conditions and whether correlations exist between marijuana use, mental health conditions, and concomitant use of psychotropic medications. Methods: Data were collected from an electronic medical record (EMR) as part of a retrospective chart audit. A total of 500 charts were reviewed during a six-month timeframe from December 1, 2018 to May 31, 2019 with the start date approximating the timing of when marijuana became recreationally legalized in the State of Michigan. Results: This study demonstrated a point prevalence of 15.8% since 79 of the 500 charts reviewed had marijuana use documented. Additionally, marijuana users were more likely to have a history of cocaine use, schizophrenia, antipsychotic use, and tobacco use. Conclusion: Trends identified in this study provide a comparison point for the local prevalence of marijuana use immediately post state-wide legalization, with a projected increasing trend due to the removal of legal barriers.
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Objective: As medical cannabis use increases in North America, establishing its safety profile is a priority. The objective of this study was to assess rates of emergency department (ED) visits and hospitalizations due to poisoning by cannabis, and cannabis-related mental health disorders among medically authorized cannabis patients in Ontario, Canada, between 2014 and 2017. Methods: This is a retrospective cohort study of patients who received medical cannabis authorization in Ontario, Canada, using data collected in participating cannabis clinics. Outcomes included ED visit/hospitalization with a main diagnosis code for: cannabis/cannabinoid poisoning; and mental/behavioral disorders due to cannabis use. Cox proportional hazard regressions were utilized to analyze the data. Results: From 29,153 patients who received medical authorization, 23,091 satisfied the inclusion criteria. During a median follow-up of 240 days, 14 patients visited the ED or were hospitalized for cannabis poisoning-with an incidence rate of 8.06 per 10,000 person-years (95% CI: 4.8-13.6). A total of 26 patients visited the ED or were hospitalized for mental and behavioral disorders due to cannabis use-with an incidence rate of 15.0 per 10,000 person-years (95% CI: 10.2-22.0). Predictors of cannabis-related mental and behavioral disorders include prior substance use disorders, other mental disorders, age, diabetes, and chronic obstructive pulmonary disease. Conclusions: The results suggest that the incidence of cannabis poisoning or cannabis-related mental and behavioral disorders was low among patients who were authorized to use cannabis for medical care. Identified predictors can help to target patients with potential risk of the studied outcomes.
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Background The aim of the study was to determinate whether schizophrenia patients with a history of cannabis use have a different prognosis, with regards to readmission and hospital duration, compared with those without a history of cannabis use. Method The present investigation was a cohort study of 50 087 Swedish men with data on cannabis use at the ages of 18–20 years. A total of 357 cases of schizophrenia were identified from in-patient care and followed up from 1973 to 2007. Results Schizophrenia patients with a history of cannabis use had a higher median duration of first hospital episode (59 days v. 30 days). Patients with a history of cannabis use had a higher median rate of readmission (10 times v. four times). Also, total number of hospital days was higher in patients with a history of cannabis use compared with those without (547 days v. 184 days). Patients with a history of cannabis use had an increased odds of having more than 20 hospital readmissions compared with non-users [3.1, 95% confidence interval (CI) 1.3–7.3] as well as an increased odds of hospital admission lasting more than 2 years (2.4, 95% CI 1.1–7.4) after controlling for diagnosis of personality disorders, family socio-economic position, IQ score, civil status, place of residence, risky use of alcohol and use of other drugs. Patients with a history of cannabis use were less likely to have paranoid schizophrenia compared with never users (8% v. 17%) in the first admission. Conclusions Schizophrenia patients with a history of cannabis use had a significantly higher burden of lifetime in-patient care than non-cannabis users. Not only does cannabis increase the risk of schizophrenia, but also our findings indicate that the course and prognosis of schizophrenia may be more severe than schizophrenia cases in general.
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Background and Objectives Cannabis is the most widely used illicit substance worldwide, with an estimated 160 million users. Among adolescents, rates of cannabis use are increasing, while the perception of detrimental effects of cannabis use is declining. Difficulty with memory is one of the most frequently noted cognitive deficits associated with cannabis use, but little data exist exploring how well users can identify their own memory deficits, if present. Methods The current secondary analysis sought to characterize objective verbal and visual memory performance via a neurocognitive battery in cannabis-dependent adolescents enrolled in a pharmacotherapeutic cannabis cessation clinical trial (N = 112) and compare this to a single self-reported item assessing difficulties with memory loss. Exploratory analyses also assessed dose-dependent effects of cannabis on memory performance. Results A small portion of the study sample (10%) endorsed a "serious problem" with memory loss. Those participants reporting "no problem" or "serious problem" scored similarly on visual and verbal memory tasks on the neurocognitive battery. Exploratory analyses suggested a potential relationship between days of cannabis use, amount of cannabis used, and gender with memory performance. Conclusions and Scientific Significance This preliminary and exploratory analysis suggests that a sub-set of cannabis users may not accurately perceive difficulties with memory. Further work should test this hypothesis with the use of a control group, comprehensive self-reports of memory problems, and adult populations that may have more years of cannabis use and more severe cognitive deficits. (Am J Addict 2015;24:47-52)
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Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive, and fatal disease that has long eluded therapy. Prognosis remains very poor, and currently lung transplantation offers the only hope of survival. Recently, great strides have been made in the development of pharmaceutical therapy to treat IPF. Pirfenidone, an oral antifibrotic agent, has been shown to slow progression of the disease and improve progression-free survival, offering new hope for patients suffering from IPF. Expected final online publication date for the Annual Review of Medicine Volume 67 is January 14, 2016. Please see http://www.annualreviews.org/catalog/pubdates.aspx for revised estimates.
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Studying prevalence of Diagnostic and Statistical Manual (3rd ed., rev., American Psychiatric Association, 1987) drug dependence among Americans 15-54 years old, we found about 1 in 4 (24%) had a history of tobacco dependence; about 1 in 7 (14%) had a history of alcohol dependence; and about 1 in 13 (7.5%) had a history of dependence on an inhalant or controlled drug. About one third of tobacco smokers had developed tobacco dependence and about 15% of drinkers had become alcohol dependent. Among users of the other drugs, about 15% had become dependent. Many more Americans age 15-54 have been affected by dependence on psychoactive substances than by other psychiatric disturbances now accorded a higher priority in mental health service delivery systems, prevention, and sponsored research programs.
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Cannabis is one of the most widely used psychoactive substances in the United States (U.S.). Perceived risk of use is associated with substance use; the recent debate surrounding medicalization and legalization of cannabis in the U.S. has the potential to impact perceived risk of use. Recent estimates are needed to assess temporal changes in, and identify correlates of, perceived risk of cannabis use. Utilizing data from the 2002-2012 survey years of the National Survey on Drug Use and Health, chi-squared statistics and logistic regression were used to describe temporal changes in perceived risk of regular cannabis use (i.e., once or twice a week), to explore correlates of perceived risk, and to report frequency of cannabis use. Between 2002 and 2012, perceived great risk of regular cannabis use varied significantly overall (p<0.001). The prevalence of past year non-daily (p<0.001) and daily use varied significantly during this time (p<0.001). Controlling for survey year and other confounders, characteristics associated with increased odds of perceived great risk of regular cannabis use included: female sex; Non-White race/ethnicity; age 50+; and family income of $20,000-49,999. Characteristics associated with decreased odds of perceived great risk included: ages 12-17 and 18-25; high school education or greater; total family income of $75,000+; past year non-daily and daily cannabis use; and survey years 2008-2012. Findings characterize trends of perceived risk of regular cannabis use, and past year non-daily and daily cannabis use. Longitudinal studies of the influence of legal status of cannabis at the state-level are needed. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.
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This technical report updates the 2004 American Academy of Pediatrics technical report on the legalization of marijuana. Current epidemiology of marijuana use is presented, as are definitions and biology of marijuana compounds, side effects of marijuana use, and effects of use on adolescent brain development. Issues concerning medical marijuana specifically are also addressed. Concerning legalization of marijuana, 4 different approaches in the United States are discussed: legalization of marijuana solely for medical purposes, decriminalization of recreational use of marijuana, legalization of recreational use of marijuana, and criminal prosecution of recreational (and medical) use of marijuana. These approaches are compared, and the latest available data are presented to aid in forming public policy. The effects on youth of criminal penalties for marijuana use and possession are also addressed, as are the effects or potential effects of the other 3 policy approaches on adolescent marijuana use. Recommendations are included in the accompanying policy statement. Copyright © 2015 by the American Academy of Pediatrics.
Article
Investigate the efficacy of nabilone capsules (NAB) in reducing the frequency and intensity of nightmares in subjects with PTSD. Canadian male military personnel with PTSD, who despite standard treatment continued to experience trauma-related nightmares, received double-blind treatment with 0.5mg NAB or placebo (PBO), and then titrated to the effective dose (nightmare suppression) or reaching a maximum of 3.0mg. Subjects were followed for 7 weeks and then, following a 2-week washout period, were titrated with the other study treatment and followed for an additional 7 weeks. The modified intent-to-treat (mITT) population, which included all treated subjects that met inclusion/exclusion criteria, was analyzed. Ten subjects were included in the mITT population. The mean reduction in nightmares as measured by the CAPS Recurring and Distressing Dream scores were -3.6±2.4 and -1.0±2.1 in the NAB and PBO groups, respectively (p=0.03). Mean global improvement as measured by the Clinical Global Impression of Change (CGI-C) was 1.9±1.1 (i.e. much improved) and 3.2±1.2 (i.e. minimally improved) in the NAB and PBO groups, respectively (p=0.05) Five out of 10 (50%) were much improved on NAB versus 1 out of 9 (11%) on PBO. Results for the General Well Being Questionnaire (WBQ) were 20.8±22 and -0.4±20.6 in the NAB and PBO groups, respectively (p=0.04). The proportion of subjects who experienced a treatment-related occurrence of adverse events was 50% in the NBO group and 60% in the PBO group. No event was severe nor resulted in a drop-out. This study is registered with Health Canada. In this small sample NAB provided significant relief for military personnel with PTSD, indicating that it shows promise as a clinically-relevant treatment for patients with nightmares and a history of non-response to traditional therapies. These findings need to be replicated in a larger cohort. There is a need for further exploration of the effect of nabilone on other symptoms of PTSD such as re-experiencing, hyper vigilance and insomnia. Copyright © 2014. Published by Elsevier Ltd.
Article
Background and Objectives Cannabis is the most widely used illicit substance worldwide, with an estimated 160 million users. Among adolescents, rates of cannabis use are increasing, while the perception of detrimental effects of cannabis use is declining. Difficulty with memory is one of the most frequently noted cognitive deficits associated with cannabis use, but little data exist exploring how well users can identify their own memory deficits, if present.Methods The current secondary analysis sought to characterize objective verbal and visual memory performance via a neurocognitive battery in cannabis-dependent adolescents enrolled in a pharmacotherapeutic cannabis cessation clinical trial (N = 112) and compare this to a single self-reported item assessing difficulties with memory loss. Exploratory analyses also assessed dose-dependent effects of cannabis on memory performance.ResultsA small portion of the study sample (10%) endorsed a “serious problem” with memory loss. Those participants reporting “no problem” or “serious problem” scored similarly on visual and verbal memory tasks on the neurocognitive battery. Exploratory analyses suggested a potential relationship between days of cannabis use, amount of cannabis used, and gender with memory performance.Conclusions and Scientific SignificanceThis preliminary and exploratory analysis suggests that a sub-set of cannabis users may not accurately perceive difficulties with memory. Further work should test this hypothesis with the use of a control group, comprehensive self-reports of memory problems, and adult populations that may have more years of cannabis use and more severe cognitive deficits. (Am J Addict 2014;XX:1–7)
Article
Background The use of Cannabis for Therapeutic Purposes (CTP) has recently become legal in many places. These policy and legal modifications may be related to changes in cannabis perceptions, availability and use and in the way cannabis is grown and sold. This may in turn have effects on public health and safety. To better understand the potential effects of CTP legalization on public health and safety, the current paper synthesizes and critically discusses the relevant literature. Methods Twenty-Eight studies were identified by a comprehensive search strategy, and their characteristics and main findings were systematically reviewed according to the following content themes: CTP and illegal cannabis use; CTP and other public health issues; CTP, crime and neighbourhood disadvantage. Results The research field is currently limited by a lack of theoretical and methodological rigorous studies. The review shows that the most prevalent theme of investigation so far has been the relation between CTP and illegal cannabis use. In addition, the literature review shows that there is an absence of evidence to support many common concerns related to detrimental public health and safety effects of CTP legalization. Conclusion Although lack of evidence provides some reassurance that CTP legalization may not have posed a substantial threat to public health and safety, this conclusion needs to be examined in light of the limitations of studies conducted so far. Furthermore, as CTP policy continues to evolve, including incorporation of greater commercialization, it is possible that the full effects of CTP legalization have yet to take place. Ensuring study quality will allow future research to better investigate the complex role that CTP plays in relation to society at large, and public health and safety in particular.
Article
Importance Opioid analgesic overdose mortality continues to rise in the United States, driven by increases in prescribing for chronic pain. Because chronic pain is a major indication for medical cannabis, laws that establish access to medical cannabis may change overdose mortality related to opioid analgesics in states that have enacted them.Objective To determine the association between the presence of state medical cannabis laws and opioid analgesic overdose mortality.Design, Setting, and Participants A time-series analysis was conducted of medical cannabis laws and state-level death certificate data in the United States from 1999 to 2010; all 50 states were included.Exposures Presence of a law establishing a medical cannabis program in the state.Main Outcomes and Measures Age-adjusted opioid analgesic overdose death rate per 100 000 population in each state. Regression models were developed including state and year fixed effects, the presence of 3 different policies regarding opioid analgesics, and the state-specific unemployment rate.Results Three states (California, Oregon, and Washington) had medical cannabis laws effective prior to 1999. Ten states (Alaska, Colorado, Hawaii, Maine, Michigan, Montana, Nevada, New Mexico, Rhode Island, and Vermont) enacted medical cannabis laws between 1999 and 2010. States with medical cannabis laws had a 24.8% lower mean annual opioid overdose mortality rate (95% CI, −37.5% to −9.5%; P = .003) compared with states without medical cannabis laws. Examination of the association between medical cannabis laws and opioid analgesic overdose mortality in each year after implementation of the law showed that such laws were associated with a lower rate of overdose mortality that generally strengthened over time: year 1 (−19.9%; 95% CI, −30.6% to −7.7%; P = .002), year 2 (−25.2%; 95% CI, −40.6% to −5.9%; P = .01), year 3 (−23.6%; 95% CI, −41.1% to −1.0%; P = .04), year 4 (−20.2%; 95% CI, −33.6% to −4.0%; P = .02), year 5 (−33.7%; 95% CI, −50.9% to −10.4%; P = .008), and year 6 (−33.3%; 95% CI, −44.7% to −19.6%; P < .001). In secondary analyses, the findings remained similar.Conclusions and Relevance Medical cannabis laws are associated with significantly lower state-level opioid overdose mortality rates. Further investigation is required to determine how medical cannabis laws may interact with policies aimed at preventing opioid analgesic overdose.