ARTICULOS

Blurred Boundaries: The Therapeutics and Politics of Medical Marijuana

For 5 millennia, Cannabis sativa has been used throughout the world medically,
recreationally, and spiritually. From the mid-19th century to the 1930s, American
physicians prescribed it for a plethora of indications, until the federal government started
imposing restrictions on its use, culminating in 1970 with the US Congress classifying it as
a Schedule I substance, illegal, and without medical value. Simultaneous with this
prohibition, marijuana became the United States' most widely used illicit recreational drug,
a substance generally regarded as pleasurable and relaxing without the addictive dangers of
opioids or stimulants. Meanwhile, cannabis never lost its cachet in alternative medicine
circles, going mainstream in 1995 when California became the first of 16 states to date to
legalize its medical use, despite the federal ban. Little about cannabis is straightforward. Its
main active ingredient, -9-tetrahydrocannabinol, was not isolated until 1964, and not until
the 1990s were the far-reaching modulatory activities of the endocannabinoid system in the
human body appreciated. This system's elucidation raises the possibility of many promising
pharmaceutical applications, even as draconian federal restrictions that hamstring research
show no signs of softening. Recreational use continues unabated, despite growing evidence
of marijuana's addictive potential, particularly in the young, and its propensity for inducing
and exacerbating psychotic illness in the susceptible. Public approval drives medical
marijuana legalization efforts without the scientific data normally required to justify a new
medication's introduction. This article explores each of these controversies, with the intent
of educating physicians to decide for themselves whether marijuana is panacea, scourge, or
both. PubMed searches were conducted using the following keywords: medical
marijuana, medical
cannabis, endocannabinoid
system,CB1
receptors, CB2
receptors, THC, cannabidiol, nabilone, dronabinol, nabiximols, rimonabant,marijuana
legislation, marijuana abuse, marijuana dependence, and marijuana and schizophrenia.
Bibliographies were hand searched for additional references relevant to clarifying the
relationships between medical and recreational marijuana use and abuse.
Medical marijuana diversion and associated problems in adolescent substance
treatment
Background
The prevalence of medical marijuana diversion among adolescents in substance treatment
and the relationship between medical marijuana diversion and marijuana attitudes,
availability, peer disapproval, frequency of use and substance-related problems are not
known.

Methods
80 adolescents (15-19 years) in outpatient substance treatment in Denver, Colorado,
completed an anonymous questionnaire developed for the study and the Drug Use
Screening Inventory-Revised (DUSI-R). The proportion ever obtaining marijuana from
someone with a medical marijuana license was calculated. Those ever obtaining marijuana
from someone with a medical marijuana license were compared to those never obtaining
medical marijuana with respect to marijuana attitudes, availability, peer disapproval,
frequency of use, DUSI-R substance use problem and overall problem score using ChiSquare analyses and independent t-tests.
Results
39 (48.8%) reported ever obtaining marijuana from someone with a medical marijuana
license. A significantly greater proportion of those reporting medical marijuana diversion,
compared to those who did not, reported very easy marijuana availability, no friend
disapproval of regular marijuana use and greater than 20 times of marijuana use per month
over the last year. The diversion group compared to the no diversion group also reported
more substance use problems and overall problems on the DUSI-R.
Conclusions
Diversion of medical marijuana is common among adolescents in substance treatment.
These data support a relationship between medical marijuana exposure and marijuana
availability, social norms, frequency of use, substance-related problems and general
problems among teens in substance treatment. Adolescent substance treatment should
address the impact of medical marijuana on treatment outcomes.
Marijuana Use in Pregnancy and Lactation: A Review of the Evidence.
With the legalization of recreational marijuana in many states, we anticipate more women
will be using and self-reporting marijuana use in pregnancy. Marijuana is the most common
illicit drug used inpregnancy with a prevalence of use ranging from 3-30% in various
populations. Marijuana freely crosses the placenta and is found in breast milk. It may have
adverse effects on both perinatal outcomes and fetal neurodevelopment.
Specifically, marijuana may be associated with fetal growth restriction, stillbirth and
preterm birth. However, data are far from uniform regarding adverse perinatal outcomes.
Existing studies are plagued by confounding by tobacco, other drug exposures, as well as
socio-demographic factors. In addition there is a lack of quantification
of marijuana exposure by trimester of use, and a lack of corroboration of maternal selfreport with biologic sampling which contributes to the heterogeneity of study results. There

is an emerging body of evidence indicating that marijuana may cause problems with
neurological development resulting in hyperactivity, poor cognitive function, and changes
in dopaminergic receptors. In addition, contemporary marijuanaproducts have higher
quantities of delta-9-tetrahydrocannabinol (THC) than in the 1980s when much of
the marijuana research was completed. The effects on the pregnancy and fetus may
therefore be different than those previously seen. Further research is needed to provide
evidence-based counseling of women regarding the anticipated outcomes of marijuana use
in pregnancy.
In
the
meantime
women
should
be
advised
not
to
use marijuana in pregnancy or while lactating.
Neural Effects of Positive and Negative Incentives during Marijuana Withdrawal
In spite of evidence suggesting two possible mechanisms related to drug-seeking behavior,
namely reward-seeking and harm avoidance, much of the addiction literature has focused
largely on positive incentivization mechanisms associated with addiction. In this study, we
examined the contributing neural mechanisms of avoidance of an aversive state to drugseeking behavior during marijuana withdrawal. To that end, marijuana users were scanned
while performing the monetary incentive delay task in order to assess positive and negative
incentive processes. The results showed a group x incentive interaction, such that marijuana
users had greater response in areas that underlie reward processes during positive incentives
while controls showed greater response in the same areas, but to negative incentives.
Furthermore, a negative correlation between withdrawal symptoms and response in the
amygdala during negative incentives was found in the marijuana users. These findings
suggest that although marijuana users have greater reward sensitivity and less harm
avoidance than controls, that attenuated amygdala response, an area that underlies fear and
avoidance, was present in marijuana users with greater marijuana withdrawal symptoms.
This is concordant with models of drug addiction that involve multiple sources of
reinforcement in substance use disorders, and suggests the importance of strategies that
focus on respective mechanisms.
The Spread of Sleep Loss Influences Drug Use in Adolescent Social Networks
Troubled sleep is a commonly cited consequence of adolescent drug use, but it has rarely
been studied as a cause. Nor have there been any studies of the extent to which sleep
behavior can spread in social networks from person to person to person. Here we map the
social networks of 8,349 adolescents in order to study how sleep behavior spreads, how
drug use behavior spreads, and how a friend's sleep behavior influences one's own drug use.
We find clusters of poor sleep behavior and drug use that extend up to four degrees of
separation (to one's friends' friends' friends' friends) in the social network. Prospective
regression models show that being central in the network negatively influences future sleep
outcomes, but not vice versa. Moreover, if a friend sleeps 7 hours, it increases the

likelihood a person sleeps 7 hours by 11%. If a friend uses marijuana, it increases the
likelihood of marijuana use by 110%. Finally, the likelihood that an individual uses drugs
increases by 19% when a friend sleeps 7 hours, and a mediation analysis shows that 20%
of this effect results from the spread of sleep behavior from one person to another. This is
the first study to suggest that the spread of one behavior in social networks influences the
spread of another. The results indicate that interventions should focus on healthy sleep to
prevent drug use and targeting specific individuals may improve outcomes across the entire
social network.
Structural and Functional Imaging Studies in Chronic Cannabis Users: A Systematic
Review of Adolescent and Adult Findings
Background
The growing concern about cannabis use, the most commonly used illicit drug worldwide,
has led to a significant increase in the number of human studies using neuroimaging
techniques to determine the effect of cannabis on brain structure and function. We
conducted a systematic review to assess the evidence of the impact of chronic cannabis use
on brain structure and function in adults and adolescents.
Methods
Papers published until August 2012 were included from EMBASE, Medline, PubMed and
LILACS databases following a comprehensive search strategy and pre-determined set of
criteria for article selection. Only neuroimaging studies involving chronic cannabis users
with a matched control group were considered.
Results
One hundred and forty-two studies were identified, of which 43 met the established criteria.
Eight studies were in adolescent population. Neuroimaging studies provide evidence of
morphological brain alterations in both population groups, particularly in the medial
temporal and frontal cortices, as well as the cerebellum. These effects may be related to the
amount of cannabis exposure. Functional neuroimaging studies suggest different patterns of
resting global and brain activity during the performance of several cognitive tasks both in
adolescents and adults, which may indicate compensatory effects in response to chronic
cannabis exposure.
Limitations
However, the results pointed out methodological limitations of the work conducted to date
and considerable heterogeneity in the findings.

Conclusion
Chronic cannabis use may alter brain structure and function in adult and adolescent
population. Further studies should consider the use of convergent methodology, prospective
large samples involving adolescent to adulthood subjects, and data-sharing initiatives.
9-Tetrahydrocannabinol (THC) enhances lipopolysaccharide-stimulated tissue factor
in human monocytes and monocyte-derived microvesicl
Background
Immunomodulatory effects in humans of 9Tetrahydrocannabinol (THC), the
psychoactive component of marijuana are controversial. Tissue factor (TF), the activator of
the extrinsic coagulation cascade, is increased on circulating activated monocytes and is
expressed on microvesicles released from activated monocytes during inflammatory
conditions, which perpetuate coagulopathies in a number of diseases. In view of the
increased medicinal use of marijuana, effects of THC on human monocytes and monocytederived microvesicles activated by lipopolysaccharide (LPS) were investigated.
Findings
Peak levels of TF procoagulant activity developed in monocytes or microvesicles 6 h
following LPS treatment and were unaltered by THC. After 24 h of LPS stimulation, TF
activity declined in control-treated or untreated cells and microvesicles, but persisted with
THC treatment. Peak TF protein occurred within 6 h of LPS treatment independent of
THC; by 24 h, TF protein declined to almost undetectable levels without THC, but was
about 4-fold greater with THC. Steady-state TF mRNA levels were similar up to 2 h in the
presence of LPS with or without THC, while 10-fold greater TF mRNA levels persisted
over 324 h with THC treatment. Activation of MAPK or NF-B pathways was unaltered
by THC treatment and inflammatory cytokine IL-6 levels were unchanged. In contrast,
TNF and IL-8 levels were enhanced by 2050 %.
Conclusions
THC enhances TF expression in activated monocytes resulting in elevated procoagulant
activity. Marijuana use could potentiate coagulopathies in individuals with chronic immune
activation such as HIV-1 infection or inflammatory bowel disease
Cannabis in medicine: a national educational needs assessment among Canadian
physician
Background
There is increasing global awareness and interest in the use of cannabis for therapeutic
purposes (CTP). It is clear that health care professionals need to be involved in these
decisions, but often lack the education needed to engage in informed discussions with
patients. This study was conducted to determine the educational needs of Canadian
physicians regarding CTP.

Methods
A national needs assessment survey was developed based on previous survey tools. The
survey was approved by the Research Ethics Board of the McGill University Health Centre
Research Institute and was provided online using LimeSurvey. Several national physician
organizations and medical education organizations informed their members of the survey.
The target audience was Canadian physicians. We sought to identify and rank using 5-point
Likert scales the most common factors involved in decision making about using CTP in the
following categories: knowledge, experience, attitudes, and barriers. Preferred educational
approaches and physician demographics were collected. Gap analysis was conducted to
determine the magnitude and importance of differences between perceived and desired
knowledge on all decision factors.
Results
Four hundred and twenty six responses were received, and physician responses were
distributed across Canada consistent with national physician distribution. The most desired
knowledge concerned potential risks of using CTP and safety, warning signs and
precautions for patients using CTP. The largest gap between perceived current and desired
knowledge levels was dosing and the development of treatment plans.
Conclusions
We have identified several key educational needs among Canadian physicians regarding
CTP. These data can be used to develop resources and educational programs to support
clinicians in this area, as well as to guide further research to inform these gaps.
The Social Contagion Effect of Marijuana Use among Adolescents
Background
Research on adolescent substance use has consistently identified a strong relationship
between adolescent behavior and the behavior of their peers. However, peer effects are
difficult to estimate and causal interpretations must be undertaken with caution since
individuals in most cases choose with whom to associate. In this paper we seek to
empirically quantify the causal role of peer social networks in explaining marijuana usage
among adolescents.
Methods and Findings
Using data from a nationally representative sample of adolescents we utilize a multivariate
structural model with school-level fixed effects to account for the problems of contextual
effects, correlated effects and peer selections to purge the potential biases from the
estimates of peer influence. Our peer group measures are drawn not only from the
nomination of close friends (N = 6,377), but also from classmates (N = 19,335). Marijuana
usage among the peer groups were constructed using the peers' own report of their
marijuana consumption. Controlling for parent level characteristics, and other demographic
parameters, we find that a 10% increase in the proportion of close friends and classmates

who use marijuana increases the probability that an individual chooses to use marijuana by
5%.
Conclusion
Our findings indicate that peer effects are important determinants of marijuana use even
after controlling for potential biases We also found evidence to show that the influence of
close friends and the more exogenous classmates are quite similar in magnitude under our
preferred specification, supporting theory predicting the importance of peer influence.
Effective policy aimed at reducing marijuana usage among adolescents would consider
these significant peer effects.
Impacts of Surface Water Diversions for Marijuana Cultivation on Aquatic Habitat in
Four Northwestern California Watersheds
Abstract
Marijuana (Cannabis sativa L.) cultivation has proliferated in northwestern California since
at least the mid-1990s. The environmental impacts associated with marijuana cultivation
appear substantial, yet have been difficult to quantify, in part because cultivation is
clandestine and often occurs on private property. To evaluate the impacts of water
diversions at a watershed scale, we interpreted high-resolution aerial imagery to estimate
the number of marijuana plants being cultivated in four watersheds in northwestern
California, USA. Low-altitude aircraft flights and search warrants executed with law
enforcement at cultivation sites in the region helped to validate assumptions used in aerial
imagery interpretation. We estimated the water demand of marijuana irrigation and the
potential effects water diversions could have on stream flow in the study watersheds. Our
results indicate that water demand for marijuana cultivation has the potential to divert
substantial portions of streamflow in the study watersheds, with an estimated flow
reduction of up to 23% of the annual seven-day low flow in the least impacted of the study
watersheds. Estimates from the other study watersheds indicate that water demand for
marijuana cultivation exceeds streamflow during the low-flow period. In the most impacted
study watersheds, diminished streamflow is likely to have lethal or sub-lethal effects on
state-and federally-listed salmon and steelhead trout and to cause further decline of
sensitive amphibian species.